Sources and method
How we worked – and where the limits of this review lie.
Primary sources
On 25 October 2026 we saved and analysed the following publicly accessible sources:
- the archive eltayebat.com: home page, food list, 17 rule pages in Arabic and English, and 339 studies cited there;
- 307 video pages with transcripts stored in the archive (March 2021 to April 2026);
- the unofficial sites altayybat.com and mytayibat.com.
According to the archive, the transcripts come from YouTube subtitles or an AI transcription. They contain no timestamps, may contain errors, and do not always distinguish between different speakers. We did not watch the videos themselves individually.
Who said what? Source status
Each statement has a source status:
- Video transcript: Elawady's own words (machine-transcribed). Arabic quotations were checked automatically for verbatim agreement with the transcript.
- Archive quote: a quotation the archive attributes to Elawady without naming the video. We searched for where these quotations occur in the transcripts. Only one was found verbatim, most as paraphrases.
- Archive editors: texts and study selection by the archive operators. According to the archive, the studies were compiled “independently of Dr. Diaa's words”. When we assess how a study is used, we therefore assess the archive, not Elawady.
- Food list of the archive and third-party sites: system rules without a reference, or unofficial presentations. Where the sources contradict each other, we show all versions.
Verification of the cited studies
All 339 studies cited by the archive were automatically matched against the PubMed database (via the official interface of the US National Library of Medicine) or Crossref: existence, title, year, journal, DOI, retraction and correction notices.
- All 339 studies exist. None has been retracted.
- For 8 entries, the PMID given by the archive led to an entirely different paper. We identified the correct publication by title search and marked it.
- PubMed lists corrections (errata) for 22 studies. This is noted for each study.
Independent cross-check
For each statement we also searched for independent evidence: systematic reviews, meta-analyses, randomised trials, large cohort studies, guidelines and statements by authorities and professional societies (including WHO, EFSA, BfR, BVL, the European Commission, IARC, ADA/EASD, NHS). Every study added was also checked via PubMed, and every official page was actually retrieved. We explicitly also searched for evidence supporting Elawady's position. The search logs are documented in the project.
Assessing studies and statements
We explain the basics under Understanding science. In short:
- Each study is assessed along several dimensions (including methodological quality, risk of bias, precision, directness, regional transferability) and, if cited by the archive, for the adequacy of how it is reported.
- Each statement receives a verdict on a seven-point scale and, separately, a certainty of evidence following GRADE logic.
- Studies are classified per statement as supporting, contradicting/limiting or mixed.
- All assessments are provisional until an external expert review has taken place.
Limits
- Most studies were checked on the basis of the abstract, only a few in full text. This is stated for each.
- Bias tools (RoB 2, ROBINS-E, AMSTAR 2, ROBIS) were applied for orientation only. No full formal assessment with independent double review took place.
- Some official documents (e.g. EUR-Lex, Egyptian regulations) could not be retrieved for technical reasons. This is noted for the sources concerned.
- The research was carried out with the support of an AI system (see About the project).
Study register
| ID | Authors / Title | Year | DOI / PMID | Study design | Population | Results | 7. Weaknesses | Methodological quality | Claims |
|---|---|---|---|---|---|---|---|---|---|
| A-ABX-01 | Association of antibiotics in infancy with early childhood obesity. Bailey LC, Forrest CB, Zhang P et al. | 2014 | PMID 25265089 DOI 10.1001/jamapediatrics.2014.1539 | Cohort study | Children in CHOP primary-care network | Children with 4+ antibiotic courses before age 2 were about 11% more likely to be obese. | Observational; residual confounding; Infections may confound | moderate | C-ABX-05 |
| A-ABX-02 | Infant antibiotic exposures and early-life body mass. Trasande L, Blustein J, Liu M et al. | 2013 | PMID 22907693 DOI 10.1038/ijo.2012.132 | Cohort study | Children born >=2500 g in Avon, UK, 1991-1992 (92.6% white; slightly more affluent than UK population; 85% of eligible births captured) | Antibiotics before 6 months were linked to slightly higher body mass later. | Parental recall of antibiotic use over 3-9 months; no type, dose or route; Confounding by indication (infections) not addressed; residual confounding acknowledged by authors | moderate | C-ABX-05 |
| A-ABX-03 | Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cox LM, Yamanishi S, Sohn J et al. | 2014 | PMID 25126780 DOI 10.1016/j.cell.2014.05.052 | Animal study | Laboratory mice (C57BL/6J, male and female; germ-free female Swiss-Webster recipients) | Low-dose penicillin early in life made mice fatter via their gut bacteria. | Mice; very small groups (3-10) with many t-tests and no multiplicity correction; Sub-therapeutic continuous dosing (growth-promoter model) unlike short human therapeutic courses | moderate | C-ABX-05 C-RES-05 |
| A-ABX-04 | Antibiotic exposure in the first two years of life and development of asthma and other allergic diseases by 7.5 yr: a dose-dependent relationship. Hoskin-Parr L, Teyhan A, Blocker A et al. | 2013 | PMID 24299467 DOI 10.1111/pai.12153 | Cohort study | Children | More antibiotic courses were linked to more asthma at age 7. | Maternal report; Protopathic bias likely | moderate | C-ABX-06 |
| A-ABX-05 | Antibiotic exposure by 6 months and asthma and allergy at 6 years: Findings in a cohort of 1,401 US children. Risnes KR, Belanger K, Murk W et al. | 2011 | PMID 21190986 DOI 10.1093/aje/kwq400 | Cohort study | US children | Antibiotics before 6 months were linked to asthma at age 6. | Small; Two errata | moderate | C-ABX-06 |
| A-ABX-06 | Antibiotic use in children is associated with increased risk of asthma. Marra F, Marra CA, Richardson K et al. | 2009 | PMID 19255032 DOI 10.1542/peds.2008-1146 | Cohort study | BC births 1997-2003 | Infant antibiotics were linked to a small increased asthma risk. | No sibling control | moderate | C-ABX-06 |
| A-ABX-07 | Antibiotics associated with increased risk of new-onset Crohn's disease but not ulcerative colitis: a meta-analysis. Ungaro R, Bernstein CN, Gearry R et al. | 2014 | PMID 25223575 DOI 10.1038/ajg.2014.246 | Meta-analysis | 7208 IBD patients | Antibiotic exposure was linked to higher odds of Crohn's disease, especially in children. | Observational studies only; Heterogeneity not in abstract | moderate | C-ABX-07 |
| A-ABX-08 | Antibiotic exposure and IBD development among children: a population-based cohort study. Kronman MP, Zaoutis TE, Haynes K et al. | 2012 | PMID 23008454 DOI 10.1542/peds.2011-3886 | Cohort study | UK children | IBD was more common after antianaerobic antibiotics, but absolute rates remained low. | Protopathic bias possible | moderate | C-ABX-07 |
| A-ABX-09 | Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Dethlefsen L, Relman DA | 2011 | PMID 20847294 DOI 10.1073/pnas.1000087107 | Case series / case report | 3 healthy adults | In 3 people, gut bacteria changed quickly and did not fully return to the original state. | n=3; No clinical outcomes | moderate | C-ABX-04 |
| A-ABX-10 | Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome. Jakobsson HE, Jernberg C, Andersson AF et al. | 2010 | PMID 20352091 DOI 10.1371/journal.pone.0009836 | Cohort study | Adults treated vs untreated controls | Changes and resistance genes persisted in some people up to 4 years. | Small | moderate | C-ABX-04 |
| A-ABX-11 | Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability. Yassour M, Vatanen T, Siljander H et al. | 2016 | PMID 27306663 DOI 10.1126/scitranslmed.aad0917 | Cohort study | 39 children | Children given antibiotics had less diverse gut bacteria. | n=39 | moderate | C-ABX-04 |
| A-ABX-12 | Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection. Brown KA, Khanafer N, Daneman N et al. | 2013 | PMID 23478961 DOI 10.1128/AAC.02176-12 | Meta-analysis | Non-hospitalised | Some antibiotics (e.g. clindamycin) strongly raise C. difficile risk; tetracyclines did not. | Few studies | moderate | C-ABX-09 |
| A-ABX-13 | Azithromycin and the risk of cardiovascular death. Ray WA, Murray KT, Hall K et al. | 2012 | PMID 22591294 DOI 10.1056/NEJMoa1003833 | Cohort study | Tennessee Medicaid enrollees aged 30-74 years without life-threatening non-cardiovascular illness (azithromycin users 77.5% women, mean age 48.6) | Azithromycin was linked to about 47 extra heart deaths per million courses compared with amoxicillin. | Observational; residual confounding (smoking, BMI, infection severity) possible as acknowledged; Small numbers of events (29 CV deaths on azithromycin) | high | C-ABX-08 |
| A-ABX-14 | Increased risk of achilles tendon rupture with quinolone antibacterial use, especially in elderly patients taking oral corticosteroids. van der Linden PD, Sturkenboom MC, Herings RM et al. | 2003 | PMID 12912715 DOI 10.1001/archinte.163.15.1801 | Case-control study | UK GP patients | Current quinolone use was linked to about 4 times higher odds of Achilles rupture. | Case-control | moderate | C-ABX-09 |
| A-ABX-15 | Risk of Aortic Dissection and Aortic Aneurysm in Patients Taking Oral Fluoroquinolone. Lee CC, Lee MT, Chen YS et al. | 2015 | PMID 26436523 DOI 10.1001/jamainternmed.2015.5389 | Case-control study | 1 million insured | Current use was linked to higher risk of rare aortic events. | Observational | moderate | C-ABX-09 |
| A-ABX-16 | Fluoroquinolone use and risk of aortic aneurysm and dissection: nationwide cohort study. Pasternak B, Inghammar M, Svanström H | 2018 | PMID 29519881 DOI 10.1136/bmj.k678 | Cohort study | Treatment episodes | About 82 extra cases per million treatment courses compared with amoxicillin. | Observational | high | C-ABX-09 |
| A-ABX-17 | Antibiotic use in relation to the risk of breast cancer. Velicer CM, Heckbert SR, Lampe JW et al. | 2004 | PMID 14970061 DOI 10.1001/jama.291.7.827 | Case-control study | Women >19 y | More antibiotic use was linked to breast cancer, but cause and effect could not be determined. | Minimal adjustment; Confounding by indication | low | C-ABX-10 |
| A-ABX-18 | Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Antimicrobial Resistance Collaborators | 2022 | PMID 35065702 DOI 10.1016/S0140-6736(21)02724-0 | Risk assessment | Global | About 1.27 million deaths were directly caused by resistant bacteria in 2019. | Model-based; sparse data in many countries | high | C-ABX-02 C-ABX-03 C-ABX-12 |
| A-ABX-19 | Prevalence of Inappropriate Antibiotic Prescriptions Among US Ambulatory Care Visits, 2010-2011. Fleming-Dutra KE, Hersh AL, Shapiro DJ et al. | 2016 | PMID 27139059 DOI 10.1001/jama.2016.4151 | Cross-sectional study | US ambulatory visits | About 30% of outpatient antibiotic prescriptions were judged unnecessary. | Appropriateness estimated, not chart-reviewed | high | C-ABX-01 C-ABX-12 |
| A-ABX-20 | Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis. Costelloe C, Metcalfe C, Lovering A et al. | 2010 | PMID 20483949 DOI 10.1136/bmj.c2096 | Meta-analysis | Patients | After an antibiotic, resistant bacteria are more common for months. | Mostly observational | moderate | C-ABX-01 |
| A-ABX-21 | Risk of meticillin resistant Staphylococcus aureus and Clostridium difficile in patients with a documented penicillin allergy: population based matched cohort study. Blumenthal KG, Lu N, Zhang Y et al. | 2018 | PMID 29950489 DOI 10.1136/bmj.k2400 | Cohort study | UK adults | People labelled penicillin-allergic had more MRSA and C. difficile, partly due to alternative antibiotics. | Observational | high | C-ABX-09 |
| A-BAR-01 | Perioperative safety in the longitudinal assessment of bariatric surgery. Longitudinal Assessment of Bariatric Surgery (LABS) Consortium, Flum DR, Belle SH et al. | 2009 | PMID 19641201 DOI 10.1056/NEJMoa0901836 | Cohort study | Adults with extreme obesity (median BMI 46.5) undergoing first-time RYGB or LAGB | About 3 in 1000 patients died within 30 days; 4.3% had a serious complication. | Only 30-day outcomes; Sleeve gastrectomy (n=117) excluded from outcome analyses | high | C-BAR-01 |
| A-BAR-02 | Effects of bariatric surgery on mortality in Swedish obese subjects. Sjöström L, Narbro K, Sjöström CD et al. | 2007 | PMID 17715408 DOI 10.1056/NEJMoa066254 | Cohort study | Adults with obesity in Sweden | Over about 11 years, people who had surgery had roughly 24-29% lower risk of dying than matched controls. | Not randomized (self-selection); Mostly older procedures (VBG, banding); few bypass, no sleeve | moderate | C-BAR-01 C-BAR-12 |
| A-BAR-03 | Long-term mortality after gastric bypass surgery. Adams TD, Gress RE, Smith SC et al. | 2007 | PMID 17715409 DOI 10.1056/NEJMoa066603 | Cohort study | Severely obese adults, Utah | Total deaths were 40% lower after surgery, while deaths from accidents and suicide were higher (11.1 vs 6.4 per 10,000 person-years). | Retrospective; controls from licence registry with limited health data; Residual confounding | moderate | C-BAR-01 C-BAR-07 C-BAR-12 |
| A-BAR-04 | Weight and Metabolic Outcomes 12 Years after Gastric Bypass. Adams TD, Davidson LE, Litwin SE et al. | 2017 | PMID 28930514 DOI 10.1056/NEJMoa1700459 | Cohort study | Adults 18-72 years with severe obesity (mean baseline BMI about 45-47; 84% women in surgery group) | Half of the patients with diabetes were still in remission after 12 years; new diabetes was about 90% less frequent than in non-operated people. | Non-randomized; residual confounding acknowledged by authors; Small diabetic subgroup (n=84-88) with wide CIs for remission ORs | moderate | C-BAR-08 C-BAR-14 |
| A-BAR-05 | Life Expectancy after Bariatric Surgery in the Swedish Obese Subjects Study. Carlsson LMS, Sjöholm K, Jacobson P et al. | 2020 | PMID 33053284 DOI 10.1056/NEJMoa2002449 | Cohort study | Swedish adults with obesity; general-population reference sample | Operated patients lived about 3 years longer than non-operated patients with obesity, but still about 5.5 years less than the general population (non-operated: about 8.5 years less). | Not randomized; Old procedures; little sleeve data | moderate | C-BAR-01 C-BAR-09 C-BAR-10 C-BAR-12 |
| A-BAR-06 | Seven-Year Weight Trajectories and Health Outcomes in the Longitudinal Assessment of Bariatric Surgery (LABS) Study. Courcoulas AP, King WC, Belle SH et al. | 2018 | PMID 29214306 DOI 10.1001/jamasurg.2017.5025 | Cohort study | US adults undergoing bariatric surgery | About 60% of bypass patients with diabetes were still in remission at 7 years. | No non-surgical control; No sleeve gastrectomy | moderate | C-BAR-08 |
| A-BAR-07 | Effect of Laparoscopic Sleeve Gastrectomy vs Roux-en-Y Gastric Bypass on Weight Loss, Comorbidities, and Reflux at 10 Years in Adult Patients With Obesity: The SLEEVEPASS Randomized Clinical Trial. Salminen P, Grönroos S, Helmiö M et al. | 2022 | PMID 35731535 DOI 10.1001/jamasurg.2022.2229 | Randomised controlled trial | Adults 18-60 with severe obesity (median BMI 44.6) | Esophagitis was found in 31% after sleeve vs 7% after bypass; Barrett's esophagus was 4% in both groups. | 77% endoscopy completion; No non-surgical arm | high | C-BAR-02 C-BAR-03 C-BAR-04 C-BAR-10 C-BAR-14 |
| A-BAR-08 | Reflux, Sleeve Dilation, and Barrett's Esophagus after Laparoscopic Sleeve Gastrectomy: Long-Term Follow-Up. Felsenreich DM, Kefurt R, Schermann M et al. | 2017 | PMID 28593484 DOI 10.1007/s11695-017-2748-9 | Case series / case report | SG patients without preoperative symptomatic reflux or hiatal hernia | Many patients had reflux and 15% had Barrett's changes, but the study was very small. | Very small; Early SG technique | low | C-BAR-02 C-BAR-04 |
| A-BAR-09 | Systematic Endoscopy 5 Years After Sleeve Gastrectomy Results in a High Rate of Barrett's Esophagus: Results of a Multicenter Study. Sebastianelli L, Benois M, Vanbiervliet G et al. | 2019 | PMID 30666544 DOI 10.1007/s11695-019-03704-y | Cross-sectional study | SG patients without preoperative BE | About 1 in 5 had Barrett's changes; reflux symptoms rose from 22% to 76%. | Small; No control | low | C-BAR-02 C-BAR-03 C-BAR-04 |
| A-BAR-10 | Causes of small bowel obstruction after Roux-en-Y gastric bypass: a review of 2,395 cases at a single institution. Elms L, Moon RC, Varnadore S et al. | 2014 | PMID 24380988 DOI 10.1007/s00464-013-3361-1 | Case series / case report | LRYGB patients | About 4 in 100 patients needed another operation for possible bowel obstruction. | Single centre; Retrospective | low | C-BAR-14 |
| A-BAR-11 | Risk Factors for Marginal Ulcer After Gastric Bypass Surgery for Obesity: A Population-based Cohort Study. Sverdén E, Mattsson F, Sondén A et al. | 2016 | PMID 26106845 DOI 10.1097/SLA.0000000000001300 | Cohort study | Gastric bypass patients | Diabetes and earlier ulcers increased the risk of ulcers at the new stomach connection. | Register data | moderate | C-BAR-14 |
| A-BAR-12 | Early complications after laparoscopic gastric bypass surgery: results from the Scandinavian Obesity Surgery Registry. Stenberg E, Szabo E, Agren G et al. | 2014 | PMID 24374541 DOI 10.1097/SLA.0000000000000431 | Cohort study | Primary LRYGB patients | Serious complications 3.4%; deaths within 90 days 4 in 10,000. | Short-term only | high | C-BAR-01 |
| A-BAR-13 | Prevalence of alcohol use disorders before and after bariatric surgery. King WC, Chen JY, Mitchell JE et al. | 2012 | PMID 22710289 DOI 10.1001/jama.2012.6147 | Cohort study | Adults (78.8% female, 87.0% white, median age 47, median BMI 45.8) undergoing a first bariatric procedure (69.9% RYGB, 25.2% LAGB, 2.6% sleeve, 1.5% banded bypass, 0.8% BPD-DS) | Alcohol use disorder symptoms rose from 7.6% before surgery to 9.6% in the second year, mostly after gastric bypass. | No non-surgical control group (authors); Self-report; possible under-reporting before surgery and after a safety-referral trigger (authors) | moderate | C-BAR-07 |
| A-BAR-14 | Alcohol and other substance use after bariatric surgery: prospective evidence from a U.S. multicenter cohort study. King WC, Chen JY, Courcoulas AP et al. | 2017 | PMID 28528115 DOI 10.1016/j.soard.2017.03.021 | Cohort study | Adults with severe obesity undergoing first RYGB or LAGB (79.2% women, median age 47, median BMI 45.6, 87.0% white) | One in five bypass patients reported new alcohol problem symptoms within 5 years. | No non-surgical control and no randomization; findings cannot necessarily be attributed to surgery (authors); Retention 66-78% per year; MAR assumption | moderate | C-BAR-07 C-BAR-14 |
| A-BAR-15 | Self-harm Emergencies After Bariatric Surgery: A Population-Based Cohort Study. Bhatti JA, Nathens AB, Thiruchelvam D et al. | 2016 | PMID 26444444 DOI 10.1001/jamasurg.2015.3414 | Cohort study | Ontario adults undergoing bariatric surgery (98.5% gastric bypass) | Emergency visits for self-harm rose from 2.33 to 3.63 per 1000 patient-years after surgery. | Time trends not controlled; Only gastric bypass | moderate | C-BAR-07 |
| A-BAR-16 | Risk of suicide and non-fatal self-harm after bariatric surgery: results from two matched cohort studies. Neovius M, Bruze G, Jacobson P et al. | 2018 | PMID 29329975 DOI 10.1016/S2213-8587(17)30437-0 | Cohort study | Swedish adults with obesity attempting weight loss. SOS: age 37-60, BMI >=34 (men)/>=38 (women), excluding drug/alcohol abuse and psychiatric contraindications. SOReg/Itrim: age >=18, BMI 30-49.9 | Self-harm and suicide were more frequent after surgery, but absolute risks were low. | Non-randomised; selection bias and residual confounding acknowledged (self-harm history more common in SOS surgery group: 3.4% vs 1.9%); Itrim participants paid for treatment (socioeconomic selection), partly addressed by adjustment | moderate | C-BAR-01 C-BAR-07 |
| A-BAR-17 | Risk of fracture after bariatric surgery in the United Kingdom: population based, retrospective cohort study. Lalmohamed A, de Vries F, Bazelier MT et al. | 2012 | PMID 22867649 DOI 10.1136/bmj.e5085 | Cohort study | UK adults BMI>=30 | No significant increase in fractures in the first 2-3 years. | Mean follow-up 2.2 years; Many banding procedures likely | moderate | C-BAR-06 |
| A-BAR-18 | Bone loss after bariatric surgery: discordant results between DXA and QCT bone density. Yu EW, Bouxsein ML, Roy AE et al. | 2014 | PMID 23929784 DOI 10.1002/jbmr.2063 | Cohort study | Morbidly obese adults | Spine bone density fell about 3% in one year; hip loss seen on DXA was not confirmed by CT. | Small; 1 year | moderate | C-BAR-06 |
| A-BAR-19 | Bone Density and Trabecular Morphology at Least 10 Years After Gastric Bypass and Gastric Banding. Lindeman KG, Rushin CC, Cheney MC et al. | 2020 | PMID 32663365 DOI 10.1002/jbmr.4112 | Cross-sectional study | 25 RYGB, 25 AGB, BMI-matched controls | Bypass patients had weaker bone structure than people of the same weight; band patients did not. | Small; Cross-sectional | moderate | C-BAR-06 |
| A-BAR-20 | Bariatric surgery and long-term nutritional issues. Lupoli R, Lembo E, Saldalamacchia G et al. | 2017 | PMID 29204255 DOI 10.4239/wjd.v8.i11.464 | Narrative review | Bariatric patients | Deficiencies are common but can be prevented with lifelong supplements and monitoring. | Non-systematic narrative review; selection of cited studies not described; Wide prevalence ranges from heterogeneous studies and definitions | low | C-BAR-05 C-BAR-10 |
| A-BAR-21 | Nutritional deficiencies after bariatric surgery. Bal BS, Finelli FC, Shope TR et al. | 2012 | PMID 22525731 DOI 10.1038/nrendo.2012.48 | Narrative review | Bariatric patients | Protein, vitamins and minerals can become deficient; many patients were already deficient before surgery. | Non-systematic; 2012 | low | C-BAR-05 |
| A-BAR-22 | Outcomes of pregnancy after bariatric surgery. Johansson K, Cnattingius S, Näslund I et al. | 2015 | PMID 25714159 DOI 10.1056/NEJMoa1405789 | Cohort study | Singleton pregnancies | Less gestational diabetes and fewer large babies, but more small babies. | Small number of deaths | moderate | C-BAR-01 |
| A-BAR-23 | Association of bariatric surgery with long-term remission of type 2 diabetes and with microvascular and macrovascular complications. Sjöström L, Peltonen M, Jacobson P et al. | 2014 | PMID 24915261 DOI 10.1001/jama.2014.5988 | Cohort study | SOS participants with T2D at baseline | Remission fell from 72% at 2 years to 30% at 15 years after surgery (controls: 16% to 6.5%); diabetes complications were about halved. | Low participation at 15 years (41-47%); Non-randomized | moderate | C-BAR-08 |
| A-BAR-24 | Bariatric Surgery versus Intensive Medical Therapy for Diabetes - 5-Year Outcomes. Schauer PR, Bhatt DL, Kirwan JP et al. | 2017 | PMID 28199805 DOI 10.1056/NEJMoa1600869 | Randomised controlled trial | Adults 20-60 years with uncontrolled T2D (HbA1c >7.0%) and BMI 27-43; analysed patients: mean age 49, 66% women, HbA1c 9.2%, BMI 37 (37% BMI <35), diabetes duration 8.4 years, 44% on insulin | After 5 years, 23-29% of operated patients reached near-normal HbA1c vs 5% with medicines alone. | Single centre, small; underpowered for hard clinical endpoints and for RYGB vs sleeve differences (authors); Non-blinded | moderate | C-BAR-08 C-BAR-10 C-BAR-14 |
| A-CHK-01 | Multidrug-Resistant Staphylococcus aureus in US Meat and Poultry. Waters AE, Contente-Cuomo T, Buchhagen J et al. | 2011 | PMID 21498385 DOI 10.1093/cid/cir181 | Cross-sectional study | Retail beef (ground), chicken (breasts, thighs), pork (chops, ground) and turkey (ground, cutlets) from 80 brands in 26 grocery stores | Almost half of meat samples carried S. aureus; about half of the isolates were multidrug-resistant, but for chicken it was about a quarter and no MRSA was found on chicken. | Small sample; authors state it was insufficient to estimate prevalence accurately; Convenience sampling; sampling period not reported | moderate | C-CHK-05 |
| A-CHK-02 | Dutch patients, retail chicken meat and poultry share the same ESBL genes, plasmids and strains. Leverstein-van Hall MA, Dierikx CM, Cohen Stuart J et al. | 2011 | PMID 21463397 DOI 10.1111/j.1469-0691.2011.03497.x | Cross-sectional study | Retail chicken, poultry, human clinical samples from 31 labs | Most retail chicken had ESBL bacteria, and many human isolates shared the same genes and plasmids. | Cross-sectional; direction of transmission inferred; 2009 data | high | C-CHK-05 |
| A-CHK-03 | Extended-spectrum β-lactamase genes of Escherichia coli in chicken meat and humans, The Netherlands. Overdevest I, Willemsen I, Rijnsburger M et al. | 2011 | PMID 21762575 DOI 10.3201/eid1707.110209 | Cross-sectional study | Retail chicken; patients in 4 hospitals | Four in five chicken samples had ESBL genes, matching those found in people. | Directionality inferred; Sample sizes not in abstract | moderate | C-CHK-05 |
| A-CHK-04 | Roxarsone, inorganic arsenic, and other arsenic species in chicken: a U.S.-based market basket sample. Nachman KE, Baron PA, Raber G et al. | 2013 | PMID 23694900 DOI 10.1289/ehp.1206245 | Measurement / residue study | Conventional, antibiotic-free and organic retail chicken in 10 US metro areas | Conventional chicken had about three times more inorganic arsenic than organic chicken; estimated extra cancer risk was small. | Speciation only in samples with total As >=10 ug/kg DW (selection of higher-arsenic samples); Breast meat only; one sampling period (2010-2011) before US withdrawal of roxarsone | moderate | C-CHK-07 |
| A-CHK-05 | Global trends in antimicrobial use in food animals. Van Boeckel TP, Brower C, Gilbert M et al. | 2015 | PMID 25792457 DOI 10.1073/pnas.1503141112 | Other | Global livestock (cattle, chicken, pigs) | Models estimated about 63,000 tons used in 2010 with a projected 67% increase by 2030. | Extrapolation from high-income data; Model uncertainty larger than reported SD may suggest | moderate | C-CHK-05 |
| A-CHK-06 | Modern organic and broiler chickens sold for human consumption provide more energy from fat than protein. Wang Y, Lehane C, Ghebremeskel K et al. | 2010 | PMID 19728900 DOI 10.1017/S1368980009991157 | Other | Whole chickens and cuts (skinless breast fillets, breast with skin, legs with skin, whole birds with skin) from organic farms and supermarkets ('farmed' = conventional); one wild pheasant as reference | Whole chickens with skin had more energy from fat than protein; skinless breast was lean, and organic chickens were similar. | Total sample size not reported; very small subgroups (often n=2-3); Opportunistic sourcing including media-supplied samples; no sampling frame | low | C-CHK-11 |
| A-CHK-07 | Fluoroquinolone-resistant Campylobacter infections: eating poultry outside of the home and foreign travel are risk factors. Kassenborg HD, Smith KE, Vugia DJ et al. | 2004 | PMID 15095200 DOI 10.1086/381597 | Case-control study | Patients with Campylobacter infection and matched controls | Domestic resistant infections were linked to eating chicken or turkey at restaurants. | Very wide CI (only 33 pairs); Recall bias | moderate | C-CHK-05 C-CHK-09 |
| A-CHK-08 | Fluoroquinolone-resistant Campylobacter species and the withdrawal of fluoroquinolones from use in poultry: a public health success story. Nelson JM, Chiller TM, Powers JH et al. | 2007 | PMID 17342653 DOI 10.1086/512369 | Narrative review | US | Resistance concerns led the US to withdraw enrofloxacin from poultry in 2005. | Narrative; Authors from US agencies | moderate | C-CHK-05 |
| A-CHK-09 | High concentrations of the carcinogen 2-amino-1-methyl-6-phenylimidazo- [4,5-b]pyridine (PhIP) occur in chicken but are dependent on the cooking method. Sinha R, Rothman N, Brown ED et al. | 1995 | PMID 7553619 | Measurement / residue study | Chicken breasts and whole chickens | Well-done grilled or fried chicken breast had high PhIP levels; stewed chicken had none. | 1995 data; No health outcome | moderate | C-CHK-10 |
| A-CHK-10 | A large prospective study of meat consumption and colorectal cancer risk: an investigation of potential mechanisms underlying this association. Cross AJ, Ferrucci LM, Risch A et al. | 2010 | PMID 20215514 DOI 10.1158/0008-5472.CAN-09-3929 | Cohort study | US adults | Red and processed meat and some cooking mutagens were linked to colorectal cancer. | Self-reported cooking; database estimates; Red/processed meat, not poultry | moderate | C-CHK-10 |
| A-CHK-11 | Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Liu YY, Wang Y, Walsh TR et al. | 2016 | PMID 26603172 DOI 10.1016/S1473-3099(15)00424-7 | Other | E. coli and K. pneumoniae from food animals, raw meat and inpatients in five provinces | A transferable gene making bacteria resistant to the last-resort antibiotic colistin was found in animals, meat and some patients. | China-specific surveillance; Index strain from a pig; poultry-specific share not given in abstract | high | C-CHK-05 |
| A-CHK-12 | Consumption of meat and dairy and lymphoma risk in the European Prospective Investigation into Cancer and Nutrition. Rohrmann S, Linseisen J, Jakobsen MU et al. | 2011 | PMID 20473877 DOI 10.1002/ijc.25387 | Cohort study | European adults | No overall link; poultry was linked to some lymphoma subtypes, possibly by chance. | Multiple subgroup tests; Authors note chance plausible | moderate | C-CHK-01 |
| A-CHK-13 | Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome. Chen Y, Liang W, Yang S et al. | 2013 | PMID 23623390 DOI 10.1016/S0140-6736(13)60903-4 | Case series / case report | Four hospital inpatients (3 men, 1 woman; age 39-68, mean 56) with laboratory-confirmed H7N9 pneumonia at three hospitals in Zhejiang; 86 birds (20 chickens, 4 quails, 5 pigeons, 57 ducks) from six epidemiologically linked wet markets | Four patients caught H7N9 after contact with live poultry; two died. | Only four patients, all severe hospitalised cases (selection towards severity); Genome comparison for a single human-chicken pair | moderate | C-CHK-13 |
| A-CHK-14 | MRSA in conventional and alternative retail pork products. O'Brien AM, Hanson BM, Farina SA et al. | 2012 | PMID 22276147 DOI 10.1371/journal.pone.0030092 | Cross-sectional study | Retail pork from 36 stores | Pork raised without antibiotics carried MRSA as often as conventional pork. | Pork, not poultry | moderate | C-CHK-05 |
| A-CHK-15 | Lower prevalence of antibiotic-resistant Enterococci on U.S. conventional poultry farms that transitioned to organic practices. Sapkota AR, Hulet RM, Zhang G et al. | 2011 | PMID 21827979 DOI 10.1289/ehp.1003350 | Cross-sectional study | 10 conventional and 10 newly organic poultry houses | Poultry houses that switched to organic had far fewer multidrug-resistant bacteria. | Small number of houses; Farm environment, not meat | moderate | C-CHK-05 |
| A-CHK-16 | Poultry Consumption and Arsenic Exposure in the U.S. Population. Nigra AE, Nachman KE, Love DC et al. | 2017 | PMID 27735790 DOI 10.1289/EHP351 | Cross-sectional study | US participants >=6 years with undetectable arsenobetaine | Heavy poultry eaters had about 12% higher urine arsenic. | Single 24-h recall; Cross-sectional | moderate | C-CHK-07 |
| A-CHK-17 | National Outbreak of Multidrug Resistant Salmonella Heidelberg Infections Linked to a Single Poultry Company. Gieraltowski L, Higa J, Peralta V et al. | 2016 | PMID 27631492 DOI 10.1371/journal.pone.0162369 | Outbreak report | 634 case-patients with laboratory-confirmed S. Heidelberg (1 of 7 PFGE patterns) in 29 states and Puerto Rico (77% California); median age 18 years (<1-93) | 634 people fell ill from resistant Salmonella traced to one company's chicken. | No formal analytic study; comparison with an older (2006-2007) population survey; Recall bias for foods and brands (interviews weeks after onset); brand data available for only 175 cases | moderate | C-CHK-05 C-CHK-08 C-CHK-09 |
| A-CHK-18 | Increased risk of pneumonia in residents living near poultry farms: does the upper respiratory tract microbiota play a role? Smit LAM, Boender GJ, de Steenhuijsen Piters WAA et al. | 2017 | PMID 28702305 DOI 10.1186/s41479-017-0027-0 | Cross-sectional study | (i) 92,548 GP patients (70,142 adults 18-70 y, 22,406 children) in Noord-Brabant, a region with dense intensive livestock farming; (ii) 126 adults hospitalised with CAP near Tilburg (26 living <1 km, 100 >=1 km from a poultry farm), no antibiotics in prior 2 weeks, C. burnetii-negative | People living within about 1 km of poultry farms had 11% more pneumonia. | Kernel model contains no individual-level confounder adjustment (e.g. smoking, SES, age structure); Exposure is residential distance only; no measured PM/endotoxin; misclassification from activity patterns acknowledged | moderate | C-CHK-13 |
| A-CHK-19 | Broiler chickens, broiler chicken meat, pigs and pork as sources of ExPEC related virulence genes and resistance in Escherichia coli isolates from community-dwelling humans and UTI patients. Jakobsen L, Spangholm DJ, Pedersen K et al. | 2010 | PMID 20656368 DOI 10.1016/j.ijfoodmicro.2010.06.025 | Cross-sectional study | 964 E. coli isolates | E. coli from meat had virulence genes similar to those from patients with urinary infections. | Gene presence, not transmission proof | moderate | C-CHK-05 |
| A-CHM-01 | Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Cardinale D, Colombo A, Bacchiani G et al. | 2015 | PMID 25948538 DOI 10.1161/CIRCULATIONAHA.114.013777 | Cohort study | Heterogeneous adult cohort receiving anthracycline-containing chemotherapy | About 9 in 100 patients developed a measurable drop in heart pumping function, mostly within one year; most recovered fully or partly with heart medication. | Single centre; heterogeneous cancers; No untreated comparison group | moderate | C-CHM-01 |
| A-CHM-02 | Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. Lipshultz SE, Colan SD, Gelber RD et al. | 1991 | PMID 1997853 DOI 10.1056/NEJM199103213241205 | Cohort study | Children treated for ALL with doxorubicin 1-15 years earlier, in continuous remission | More than half of 115 childhood leukaemia survivors had heart function abnormalities, more often at higher doses. | Small, single-institution sample; Historical high cumulative doses | moderate | C-CHM-01 |
| A-CHM-03 | Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. Mulrooney DA, Yeazel MW, Kawashima T et al. | 2009 | PMID 19996459 DOI 10.1136/bmj.b4606 | Cohort study | Five-year survivors of childhood cancer diagnosed <21 years in 1970-1986 | Survivors reported heart failure about 6 times as often as siblings (1.7% vs 0.2%); by 30 years after diagnosis about 4% had heart failure. Risk rose with anthracycline dose and heart radiation. | Self/proxy-reported outcomes; medical-record validation attempted but abandoned (e.g. records obtainable for only 103 of 292 CHF reporters); Possible surveillance bias (exposed survivors monitored more) inflating relative hazards (authors) | moderate | C-CHM-01 C-CHM-06 |
| A-CHM-04 | Risk of ischemic heart disease in women after radiotherapy for breast cancer. Darby SC, Ewertz M, McGale P et al. | 2013 | PMID 23484825 DOI 10.1056/NEJMoa1209825 | Case-control study | Women irradiated for breast cancer 1958-2001 | Each extra Gray of average heart dose increased the rate of major coronary events by about 7%. | Historical techniques with higher heart doses; Case-control design | high | C-CHM-02 C-CHM-01 |
| A-CHM-05 | Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. Romond EH, Perez EA, Bryant J et al. | 2005 | PMID 16236738 DOI 10.1056/NEJMoa052122 | Randomised controlled trial | Women with surgically removed HER2-positive breast cancer | Fewer recurrences and a third fewer deaths; serious heart problems in about 3-4 in 100 treated women. | Interim analysis (early stopping can overestimate effect); Joint analysis amended post hoc | high | C-CHM-01 C-CHM-09 |
| A-CHM-06 | Breast cancer following radiotherapy and chemotherapy among young women with Hodgkin disease. Travis LB, Hill DA, Dores GM et al. | 2003 | PMID 12876089 DOI 10.1001/jama.290.4.465 | Case-control study | 3,817 female 1-year survivors of HD diagnosed at age <=30 years, 1965-1994 | Risk was about 3 times higher with >=4 Gy and 8 times higher with >40 Gy to the breast. | Wide CIs; Historical mantle-field doses much higher than modern involved-site RT | high | C-CHM-03 |
| A-CHM-07 | Proportion of second cancers attributable to radiotherapy treatment in adults: a cohort study in the US SEER cancer registries. Berrington de Gonzalez A, Curtis RE, Kry SF et al. | 2011 | PMID 21454129 DOI 10.1016/S1470-2045(11)70061-4 | Cohort study | Adults aged 20+ with a first primary invasive solid cancer at 15 sites routinely treated with radiotherapy (oral/pharynx, salivary gland, rectum, anus, larynx, lung, soft tissue, breast, cervix, endometrium, prostate, testis [seminoma], eye/orbit, brain/CNS, thyroid), SEER-9 registries, surviving >=5 years | About 5 extra cancers per 1,000 treated patients within 15 years; 8% of second cancers in irradiated patients. | No randomisation; confounding by indication (authors); No data on smoking, chemotherapy or hormonal therapy; higher RRs for smoking-related second cancers suggest residual confounding by smoking (authors) | moderate | C-CHM-03 C-CHM-09 |
| A-CHM-08 | Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. Fisher B, Costantino JP, Redmond CK et al. | 1994 | PMID 8133536 DOI 10.1093/jnci/86.7.527 | Randomised controlled trial | Node-negative ER-positive invasive breast cancer | Uterine cancer about 1.6 vs 0.2 per 1,000 women per year; 38% fewer recurrence-type events. | Small number of endometrial events; Data-integrity issue disclosed in the abstract (fraudulent records from one investigator) | moderate | C-CHM-03 C-CHM-09 |
| A-CHM-09 | Neuropsychologic impact of standard-dose systemic chemotherapy in long-term survivors of breast cancer and lymphoma. Ahles TA, Saykin AJ, Furstenberg CT et al. | 2002 | PMID 11786578 DOI 10.1200/JCO.2002.20.2.485 | Cross-sectional study | 5-year disease-free survivors of breast cancer or lymphoma | 39% of chemotherapy-treated vs 14% of locally treated survivors scored in the lowest quarter on memory/thinking tests. | Small sample; Cross-sectional; no pre-treatment baseline | low | C-CHM-04 |
| A-CHM-10 | Meta-analysis of cognitive functioning in breast cancer survivors previously treated with standard-dose chemotherapy. Jim HS, Phillips KM, Chait S et al. | 2012 | PMID 22927526 DOI 10.1200/JCO.2011.39.5640 | Meta-analysis | Breast cancer survivors | Breast-cancer survivors performed slightly worse in two of eight areas of thinking. | Heterogeneous designs; Small total sample | moderate | C-CHM-04 |
| A-CHM-11 | Reduction in Late Mortality among 5-Year Survivors of Childhood Cancer. Armstrong GT, Chen Y, Yasui Y et al. | 2016 | PMID 26761625 DOI 10.1056/NEJMoa1510795 | Cohort study | Five-year survivors of childhood cancer diagnosed <21 years with leukaemia, CNS malignancy, Hodgkin lymphoma, non-Hodgkin lymphoma, Wilms tumour, neuroblastoma, soft tissue sarcoma or bone tumour, initially treated 1970-1999 at 31 US/Canadian institutions (about 20% of US children diagnosed in the period) | 15-year death rate after surviving 5 years dropped from 12.4% to 6.0% between the 1970s and 1990s. | Observational era comparison; changes in supportive care, screening and medical care cannot be measured (authors); Health-related deaths cannot be directly attributed to treatment sequelae (authors) | high | C-CHM-06 C-CHM-09 C-CHM-13 |
| A-CHM-12 | Chronic health conditions in adult survivors of childhood cancer. Oeffinger KC, Mertens AC, Sklar CA et al. | 2006 | PMID 17035650 DOI 10.1056/NEJMsa060185 | Cohort study | Adults diagnosed with childhood cancer 1970-1986 | 62% had at least one chronic condition and 27.5% a severe one. | Self-reported conditions; Historical treatments | high | C-CHM-06 |
| A-CHM-13 | Comprehensive Audiometric Analysis of Hearing Impairment and Tinnitus After Cisplatin-Based Chemotherapy in Survivors of Adult-Onset Cancer. Frisina RD, Wheeler HE, Fossa SD et al. | 2016 | PMID 27354478 DOI 10.1200/JCO.2016.66.8822 | Cross-sectional study | North American male germ-cell tumour survivors | Almost 1 in 5 testicular-cancer survivors had severe-to-profound hearing loss; 40% had tinnitus. | Cross-sectional; Single cancer type, men only | moderate | C-CHM-05 |
| A-CHM-14 | Toxicities Associated with Cisplatin-Based Chemotherapy and Radiotherapy in Long-Term Testicular Cancer Survivors. Fung C, Dinh P, Ardeshir-Rouhani-Fard S et al. | 2018 | PMID 29670654 DOI 10.1155/2018/8671832 | Narrative review | Long-term testicular cancer survivors (TCS), disease-free >=5 years after primary treatment with cisplatin-based chemotherapy and/or radiotherapy; single-dose carboplatin and 1-2 cycles of BEP for stage I disease explicitly not reviewed | 10-year relative survival is 95%; heart disease and second cancers are the main serious late effects. | Narrative review; no systematic search, eligibility criteria or risk-of-bias appraisal; Selection of cited studies not reproducible; overlapping registry cohorts in SMN table (authors note overlap) | low | C-CHM-05 C-CHM-09 C-CHM-13 C-CHM-11 |
| A-CHM-15 | Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia: the University of Chicago series. Smith SM, Le Beau MM, Huo D et al. | 2003 | PMID 12623843 DOI 10.1182/blood-2002-11-3343 | Case series / case report | Patients referred with t-MDS/t-AML since 1972 | In 306 patients, median survival after diagnosis was 8 months. | No denominator; cannot estimate incidence; Referral bias | low | C-CHM-03 |
| A-CHM-16 | Early palliative care for patients with metastatic non-small-cell lung cancer. Temel JS, Greer JA, Muzikansky A et al. | 2010 | PMID 20818875 DOI 10.1056/NEJMoa1000678 | Randomised controlled trial | Ambulatory patients with newly diagnosed metastatic NSCLC | Better quality of life, less depression, and longer median survival (11.6 vs 8.9 months) when added to cancer care. | Single centre, small; Survival a secondary outcome | moderate | C-CHM-07 |
| A-CHM-17 | Chemotherapy Use, Performance Status, and Quality of Life at the End of Life. Prigerson HG, Bao Y, Shah MA et al. | 2015 | PMID 26203912 DOI 10.1001/jamaoncol.2015.2378 | Cohort study | Adults (>=20 y) with end-stage cancer (distant metastases, refractory to >=1 chemotherapy line, physician-estimated life expectancy <=6 months) with an informal caregiver; ECOG 0: 2.9%, 1: 39.1%, 2: 37.2%, 3: 18.6%, 4: 2.2% | In patients still fit, chemotherapy near death was linked to worse quality of the last week. | Non-randomised; strong confounding by indication (chemotherapy users younger, fitter, academic centres) and no adjustment in stratum-specific models; Only decedents analysed (312 of 661 participants); patients who lived longer, possibly due to treatment, are excluded | moderate | C-CHM-07 |
| A-CHM-18 | Aggressiveness of cancer care near the end of life: is it a quality-of-care issue? Earle CC, Landrum MB, Souza JM et al. | 2008 | PMID 18688053 DOI 10.1200/JCO.2007.15.8253 | Narrative review | Cancer patients near death (US data) | Review of chemotherapy overuse and late hospice referral in the USA. | Narrative; no abstract numbers | low | C-CHM-07 |
| A-CHM-19 | The financial toxicity of cancer treatment: a pilot study assessing out-of-pocket expenses and the insured cancer patient's experience. Zafar SY, Peppercorn JM, Schrag D et al. | 2013 | PMID 23442307 DOI 10.1634/theoncologist.2012-0279 | Cross-sectional study | Insured US cancer patients contacting a copay foundation plus academic-centre comparison | 42% reported a heavy financial burden and many skipped medicines to save money. | Pilot, selected sample; US-specific | low | C-CHM-08 |
| A-DRY-01 | Milk intake and risk of mortality and fractures in women and men: cohort studies. Michaëlsson K, Wolk A, Langenskiöld S et al. | 2014 | PMID 25352269 DOI 10.1136/bmj.g6015 | Cohort study | 61,433 women aged 39-74 (baseline 1987-90) and 45,339 men aged 45-79 (baseline 1997) in three central Swedish counties. | Women drinking 3 or more glasses a day had a 1.93-fold mortality hazard compared with less than 1 glass (17.7 vs 10.7 deaths per 1,000 person-years); no fewer hip fractures. Yogurt/fermented milk and cheese showed the opposite: lower mortality. | Observational; residual confounding acknowledged (socioeconomic nuances; in men high milk intake went with lower education and more smoking); Reverse causation not excluded by authors | moderate | C-DRY-02 C-DRY-03 C-DRY-11 |
| A-DRY-02 | Dairy products, calcium, and prostate cancer risk: a systematic review and meta-analysis of cohort studies. Aune D, Navarro Rosenblatt DA, Chan DS et al. | 2015 | PMID 25527754 DOI 10.3945/ajcn.113.067157 | Meta-analysis | Men in prospective cohorts. | About 7% higher risk per 400 g dairy a day and 9% per 50 g cheese a day. | Small relative risks; Possible detection bias (PSA screening) | high | C-DRY-04 C-DRY-11 |
| A-DRY-03 | Dairy products, calcium, and prostate cancer risk in the Physicians' Health Study. Chan JM, Stampfer MJ, Ma J et al. | 2001 | PMID 11566656 DOI 10.1093/ajcn/74.4.549 | Cohort study | US male physicians | More than 2.5 servings/day: 34% higher relative risk. | Abbreviated dietary questionnaire; Single baseline assessment | moderate | C-DRY-04 |
| A-DRY-04 | Consumption of milk and calcium in midlife and the future risk of Parkinson disease. Park M, Ross GW, Petrovitch H et al. | 2005 | PMID 15781824 DOI 10.1212/01.WNL.0000154532.98495.BF | Cohort study | Japanese-American men aged 45-68 in Hawaii | Incidence rose from 6.9 to 14.9 per 10,000 person-years. | Single dietary assessment decades before outcome; Few cases (128) | moderate | C-DRY-09 |
| A-DRY-05 | Dairy products and ovarian cancer: a pooled analysis of 12 cohort studies. Genkinger JM, Hunter DJ, Spiegelman D et al. | 2006 | PMID 16492930 DOI 10.1158/1055-9965.EPI-05-0484 | Meta-analysis | Women in 12 cohorts (North America, Europe) | No link for milk, cheese, yogurt or calcium; borderline result only for very high lactose. | Few cases per subgroup; Single dietary assessment in many cohorts | high | C-DRY-05 |
| A-DRY-06 | Milk and lactose intakes and ovarian cancer risk in the Swedish Mammography Cohort. Larsson SC, Bergkvist L, Wolk A | 2004 | PMID 15531686 DOI 10.1093/ajcn/80.5.1353 | Cohort study | Swedish women aged 38-76 | Serous ovarian cancer about twice as common with >=2 glasses of milk/day; other subtypes not linked. | Few cases (125 serous); Subgroup finding; multiple testing | moderate | C-DRY-05 |
| A-DRY-07 | High school dietary dairy intake and teenage acne. Adebamowo CA, Spiegelman D, Danby FW et al. | 2005 | PMID 15692464 DOI 10.1016/j.jaad.2004.08.007 | Cross-sectional study | US nurses (NHS II) reporting high-school diet in 1998 and severe teenage acne in 1989 | Total milk PR 1.22 (1.03-1.44) | Self-reported acne; Recall of adolescent diet decades later (A-DRY-07) | low | C-DRY-08 |
| A-DRY-08 | Milk consumption and acne in adolescent girls. Adebamowo CA, Spiegelman D, Berkey CS et al. | 2006 | PMID 17083856 | Cohort study | Girls in the Growing Up Today Study | Highest (>=2 servings/day) vs lowest (<1/week): total milk PR 1.20 (1.09-1.31), whole 1.19 (1.06-1.32), low-fat 1.17 (1.04-1.31), skim 1.19 (1.08-1.31). | Self-reported acne; Acne assessed once by questionnaire | moderate | C-DRY-08 |
| A-DRY-09 | Milk consumption and acne in teenaged boys. Adebamowo CA, Spiegelman D, Berkey CS et al. | 2008 | PMID 18194824 DOI 10.1016/j.jaad.2007.08.049 | Cohort study | Boys in the Growing Up Today Study | Highest (>2 servings/day) vs lowest (<1/wk): total milk PR 1.16 (1.01-1.34), whole/2% 1.10 (0.94-1.28), low-fat 1.17 (0.99-1.39), skim 1.19 (1.01-1.40). | Self-reported acne; Acne assessed once by questionnaire | moderate | C-DRY-08 |
| A-DRY-10 | Effects of milk containing only A2 beta casein versus milk containing both A1 and A2 beta casein proteins on gastrointestinal physiology, symptoms of discomfort, and cognitive behavior of people with self-reported intolerance to traditional cows' milk. Jianqin S, Leiming X, Lu X et al. | 2016 | PMID 27039383 DOI 10.1186/s12937-016-0147-z | Randomised controlled trial | Han Chinese adults aged 25-68 (mean 46.6 +/- 14.0 y; 21 men, 24 women) with irregular milk consumption and self-reported mild-to-moderate digestive discomfort after milk; 23/45 lactose intolerant by urinary galactose test. Recruited via community-hospital noticeboards; IBS, constipation and unmedicated IBD excluded. | People who felt milk did not agree with them had more symptoms with ordinary milk than with A2 milk. | Industry-funded; company employee conceived the study and selected outcomes; company-supplied products and company-funded medical writing; Small exploratory trial (n=45), no sample-size calculation, 2-week periods | low | C-DRY-02 C-DRY-07 |
| A-DRY-11 | Intake of dairy foods and risk of Parkinson disease. Hughes KC, Gao X, Kim IY et al. | 2017 | PMID 28596209 DOI 10.1212/WNL.0000000000004057 | Cohort study | US nurses and health professionals | Skim/low-fat milk HR 1.39; total dairy not significant in these cohorts. | Observational; Modest effects | moderate | C-DRY-09 |
| A-DRY-12 | Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes: The TRIGR Randomized Clinical Trial. Writing Group for the TRIGR Study Group, Knip M, Åkerblom HK et al. | 2018 | PMID 29297078 DOI 10.1001/jama.2017.19826 | Randomised controlled trial | Infants with HLA-conferred susceptibility and a first-degree relative with T1D | Type 1 diabetes in 8.4% vs 7.6%; no significant difference. | Specific high-risk infant population; Compares formula types, not dairy vs no dairy in adults | high | C-DRY-12 |
| A-DRY-13 | Dairy Product Consumption and Risk of Non-Hodgkin Lymphoma: A Meta-Analysis. Wang J, Li X, Zhang D | 2016 | PMID 26927171 DOI 10.3390/nu8030120 | Meta-analysis | Participants of 16 articles | Cohort studies found no association (RR 1.02). | Association driven by case-control studies (recall bias); Null in cohort studies | low | C-DRY-12 |
| A-DRY-14 | Does milk intake promote prostate cancer initiation or progression via effects on insulin-like growth factors (IGFs)? A systematic review and meta-analysis. Harrison S, Lennon R, Holly J et al. | 2017 | PMID 28361446 DOI 10.1007/s10552-017-0883-1 | Systematic review | Humans (observational and experimental) and animals | IGF-I +0.10 SD per SD of milk; prostate cancer OR 1.09 per SD IGF-I. | Milk-IGF effect size is a visual estimate from albatross plots, not a pooled estimate; heterogeneous exposures (milk, dairy products, dairy protein); Largest milk-IGF effects come from very small, short-term trials in children with large doses | high | C-DRY-04 C-DRY-06 |
| A-DRY-15 | Galactose-Induced Skin Aging: The Role of Oxidative Stress. Umbayev B, Askarova S, Almabayeva A et al. | 2020 | PMID 32655772 DOI 10.1155/2020/7145656 | Narrative review | In vitro and animal models; galactosemia | Describes how high-dose galactose ages cells in experiments; no data on drinking milk. | Narrative, non-systematic; Animal/in vitro D-galactose models use non-dietary doses/routes | very low | C-DRY-12 |
| A-EGG-01 | The Belgian PCB and dioxin incident of January-June 1999: exposure data and potential impact on health. van Larebeke N, Hens L, Schepens P et al. | 2001 | PMID 11333188 DOI 10.1289/ehp.01109265 | Measurement / residue study | Belgian food chain (feed, cattle, pork, poultry, eggs, milk, fat-containing foods); population of 10 million | After contaminated feed was distributed, some eggs reached very high dioxin and PCB levels; modelled extra cancers ranged from 40 to 8,000. | Incident-specific; maxima are not representative of normal supply; Cancer estimate is a model with a 200-fold range | moderate | C-EGG-08 |
| A-EGG-02 | Level changes and human dietary exposure assessment of halogenated flame retardant levels in free-range chicken eggs: A case study of a former e-waste recycling site, South China. Huang CC, Zeng YH, Luo XJ et al. | 2018 | PMID 29631140 DOI 10.1016/j.scitotenv.2018.03.386 | Measurement / residue study | Free-range chicken eggs from Baihe village | Pollutant levels fell after regulation; in the worst case, exposure margins indicated possible concern. | Single highly polluted site; Worst-case scenario (highly polluted eggs) | moderate | C-EGG-08 |
| A-EGG-03 | PCDD/Fs and Dioxin-like PCBs in Chicken Eggs and Soils in Dong Nai Province, Southern Vietnam: Impacts of Raising Methods and Nearby Pollution Sources. Nghiem TX, Hoang AQ, Nguyen TD et al. | 2022 | PMID 35037074 DOI 10.1007/s00128-021-03419-w | Measurement / residue study | Chicken eggs and soils near Bien Hoa Airbase and industrial areas | Some eggs, especially from free-range hens, had dioxin levels well above EU limits; the typical (median) egg was much lower. | Hotspot area (former Agent Orange airbase); Sample size not in abstract | moderate | C-EGG-08 |
| A-EGG-04 | Dioxins, PCBs, chlorinated pesticides and brominated flame retardants in free-range chicken eggs from peri-urban areas in Arusha, Tanzania: Levels and implications for human health. Polder A, Müller MB, Brynildsrud OB et al. | 2016 | PMID 26897409 DOI 10.1016/j.scitotenv.2016.02.021 | Measurement / residue study | 159 eggs from households in five locations | Some backyard eggs exceeded EU limits for dieldrin and dioxins; backyard fires were a likely source. | Pooled samples; Backyard free-range eggs only | moderate | C-EGG-08 |
| A-EGG-05 | Reviewing the relevance of dioxin and PCB sources for food from animal origin and the need for their inventory, control and management. Weber R, Herold C, Hollert H et al. | 2018 | PMID 30464877 DOI 10.1186/s12302-018-0166-9 | Narrative review | Food-producing animals (laying hens outdoors, suckler calves, beef) | In Germany, contaminated soils and old PCB materials are the main sources; outdoor hens can exceed EU limits even at low soil levels. | Narrative, not systematic; Abstract only | moderate | C-EGG-08 C-CHK-12 |
| A-EGG-06 | Per- and poly-fluoroalkyl substances in commercial organic eggs via fishmeal in feed. Granby K, Ersbøll BK, Olesen PT et al. | 2024 | PMID 37944762 DOI 10.1016/j.chemosphere.2023.140553 | Measurement / residue study | Commercial eggs from larger Danish farms (free-range, barn, organic) | Organic eggs had PFAS from fishmeal; ordinary free-range and barn eggs had little or none; removing fishmeal solved the problem. | Exposure at 95th percentile and solely from eggs; Small number of farms | moderate | C-EGG-08 |
| A-EGG-07 | Potential Health Effects of Heavy Metals and Carcinogenic Health Risk Estimation of Pb and Cd Contaminated Eggs from a Closed Gold Mine Area in Northern Thailand. Aendo P, De Garine-Wichatitsky M, Mingkhwan R et al. | 2022 | PMID 36140919 DOI 10.3390/foods11182791 | Measurement / residue study | Chicken farms, duck farms and free-grazing duck farms <25 km and >25 km from a gold mine | Eggs from free-grazing ducks near the mine had more mercury and lead. | Mining hotspot; ILCR model assumptions (Pb carcinogenicity slope) | low | C-EGG-08 |
| A-EGG-08 | Heavy metals in eggs and chicken and the associated human health risk assessment in the mining areas of Singhbhum copper belt, India. Giri S, Singh AK | 2019 | PMID 29236582 DOI 10.1080/19338244.2017.1407284 | Measurement / residue study | Locally reared chicken and eggs | Most metal levels were below national standards; combined risk index was slightly above 1 at some sites. | Hotspot; HI above 1 only at some locations | low | C-EGG-08 |
| A-EGG-09 | Antibiotic residues in poultry tissues and eggs: human health concerns? Donoghue DJ | 2003 | PMID 12710482 DOI 10.1093/ps/82.4.618 | Narrative review | US poultry supply | The author says US poultry foods are monitored and very safe. | Narrative, 2003; No data in abstract | low | C-EGG-10 |
| A-EGG-10 | Prevalence and Genetic Analysis of Salmonella enterica from a Cross-Sectional Survey of the New Zealand Egg Production Environment. Kingsbury JM, Thom K, Erskine H et al. | 2019 | PMID 31742446 DOI 10.4315/0362-028X.JFP-19-159 | Cross-sectional study | 28 commercial layer farms | Barn samples from cage farms were far more often positive (44%) than from cage-free farms (3%); most farms had no Salmonella. | Environmental samples, not eggs; Confounding by practices | moderate | C-EGG-09 |
| A-EGG-11 | Egg, red meat, and poultry intake and risk of lethal prostate cancer in the prostate-specific antigen-era: incidence and survival. Richman EL, Kenfield SA, Stampfer MJ et al. | 2011 | PMID 21930800 DOI 10.1158/1940-6207.CAPR-11-0354 | Cohort study | US male health professionals in the Health Professionals Follow-up Study, free of cancer in 1994 and reporting a PSA test (PSA era); case-only analysis of men diagnosed with clinically localised or regional prostate cancer after 1994 | Men who ate 2.5+ eggs per week had a higher rate of lethal prostate cancer (199 cases in total), but the link weakened and was not significant in a check for reverse causation. | Few events (199; 55 in the top egg category); low egg consumption limits power, as authors note; Egg association attenuated and non-significant with 2-6 year lag (HR 1.50, 0.90-2.48), raising reverse-causation/instability concerns | moderate | C-EGG-06 |
| A-EGG-12 | Associations of Dietary Cholesterol or Egg Consumption With Incident Cardiovascular Disease and Mortality. Zhong VW, Van Horn L, Cornelis MC et al. | 2019 | PMID 30874756 DOI 10.1001/jama.2019.1572 | Cohort study | US adults (mean age 51.6; 31.1% black) | More eggs or dietary cholesterol were linked to slightly more heart disease and deaths; the egg link disappeared when cholesterol intake was accounted for. | Single baseline dietary assessment; Residual confounding | moderate | C-EGG-04 |
| A-EGG-13 | Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. Tang WH, Wang Z, Levison BS et al. | 2013 | PMID 23614584 DOI 10.1056/NEJMoa1109400 | Cohort study | (1) 40 healthy adults without chronic illness or recent antibiotics/probiotics (6 received antibiotics); (2) 4,007 stable patients undergoing elective diagnostic cardiac catheterisation without acute coronary syndrome (mean age 63, 64% men, 32% diabetes, 72% hypertension, 42% prior MI) | Gut bacteria make TMAO from egg-yolk components; heart patients with the highest TMAO had more events (about 1.4-fold after adjustment, 2.5-fold unadjusted); egg eating itself was not studied against outcomes. | Cohort measured plasma TMAO only, not egg or phosphatidylcholine intake; Effect size shrinks from HR 2.54 (unadjusted) to 1.43 (fully adjusted), indicating substantial confounding (age, kidney function, disease severity) | moderate | C-EGG-05 |
| A-EGG-14 | Egg consumption and risk of type 2 diabetes: a meta-analysis of prospective studies. Djoussé L, Khawaja OA, Gaziano JM | 2016 | PMID 26739035 DOI 10.3945/ajcn.115.119933 | Meta-analysis | 12 cohorts | No overall link; higher risk only in US studies. | High heterogeneity; Observational primary studies | moderate | C-EGG-07 |
| A-EGG-15 | Vitamins A, E and fatty acid composition of the eggs of caged hens and pastured hens Karsten H.D., Patterson P.H., Stout R. et al. | 2010 | DOI 10.1017/S1742170509990214 | Other | 75 pastured sister hens and 50 caged sister hens | Pastured hens laid eggs with more omega-3 fat and vitamin E. | Small, single site; Nutrient composition, not health outcomes | moderate | C-EGG-11 |
| A-FSH-01 | Global assessment of organic contaminants in farmed salmon. Hites RA, Foran JA, Carpenter DO et al. | 2004 | PMID 14716013 DOI 10.1126/science.1091447 | Measurement / residue study | Farmed Atlantic salmon from farms/retail in Europe, North and South America; wild Pacific salmon | Around 2002, farmed salmon - especially from Europe - had more PCBs and dioxins than wild Pacific salmon. | Compares farmed Atlantic with wild Pacific salmon (different species); Historical samples (c. 2002) | high | C-FSH-01 C-FSH-02 |
| A-FSH-02 | Global assessment of polybrominated diphenyl ethers in farmed and wild salmon. Hites RA, Foran JA, Schwager SJ et al. | 2004 | PMID 15506184 DOI 10.1021/es049548m | Measurement / residue study | Same salmon set as A-FSH-01 | Farmed salmon had more PBDE flame retardants than wild salmon around 2002. | Historical; No health-risk metric in abstract | moderate | C-FSH-01 C-FSH-02 |
| A-FSH-03 | Polychlorinated biphenyls in salmon and salmon feed: global differences and bioaccumulation. Carlson DL, Hites RA | 2005 | PMID 16245806 DOI 10.1021/es048023r | Measurement / residue study | Farmed Atlantic salmon worldwide; wild NE Pacific salmon; feed samples | PCB patterns in farmed salmon matched their feed. | Historical; Few feed samples | moderate | C-FSH-01 |
| A-FSH-04 | Risk-based consumption advice for farmed Atlantic and wild Pacific salmon contaminated with dioxins and dioxin-like compounds. Foran JA, Carpenter DO, Hamilton MC et al. | 2005 | PMID 15866762 DOI 10.1289/ehp.7626 | Risk assessment | Hypothetical 70 kg adult; salmon samples from Hites 2004 | Depending on the safety criterion, northern European farmed salmon (2002 samples) allowed under 4 or under 1 meal per month. | Conservative criteria (20% above background; US EPA draft slope factor); 2002 samples | moderate | C-FSH-03 |
| A-FSH-05 | Quantitative analysis of the benefits and risks of consuming farmed and wild salmon. Foran JA, Good DH, Carpenter DO et al. | 2005 | PMID 16251623 DOI 10.1093/jn/135.11.2639 | Risk assessment | Modelled consumers | The omega-3 benefit of salmon partly offsets contaminant risk; some farmed salmon was similar to wild. | Same conservative cancer-risk framework; Old samples | moderate | C-FSH-03 |
| A-FSH-06 | Lipid composition and contaminants in farmed and wild salmon. Hamilton MC, Hites RA, Schwager SJ et al. | 2005 | PMID 16323755 DOI 10.1021/es050898y | Measurement / residue study | 459 farmed Atlantic, 135 wild Pacific salmon, 144 supermarket fillets (16 cities) | Farmed salmon had more fat, a lower omega-3:omega-6 ratio (3-4 vs ~10) and more pollutants, but was still a good omega-3 source. | Historical; Different species compared | high | C-FSH-01 C-FSH-04 C-FSH-05 |
| A-FSH-07 | Consumption advisories for salmon based on risk of cancer and noncancer health effects. Huang X, Hites RA, Foran JA et al. | 2006 | PMID 16198332 DOI 10.1016/j.envres.2005.08.011 | Risk assessment | Farmed salmon from 8 regions, retail fillets from 16 cities, 5 wild Pacific species | Using a strict US method, northern European farmed salmon (2002 samples) got an advisory of one meal per 5 months; wild salmon was also restricted. | Additive mixture assumption with upper-bound slope factors; 2002 samples | moderate | C-FSH-03 |
| A-FSH-08 | Investigation of polychlorinated dibenzo-p-dioxins, dibenzo-p-furans and selected coplanar biphenyls in Scottish farmed Atlantic salmon (Salmo salar). Jacobs M, Ferrario J, Byrne C | 2002 | PMID 11993634 DOI 10.1016/s0045-6535(01)00201-6 | Measurement / residue study | Farmed and wild Scottish Atlantic salmon | Farmed Scottish salmon had relatively high dioxins/PCBs in 1999. | Small, 1999, single region | low | C-FSH-01 |
| A-FSH-09 | The content of favorable and unfavorable polyunsaturated fatty acids found in commonly eaten fish. Weaver KL, Ivester P, Chilton JA et al. | 2008 | PMID 18589026 DOI 10.1016/j.jada.2008.04.023 | Measurement / residue study | Fish samples | Farmed salmon and trout had good omega-3 profiles; tilapia and catfish had little omega-3. | Few samples per species; No health outcomes | low | C-FSH-06 C-FSH-07 |
| A-FSH-10 | Polyunsaturated fatty acid content of wild and farmed tilapias in Thailand: effect of aquaculture practices and implications for human nutrition. Karapanagiotidis IT, Bell MV, Little DC et al. | 2006 | PMID 16756360 DOI 10.1021/jf0581877 | Measurement / residue study | Nile and red hybrid tilapia | Intensively farmed tilapia had less omega-3 than wild tilapia. | Thailand only | moderate | C-FSH-06 |
| A-FSH-11 | Antimicrobial use in aquaculture re-examined: its relevance to antimicrobial resistance and to animal and human health. Cabello FC, Godfrey HP, Tomova A et al. | 2013 | PMID 23711078 DOI 10.1111/1462-2920.12134 | Narrative review | Most aquaculture antibiotics reach the environment and may spread resistance genes to human pathogens. | Narrative, not systematic; 80% figure is an estimate | moderate | C-FSH-08 | |
| A-FSH-12 | Aquaculture as yet another environmental gateway to the development and globalisation of antimicrobial resistance. Cabello FC, Godfrey HP, Buschmann AH et al. | 2016 | PMID 27083976 DOI 10.1016/S1473-3099(16)00100-6 | Narrative review | Aquaculture antibiotics can help resistance spread globally. | Narrative | moderate | C-FSH-08 | |
| A-FSH-13 | Reconnaissance of 47 antibiotics and associated microbial risks in seafood sold in the United States. Done HY, Halden RU | 2015 | PMID 25449970 DOI 10.1016/j.jhazmat.2014.08.075 | Measurement / residue study | Shrimp, salmon, catfish, trout, tilapia, swai from 11 countries | Traces of five antibiotics were found; all samples were within US limits. | Small, pooled sample; One residue found in WILD shrimp | moderate | C-FSH-09 |
| A-FSH-14 | Aquaculture practices and potential human health risks: current knowledge and future priorities. Sapkota A, Sapkota AR, Kucharski M et al. | 2008 | PMID 18565584 DOI 10.1016/j.envint.2008.04.009 | Narrative review | Aquaculture can introduce drug residues, resistant bacteria and pollutants; risks vs wild fish need more research. | Narrative; 'can lead' | low | C-FSH-08 | |
| A-FSH-15 | Negative effects of the sea lice therapeutant emamectin benzoate at low concentrations on benthic communities around Scottish fish farms. Bloodworth JW, Baptie MC, Preedy KF et al. | 2019 | PMID 30878944 DOI 10.1016/j.scitotenv.2019.02.430 | Cross-sectional study | Benthic communities | The drug was found in 97% of seabed samples and was linked to fewer small crustaceans. | Cross-sectional; Collinearity | moderate | C-FSH-10 |
| A-FSH-16 | Salmon lice in the Pacific Ocean show evidence of evolved resistance to parasiticide treatment. Godwin SC, Bateman AW, Kuparinen A et al. | 2022 | PMID 35347162 DOI 10.1038/s41598-022-07464-1 | Other | Salmon lice collected from Atlantic salmon farms in the Broughton Archipelago, British Columbia (11 farms with bioassays; all BA farms for treatment data) | Pacific salmon lice have become much less sensitive to emamectin since 2010. | One region (11 farms), small number of bioassays (34); No genetic confirmation of resistance (lice not retained) | moderate | C-FSH-10 |
| A-FSH-17 | Levels of synthetic antioxidants (ethoxyquin, butylated hydroxytoluene and butylated hydroxyanisole) in fish feed and commercially farmed fish. Lundebye AK, Hove H, Måge A et al. | 2010 | PMID 20931417 DOI 10.1080/19440049.2010.508195 | Measurement / residue study | Farmed salmon, halibut, cod, rainbow trout; feed | A portion of farmed salmon gave up to 75% of the acceptable daily intake of BHT. | 2010 data | moderate | C-FSH-02 |
| A-FSH-18 | Determining the arsenic, cadmium, lead, copper and chromium contents by atomic absorption spectrometry in Pangasius fillets from Vietnam. Molognoni L, Vitali L, Ploêncio LA et al. | 2016 | PMID 26439310 DOI 10.1002/jsfa.7486 | Measurement / residue study | Pangasius fillets exported to Brazil | Most toxic metals were undetectable; some samples exceeded the cadmium limit. | n=20 | low | C-FSH-02 |
| A-FSH-19 | Effect of aquaculture on world fish supplies. Naylor RL, Goldburg RJ, Primavera JH et al. | 2000 | PMID 10890435 DOI 10.1038/35016500 | Narrative review | Farming carnivorous fish uses many wild fish as feed, but aquaculture overall still adds fish. | Old (2000) | moderate | C-FSH-11 | |
| A-FSH-20 | Mercury Levels in the Worldwide Farmed Fish: A Systematic Review. de Oliveira Novaes E, de Oliveira AT, Araruna LT et al. | 2025 | PMID 39715977 DOI 10.1007/s12011-024-04493-x | Systematic review | Farmed fish (50 species) | Farmed fish had low mercury and were judged safer than wild fish. | Only 18 studies; Few countries | low | C-FSH-02 C-FSH-14 |
| A-FSH-21 | Contaminant levels in Norwegian farmed Atlantic salmon (Salmo salar) in the 13-year period from 1999 to 2011. Nøstbakken OJ, Hove HT, Duinker A et al. | 2015 | PMID 25454244 DOI 10.1016/j.envint.2014.10.008 | Measurement / residue study | Market-size (3-5 kg) Norwegian farmed Atlantic salmon collected from processing plants in all coastal regions with aquaculture | Pollutant levels fell from 1999 to 2011 and no sample exceeded EU limits; the authors calculated up to 1.3 kg per week to reach the safety limit then in force, which EFSA has since made much stricter. | Uses SCF 2001 TWI (14 pg TEQ/kg bw/week); EFSA lowered the TWI to 2 pg TEQ/kg bw/week in 2018 (I-FSH-17), so the 1.3 kg figure is outdated; Other dietary sources excluded from consumption limits | high | C-FSH-01 C-FSH-02 C-FSH-03 C-FSH-13 |
| A-FSH-22 | Organic contaminants in imported salmon feed and their effects on reef ecosystems in New Zealand. McMullin RM, Chen R, Niu S et al. | 2022 | PMID 35033615 DOI 10.1016/j.envpol.2022.118853 | Measurement / residue study | Feed; reef species | Imported salmon feed had relatively low pollutant levels. | NZ-specific | moderate | C-FSH-02 |
| A-INS-01 | Effects of intensive glucose lowering in type 2 diabetes. Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME et al. | 2008 | PMID 18539917 DOI 10.1056/NEJMoa0802743 | Randomised controlled trial | Type 2 diabetes, mean age 62.2, median HbA1c 8.1%, established CVD or additional risk factors | Pushing HbA1c below 6% increased deaths by about one-fifth and did not reduce heart attacks or strokes significantly. | Strategy trial: cannot attribute harm to a specific drug; Intensive arm stopped early | high | C-INS-04 C-INS-11 |
| A-INS-02 | Intensive versus conventional glucose control in critically ill patients. NICE-SUGAR Study Investigators, Finfer S, Chittock DR et al. | 2009 | PMID 19318384 DOI 10.1056/NEJMoa0810625 | Randomised controlled trial | Adult ICU patients expected to stay >=3 days | Aiming for normal blood sugar in ICU patients raised deaths from 24.9% to 27.5%. | ICU population, not ambulatory diabetes; Open-label | high | C-INS-04 |
| A-INS-03 | Glucose control and vascular complications in veterans with type 2 diabetes. Duckworth W, Abraira C, Moritz T et al. | 2009 | PMID 19092145 DOI 10.1056/NEJMoa0808431 | Randomised controlled trial | Military veterans, mean age 60.4, diabetes 11.5 years, 40% prior CV event | Lower sugar did not reduce heart events or deaths, and side effects (mainly hypoglycaemia) were more frequent. | Smaller sample, limited power; Mostly men | moderate | C-INS-04 |
| A-INS-04 | Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study. Hemkens LG, Grouven U, Bender R et al. | 2009 | PMID 19565214 DOI 10.1007/s00125-009-1418-4 | Cohort study | Adults (>=18 years) starting first-time insulin therapy exclusively with one insulin type (human insulin, aspart, lispro or glargine), insulin-naive for 1 year and without any cancer diagnosis or suspicion for 3 years before entry; type 1 vs type 2 diabetes not distinguishable (mostly type 2: 77-92% on oral agents). Mean age 66-70 years. | Without adjustment glargine users actually had slightly fewer cancers; only after statistical dose adjustment did glargine look somewhat worse, and follow-up was under 2 years. | Very short follow-up (mean 1.63 years; glargine 1.31 years), implausibly short for insulin-induced carcinogenesis; detection or promotion of pre-existing tumours cannot be separated; Direction of the glargine effect reverses on dose adjustment (crude HR 0.85 -> adjusted 1.09-1.31); result depends on the dose-interaction model | low | C-INS-06 |
| A-INS-05 | Insulin glargine use and short-term incidence of malignancies-a population-based follow-up study in Sweden. Jonasson JM, Ljung R, Talbäck M et al. | 2009 | PMID 19588120 DOI 10.1007/s00125-009-1444-2 | Cohort study | All residents aged 35-84 with >=1 insulin prescription dispensed 1 July-31 December 2005 and alive on 1 January 2006; 61% classified type 2, 15% type 1, 23% unknown diabetes type. | Overall cancer rates were the same; women using only glargine had more breast cancer (25 cases), which the authors say may be chance. | Only 2 years of follow-up; glargine on Swedish market since 2003, implausibly short latency for carcinogenesis (authors); Breast-cancer signal based on 25 cases in one of several subgroups and sites; no correction for multiple comparisons | moderate | C-INS-06 |
| A-INS-06 | Long-term effects of insulin glargine on the risk of breast cancer. Suissa S, Azoulay L, Dell'Aniello S et al. | 2011 | PMID 21614572 DOI 10.1007/s00125-011-2190-9 | Cohort study | Women aged >=40 years with type 2 diabetes and >=1 insulin prescription between 1 September 2002 and 31 December 2006 (mean age 65); excluded gestational diabetes, type 1 diabetes, prior breast cancer. | No increase in breast cancer during the first five years; a possible increase later in a subgroup. | Positive finding rests on 10 cases in one subgroup (>5 years, prevalent users) with wide CI; p=0.031 from repeated stratified analyses (authors acknowledge chance); Overall and first-5-year results null; no cases at all >5 years in first-time glargine users | moderate | C-INS-06 |
| A-INS-07 | Basal insulin and cardiovascular and other outcomes in dysglycemia. ORIGIN Trial Investigators, Gerstein HC, Bosch J et al. | 2012 | PMID 22686416 DOI 10.1056/NEJMoa1203858 | Randomised controlled trial | People aged >=50 years with cardiovascular risk factors (59% prior CV event) plus impaired fasting glucose, impaired glucose tolerance or early type 2 diabetes (mean diabetes duration 5.4 years, median HbA1c 6.4%, BMI ~29.9); mean age 63.5, 35% female. | Over six years insulin did not change heart attacks, strokes or cancers, but caused more low-sugar episodes and 2 kg weight difference. | Open-label design (hypoglycaemia and other patient-reported outcomes susceptible to ascertainment bias); Sponsor (Sanofi) funding and representation on steering committee | high | C-INS-03 C-INS-05 C-INS-06 |
| A-INS-08 | Mortality and other important diabetes-related outcomes with insulin vs other antihyperglycemic therapies in type 2 diabetes. Currie CJ, Poole CD, Evans M et al. | 2013 | PMID 23372169 DOI 10.1210/jc.2012-3042 | Cohort study | Incident type 2 diabetes patients in UK primary care (mean age 61.9); insulin-monotherapy users had longer diabetes duration (5.2 vs 1.5 years for metformin), higher HbA1c (9.5% vs 8.5%), more prior large-vessel disease (22.3% vs 11.1%), more creatinine >130 umol/L (21.1% vs 2.2%), higher Charlson index (2.4 vs 1.6) and more GP contacts (16.8 vs 10.9/year). | People treated with insulin alone had about twice the death rate of metformin users, but they were also sicker. | Severe confounding by indication: insulin is started late in progressive disease; insulin users had 3.5-fold longer diabetes duration, more renal impairment (metformin contraindicated), more vascular disease and comorbidity; Short follow-up (~3 years) for cancer outcomes (authors) | very low | C-INS-05 C-ODD-11 |
| A-INS-09 | Survival as a function of HbA(1c) in people with type 2 diabetes: a retrospective cohort study. Currie CJ, Peters JR, Tynan A et al. | 2010 | PMID 20110121 DOI 10.1016/S0140-6736(09)61969-3 | Cohort study | Type 2 diabetes >=50 years intensified to combination orals or insulin | Both very low (6.4%) and very high (10.5%) HbA1c were linked to more deaths; lowest risk around 7.5%. | Observational; Confounding by indication | low | C-INS-05 |
| A-INS-10 | Glucose-lowering with exogenous insulin monotherapy in type 2 diabetes: dose association with all-cause mortality, cardiovascular events and cancer. Holden SE, Jenkins-Jones S, Morgan CL et al. | 2015 | PMID 25399739 DOI 10.1111/dom.12412 | Cohort study | Type 2 diabetes progressing to insulin monotherapy from 2000 | People on higher insulin doses died more often, but higher doses are needed by sicker, more insulin-resistant people. | Dose reflects insulin resistance and illness; Reverse causation | low | C-INS-03 C-INS-05 |
| A-INS-11 | Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Bowker SL, Majumdar SR, Veugelers P et al. | 2006 | PMID 16443869 DOI 10.2337/diacare.29.02.06.dc05-1558 | Cohort study | New users of metformin or sulfonylureas | Insulin users had more cancer deaths than metformin users, possibly due to other differences. | No BMI/smoking; Confounding | low | C-INS-05 |
| A-INS-12 | Glucose-lowering agents and cancer mortality rates in type 2 diabetes: assessing effects of time-varying exposure. Bowker SL, Yasui Y, Veugelers P et al. | 2010 | PMID 20407744 DOI 10.1007/s00125-010-1750-8 | Cohort study | New users of metformin or sulfonylureas aged >=30 years with >=1 year prior drug coverage and >=1 year of drug exposure after index; gestational diabetes excluded. Insulin used was human insulin (pre-analogue era). | More insulin prescriptions went with more cancer deaths, which may reflect that very ill people need more insulin. | No data on BMI, smoking, HbA1c, alcohol (authors); adjustment only for age, sex and a drug-based comorbidity score; Insulin 'dose' is number of dispensations, which rises with illness, hospital discharge and terminal care - strong reverse causation/protopathic bias for cancer death | low | C-INS-05 |
| A-INS-13 | Association between intensification of metformin treatment with insulin vs sulfonylureas and cardiovascular events and all-cause mortality among patients with diabetes. Roumie CL, Greevy RA, Grijalva CG et al. | 2014 | PMID 24915260 DOI 10.1001/jama.2014.4312 | Cohort study | US veterans (95% male, ~70% white), median age 60, incident metformin users 2001-2008 with regular VHA care; median 14 months on metformin and median HbA1c 8.1% at intensification; hospice/dialysis excluded. | Veterans who added insulin died more often than those who added a sulfonylurea, but heart attacks and strokes were not more frequent. | Residual confounding by frailty/diabetes severity (authors); before matching insulin users had far more hospitalisations (35% vs 14% in last year) and comorbidities; Excess limited to non-CV, especially cancer deaths (aHR 1.85) within ~1 year - implausible as a drug effect and suggestive of confounding/reverse causation | moderate | C-INS-03 C-INS-05 |
| A-INS-14 | The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. Bonds DE, Miller ME, Bergenstal RM et al. | 2010 | PMID 20061358 DOI 10.1136/bmj.b4909 | Cohort study | ACCORD participants with type 2 diabetes, HbA1c 7.5-11%, aged 40-79 with CVD or 55-79 with subclinical atherosclerosis/risk factors; excluded recent/frequent serious hypoglycaemia, BMI >45, creatinine >133 umol/L. | People who had severe low-sugar episodes died more often, but this did not explain why the intensive group had more deaths. | Post hoc observational analysis within an RCT: hypoglycaemia is not randomised; confounding by frailty/comorbidity likely (authors); No continuous glucose monitoring; unrecognised hypoglycaemia near death cannot be excluded; glucose missing for 15% of HMA episodes | moderate | C-INS-02 C-INS-04 C-INS-09 C-ODD-03 |
| A-INS-15 | Severe hypoglycemia and risks of vascular events and death. Zoungas S, Patel A, Chalmers J et al. | 2010 | PMID 20925543 DOI 10.1056/NEJMoa1003795 | Cohort study | Patients aged >=55 with type 2 diabetes diagnosed after age 30 and macro-/microvascular disease or >=1 CV risk factor; patients with a clear indication for long-term insulin at baseline were ineligible; intensive arm used modified-release gliclazide (a sulfonylurea) plus other drugs as required (target HbA1c <=6.5%). | Severe low-sugar episodes were followed by more heart events and deaths, probably partly because frail people get them. | Only 231 patients with severe hypoglycaemia; post hoc, non-randomised exposure; Associations with unrelated outcomes (skin, digestive, respiratory) and absence of dose-response point to confounding/frailty (authors) | moderate | C-INS-02 C-INS-04 C-INS-09 C-ODD-03 |
| A-INS-16 | Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. UKPDS Group | 1998 | PMID 9742976 | Randomised controlled trial | Newly diagnosed type 2 diabetes, median age 54 | Better sugar control with tablets or insulin cut eye/kidney complications by a quarter; insulin caused more weight gain and low-sugar episodes. | Open-label; Older drug regimens | high | C-INS-01 C-INS-03 C-INS-04 C-INS-05 C-INS-09 C-ODD-11 C-DIAB-01 |
| A-INS-17 | Increase of body weight during the first year of intensive insulin treatment in type 2 diabetes: systematic review and meta-analysis. Pontiroli AE, Miele L, Morabito A | 2011 | PMID 21645195 DOI 10.1111/j.1463-1326.2011.01433.x | Meta-analysis | Type 2 diabetes starting/intensifying insulin | The more intensive the insulin treatment, the more weight people gain in the first year. | Effect sizes not in abstract; Heterogeneous trials | moderate | C-INS-01 |
| A-INS-18 | Intensive conventional insulin therapy for type II diabetes. Metabolic effects during a 6-mo outpatient trial. Henry RR, Gumbiner B, Ditzler T et al. | 1993 | PMID 8422777 DOI 10.2337/diacare.16.1.21 | Case series / case report | Type 2 diabetes outpatients | Blood sugar normalised but patients gained almost 9 kg in six months. | n=14; No control | very low | C-INS-01 |
| A-INS-19 | Combination of insulin and metformin in the treatment of type 2 diabetes. Wulffelé MG, Kooy A, Lehert P et al. | 2002 | PMID 12453950 DOI 10.2337/diacare.25.12.2133 | Randomised controlled trial | Insulin-treated type 2 diabetes | Metformin improved sugar control and reduced insulin need and weight gain. | Short duration; Dropouts higher with metformin | moderate | C-INS-01 C-INS-05 C-INS-10 C-INS-11 |
| A-INS-20 | Insulin Injection Into Lipohypertrophic Tissue: Blunted and More Variable Insulin Absorption and Action and Impaired Postprandial Glucose Control. Famulla S, Hövelmann U, Fischer A et al. | 2016 | PMID 27411698 DOI 10.2337/dc16-0610 | Randomised controlled trial | Type 1 diabetes with lipohypertrophy | Insulin injected into lumpy fat tissue works less and less predictably. | Small n | moderate | C-INS-09 |
| A-INS-21 | Hyperinsulinemia as an independent risk factor for ischemic heart disease. Després JP, Lamarche B, Mauriège P et al. | 1996 | PMID 8596596 DOI 10.1056/NEJM199604113341504 | Case-control study | Non-diabetic men 45-76 | Men with higher fasting insulin had more heart disease. | Small number of cases; Men only | moderate | C-INS-03 |
| A-INS-22 | Insulin and risk of cardiovascular disease: a meta-analysis. Ruige JB, Assendelft WJ, Dekker JM et al. | 1998 | PMID 9529268 DOI 10.1161/01.cir.97.10.996 | Meta-analysis | General population cohorts | Higher insulin was only weakly linked to heart disease (18% higher risk). | Old assays; Heterogeneity | moderate | C-INS-03 |
| A-INS-23 | Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Calle EE, Kaaks R | 2004 | PMID 15286738 DOI 10.1038/nrc1408 | Narrative review | not applicable | Not assessed (no abstract available). | Narrative review; Not read | low | C-INS-06 |
| A-LEG-01 | Favism and Glucose-6-Phosphate Dehydrogenase Deficiency. Luzzatto L, Arese P | 2018 | PMID 29298156 DOI 10.1056/nejmra1708111 | Narrative review | Not applicable (review) | Authoritative review of favism; no abstract available to us. | No abstract available; content not verified by us | moderate | C-LEG-03 |
| A-LEG-02 | Glucose-6-phosphate dehydrogenase deficiency. Cappellini MD, Fiorelli G | 2008 | PMID 18177777 DOI 10.1016/S0140-6736(08)60073-2 | Narrative review | Global | G6PD deficiency affects over 400 million people; haemolysis is triggered by external agents and is prevented by avoiding them. | Narrative, not systematic; Abstract does not mention fava beans explicitly | moderate | C-LEG-03 C-LEG-04 C-LEG-05 |
| A-LEG-03 | Red kidney bean poisoning in the UK: an analysis of 50 suspected incidents between 1976 and 1989. Rodhouse JC, Haugh CA, Roberts D et al. | 1990 | PMID 2249712 DOI 10.1017/s095026880004810x | Outbreak report | Incidents reported to the PHLS Food Hygiene Laboratory or the Communicable Disease Surveillance Centre (Colindale), involving more than 200 cases | 50 poisoning incidents from raw or undercooked kidney beans; thorough cooking inactivates the toxin. | Passive reporting; authors document marked under-reporting; 23 of 32 incidents diagnosed on clinical history only; 6 of these had beans with <400 HAU/g | moderate | C-LEG-06 C-LEG-07 |
| A-LEG-04 | Antinutritional properties of plant lectins. Vasconcelos IM, Oliveira JT | 2004 | PMID 15302522 DOI 10.1016/j.toxicon.2004.05.005 | Narrative review | Animals, insects (review) | Active plant lectins harm animals at high intakes; human cooked-food relevance not shown. | Mainly animal and insect data; No human dose-response | moderate | C-LEG-01 C-LEG-07 |
| A-LEG-05 | Iron bioavailability and dietary reference values. Hurrell R, Egli I | 2010 | PMID 20200263 DOI 10.3945/ajcn.2010.28674F | Narrative review | Humans (isotope and intake studies) | Iron absorption is lower from vegetarian than mixed diets; in varied diets single inhibitors matter less than iron status. | Narrative; Not specific to legumes | moderate | C-LEG-08 |
| A-LEG-06 | Bioavailability of minerals in legumes. Sandberg AS | 2002 | PMID 12498628 DOI 10.1079/BJN/2002718 | Narrative review | Not applicable | Phytate reduces iron and zinc absorption, but processing reduces phytate and balanced diets are not at risk. | Narrative | moderate | C-LEG-04 C-LEG-08 |
| A-LEG-07 | Exposure of infants to phyto-oestrogens from soy-based infant formula. Setchell KD, Zimmer-Nechemias L, Cai J et al. | 1997 | PMID 9217716 DOI 10.1016/S0140-6736(96)09480-9 | Measurement / residue study | 4-month-old infants | Soy-fed infants had isoflavone blood levels hundreds of times higher than other infants. | Very small n; No clinical outcomes | moderate | C-LEG-10 |
| A-LEG-08 | Goitrogenic and estrogenic activity of soy isoflavones. Doerge DR, Sheehan DM | 2002 | PMID 12060828 DOI 10.1289/ehp.02110s3349 | Narrative review | Rats, humans (review) | Soy compounds inhibit a thyroid enzyme in the lab, but thyroid function in rats stayed normal; iodine deficiency is key. | Animal/in-vitro; Authors' concern-oriented framing | low | C-LEG-10 |
| A-LEG-09 | Soy Formula and Epigenetic Modifications: Analysis of Vaginal Epithelial Cells from Infant Girls in the IFED Study. Harlid S, Adgent M, Jefferson WN et al. | 2017 | PMID 27539829 DOI 10.1289/EHP428 | Cohort study | Healthy term singleton infant girls exclusively fed soy or cow-milk formula from birth (IFED cohort, Philadelphia); mothers mostly black, many with high-school education or less | Small study found gene-methylation differences in soy-fed girls; health meaning unknown. | Discovery scan of only 10 infants, without multiple-testing correction across 427,097 CpGs; In the scan, soy samples (4-8 weeks) and cow samples (20-32 weeks) differed strongly in age, while methylation falls with age - major confounding of the discovery signal | low | C-LEG-10 |
| A-LEG-10 | A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Halmos EP, Power VA, Shepherd SJ et al. | 2014 | PMID 24076059 DOI 10.1053/j.gastro.2013.09.046 | Randomised controlled trial | 30 IBS patients, 8 healthy controls | Diet low in fermentable sugars halved symptom scores in IBS patients; healthy people had no symptoms on either diet. | Small; Single-blind | moderate | C-LEG-12 |
| A-LEG-11 | Fatalities due to anaphylactic reactions to foods. Bock SA, Muñoz-Furlong A, Sampson HA | 2001 | PMID 11150011 DOI 10.1067/mai.2001.112031 | Case series / case report | Fatal cases reported to AAAAI registry | Most of 32 food-allergy deaths were due to peanuts or tree nuts, nearly all in people already known to be allergic. | Voluntary reporting; No denominator | moderate | C-LEG-11 |
| A-LEG-12 | Further fatalities caused by anaphylactic reactions to food, 2001-2006. Bock SA, Muñoz-Furlong A, Sampson HA | 2007 | PMID 17306354 DOI 10.1016/j.jaci.2006.12.622 | Case series / case report | US registry | Registry letter; content not available to us. | No abstract; content not verified | low | C-LEG-11 |
| A-LEG-13 | Cross-allergenicity of peanut and lupine: the risk of lupine allergy in patients allergic to peanuts. Moneret-Vautrin DA, Guérin L, Kanny G et al. | 1999 | PMID 10518837 DOI 10.1016/s0091-6749(99)70303-9 | Cross-sectional study | Peanut-allergic patients | Many peanut-allergic patients also reacted to lupin flour. | Small selected sample | moderate | C-LEG-11 |
| A-LEG-14 | Incidence of fatal food anaphylaxis in people with food allergy: a systematic review and meta-analysis. Umasunthar T, Leonardi-Bee J, Hodes M et al. | 2013 | PMID 24118190 DOI 10.1111/cea.12211 | Meta-analysis | Food-allergic people (denominator estimated by applying assumed food-allergy prevalence to defined general populations) | Among food-allergic people, fatal reactions occur about 1.8 times per million person-years, less often than accidental deaths. | Denominators rely on assumed food-allergy prevalence, not measured allergic cohorts; High heterogeneity; variable case capture (registries, media, coroners, charities) | moderate | C-LEG-11 |
| A-ODD-01 | Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. Nissen SE, Wolski K | 2007 | PMID 17517853 DOI 10.1056/NEJMoa072761 | Meta-analysis | Type 2 diabetes in trials >24 weeks, mean age 56, HbA1c 8.2% | Pooling 42 trials suggested 43% more heart attacks; the increase in heart deaths was not statistically certain. | No patient-level data; Rare events, fixed-effect model | moderate | C-ODD-05 C-ODD-09 |
| A-ODD-02 | Heart failure events with rosiglitazone in type 2 diabetes: data from the RECORD clinical trial. Komajda M, McMurray JJ, Beck-Nielsen H et al. | 2010 | PMID 20118174 DOI 10.1093/eurheartj/ehp604 | Randomised controlled trial | Type 2 diabetes aged 40-75, BMI >25 kg/m2, HbA1c >7.0-<=9.0% on maximum-dose metformin or sulfonylurea monotherapy; excluded prior HF, recent major CV event, renal impairment, uncontrolled hypertension. | Heart failure doubled with rosiglitazone (2.6 extra cases per 1,000 patient-years), but overall heart deaths did not increase. | Open-label design (investigator-identified events may be influenced by knowledge of TZD fluid retention, though adjudication was blinded); Sponsor (GSK) analysed data; authors with extensive industry ties | high | C-ODD-05 C-ODD-09 |
| A-ODD-03 | Pioglitazone use and risk of bladder cancer: population based cohort study. Tuccori M, Filion KB, Yin H et al. | 2016 | PMID 27029385 DOI 10.1136/bmj.i1541 | Cohort study | Patients aged >=40 newly treated with non-insulin antidiabetic drugs who initiated a new drug class 2000-2013; excluded prior insulin, gestational diabetes, PCOS, prior bladder cancer, <1 year follow-up. Mean age 63.7; 56.8% male. | Pioglitazone users had 63% more bladder cancer, about 3 extra cases per 10,000 people per year. | Observational; residual confounding (occupational exposures, diet, ethnicity) possible; Only 54 exposed cases; dose-response steps imprecise and nearly flat across dose categories | moderate | C-ODD-05 C-ODD-12 |
| A-ODD-04 | Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. de Jager J, Kooy A, Lehert P et al. | 2010 | PMID 20488910 DOI 10.1136/bmj.c2181 | Randomised controlled trial | Patients aged 30-80 with insulin-treated type 2 diabetes at three non-academic hospital outpatient clinics; mean diabetes duration 12-14 years, mean insulin ~61-64 IU/day. | Over 4 years metformin lowered B12 by 19%, causing deficiency in about 1 of every 14 users. | Secondary analysis; trial powered for other endpoints; Baseline imbalance despite randomisation (metformin group older, 64 vs 59 years; fewer smokers 19% vs 30%) | high | C-ODD-05 C-ODD-07 |
| A-ODD-05 | Association of biochemical B₁₂ deficiency with metformin therapy and vitamin B₁₂ supplements: the National Health and Nutrition Examination Survey, 1999-2006. Reinstatler L, Qi YP, Williamson RS et al. | 2012 | PMID 22179958 DOI 10.2337/dc11-1582 | Cross-sectional study | US non-institutionalised adults >=50 years; type 2 diabetes defined as physician diagnosis after age 30 without insulin within 1 year. Excluded: HIV, high creatinine, prescription B12 injections, prediabetes, pregnancy, type 1 diabetes, metformin users without diabetes. | 5.8% of metformin users had B12 deficiency vs 2.4% of other diabetics. | Cross-sectional; associations only, no temporality (authors); Only current metformin use; non-users may have stopped metformin (possibly because of low B12) | moderate | C-ODD-05 C-ODD-07 |
| A-ODD-06 | Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. Aroda VR, Edelstein SL, Goldberg RB et al. | 2016 | PMID 26900641 DOI 10.1210/jc.2015-3754 | Randomised controlled trial | People with prediabetes and overweight | Each year of metformin raised the odds of B12 deficiency by about 13%. | Placebo group partly unblinded after DPP; Secondary analysis | moderate | C-ODD-05 C-ODD-07 |
| A-ODD-07 | Comparative effectiveness of sulfonylurea and metformin monotherapy on cardiovascular events in type 2 diabetes mellitus: a cohort study. Roumie CL, Hung AM, Greevy RA et al. | 2012 | PMID 23128859 DOI 10.7326/0003-4819-157-9-201211060-00003 | Cohort study | Veterans >=18 years initiating metformin or sulfonylurea (glyburide or glipizide) after >=365 days without antidiabetic drugs; excluded heart failure, cancer, HIV, transplant, end-stage kidney/liver disease, respiratory failure, cocaine use, creatinine >=1.5 mg/dL. 97% male, 75% white, median age 62; median HbA1c 7.0-7.3%. | Starting a sulfonylurea instead of metformin was linked to about 1-4 extra heart events or deaths per 1,000 people per year. | Observational; residual confounding by indication (sulfonylurea users older, more loop diuretics/digoxin, lower BMI) despite adjustment; Very short median follow-up (~0.6-0.8 years) with heavy censoring (66-73% stopped therapy) - possibly informative | moderate | C-ODD-05 C-ODD-11 |
| A-ODD-08 | Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. Scirica BM, Bhatt DL, Braunwald E et al. | 2013 | PMID 23992601 DOI 10.1056/NEJMoa1307684 | Randomised controlled trial | Type 2 diabetes with or at risk for CV events | No effect on heart attacks or strokes, but more heart failure hospitalisations (3.5% vs 2.8%, i.e. 0.7 percentage points). | Short follow-up; Industry funded | high | C-ODD-04 C-ODD-05 |
| A-ODD-09 | Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. Neal B, Perkovic V, Mahaffey KW et al. | 2017 | PMID 28605608 DOI 10.1056/NEJMoa1611925 | Randomised controlled trial | Type 2 diabetes (HbA1c 7.0-10.5%) aged >=30 with symptomatic atherosclerotic CVD or >=50 with >=2 CV risk factors; eGFR >30. Mean age 63.3, 35.8% women, diabetes duration 13.5 years, 65.6% prior CVD, 14.4% heart failure, 2.3% prior amputation. | Fewer heart attacks, strokes and heart deaths (-14%), but more toe/foot amputations. | Sponsor-designed randomisation schedule, sponsor co-analysis and employee authors; Integrated analysis of two trials partly necessitated by unmasked interim data used in regulatory filing (CANVAS) | high | C-ODD-05 C-ODD-06 |
| A-ODD-10 | Diabetic Ketoacidosis and Related Events in the Canagliflozin Type 2 Diabetes Clinical Program. Erondu N, Desai M, Ways K et al. | 2015 | PMID 26203064 DOI 10.2337/dc15-1251 | Other | Patients with type 2 diabetes in the canagliflozin RCT programme (history of type 1 diabetes or DKA excluded); ~31% on background insulin. | Ketoacidosis was rare (7 per 10,000 patients), often with insulin deficiency or triggers. | Sponsor analysis by employee authors; no independent adjudication; Ascertainment by investigator-reported adverse event terms - likely underreporting (authors) | low | C-INS-08 C-ODD-02 C-ODD-05 |
| A-ODD-11 | Risk of Diabetic Ketoacidosis after Initiation of an SGLT2 Inhibitor. Fralick M, Schneeweiss S, Patorno E | 2017 | PMID 28591538 DOI 10.1056/NEJMc1701990 | Cohort study | not verifiable | Content not verified (no abstract). | Not read; letter format | low | C-ODD-02 C-ODD-05 |
| A-ODD-12 | Fournier Gangrene Associated With Sodium-Glucose Cotransporter-2 Inhibitors: A Review of Spontaneous Postmarketing Cases. Bersoff-Matcha SJ, Chamberlain C, Cao C et al. | 2019 | PMID 31060053 DOI 10.7326/M19-0085 | Case series / case report | Adults with diabetes reported to FAERS | FDA received 55 reports of this rare genital infection with SGLT2 drugs; reports cannot show how often it really happens. | No incidence/causality; Reporting bias (stimulated reporting after warnings) | very low | C-ODD-05 C-ODD-08 |
| A-ODD-13 | Effects of Canagliflozin on Fracture Risk in Patients With Type 2 Diabetes Mellitus. Watts NB, Bilezikian JP, Usiskin K et al. | 2016 | PMID 26580237 DOI 10.1210/jc.2015-3167 | Randomised controlled trial | Type 2 diabetes | More fractures in one trial with older high-risk patients, not in others. | Pooled post-hoc | moderate | C-ODD-05 |
| A-ODD-14 | Glucagonlike peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: a population-based matched case-control study. Singh S, Chang HY, Richards TM et al. | 2013 | PMID 23440284 DOI 10.1001/jamainternmed.2013.2720 | Case-control study | Adults 18-64 with type 2 diabetes | Users had about twice the odds of pancreatitis, but they also had more risk factors. | Strong confounding; Claims data | low | C-ODD-04 C-ODD-05 |
| A-ODD-15 | Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss. Sodhi M, Rezaeianzadeh R, Kezouh A et al. | 2023 | PMID 37796527 DOI 10.1001/jama.2023.19574 | Cohort study | not verifiable | Not verified (no abstract). | Not read | low | C-ODD-04 C-ODD-05 |
| A-ODD-16 | Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide. Hathaway JT, Shah MP, Hathaway DB et al. | 2024 | PMID 38958939 DOI 10.1001/jamaophthalmol.2024.2296 | Cohort study | Patients evaluated by neuro-ophthalmologists at one academic institution | In an eye-clinic registry, semaglutide users had about 4 times more NAION, but numbers were small. | Referral population (selection bias); Few events | low | C-ODD-05 C-ODD-10 |
| A-ODD-17 | Effects of intensive glucose lowering in type 2 diabetes. Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME et al. | 2008 | PMID 18539917 DOI 10.1056/NEJMoa0802743 | Randomised controlled trial | Type 2 diabetes, mean age 62.2, median HbA1c 8.1%, established CVD or additional risk factors | Pushing HbA1c below 6% increased deaths by about one-fifth and did not reduce heart attacks or strokes significantly. | Strategy trial: cannot attribute harm to a specific drug; Intensive arm stopped early | high | C-INS-04 |
| A-ODD-18 | Glucose control and vascular complications in veterans with type 2 diabetes. Duckworth W, Abraira C, Moritz T et al. | 2009 | PMID 19092145 DOI 10.1056/NEJMoa0808431 | Randomised controlled trial | Military veterans, mean age 60.4, diabetes 11.5 years, 40% prior CV event | Lower sugar did not reduce heart events or deaths, and side effects (mainly hypoglycaemia) were more frequent. | Smaller sample, limited power; Mostly men | moderate | C-INS-04 |
| A-ORG-01 | Association of Long-Term Risk of Respiratory, Allergic, and Infectious Diseases With Removal of Adenoids and Tonsils in Childhood. Byars SG, Stearns SC, Boomsma JJ | 2018 | PMID 29879264 DOI 10.1001/jamaoto.2018.0614 | Cohort study | Children born in Denmark 1979-1999 | Children who had the operations had more respiratory illnesses later (2-3 times for upper airway disease), but the study cannot prove the operation caused it. | Confounding by indication (children operated for recurrent infections/obstruction may be prone to respiratory disease); Wide CIs for specific outcomes | moderate | C-ORG-01 C-ORG-03 C-ORG-16 |
| A-ORG-02 | Tonsillectomy associated with an increased risk of autoimmune diseases: A national cohort study. Ji J, Sundquist J, Sundquist K | 2016 | PMID 27344241 DOI 10.1016/j.jaut.2016.06.007 | Cohort study | All tonsillectomized persons in Sweden | People who had tonsils removed were diagnosed with autoimmune diseases 34% more often than the general population. | Comparison with general population, not with matched non-operated persons with similar infections; No adjustment for confounders beyond standardization | low | C-ORG-04 C-ORG-16 |
| A-ORG-03 | A randomized trial of adenotonsillectomy for childhood sleep apnea. Marcus CL, Moore RH, Rosen CL et al. | 2013 | PMID 23692173 DOI 10.1056/NEJMoa1215881 | Randomised controlled trial | Children 5-9 years with OSA (AHI >=2 or OAI >=1) without prolonged desaturation, suitable for surgery; 53% black, about 47% overweight/obese | Surgery normalized sleep studies in 79% vs 46% with waiting and improved behaviour and quality of life. | Short follow-up (7 months); Primary outcome negative | high | C-ORG-01 C-ORG-03 C-ORG-15 |
| A-ORG-04 | Appendectomy and protection against ulcerative colitis. Andersson RE, Olaison G, Tysk C et al. | 2001 | PMID 11248156 DOI 10.1056/NEJM200103153441104 | Cohort study | Swedish patients appendectomized before age 50 | People whose inflamed appendix was removed before age 20 later had less ulcerative colitis; removal for non-inflamed appendix showed no difference. | Observational; Cannot separate effect of removal from effect of the inflammation | moderate | C-ORG-05 C-ORG-16 |
| A-ORG-05 | Risk of Gastrointestinal Cancers among Patients with Appendectomy: A Large-Scale Swedish Register-Based Cohort Study during 1970-2009. Song H, Abnet CC, Andrén-Sandberg Å et al. | 2016 | PMID 26959234 DOI 10.1371/journal.pone.0151262 | Cohort study | All patients born before 2003 with appendectomy in Sweden 1970-2009 (mean age 32.5 years; 54.7% women); 327,496 appendicitis, 152,886 other diagnoses (negative or incidental appendectomy) | No increased risk of stomach, colon or rectal cancer after appendix removal. | SIR comparison with general population; no adjustment for BMI, smoking, diet, socioeconomic status (authors); Surveillance/detection bias (authors; e.g. early cardia cancer excess) | moderate | C-ORG-05 C-ORG-16 C-ORG-17 |
| A-ORG-06 | Intestinal cancer after cholecystectomy: is bile involved in carcinogenesis? Lagergren J, Ye W, Ekbom A | 2001 | PMID 11522737 DOI 10.1053/gast.2001.27083 | Cohort study | Swedish cholecystectomized patients | After gallbladder removal, rare small-bowel cancers were about 1.8 times as frequent and right-sided colon cancer 1.16 times as frequent as in the population. | Comparison with general population; gallstone disease itself and lifestyle not controlled; No confounder adjustment | low | C-ORG-06 C-ORG-16 |
| A-ORG-07 | Cholecystectomy and NAFLD: does gallbladder removal have metabolic consequences? Nervi F, Arrese M | 2013 | PMID 23735917 DOI 10.1038/ajg.2013.84 | Other | A US survey found fatty liver more often in people without a gallbladder; cause unclear. | Editorial; cross-sectional underlying data; reverse causation possible | very low | C-ORG-06 C-ORG-16 | |
| A-ORG-08 | Small Intestinal Bacterial Overgrowth Diagnosed by Glucose Hydrogen Breath Test in Post-cholecystectomy Patients. Sung HJ, Paik CN, Chung WC et al. | 2015 | PMID 26351251 DOI 10.5056/jnm15020 | Cross-sectional study | Post-cholecystectomy patients with symptoms, FGID patients, healthy controls | Breath tests were positive more often in symptomatic patients after gallbladder removal. | Small; Symptomatic selected patients | low | C-ORG-16 |
| A-ORG-09 | Postcholecystectomy diarrhoea rate and predictive factors: a systematic review of the literature. Farrugia A, Attard JA, Khan S et al. | 2022 | PMID 35177439 DOI 10.1136/bmjopen-2020-046172 | Systematic review | Adults (18-85 years) after cholecystectomy (1855 laparoscopic, 378 open where reported; 2250 women, 787 men where reported) | About 13% of patients developed diarrhoea after the operation. | Crude unweighted pooling; no CIs or heterogeneity assessment despite 2.1-57.2% range; Most included studies not powered for PCD, lacked control groups, used non-validated questionnaires and recall (authors) | low | C-ORG-01 C-ORG-08 |
| A-ORG-10 | Hysterectomy and risk of cardiovascular disease: a population-based cohort study. Ingelsson E, Lundholm C, Johansson AL et al. | 2011 | PMID 21186237 DOI 10.1093/eurheartj/ehq477 | Cohort study | Swedish women with benign hysterectomy | Women operated before 50 had about 18% more cardiovascular disease later. | Register confounding (indications, metabolic profile) | moderate | C-ORG-10 C-ORG-16 |
| A-ORG-11 | Cardiovascular and metabolic morbidity after hysterectomy with ovarian conservation: a cohort study. Laughlin-Tommaso SK, Khan Z, Weaver AL et al. | 2018 | PMID 29286988 DOI 10.1097/GME.0000000000001043 | Cohort study | Olmsted County women | Later heart and metabolic problems were modestly more frequent, especially after surgery at age 35 or younger. | Single county; Observational | moderate | C-ORG-10 C-ORG-16 |
| A-ORG-12 | Long term effects of hysterectomy on mortality: nested cohort study. Iversen L, Hannaford PC, Elliott AM et al. | 2005 | PMID 15930026 DOI 10.1136/bmj.38483.669178.8F | Cohort study | UK women | Women who had a hysterectomy did not die earlier over about 20 years. | Oophorectomy status not separated in abstract | moderate | C-ORG-10 C-ORG-16 |
| A-ORG-13 | Long-term mortality associated with oophorectomy compared with ovarian conservation in the nurses' health study. Parker WH, Feskanich D, Broder MS et al. | 2013 | PMID 23635669 DOI 10.1097/AOG.0b013e3182864350 | Cohort study | NHS participants with hysterectomy for benign disease | Removing the ovaries was linked to somewhat higher death rates (16.8% vs 13.3% over 28 years), mainly in women under 50 who never took estrogen. | Observational; reasons for oophorectomy unknown (authors' limitation); Self-reported oophorectomy (>90% accurate) | moderate | C-ORG-09 C-ORG-16 |
| A-ORG-14 | Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Rocca WA, Bower JH, Maraganore DM et al. | 2007 | PMID 17761551 DOI 10.1212/01.wnl.0000276984.19542.e6 | Cohort study | Olmsted County women, oophorectomy before menopause, non-cancer indication | Women who had ovaries removed before menopause had 46% higher risk of cognitive impairment or dementia later. | Proxy interviews; Observational | moderate | C-ORG-11 C-ORG-16 |
| A-ORG-15 | Accelerated Accumulation of Multimorbidity After Bilateral Oophorectomy: A Population-Based Cohort Study. Rocca WA, Gazzuola-Rocca L, Smith CY et al. | 2016 | PMID 27693001 DOI 10.1016/j.mayocp.2016.08.002 | Cohort study | Premenopausal women with bilateral oophorectomy <50 | Women who had both ovaries removed before 46 accumulated chronic diseases faster. | Higher baseline multimorbidity | moderate | C-ORG-09 C-ORG-16 |
| A-ORG-16 | Long-term risks after splenectomy among 8,149 cancer-free American veterans: a cohort study with up to 27 years follow-up. Kristinsson SY, Gridley G, Hoover RN et al. | 2014 | PMID 24056815 DOI 10.3324/haematol.2013.092460 | Cohort study | Cancer-free US veterans with splenectomy among >4 million hospitalized veterans | Serious infections were 2-3 times more frequent and blood clots about 2 times more frequent after spleen removal. | Indications for splenectomy (trauma, haematologic disease) may confound; Male veterans only | moderate | C-ORG-12 C-ORG-13 C-ORG-16 |
| A-ORG-17 | Risk of cardiovascular events and pulmonary hypertension following splenectomy - a Danish population-based cohort study from 1996-2012. Rørholt M, Ghanima W, Farkas DK et al. | 2017 | PMID 28572164 DOI 10.3324/haematol.2016.157008 | Cohort study | Danish splenectomized patients | Compared with patients with the same diseases, only stroke risk stayed higher; heart attack risk was explained by the underlying disease. | 5-year follow-up | high | C-ORG-13 C-ORG-16 |
| A-ORG-18 | Overwhelming post-splenectomy sepsis in patients with asplenia and hyposplenia: a retrospective cohort study. Chong J, Jones P, Spelman D et al. | 2017 | PMID 27776576 DOI 10.1017/S0950268816002405 | Cohort study | Asplenic or hyposplenic registrants of the Victorian Spleen Registry (median age at splenectomy 38 years; mean 11 years since splenectomy) | Severe infections needing intensive care occurred in about 1 per 1000 patient-years. | Retrospective self-report at registration (recall bias; deaths before registration missed; possible registration because of infection); No non-splenectomised comparator, so excess risk cannot be quantified | moderate | C-ORG-12 |
| A-ORG-19 | Current thyroid cancer trends in the United States. Davies L, Welch HG | 2014 | PMID 24557566 DOI 10.1001/jamaoto.2014.1 | Ecological study | Adults in 9 SEER areas | Diagnoses nearly tripled from 1975 to 2009 while deaths stayed at about 0.5 per 100,000. | Ecological; cannot prove individual overdiagnosis | high | C-ORG-14 C-ORG-15 |
| A-ORG-20 | The enigma of persistent symptoms in hypothyroid patients treated with levothyroxine: A narrative review. Perros P, Van Der Feltz-Cornelis C, Papini E et al. | 2023 | PMID 33783849 DOI 10.1111/cen.14473 | Narrative review | A minority keep symptoms despite normal blood tests; causes are debated. | Narrative | low | C-ORG-16 | |
| A-PPI-01 | Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease. Lazarus B, Chen Y, Wilson FP et al. | 2016 | PMID 26752337 DOI 10.1001/jamainternmed.2015.7193 | Cohort study | ARIC: community-based adults (visit 4, mean age ~62.5 y) from four US communities with eGFR >=60; Geisinger: patients of a rural Pennsylvania health system with outpatient eGFR >=60 (mean age ~50 y) | PPI users had about 1.2–1.5 times the rate of new chronic kidney disease compared with non-users or H2-blocker users. | Observational; PPI users more obese, hypertensive and on more medications - residual confounding by indication; Only 322 baseline PPI users in ARIC; exposure largely single baseline (updates from 2006) | moderate | C-PPI-01 |
| A-PPI-02 | Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury. Xie Y, Bowe B, Li T et al. | 2017 | PMID 28237709 DOI 10.1016/j.kint.2016.12.021 | Cohort study | Incident users of acid suppression | Compared with H2-blocker users, PPI users had 19–30% higher rates of kidney decline. | Mostly older male veterans; Residual confounding | moderate | C-PPI-01 |
| A-PPI-03 | Association Between Proton Pump Inhibitor Use and Risk of Progression of Chronic Kidney Disease. Klatte DCF, Gasparini A, Xu H et al. | 2017 | PMID 28583827 DOI 10.1053/j.gastro.2017.05.046 | Cohort study | New users of PPIs and H2 blockers in Stockholm | PPI starters had about 26% higher risk of kidney function decline than H2-blocker starters. | Short follow-up; Authors acknowledge residual confounding | moderate | C-PPI-01 |
| A-PPI-04 | Association of Proton Pump Inhibitors With Risk of Dementia: A Pharmacoepidemiological Claims Data Analysis. Gomm W, von Holt K, Thomé F et al. | 2016 | PMID 26882076 DOI 10.1001/jamaneurol.2015.4791 | Cohort study | Persons ≥75 years free of dementia | Regular PPI users were diagnosed with dementia 1.44 times as often. | Claims-based diagnoses; No data on education, lifestyle | low | C-PPI-09 |
| A-PPI-05 | Proton pump inhibitors therapy and risk of Clostridium difficile infection: Systematic review and meta-analysis. Trifan A, Stanciu C, Girleanu I et al. | 2017 | PMID 29085200 DOI 10.3748/wjg.v23.i35.6500 | Meta-analysis | Adults in 56 observational studies | PPI users had about twice the odds of C. difficile infection. | Observational primary studies; High heterogeneity | moderate | C-PPI-02 |
| A-PPI-06 | Clostridium difficile-associated diarrhea and proton pump inhibitor therapy: a meta-analysis. Janarthanan S, Ditah I, Adler DG et al. | 2012 | PMID 22710578 DOI 10.1038/ajg.2012.179 | Meta-analysis | Hospitalised patients | Pooled risk about 1.7-fold higher with PPIs. | Observational inputs; Only Medline/PubMed searched | moderate | C-PPI-02 |
| A-PPI-07 | Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis. Eom CS, Jeon CY, Lim JW et al. | 2011 | PMID 21173070 DOI 10.1503/cmaj.092129 | Meta-analysis | Adults in 31 studies | PPI users had 27% higher odds of pneumonia in observational studies, with large differences between studies. | Very high heterogeneity for PPIs; PPI evidence observational only | moderate | C-PPI-05 |
| A-PPI-08 | Long-term proton pump inhibitor therapy and risk of hip fracture. Yang YX, Lewis JD, Epstein S et al. | 2006 | PMID 17190895 DOI 10.1001/jama.296.24.2947 | Case-control study | Patients >50 years using PPIs or no acid suppression | Use for more than a year was associated with 44% higher odds of hip fracture. | Observational; Confounding by frailty, comorbidity and falls risk | moderate | C-PPI-05 |
| A-PPI-09 | Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. Lam JR, Schneider JL, Zhao W et al. | 2013 | PMID 24327038 DOI 10.1001/jama.2013.280490 | Case-control study | KPNC members | Two or more years of PPI supply was associated with 65% higher odds of B12 deficiency. | Case-control; Testing bias (users may be tested more) | moderate | C-PPI-03 C-PPI-04 |
| A-PPI-10 | Proton pump inhibitors and hypomagnesemia in the general population: a population-based cohort study. Kieboom BC, Kiefte-de Jong JC, Eijgelsheim M et al. | 2015 | PMID 26123862 DOI 10.1053/j.ajkd.2015.05.012 | Cross-sectional study | General population ≥45 | PPI users had twice the odds of low magnesium, especially with long use and loop diuretics. | Single Mg measurement; Cross-sectional | moderate | C-PPI-03 C-PPI-04 |
| A-PPI-11 | Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study. Cheung KS, Chan EW, Wong AYS et al. | 2018 | PMID 29089382 DOI 10.1136/gutjnl-2017-314605 | Cohort study | Adults after clarithromycin-based triple therapy | Long-term PPI use was linked to more gastric cancer, about 4 extra cases per 10,000 person-years. | Few events (153); Wide CIs | moderate | C-PPI-09 |
| A-PPI-12 | Estimates of all cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: cohort study. Xie Y, Bowe B, Yan Y et al. | 2019 | PMID 31147311 DOI 10.1136/bmj.l1580 | Cohort study | New users of PPIs or H2 blockers | PPI users had an estimated 45 more deaths per 1,000 over about 10 years than H2-blocker users. | Older, white, male veterans; Residual confounding and channelling bias acknowledged by authors | moderate | C-PPI-01 |
| A-PPI-13 | Risk of death among users of Proton Pump Inhibitors: a longitudinal observational cohort study of United States veterans. Xie Y, Bowe B, Li T et al. | 2017 | PMID 28676480 DOI 10.1136/bmjopen-2016-015735 | Cohort study | New users of PPI or H2 blockers; plus PPI vs no PPI cohorts | PPI users had about 15–34% higher hazard of death depending on method. | Observational; Same database as A-PPI-12 (not independent) | moderate | C-PPI-01 |
| A-PPI-14 | Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Reimer C, Søndergaard B, Hilsted L et al. | 2009 | PMID 19362552 DOI 10.1053/j.gastro.2009.03.058 | Randomised controlled trial | Healthy volunteers | After stopping esomeprazole, 44% of healthy volunteers had acid symptoms vs 15% on placebo. | Small; Short follow-up after withdrawal (4 weeks) | high | C-PPI-06 C-PPI-07 |
| A-PPI-15 | Proton pump inhibitors alter the composition of the gut microbiota. Jackson MA, Goodrich JK, Maxan ME et al. | 2016 | PMID 26719299 DOI 10.1136/gutjnl-2015-310861 | Cross-sectional study | Healthy twins | PPI users had fewer typical gut bacteria and more mouth bacteria in stool. | Composition change ≠ disease; Cross-sectional main analysis | moderate | C-PPI-02 |
| A-PPI-16 | Proton pump inhibitors affect the gut microbiome. Imhann F, Bonder MJ, Vich Vila A et al. | 2016 | PMID 26657899 DOI 10.1136/gutjnl-2015-310376 | Cross-sectional study | Three Dutch cohorts | PPI users had less diverse gut bacteria and more potentially harmful bacteria. | Cross-sectional; Composition ≠ outcome | moderate | C-PPI-02 |
| A-PPI-17 | Proton pump inhibitor use and the risk of small intestinal bacterial overgrowth: a meta-analysis. Lo WK, Chan WW | 2013 | PMID 23270866 DOI 10.1016/j.cgh.2012.12.011 | Meta-analysis | Adults in 11 studies | Association found only with the culture test, not with breath tests. | Small studies; Publication bias | low | C-PPI-02 |
| A-PPI-18 | Analysis of Ranitidine-Associated N-Nitrosodimethylamine Production Under Simulated Physiologic Conditions. Braunstein LZ, Kantor ED, O'Connell K et al. | 2021 | PMID 33512515 DOI 10.1001/jamanetworkopen.2020.34766 | Laboratory / cell study | Commercial ranitidine 150/300 mg tablets | In simulated stomach fluid with very high nitrite, a tablet produced up to 320,000 ng NDMA. | In vitro only; Very high nitrite concentrations | low | C-PPI-08 |
| A-SOD-01 | Sugar-sweetened beverages and risk of metabolic syndrome and type 2 diabetes: a meta-analysis. Malik VS, Popkin BM, Bray GA et al. | 2010 | PMID 20693348 DOI 10.2337/dc10-1079 | Meta-analysis | Adults in prospective cohorts | People in the highest intake group had a 26% higher risk of type 2 diabetes than those drinking almost none. | Only MEDLINE, English only; no protocol registration; No formal risk-of-bias assessment of cohorts | low | C-SOD-01 |
| A-SOD-02 | Sugar- and Artificially Sweetened Beverages and the Risks of Incident Stroke and Dementia: A Prospective Cohort Study. Pase MP, Himali JJ, Beiser AS et al. | 2017 | PMID 28428346 DOI 10.1161/STROKEAHA.116.016027 | Cohort study | Framingham Heart Study Offspring participants (predominantly of European descent): stroke sample aged >45 (mean 62, 45% men); dementia sample aged >60 (mean 69, 46% men) | Daily diet-soda drinkers had about three times more ischaemic strokes and Alzheimer's disease, but with very few cases and wide uncertainty. | Few events; very wide CIs; Reverse causation/confounding by indication: daily ASB drinkers had more diabetes (22% vs 7%), higher BMI and hypertension treatment | moderate | C-SOD-06 |
| A-SOD-03 | Colas, but not other carbonated beverages, are associated with low bone mineral density in older women: The Framingham Osteoporosis Study. Tucker KL, Morita K, Qiao N et al. | 2006 | PMID 17023723 DOI 10.1093/ajcn/84.4.936 | Cross-sectional study | Older women and men | Women drinking cola daily had 3.7% lower hip bone density; other fizzy drinks showed no link. | Cross-sectional; Effect only in women and at hip | moderate | C-SOD-08 C-SOD-13 C-SOD-14 |
| A-SOD-04 | Relation between consumption of sugar-sweetened drinks and childhood obesity: a prospective, observational analysis. Ludwig DS, Peterson KE, Gortmaker SL | 2001 | PMID 11229668 DOI 10.1016/S0140-6736(00)04041-1 | Cohort study | Schoolchildren aged ~11.7 y | Each extra daily sugary drink was linked with higher BMI and 60% higher odds of obesity. | Small sample; Short follow-up | moderate | C-SOD-02 |
| A-SOD-05 | Long-Term Consumption of Sugar-Sweetened and Artificially Sweetened Beverages and Risk of Mortality in US Adults. Malik VS, Li Y, Pan A et al. | 2019 | PMID 30882235 DOI 10.1161/CIRCULATIONAHA.118.037401 | Cohort study | US female nurses (NHS, aged 30-55 at entry) and male health professionals (HPFS, aged 40-75), predominantly non-Hispanic white, free of diabetes, CVD and cancer at baseline | Two or more sugary drinks a day: 21% higher death risk; diet drinks linked only at the highest intake and only in women. | Observational; residual confounding (SSB drinkers smoke more, poorer diet; AHEI 42.7 vs 50.6); Reverse causation likely for ASB (higher BMI and hypertension among ASB drinkers) (authors) | high | C-SOD-03 C-SOD-10 |
| A-SOD-06 | Soft drinks, fructose consumption, and the risk of gout in men: prospective cohort study. Choi HK, Curhan G | 2008 | PMID 18244959 DOI 10.1136/bmj.39449.819271.BE | Cohort study | Male health professionals without gout | Two or more sugary sodas a day: 85% higher gout risk; fruit juice also linked; diet soda not. | Men health professionals only; Wide CI at highest intake | moderate | C-SOD-05 C-SUG-06 |
| A-SOD-07 | Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. Stanhope KL, Schwarz JM, Keim NL et al. | 2009 | PMID 19381015 DOI 10.1172/JCI37385 | Other | Overweight/obese adults aged 40-72 (BMI 25-35), postmenopausal women and men; without diabetes, renal/hepatic disease, hypertension, TG >400 mg/dl; non-smokers; habitual intake <=1 sugar-sweetened beverage/day | At very high doses, fructose drinks increased belly fat and worsened blood fats more than glucose drinks. | Small sample (32 completers); DNL subset only 18; Allocation by matching; randomisation not described | low | C-SOD-04 C-SRC-37 |
| A-SOD-08 | Consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice and incidence of type 2 diabetes: systematic review, meta-analysis, and estimation of population attributable fraction. Imamura F, O'Connor L, Ye Z et al. | 2015 | PMID 26199070 DOI 10.1136/bmj.h3576 | Meta-analysis | Adults without diabetes | Each daily sugary drink was linked with 13-18% more diabetes; diet drinks and juice also showed (possibly biased) links. | Protocol not registered; High heterogeneity for SSB (I2 79-89%) | high | C-SOD-01 C-SOD-10 C-SUG-06 |
| A-SOD-09 | Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Suez J, Korem T, Zeevi D et al. | 2014 | PMID 25231862 DOI 10.1038/nature13793 | Animal study | Mice; healthy human subjects | In mice, sweeteners changed gut bacteria and caused glucose intolerance; a small human test showed similar effects. | Human data small (size not in abstract); Commercial formulations contained glucose fillers (not in abstract) | moderate | C-SOD-07 |
| A-SOD-10 | Sugar-sweetened beverages, weight gain, and incidence of type 2 diabetes in young and middle-aged women. Schulze MB, Manson JE, Ludwig DS et al. | 2004 | PMID 15328324 DOI 10.1001/jama.292.8.927 | Cohort study | Women aged young/middle-aged | Women drinking one or more sugary drinks daily had 83% higher diabetes risk; fruit punch similar. | Observational design; residual confounding possible; Self-reported dietary intake | high | C-SOD-01 C-SOD-02 |
| A-SOD-11 | Added Sugars and Cardiovascular Disease Risk in Children: A Scientific Statement From the American Heart Association. Vos MB, Kaar JL, Welsh JA et al. | 2017 | PMID 27550974 DOI 10.1161/CIR.0000000000000439 | Guideline / position statement | Children | The AHA recommends no more than about 6 teaspoons of added sugar a day for children and none under age 2. | Narrative, non-systematic literature review; no protocol, no formal risk-of-bias appraisal of included studies; Endpoints are CVD risk factors in children, not clinical CVD events | moderate | C-SOD-03 C-SUG-01 |
| A-SOD-12 | Sugar-sweetened beverage, diet soda, and fatty liver disease in the Framingham Heart Study cohorts. Ma J, Fox CS, Jacques PF et al. | 2015 | PMID 26055949 DOI 10.1016/j.jhep.2015.03.032 | Cross-sectional study | Adults | Daily sugary-drink consumers had 61% higher odds of fatty liver; diet soda showed no link. | Cross-sectional; Observational design; residual confounding possible | moderate | C-SOD-04 |
| A-SOD-13 | Carbonated beverages and chronic kidney disease. Saldana TM, Basso O, Darden R et al. | 2007 | PMID 17525693 DOI 10.1097/EDE.0b013e3180646338 | Case-control study | Newly diagnosed CKD patients and community controls | People with kidney disease more often reported drinking two or more colas a day; authors called this preliminary. | Case-control: recall and selection bias; Old data | low | C-SOD-09 |
| A-SOD-14 | Sweetened beverage consumption, incident coronary heart disease, and biomarkers of risk in men. de Koning L, Malik VS, Kellogg MD et al. | 2012 | PMID 22412070 DOI 10.1161/CIRCULATIONAHA.111.067017 | Cohort study | Male health professionals | Men with highest sugary-drink intake had 20% more heart disease; diet drinks showed no link. | Observational design; residual confounding possible; Self-reported dietary intake | high | C-SOD-03 C-SOD-10 |
| A-SOD-15 | Sweetened beverage consumption and risk of coronary heart disease in women. Fung TT, Malik V, Rexrode KM et al. | 2009 | PMID 19211821 DOI 10.3945/ajcn.2008.27140 | Cohort study | Women aged 34-59 without CHD, stroke, diabetes | Two or more sugary drinks a day: 35% higher heart disease risk; diet drinks not linked. | Observational design; residual confounding possible; Self-reported dietary intake | high | C-SOD-03 C-SOD-10 |
| A-SOD-16 | Added sugar intake and cardiovascular diseases mortality among US adults. Yang Q, Zhang Z, Gregg EW et al. | 2014 | PMID 24493081 DOI 10.1001/jamainternmed.2013.13563 | Cohort study | US adults (nationally representative) | People getting 25% or more of calories from added sugar had nearly three times the CVD death risk of those under 10%. | Single baseline exposure; not updated over up to 18 years (authors); Only ~8% of NHANES III participants had a second 24-h recall for the usual-intake model | moderate | C-SOD-03 C-SUG-01 |
| A-SOD-17 | Association Between Soft Drink Consumption and Mortality in 10 European Countries. Mullee A, Romaguera D, Pearson-Stuttard J et al. | 2019 | PMID 31479109 DOI 10.1001/jamainternmed.2019.2478 | Cohort study | EPIC participants from the general populations of 10 European countries; mean age 50.8 years; 71.1% women; free of cancer, heart disease, stroke and diabetes at baseline | Two or more soft drinks a day were linked with higher death rates; for diet drinks the link was even stronger, which may partly reflect who chooses diet drinks. | Single baseline assessment of soft-drink intake (authors); Residual confounding acknowledged by authors | high | C-SOD-03 C-SOD-10 |
| A-SOD-18 | Reducing consumption of sugar-sweetened beverages is associated with reduced blood pressure: a prospective study among United States adults. Chen L, Caballero B, Mitchell DC et al. | 2010 | PMID 20497980 DOI 10.1161/CIRCULATIONAHA.109.911164 | Cohort study | Adults with elevated BP (mean 134.9/84.8) | One sugary drink less per day was linked with about 1.8 mmHg lower systolic BP. | Observational analysis within trial; Self-reported intake | moderate | C-SOD-03 |
| A-SOD-19 | Effect of sugar-sweetened beverages on oral health: a systematic review and meta-analysis. Valenzuela MJ, Waterhouse B, Aggarwal VR et al. | 2021 | PMID 32830237 DOI 10.1093/eurpub/ckaa147 | Meta-analysis | General populations, children and adults (21 studies permanent dentition, 9 primary, 8 mixed) | More sugary drinks were linked with more tooth decay and erosion, increasing with amount. | Almost exclusively cross-sectional studies: temporality not established; Pooled data were unadjusted for confounders such as socio-economic status and fluoridation (authors) | low | C-SOD-11 |
| A-SOD-20 | Sugar-sweetened beverages and weight gain in children and adults: a systematic review and meta-analysis. Malik VS, Pan A, Willett WC et al. | 2013 | PMID 23966427 DOI 10.3945/ajcn.113.058362 | Meta-analysis | Children and adults | Adding sugary drinks increased adult weight by about 0.85 kg in trials; cohorts show weight gain per serving. | Child RCT estimate imprecise (random effects CI crosses 0); Overlap with other reviews | high | C-SOD-02 |
| A-SOD-21 | Liquid versus solid carbohydrate: effects on food intake and body weight. DiMeglio DP, Mattes RD | 2000 | PMID 10878689 DOI 10.1038/sj.ijo.0801229 | Randomised controlled trial | Healthy adults (7 men, 8 women) | People ate less to balance jelly-bean calories but not soda calories, and gained weight only with soda. | Very small; Randomisation not described in abstract | low | C-SOD-02 |
| A-SOD-22 | Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. Bray GA, Nielsen SJ, Popkin BM | 2004 | PMID 15051594 DOI 10.1093/ajcn/79.4.537 | Ecological study | US population | HFCS consumption rose at the same time as obesity in the US; this suggests but does not prove a link. | Ecological: cannot show causation; HFCS is US-specific | very low | C-SOD-04 |
| A-SOD-23 | Sugar and artificially sweetened beverages and risk of obesity, type 2 diabetes mellitus, hypertension, and all-cause mortality: a dose-response meta-analysis of prospective cohort studies. Qin P, Li Q, Zhao Y et al. | 2020 | PMID 32529512 DOI 10.1007/s10654-020-00655-y | Meta-analysis | Adults | Each extra 250 mL/day of sugary drinks was linked with 12-19% higher risks of obesity and diabetes; diet drinks showed similar links. | High heterogeneity; Cohorts only | moderate | C-SOD-01 C-SOD-02 C-SOD-03 C-SOD-10 |
| A-SUP-01 | Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. Bolland MJ, Avenell A, Baron JA et al. | 2010 | PMID 20671013 DOI 10.1136/bmj.c3691 | Meta-analysis | Mostly older women (patient-level median age 74.5 y, ~78% women, 97% white) in trials of calcium >=500 mg/day, >=100 participants, mean age >40, >1 year; calcium+vitamin D vs placebo trials excluded | In trials, people taking calcium had 31% more heart attacks than with placebo (143 vs 111 events). | CV events were not primary endpoints and were collected non-uniformly; blinded adjudication in only some trials; Borderline significance (P=0.035/0.038); stroke, composite and death not significant | moderate | C-SUP-04 |
| A-SUP-02 | Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women's Health Initiative limited access dataset and meta-analysis. Bolland MJ, Grey A, Avenell A et al. | 2011 | PMID 21505219 DOI 10.1136/bmj.d2040 | Meta-analysis | Postmenopausal women (WHI) + 8 trials | In women not already using calcium, calcium plus vitamin D was linked to about 13–22% more CV events. | Post-hoc subgroup analysis; Same author group | moderate | C-SUP-04 |
| A-SUP-03 | Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Miller ER, Pastor-Barriuso R, Dalal D et al. | 2005 | PMID 15537682 DOI 10.7326/0003-4819-142-1-200501040-00110 | Meta-analysis | 135,967 participants in 19 trials | In high-dose trials, 39 more deaths per 10,000 people with vitamin E. | High-dose trials small, in chronically ill patients (authors' limitation); Generalisability to healthy adults uncertain | moderate | C-SUP-03 |
| A-SUP-04 | Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. Omenn GS, Goodman GE, Thornquist MD et al. | 1996 | PMID 8602180 DOI 10.1056/NEJM199605023341802 | Randomised controlled trial | Smokers, former smokers, asbestos-exposed workers | Lung cancer was 28% more frequent with the supplements; the trial was stopped early. | Early stopping can exaggerate effects; High-risk population only | high | C-SUP-02 |
| A-SUP-05 | The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group | 1994 | PMID 8127329 DOI 10.1056/NEJM199404143301501 | Randomised controlled trial | Male smokers 50–69 years | Beta-carotene raised lung cancer by 18% and deaths by 8%; vitamin E did not prevent lung cancer. | Male smokers only; Low vitamin E dose | high | C-SUP-02 C-SUP-03 |
| A-SUP-06 | Dietary supplements and mortality rate in older women: the Iowa Women's Health Study. Mursu J, Robien K, Harnack LJ et al. | 2011 | PMID 21987192 DOI 10.1001/archinternmed.2011.445 | Cohort study | Postmenopausal women aged 55-69 in 1986 (mean 61.6 y), 99% white, Iowa | Several supplements were linked to slightly more deaths; calcium to fewer. | Observational; confounding by indication and reverse causation (e.g. iron for anaemia due to illness) possible; Self-reported supplement use; supplement questionnaire not separately validated | low | C-SUP-04 C-SUP-06 |
| A-SUP-07 | n-3 fatty acids and cardiovascular events after myocardial infarction. Kromhout D, Giltay EJ, Geleijnse JM et al. | 2010 | PMID 20929341 DOI 10.1056/NEJMoa1003603 | Randomised controlled trial | Post-MI patients 60–80 years | No reduction in cardiovascular events. | Low dose via margarine; Well-treated patients | high | C-SUP-01 C-SUP-05 |
| A-SUP-08 | Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. Manson JE, Cook NR, Lee IM et al. | 2019 | PMID 30415637 DOI 10.1056/NEJMoa1811403 | Randomised controlled trial | Men ≥50, women ≥55 | No reduction in major cardiovascular events or cancer. | Secondary MI benefit | high | C-SUP-01 C-SUP-05 |
| A-SUP-09 | Effects of n-3 Fatty Acid Supplements in Diabetes Mellitus. ASCEND Study Collaborative Group, Bowman L, Mafham M et al. | 2018 | PMID 30146932 DOI 10.1056/NEJMoa1804989 | Randomised controlled trial | Diabetes without ASCVD | No reduction in serious vascular events. | Olive-oil placebo | high | C-SUP-01 C-SUP-05 |
| A-SUP-10 | Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk: The STRENGTH Randomized Clinical Trial. Nicholls SJ, Lincoff AM, Garcia M et al. | 2020 | PMID 33190147 DOI 10.1001/jama.2020.22258 | Randomised controlled trial | Statin-treated, high CV risk, hypertriglyceridaemia, low HDL | No benefit vs corn oil; more GI side effects. | Stopped for futility | high | C-SUP-01 C-SUP-05 |
| A-SUP-11 | Effect of Long-Term Marine ɷ-3 Fatty Acids Supplementation on the Risk of Atrial Fibrillation in Randomized Controlled Trials of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis. Gencer B, Djousse L, Al-Ramady OT et al. | 2021 | PMID 34612056 DOI 10.1161/CIRCULATIONAHA.121.055654 | Meta-analysis | Participants in CV outcome RCTs | Omega-3 pills raised AF risk by 25%, more at higher doses. | AF often not prespecified; Few trials | high | C-SUP-05 |
| A-SUP-12 | Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Abdelhamid AS, Brown TJ, Brainard JS et al. | 2020 | PMID 32114706 DOI 10.1002/14651858.CD003177.pub5 | Meta-analysis | Adults in 86 RCTs | Little or no effect on deaths; small reductions in coronary events (low certainty). | Low certainty for small benefits | high | C-SUP-01 C-SUP-05 |
| A-SUP-13 | Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. Clegg DO, Reda DJ, Harris CL et al. | 2006 | PMID 16495392 DOI 10.1056/NEJMoa052771 | Randomised controlled trial | Symptomatic knee osteoarthritis | Not better than placebo overall. | High placebo response; Exploratory subgroup | high | C-SUP-01 C-SUP-07 |
| A-SUP-14 | Ascorbic acid supplements and kidney stone incidence among men: a prospective study. Thomas LD, Elinder CG, Tiselius HG et al. | 2013 | PMID 23381591 DOI 10.1001/jamainternmed.2013.2296 | Cohort study | Men (per title) | Not read (no abstract). | Letter format; not read | low | C-SUP-07 |
| A-SUP-15 | Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial. Stranges S, Marshall JR, Natarajan R et al. | 2007 | PMID 17620655 DOI 10.7326/0003-4819-147-4-200708210-00175 | Randomised controlled trial | Dermatology clinic patients without T2D, low-selenium areas | Selenium pills were linked to more new diabetes (HR 1.55). | Secondary outcome; Self-reported diagnosis | moderate | C-SUP-07 |
| A-SUP-16 | Vitamin A intake and hip fractures among postmenopausal women. Feskanich D, Singh V, Willett WC et al. | 2002 | PMID 11754708 DOI 10.1001/jama.287.1.47 | Cohort study | Postmenopausal women | Women with the highest retinol intake had about 1.9 times the risk of hip fracture. | Observational; FFQ measurement error | moderate | C-SUP-07 |
| A-SUP-17 | Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. Cole BF, Baron JA, Sandler RS et al. | 2007 | PMID 17551129 DOI 10.1001/jama.297.21.2351 | Randomised controlled trial | Recent colorectal adenoma history | No prevention of polyps; possible increase in advanced lesions (borderline). | Second follow-up 59.5%; Borderline results | moderate | C-SUP-06 |
| A-SUP-18 | Cancer incidence and mortality after treatment with folic acid and vitamin B12. Ebbing M, Bønaa KH, Nygård O et al. | 2009 | PMID 19920236 DOI 10.1001/jama.2009.1622 | Randomised controlled trial | Ischaemic heart disease patients | More cancer and deaths with folic acid plus B12 in heart patients. | Post-trial observational follow-up; Not prespecified for cancer | moderate | C-SUP-06 |
| A-SUP-19 | Homocysteine lowering with folic acid and B vitamins in vascular disease. Lonn E, Yusuf S, Arnold MJ et al. | 2006 | PMID 16531613 DOI 10.1056/NEJMoa060900 | Randomised controlled trial | Vascular disease or diabetes, ≥55 years | No reduction in major CV events; fewer strokes. | high | C-SUP-07 | |
| A-SUP-20 | Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. Sanders KM, Stuart AL, Williamson EJ et al. | 2010 | PMID 20460620 DOI 10.1001/jama.2010.594 | Randomised controlled trial | Community-dwelling women ≥70 at high fracture risk | More falls and fractures with 500,000 IU once a year. | Unusual bolus regimen | high | C-SUP-07 |
| A-SUP-21 | Monthly High-Dose Vitamin D Treatment for the Prevention of Functional Decline: A Randomized Clinical Trial. Bischoff-Ferrari HA, Dawson-Hughes B, Orav EJ et al. | 2016 | PMID 26747333 DOI 10.1001/jamainternmed.2015.7148 | Randomised controlled trial | ≥70 years with prior fall | More people fell with the higher monthly doses. | Small; Secondary outcome falls | moderate | C-SUP-07 |
| A-SUP-22 | Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. Manson JE, Cook NR, Lee IM et al. | 2019 | PMID 30415629 DOI 10.1056/NEJMoa1809944 | Randomised controlled trial | Men ≥50, women ≥55 | No prevention of cancer or heart disease; no safety problems. | Mostly vitamin-D-replete population | high | C-SUP-01 C-SUP-07 |
| A-SUP-23 | Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Klein EA, Thompson IM, Tangen CM et al. | 2011 | PMID 21990298 DOI 10.1001/jama.2011.1437 | Randomised controlled trial | Relatively healthy men aged >=50 (African American) or >=55 (others) with PSA <=4.0 ng/mL and non-suspicious DRE; median age 62-63; 79% white, 12-13% African American | Vitamin E pills raised prostate cancer by 17% (1.6 extra cases per 1,000 men per year). | Absolute effect small (1.6 per 1000 person-years); About 16-21% of cancers diagnosed during unblinded follow-up after supplements stopped | high | C-SUP-03 |
| A-SUP-24 | Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. Bjelakovic G, Nikolova D, Gluud LL et al. | 2007 | PMID 17327526 DOI 10.1001/jama.297.8.842 | Meta-analysis | Adults in 68 RCTs | In low-bias trials, beta-carotene, vitamin A and vitamin E were linked to slightly more deaths. | Exclusion of zero-death trials and methods were debated; Heterogeneous populations | moderate | C-SUP-02 C-SUP-03 |
| A-SUP-25 | Multivitamins in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. Sesso HD, Christen WG, Bubes V et al. | 2012 | PMID 23117775 DOI 10.1001/jama.2012.14805 | Randomised controlled trial | Male US physicians ≥50 | No reduction in heart attacks or strokes; no increase in deaths. | Healthy physicians | high | C-SUP-01 C-SUP-06 |
| A-SUP-26 | Multivitamin-multimineral supplementation and mortality: a meta-analysis of randomized controlled trials. Macpherson H, Pipingas A, Pase MP | 2013 | PMID 23255568 DOI 10.3945/ajcn.112.049304 | Meta-analysis | Independently living adults | No effect on mortality. | Heterogeneous products | high | C-SUP-01 C-SUP-06 |
| A-SUP-27 | Long-term multivitamin supplementation and cognitive function in men: a randomized trial. Grodstein F, O'Brien J, Kang JH et al. | 2013 | PMID 24490265 DOI 10.7326/0003-4819-159-12-201312170-00006 | Randomised controlled trial | Male physicians ≥65 | No benefit for cognition. | Well-nourished; dose low | high | C-SUP-01 |
| A-SUP-28 | Enough is enough: Stop wasting money on vitamin and mineral supplements. Guallar E, Stranges S, Mulrow C et al. | 2013 | PMID 24490268 DOI 10.7326/0003-4819-159-12-201312170-00011 | Other | Opinion; not read. | Opinion, not data | very low | C-SUP-01 | |
| A-SUP-29 | Supplemental Vitamins and Minerals for CVD Prevention and Treatment. Jenkins DJA, Spence JD, Giovannucci EL et al. | 2018 | PMID 29852980 DOI 10.1016/j.jacc.2018.04.020 | Meta-analysis | RCT participants | Mostly no effect; folic acid may reduce stroke; antioxidant mixtures may increase mortality. | Abstract lacks numbers | moderate | C-SUP-01 C-SUP-04 |
| A-SUP-30 | Vitamin, Mineral, and Multivitamin Supplementation to Prevent Cardiovascular Disease and Cancer: US Preventive Services Task Force Recommendation Statement. US Preventive Services Task Force, Mangione CM, Barry MJ et al. | 2022 | PMID 35727271 DOI 10.1001/jama.2022.8970 | Guideline / position statement | Community-dwelling, non-pregnant adults | Recommends against beta-carotene and vitamin E; evidence insufficient for most others. | Excludes pregnancy and deficiency | high | C-SUP-01 C-SUP-02 C-SUP-03 C-SUP-10 |
| A-UPF-01 | Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake. Hall KD, Ayuketah A, Brychta R et al. | 2019 | PMID 31105044 DOI 10.1016/j.cmet.2019.05.008 | Randomised controlled trial | 10 men and 10 women, weight-stable, age 31.2±1.6 y (mean±SE), BMI 27±1.5 kg/m2 | People ate about 500 calories more per day and gained weight on ultra-processed food. | Small (n=20) and short (2 weeks per diet); No run-in or washout period; possible carry-over (authors) | high | C-UPF-02 C-SRC-22 |
| A-UPF-02 | Association Between Ultraprocessed Food Consumption and Risk of Mortality Among Middle-aged Adults in France. Schnabel L, Kesse-Guyot E, Allès B et al. | 2019 | PMID 30742202 DOI 10.1001/jamainternmed.2018.7289 | Cohort study | Adults >=45 y, 73% women | Each 10% more ultra-processed food was linked with 14% higher death risk. | Volunteer cohort, mostly women; Few deaths | moderate | C-UPF-03 |
| A-UPF-03 | Association between consumption of ultra-processed foods and all cause mortality: SUN prospective cohort study. Rico-Campà A, Martínez-González MA, Alvarez-Alvarez I et al. | 2019 | PMID 31142450 DOI 10.1136/bmj.l1949 | Cohort study | Spanish university graduates aged 20-91 (mean age 37.6, SD 12.3); 12,113 women, 7,786 men; participants with prevalent disease were included and adjusted for | More than four servings a day was linked with 62% higher death risk. | Few deaths (335), so imprecise estimates; cause-specific analyses underpowered and non-significant; FFQ not designed for NOVA; some UPF items missing; serving counts may misclassify | moderate | C-UPF-03 |
| A-UPF-04 | Ultra-processed food intake and risk of cardiovascular disease: prospective cohort study (NutriNet-Santé). Srour B, Fezeu LK, Kesse-Guyot E et al. | 2019 | PMID 31142457 DOI 10.1136/bmj.l1451 | Cohort study | French adults >=18 years without CVD at baseline; 79.2% women; mean age 42.7 (SD 14.5); healthier, more educated, less often overweight and diabetic than the French population | Each 10% more ultra-processed food was linked with 12% more cardiovascular disease. | Short median follow-up (5.2 years); Almost half of events are transient ischaemic attacks (674/1,409) and many angioplasties; few myocardial infarctions (106) and strokes (155) | moderate | C-UPF-03 |
| A-UPF-05 | Ultraprocessed Food Consumption and Risk of Type 2 Diabetes Among Participants of the NutriNet-Santé Prospective Cohort. Srour B, Fezeu LK, Kesse-Guyot E et al. | 2020 | PMID 31841598 DOI 10.1001/jamainternmed.2019.5942 | Cohort study | Adults >=18, 79% women | Each 10% more ultra-processed food was linked with 15% more diabetes. | NOVA misclassification possible; Residual confounding | moderate | C-UPF-03 |
| A-UPF-06 | Consumption of ultra-processed foods and cancer risk: results from NutriNet-Santé prospective cohort. Fiolet T, Srour B, Sellem L et al. | 2018 | PMID 29444771 DOI 10.1136/bmj.k322 | Cohort study | French adult volunteers >=18 years without cancer at baseline; 78.3% women; mean age 42.8 (SD 14.8) | Each 10% more ultra-processed food was linked with 12% more cancer. | Short median follow-up (5 years) relative to cancer latency (authors); Volunteer, health-conscious, mostly female cohort (authors) | moderate | C-UPF-03 |
| A-UPF-07 | Ultra-processed food consumption is associated with increased risk of all-cause and cardiovascular mortality in the Moli-sani Study. Bonaccio M, Di Castelnuovo A, Costanzo S et al. | 2021 | PMID 33333551 DOI 10.1093/ajcn/nqaa299 | Cohort study | Adults mean age 55 | Highest consumers had 58% higher cardiovascular death risk; sugar content explained about a third of the heart/stroke link. | NOVA misclassification possible; Residual confounding | moderate | C-UPF-03 |
| A-UPF-08 | Ultraprocessed food consumption and risk of overweight and obesity: the University of Navarra Follow-Up (SUN) cohort study. Mendonça RD, Pimenta AM, Gea A et al. | 2016 | PMID 27733404 DOI 10.3945/ajcn.116.135004 | Cohort study | Middle-aged graduates not overweight at baseline | Highest consumers had 26% higher risk of becoming overweight. | NOVA misclassification possible; Residual confounding | moderate | C-UPF-02 |
| A-UPF-09 | Ultra-processed food intake in association with BMI change and risk of overweight and obesity: A prospective analysis of the French NutriNet-Santé cohort. Beslay M, Srour B, Méjean C et al. | 2020 | PMID 32853224 DOI 10.1371/journal.pmed.1003256 | Cohort study | Adults, 78% women | Each 10% more ultra-processed food: 11% higher risk of overweight. | NOVA misclassification possible; Residual confounding | moderate | C-UPF-02 |
| A-UPF-10 | Consumption of ultra-processed foods and body fat during childhood and adolescence: a systematic review. Costa CS, Del-Ponte B, Assunção MCF et al. | 2018 | PMID 28676132 DOI 10.1017/S1368980017001331 | Systematic review | Healthy children and adolescents | Most studies found more body fat in children eating more ultra-processed foods, including sweets and soft drinks. | No pooling; Heterogeneous exposures | low | C-UPF-02 |
| A-UPF-11 | Prospective association between ultra-processed food consumption and incident depressive symptoms in the French NutriNet-Santé cohort. Adjibade M, Julia C, Allès B et al. | 2019 | PMID 30982472 DOI 10.1186/s12916-019-1312-y | Cohort study | Adults 18-86 without depressive symptoms at baseline | Each 10% more ultra-processed food: 21% more new depressive symptoms. | Symptom scale, not diagnosis; NOVA misclassification possible | moderate | C-UPF-04 |
| A-UPF-12 | Association of ultra-processed food intake with risk of inflammatory bowel disease: prospective cohort study. Narula N, Wong ECL, Dehghan M et al. | 2021 | PMID 34261638 DOI 10.1136/bmj.n1554 | Cohort study | Adults aged 35-70 from 21 low-, middle- and high-income countries (incl. Iran, Palestine, Saudi Arabia, UAE, Turkey; no Western European country except Sweden and Poland) | Five or more servings a day: 82% higher IBD risk; legumes, dairy and vegetables showed no link. | Few cases (467), especially Crohn's disease (90): imprecise estimates; Self-reported IBD; only ~20% validated; systematic recording started only in 2014 (authors) | moderate | C-UPF-05 |
| A-UPF-13 | Ultra-processed food exposure and adverse health outcomes: umbrella review of epidemiological meta-analyses. Lane MM, Gamage E, Du S et al. | 2024 | PMID 38418082 DOI 10.1136/bmj-2023-077310 | Systematic review | Pooled populations across the life course (mostly adults; 5 pooled analyses in children/adolescents) | UPF was linked to 32 of 45 health outcomes; certainty was mostly low. | All underlying evidence observational; confounder adjustment and sensitivity analyses of primary studies not assessed (authors); Many pooled analyses based on 2-4 studies, often cross-sectional (e.g. anxiety, common mental disorders, obesity) | high | C-UPF-03 C-UPF-04 C-UPF-05 |
| A-UPF-14 | Consumption of ultra-processed foods and health status: a systematic review and meta-analysis. Pagliai G, Dinu M, Madarena MP et al. | 2021 | PMID 32792031 DOI 10.1017/S0007114520002688 | Meta-analysis | Adults | Highest consumers had 25% higher death risk and 29% higher CVD risk in cohorts. | Few studies per outcome | moderate | C-UPF-03 C-UPF-04 |
| A-UPF-15 | Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Chassaing B, Koren O, Goodrich JK et al. | 2015 | PMID 25731162 DOI 10.1038/nature14232 | Animal study | Mice (mostly 4 weeks old at start; also 4-month-old mice); male or female within experiments | Two common emulsifiers caused gut inflammation and metabolic problems in mice. | Animal model; human relevance unknown (authors); Exposure 0.1-1.0% in all drinking water or chow; relation to actual human intake not quantified | moderate | C-UPF-05 C-UPF-06 |
| A-UPF-16 | Randomized Controlled-Feeding Study of Dietary Emulsifier Carboxymethylcellulose Reveals Detrimental Impacts on the Gut Microbiota and Metabolome. Chassaing B, Compher C, Bonhomme B et al. | 2022 | PMID 34774538 DOI 10.1053/j.gastro.2021.11.006 | Randomised controlled trial | Healthy adults | Seven people eating CMC for 11 days had changes in gut bacteria and mild discomfort. | Very small; Short | moderate | C-UPF-06 |
| A-UPF-17 | Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Suez J, Korem T, Zeevi D et al. | 2014 | PMID 25231862 DOI 10.1038/nature13793 | Animal study | Mice; healthy humans | Same paper as A-SOD-09. | Duplicate of A-SOD-09 | moderate | C-SOD-07 |
| A-UPF-18 | Artificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort study. Debras C, Chazelas E, Srour B et al. | 2022 | PMID 35324894 DOI 10.1371/journal.pmed.1003950 | Cohort study | Adults | Higher sweetener consumers had 13% more cancer. | Selection bias, residual confounding, reverse causation (authors) | moderate | C-UPF-07 |
| A-UPF-19 | Artificial sweeteners and risk of cardiovascular diseases: results from the prospective NutriNet-Santé cohort. Debras C, Chazelas E, Sellem L et al. | 2022 | PMID 36638072 DOI 10.1136/bmj-2022-071204 | Cohort study | Adults, 79.8% women | Higher sweetener intake: 9% higher cardiovascular risk. | Reverse causation; Residual confounding | moderate | C-UPF-07 |
| A-UPF-20 | Carcinogenicity of aspartame, methyleugenol, and isoeugenol. Riboli E, Beland FA, Lachenmeier DW et al. | 2023 | PMID 37454664 DOI 10.1016/S1470-2045(23)00341-8 | Risk assessment | Not applicable | IARC placed aspartame in Group 2B ('possibly carcinogenic') on limited evidence. | Hazard identification, not risk assessment: does not address the dose at which any risk occurs; Human evidence limited to a few observational ASB studies with possible chance, bias or confounding | moderate | C-UPF-08 |
| A-UPF-21 | Safety assessment of titanium dioxide (E171) as a food additive. EFSA Panel on Food Additives and Flavourings (FAF), Younes M, Aquilina G et al. | 2021 | PMID 33976718 DOI 10.2903/j.efsa.2021.6585 | Risk assessment | Not applicable | EFSA could not rule out DNA damage and concluded E171 is no longer safe; the EU then banned it. | Precautionary conclusion driven by an unresolved genotoxicity concern, not by demonstrated harm in humans; No human outcome data; no adequate carcinogenicity study of TiO2 nanoparticles | high | C-UPF-09 C-UPF-11 |
| A-UPF-22 | Ultra-processed foods: what they are and how to identify them. Monteiro CA, Cannon G, Levy RB et al. | 2019 | PMID 30744710 DOI 10.1017/S1368980018003762 | Narrative review | Not applicable | NOVA's authors explain that products with industrial ingredients or cosmetic additives (e.g., emulsifiers, flavours, emulsifying salts) are ultra-processed. | Commentary; reliability not tested here | moderate | C-UPF-01 C-UPF-12 C-SUG-05 |
| A-UPF-23 | Trans fatty acids and cardiovascular disease. Mozaffarian D, Katan MB, Ascherio A et al. | 2006 | PMID 16611951 DOI 10.1056/NEJMra054035 | Narrative review | Not applicable | A review of trans fats and heart disease; no abstract was available to assess. | Content not reviewed (no abstract) | moderate | C-UPF-03 |
| A-VEG-01 | Multistate Outbreak of Escherichia coli O157:H7 Infections Associated with Consumption of Fresh Spinach: United States, 2006. Sharapov UM, Wendel AM, Davis JP et al. | 2016 | PMID 28221950 DOI 10.4315/0362-028X.JFP-15-556 | Outbreak report | Case patients in 27 states | 225 people fell ill and 5 died after eating contaminated bagged spinach. | Single event | high | C-VEG-03 |
| A-VEG-02 | German outbreak of Escherichia coli O104:H4 associated with sprouts. Buchholz U, Bernard H, Werber D et al. | 2011 | PMID 22029753 DOI 10.1056/NEJMoa1106482 | Outbreak report | HUS cases and controls; restaurant visitors | Investigation identified sprouts, not cucumbers, as the source. | Recall bias; Strain not found on seeds | high | C-VEG-04 |
| A-VEG-03 | Multistate Outbreak of Listeriosis Associated with Packaged Leafy Green Salads, United States and Canada, 2015-2016. Self JL, Conrad A, Stroika S et al. | 2019 | PMID 31310227 DOI 10.3201/eid2508.180761 | Outbreak report | Case-patients | 33 listeriosis cases linked to salads from one factory. | Small | high | C-VEG-03 |
| A-VEG-04 | Outbreak of Salmonella Newport infections linked to cucumbers--United States, 2014. Angelo KM, Chu A, Anand M et al. | 2015 | PMID 25695319 | Outbreak report | Patients in 29 states + DC | 275 people infected; cucumbers likely source. | Evidence 'suggests' | moderate | C-VEG-03 |
| A-VEG-05 | Dietary oxalate and calcium oxalate nephrolithiasis. Khan SR, Glenton PA, Byer KJ | 2007 | PMID 17870111 DOI 10.1016/j.juro.2007.06.046 | Animal study | Male Sprague-Dawley rats | Rats fed an oxalate precursor developed kidney crystals that partly cleared after stopping it. | Animal model; Precursor, not vegetables | low | C-VEG-05 |
| A-VEG-06 | Oxalate nephropathy due to 'juicing': case report and review. Getting JE, Gregoire JR, Phul A et al. | 2013 | PMID 23830537 DOI 10.1016/j.amjmed.2013.03.019 | Case series / case report | Index patient + 65 Mayo Clinic patients with biopsy-proven renal CaOx crystals | Rare kidney failure from heavy oxalate-rich juicing, mainly in people with kidney disease. | Case series; selection | low | C-VEG-06 |
| A-VEG-07 | Myxedema coma induced by ingestion of raw bok choy. Chu M, Seltzer TF | 2010 | PMID 20484407 DOI 10.1056/NEJMc0911005 | Case series / case report | One patient | One elderly woman with extreme raw bok choy intake; no generalisation possible. | Single case; No abstract | very low | C-VEG-10 |
| A-VEG-08 | Methemoglobinemia caused by the ingestion of courgette soup given in order to resolve constipation in two formula-fed infants. Savino F, Maccario S, Guidi C et al. | 2006 | PMID 16809905 DOI 10.1159/000094301 | Case series / case report | Two formula-fed infants aged 1 and 2 months | Two infants under 3 months developed methaemoglobinaemia from concentrated courgette soup. | Two cases | low | C-VEG-07 C-VEG-08 |
| A-VEG-09 | [Food poisoning by cucurbitacines]. Jung C, Steuber B, Schwörer H | 2020 | PMID 32668470 DOI 10.1055/a-1163-9741 | Case series / case report | One 66-year-old woman | A woman developed bloody colitis after eating bitter zucchini; recovered in 2 days. | Single case | low | C-VEG-09 |
| A-VEG-10 | Hair Loss Associated With Cucurbit Poisoning. Assouly P | 2018 | PMID 29590275 DOI 10.1001/jamadermatol.2017.6128 | Case series / case report | Case(s) | Case report; content not available to us. | No abstract | very low | C-VEG-09 |
| A-VEG-11 | Toxic squash syndrome: a case report. Prudhomme N, Pan A, Hendin A | 2022 | PMID 35869358 DOI 10.1007/s43678-022-00358-1 | Case series / case report | Case | Case report; content not available to us. | No abstract | very low | C-VEG-09 |
| A-VEG-12 | Profilin is a relevant melon allergen susceptible to pepsin digestion in patients with oral allergy syndrome. Rodriguez-Perez R, Crespo JF, Rodríguez J et al. | 2003 | PMID 12642849 DOI 10.1067/mai.2003.74 | Laboratory / cell study | Patients with melon OAS confirmed by DBPCFC | Allergic patients react to profilin in melon and related cucurbits; it is quickly digested in the stomach. | Small selected group | moderate | C-VEG-11 |
| A-VEG-13 | Organic diets significantly lower children's dietary exposure to organophosphorus pesticides. Lu C, Toepel K, Irish R et al. | 2006 | PMID 16451864 DOI 10.1289/ehp.8418 | Other | Children aged 3-11 years from public and Montessori elementary schools in suburban Seattle, consuming exclusively conventional diets; selected to be not very selective about food taste | Pesticide traces in children's urine dropped to undetectable when they ate organic food. | Very small, non-representative sample (authors: do not generalise); No health outcomes; no comparison with acceptable daily intakes | moderate | C-VEG-13 |
| A-VEG-14 | Organophosphorus pesticide exposure of urban and suburban preschool children with organic and conventional diets. Curl CL, Fenske RA, Elgethun K | 2003 | PMID 12611667 DOI 10.1289/ehp.5754 | Cross-sectional study | Preschool children | Children on conventional diets had about six times more pesticide metabolites in urine. | Small; Cross-sectional | moderate | C-VEG-13 |
| A-VEG-15 | Do dietary lectins cause disease? Freed DL | 1999 | PMID 10205084 DOI 10.1136/bmj.318.7190.1023 | Narrative review | Not applicable | Opinion piece asking whether lectins cause disease; content not available to us. | Opinion; no data | very low | C-LEG-07 |
| A-VEG-16 | Cryptic diversity of cellulose-degrading gut bacteria in industrialized humans. Moraïs S, Winkler S, Zorea A et al. | 2024 | PMID 38484069 DOI 10.1126/science.adj9223 | Other | Metagenome-assembled genomes (4941 rumen MAGs, 92,143 human MAGs) and 1989 gut metagenome samples from humans (industrialised, rural, hunter-gatherer, 1000-2000-year-old paleofaeces) and 75 animal species (non-human primates, ruminants) | Humans carry cellulose-digesting bacteria; they are common in traditional populations and rare in industrialised ones. | No health outcomes and no measurement of actual cellulose fermentation in people; Prevalence comparisons are ecological and confounded by diet, antibiotics, sequencing depth and cohort methods | high | C-VEG-01 C-VEG-02 |
| A-VEG-17 | Interaction Between Dietary Vitamin K Intake and Anticoagulation by Vitamin K Antagonists: Is It Really True?: A Systematic Review. Violi F, Lip GY, Pignatelli P et al. | 2016 | PMID 26962786 DOI 10.1097/MD.0000000000002895 | Systematic review | Patients treated with vitamin K antagonists (mostly warfarin; also phenprocoumon, acenocoumarol) for AF, prosthetic valves or VTE | Review found no good evidence that patients on warfarin should restrict leafy greens; stable intake matters. | Only MEDLINE and Cochrane searched; No protocol registration; no meta-analysis | low | C-VEG-12 |
| A-WHT-01 | Associations of cereal grains intake with cardiovascular disease and mortality across 21 countries in Prospective Urban and Rural Epidemiology study: prospective cohort study. Swaminathan S, Dehghan M, Raj JM et al. | 2021 | PMID 33536317 DOI 10.1136/bmj.m4948 | Cohort study | Adults aged 35-70 y, urban and rural, 21 low-, middle- and high-income countries | People eating about 7 portions/day of refined grains had 27% higher mortality and 33% more major heart events than those eating very little. | Diet measured once at baseline by FFQ; Residual confounding acknowledged by authors | high | C-WHT-03 C-WHT-01 C-GRN-05 |
| A-WHT-02 | Whole grain consumption and risk of cardiovascular disease, cancer, and all cause and cause specific mortality: systematic review and dose-response meta-analysis of prospective studies. Aune D, Keum N, Giovannucci E et al. | 2016 | PMID 27301975 DOI 10.1136/bmj.i2716 | Meta-analysis | Participants of prospective cohorts | Each 3 servings/day of whole grains linked to 17% lower mortality and 19% lower CHD. | Observational primary studies; healthy-user and socioeconomic confounding acknowledged; High heterogeneity for all-cause mortality (I2 83%) and diabetes mortality | high | C-WHT-04 C-WHT-03 C-GRN-08 C-GRN-04 |
| A-WHT-03 | White rice consumption and risk of type 2 diabetes: meta-analysis and systematic review. Hu EA, Pan A, Malik V et al. | 2012 | PMID 22422870 DOI 10.1136/bmj.e1454 | Meta-analysis | Adults free of self-reported diabetes at baseline in 4 prospective cohort studies (7 cohort analyses): Shanghai Women's Health Study (China), JPHC (Japan; men and women analysed separately), HPFS, NHS, NHS II (USA), Melbourne Collaborative Cohort Study (Australia); ages 26-87 years | Each daily serving of white rice was linked to 11% higher diabetes risk; strongest in China/Japan. | Only 4 articles / 7 comparisons; Egger test underpowered; Substantial overall heterogeneity (I2=72.2%); the single overall estimate mixes very different intake ranges | moderate | C-GRN-05 C-WHT-05 |
| A-WHT-04 | Whole grain and refined grain consumption and the risk of type 2 diabetes: a systematic review and dose-response meta-analysis of cohort studies. Aune D, Norat T, Romundstad P et al. | 2013 | PMID 24158434 DOI 10.1007/s10654-013-9852-5 | Meta-analysis | Cohort participants | More whole grains: 32% lower diabetes risk per 3 servings/day; refined grains: no clear link. | High heterogeneity; Observational | moderate | C-WHT-05 C-GRN-05 |
| A-WHT-05 | A prospective study of dietary glycemic load, carbohydrate intake, and risk of coronary heart disease in US women. Liu S, Willett WC, Stampfer MJ et al. | 2000 | PMID 10837285 DOI 10.1093/ajcn/71.6.1455 | Cohort study | 75,521 US women aged 38-63 y | Women with the highest dietary glycaemic load had about twice the CHD risk. | Women only, US nurses; GL is a whole-diet measure | moderate | C-WHT-05 |
| A-WHT-06 | Relation between a diet with a high glycemic load and plasma concentrations of high-sensitivity C-reactive protein in middle-aged women. Liu S, Manson JE, Buring JE et al. | 2002 | PMID 11864854 DOI 10.1093/ajcn/75.3.492 | Cross-sectional study | 244 healthy women | Women with high GL diets had higher CRP. | Small, cross-sectional; Surrogate outcome | low | C-WHT-05 |
| A-WHT-07 | Glycemic index, glycemic load, and risk of type 2 diabetes: results from 3 large US cohorts and an updated meta-analysis. Bhupathiraju SN, Tobias DK, Malik VS et al. | 2014 | PMID 24787496 DOI 10.3945/ajcn.113.079533 | Cohort study | 74,248 NHS women, 90,411 NHS II women, 40,498 HPFS men | Diets high in fast-acting carbs and low in cereal fibre linked to ~50% higher diabetes risk. | Observational; US health professionals | high | C-WHT-05 C-FRU-01 |
| A-WHT-08 | Dietary glycemic load and index and risk of coronary heart disease in a large italian cohort: the EPICOR study. Sieri S, Krogh V, Berrino F et al. | 2010 | PMID 20386010 DOI 10.1001/archinternmed.2010.15 | Cohort study | 15,171 men, 32,578 women | High GL linked to CHD in women, not men. | Few cases in women (158); Sex-specific findings | moderate | C-WHT-05 |
| A-WHT-09 | Whole- and refined-grain intakes are differentially associated with abdominal visceral and subcutaneous adiposity in healthy adults: the Framingham Heart Study. McKeown NM, Troy LM, Jacques PF et al. | 2010 | PMID 20881074 DOI 10.3945/ajcn.2009.29106 | Cross-sectional study | 2834 adults 32-83 y | More refined grains, more visceral fat; more whole grains, less. | Cross-sectional; FFQ | moderate | C-WHT-06 |
| A-WHT-10 | Glycemic load, glycemic index, bread and incidence of overweight/obesity in a Mediterranean cohort: the SUN project. de la Fuente-Arrillaga C, Martinez-Gonzalez MA, Zazpe I et al. | 2014 | PMID 25335643 DOI 10.1186/1471-2458-14-1091 | Cohort study | 9267 Spanish university graduates | 2+ portions/day white bread linked to 40% higher odds of becoming overweight, but not to yearly weight gain. | Graduates only; Mixed results | moderate | C-WHT-06 |
| A-WHT-11 | Associations of Whole Grain and Refined Grain Consumption With Metabolic Syndrome. A Meta-Analysis of Observational Studies. Guo H, Ding J, Liang J et al. | 2021 | PMID 34277690 DOI 10.3389/fnut.2021.695620 | Meta-analysis | Observational study participants | Refined grains linked to 37% higher MetS risk in pooled observational studies. | Half cross-sectional; Wide CI | low | C-WHT-06 |
| A-WHT-12 | Whole-grain intake is favorably associated with metabolic risk factors for type 2 diabetes and cardiovascular disease in the Framingham Offspring Study. McKeown NM, Meigs JB, Liu S et al. | 2002 | PMID 12145012 DOI 10.1093/ajcn/76.2.390 | Cross-sectional study | 2941 adults | Whole grains linked to slightly better markers; refined grains showed no trend. | Cross-sectional | low | C-WHT-06 |
| A-WHT-13 | Whole grain, bran, and germ intake and risk of type 2 diabetes: a prospective cohort study and systematic review. de Munter JS, Hu FB, Spiegelman D et al. | 2007 | PMID 17760498 DOI 10.1371/journal.pmed.0040261 | Cohort study | 161,737 US women | Highest whole grain intake: about 25-37% lower diabetes risk. | Observational | high | C-WHT-05 C-WHT-04 |
| A-WHT-14 | Dietary fibre and incidence of type 2 diabetes in eight European countries: the EPIC-InterAct Study and a meta-analysis of prospective studies. InterAct Consortium | 2015 | PMID 26021487 DOI 10.1007/s00125-015-3585-9 | Cohort study | EPIC-InterAct: 340,234 eligible EPIC participants; analysed 26,088 (11,559 incident T2D cases, subcohort 15,258 incl. 729 cases), mean subcohort age 52.4 years. Meta-analysis: 617,968 participants, 41,066 cases (8 US, 5 European, 3 Australian, 3 Asian cohorts) | Each extra 10 g/day of cereal fibre linked to 25% lower diabetes risk. | EPIC-InterAct: associations null after BMI adjustment (BMI may be confounder and mediator); Diet measured only at baseline; FFQ measurement error | high | C-WHT-05 |
| A-WHT-15 | Glycemic index, glycemic load, and dietary fiber intake and incidence of type 2 diabetes in younger and middle-aged women. Schulze MB, Liu S, Rimm EB et al. | 2004 | PMID 15277155 DOI 10.1093/ajcn/80.2.348 | Cohort study | 91,249 women | High GI linked to 59% higher risk; cereal fibre to 36% lower risk. | Observational; GL null | moderate | C-WHT-05 |
| A-WHT-16 | Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Drago S, El Asmar R, Di Pierro M et al. | 2006 | PMID 16635908 DOI 10.1080/00365520500235334 | Laboratory / cell study | IEC6, Caco2 cells; biopsies from coeliac (remission) and non-coeliac patients | Gliadin briefly loosened gut tissue samples; strongly in coeliac tissue, slightly in others. | Lab/ex vivo only; no clinical outcomes | moderate | C-WHT-09 |
| A-WHT-17 | Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3. Lammers KM, Lu R, Brownley J et al. | 2008 | PMID 18485912 DOI 10.1053/j.gastro.2008.03.023 | Laboratory / cell study | Cell lines, mice, biopsies | Gliadin binds a receptor and increases permeability in mouse tissue. | Lab; COI | moderate | C-WHT-09 |
| A-WHT-18 | White rice consumption and risk of cardiometabolic and cancer outcomes: A systematic review and dose-response meta-analysis of prospective cohort studies. Lai H, Sun M, Liu Y et al. | 2023 | PMID 35852223 DOI 10.1080/10408398.2022.2101984 | Meta-analysis | Cohorts | More white rice linked to more diabetes (16 more cases per 1000), not to heart disease or cancer. | Observational | moderate | C-GRN-05 |
| A-FOOD-01 | Is there a dose-response relation of dietary glycemic load to risk of type 2 diabetes? Meta-analysis of prospective cohort studies. Livesey G et al. | 2013 | PMID 23364021 DOI 10.3945/ajcn.112.041467 | Meta-analysis | Healthy adults in prospective cohorts | Diets with more glycaemic load were linked to higher diabetes risk (45% per 100 g/day). | Whole-diet GL, not single foods; Observational | high | C-FRU-01 C-WHT-05 |
| A-FOOD-02 | Glycemic index, glycemic load, and chronic disease risk--a meta-analysis of observational studies. Barclay AW et al. | 2008 | PMID 18326601 DOI 10.1093/ajcn/87.3.627 | Meta-analysis | Cohort participants | Low-GI/GL diets linked to lower diabetes and heart disease risk. | Whole-diet measures; Observational | moderate | C-FRU-01 C-WHT-05 |
| I-ABX-01 | Global burden of bacterial antimicrobial resistance 1990-2021: a systematic analysis with forecasts to 2050. GBD 2021 Antimicrobial Resistance Collaborators | 2024 | PMID 39299261 DOI 10.1016/S0140-6736(24)01867-1 | Risk assessment | Global | About 1.14 million deaths were caused by resistance in 2021; better care and access to antibiotics could prevent tens of millions of deaths. | Sparse data in many LMICs; 7 countries with no data; heavy reliance on covariates and modelling; Pre-2000 resistance largely modelled | high | C-ABX-02 C-ABX-12 |
| I-ABX-02 | The burden of bacterial antimicrobial resistance in the WHO Eastern Mediterranean Region 1990-2021: a cross-country systematic analysis with forecasts to 2050. EMR Antimicrobial Resistance Collaborators | 2025 | PMID 41082884 DOI 10.1016/S2468-2667(25)00201-4 | Risk assessment | EMR countries | About 92,800 deaths in the region were attributed to resistance in 2021. | Model-based | high | C-ABX-02 |
| I-ABX-03 | Antibiotics in fetal and early life and subsequent childhood asthma: nationwide population based study with sibling analysis. Örtqvist AK et al. | 2014 | PMID 25432937 DOI 10.1136/bmj.g6979 | Cohort study | Children born in Sweden 2006-2010 to pregnancies starting from 1 July 2005, followed to end of 2011 (school age at most) | When siblings were compared, most of the antibiotic-asthma link disappeared. | Indication (respiratory infection) not recorded; residual confounding by indication and reverse causation for airway antibiotics; Sibling analyses rely on exposure-discordant pairs; wider CIs (e.g. urinary/skin 0.47-1.55); sensitive to non-shared confounding and measurement error | high | C-ABX-06 |
| I-ABX-04 | Early-life exposure to antibiotics and excess body weight in childhood and adolescence: A systematic review and meta-analysis. Chagas AP et al. | 2023 | PMID 37573229 DOI 10.1016/j.orcp.2023.07.001 | Meta-analysis | Children and adolescents | A small association (about 9-10% higher odds) was found, but certainty was very low. | Observational primary studies | moderate | C-ABX-05 |
| I-ABX-05 | Antibiotic exposure in early life and childhood overweight and obesity: A systematic review and meta-analysis. Rasmussen SH et al. | 2018 | PMID 29359849 DOI 10.1111/dom.13230 | Meta-analysis | 527,504 children | Slightly higher risk, mainly with repeated or very early treatment. | Observational | moderate | C-ABX-05 |
| I-ABX-06 | Antibiotic use and the development of inflammatory bowel disease: a national case-control study in Sweden. Nguyen LH et al. | 2020 | PMID 32818437 DOI 10.1016/S2468-1253(20)30267-3 | Case-control study | Swedish residents aged >=16 years with incident, histology-confirmed IBD (2007-2016), up to 5 general-population controls matched on age, sex, county and calendar year, plus IBD-free full siblings | More antibiotic use was linked to IBD, also when compared with siblings. | Indication for antibiotics not available; confounding by indication (e.g. infections, prodromal GI symptoms) possible despite lead-in; Residual confounding by health-care-seeking and comorbidity (adjusted only via encounter counts and education) | high | C-ABX-07 |
| I-ABX-07 | Time to Treatment and Mortality during Mandated Emergency Care for Sepsis. Seymour CW et al. | 2017 | PMID 28528569 DOI 10.1056/NEJMoa1703058 | Cohort study | Adults (>17 years) with severe sepsis or septic shock (Sepsis-2 criteria) and sepsis protocol initiated in the emergency department within 6 h of arrival, in 149 New York hospitals (median age 73) | Each hour of delay in antibiotics was linked to about 4% higher odds of death. | Not randomised; residual confounding (e.g. diagnostic difficulty delaying treatment); Appropriateness of antibiotic choice not known | high | C-ABX-12 |
| I-ABX-08 | Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Kumar A et al. | 2006 | PMID 16625125 DOI 10.1097/01.CCM.0000217961.75225.E9 | Cohort study | Adults with septic shock | Each hour of delay reduced survival by about 7.6% on average. | Retrospective | moderate | C-ABX-12 |
| I-ABX-09 | Antibiotics for acute otitis media in children. Venekamp RP et al. | 2023 | PMID 37965923 DOI 10.1002/14651858.CD000219.pub5 | Systematic review | Children with AOM | Antibiotics helped only a little with pain and caused side effects; serious complications were rare either way. | High-income settings only | high | C-ABX-12 |
| I-ABX-10 | Pelvic Inflammatory Disease: Diagnosis, Management, and Prevention. Curry A et al. | 2019 | PMID 31524362 | Narrative review | Sexually active women | Untreated infection (often gonorrhoea or chlamydia) can cause infertility; antibiotics are the treatment. | Narrative review | moderate | C-ABX-13 |
| I-ABX-11 | Antibiotic-associated Vulvovaginal Candidiasis. Xu J & Sobel JD | 2003 | PMID 14642189 DOI 10.1007/s11908-003-0091-x | Narrative review | Women | Antibiotics may trigger yeast infections, but evidence is limited and conflicting. | Old; Narrative | low | C-ABX-11 |
| I-BAR-01 | Association of metabolic-bariatric surgery with long-term survival in adults with and without diabetes: a one-stage meta-analysis of matched cohort and prospective controlled studies with 174 772 participants. Syn NL et al. | 2021 | PMID 33965067 DOI 10.1016/S0140-6736(21)00591-2 | Meta-analysis | Adults with severe obesity | Across 174,772 people, surgery was linked to about half the risk of death and about 6 more years of median life expectancy; sleeve showed similar effects to bypass. | Observational primary studies (confounding, healthy-patient selection); Reconstructed IPD | moderate | C-BAR-01 C-BAR-09 C-BAR-10 |
| I-BAR-02 | Long-Term Outcomes of Medical Management vs Bariatric Surgery in Type 2 Diabetes. Courcoulas AP et al. | 2024 | PMID 38411644 DOI 10.1001/jama.2024.0318 | Randomised controlled trial | T2D, mean BMI 36.4 | Blood sugar control stayed better after surgery; full remission was uncommon in both groups but more frequent after surgery (12.7% vs 0%). | 86% enrolment into follow-up; Crossover 25% | moderate | C-BAR-05 C-BAR-06 C-BAR-08 |
| I-BAR-03 | Metabolic surgery versus conventional medical therapy in patients with type 2 diabetes: 10-year follow-up of an open-label, single-centre, randomised controlled trial. Mingrone G et al. | 2021 | PMID 33485454 DOI 10.1016/S0140-6736(20)32649-0 | Randomised controlled trial | T2D >5 years, BMI>=35 | More than half of those in remission at 2 years relapsed, but their sugar control stayed good (HbA1c 6.7%) and complications were fewer than with medicines alone. | Very small; Single centre | moderate | C-BAR-08 C-BAR-14 |
| I-BAR-04 | Risk of De Novo Barrett's Esophagus Post Sleeve Gastrectomy: A Systematic Review and Meta-Analysis of Studies With Long-Term Follow-Up. Chandan S et al. | 2025 | PMID 39059544 DOI 10.1016/j.cgh.2024.06.041 | Meta-analysis | SG patients | About 5.6% developed new Barrett's esophagus; reflux and acid-medication use were about 3 times more frequent after sleeve. | Mostly observational, heterogeneous; Pre-post comparison, no non-surgical control | moderate | C-BAR-02 C-BAR-03 C-BAR-04 C-BAR-12 |
| I-BAR-05 | Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric Bypass on Weight Loss in Patients With Morbid Obesity: The SM-BOSS Randomized Clinical Trial. Peterli R et al. | 2018 | PMID 29340679 DOI 10.1001/jama.2017.20897 | Randomised controlled trial | Morbid obesity, mean BMI 43.9 | Reflux got worse in about 32% after sleeve vs 6% after bypass. | Reflux exploratory endpoint | high | C-BAR-02 C-BAR-03 C-BAR-14 |
| I-BAR-06 | Risk of Suicide and Self-harm Is Increased After Bariatric Surgery-a Systematic Review and Meta-analysis. Castaneda D et al. | 2019 | PMID 30343409 DOI 10.1007/s11695-018-3493-4 | Meta-analysis | Bariatric patients | Self-harm attempts were about twice as common after surgery as before; suicides occurred in about 2.7 per 1000 patients. | Observational studies; Overlap with Bhatti/Neovius | moderate | C-BAR-07 |
| I-BAR-07 | Change in fracture risk and fracture pattern after bariatric surgery: nested case-control study. Rousseau C et al. | 2016 | PMID 27814663 DOI 10.1136/bmj.i3794 | Case-control study | Severely obese adults undergoing bariatric surgery in Quebec (72.3% women, mean age 42.6 years), matched by age (+-3 years) and sex 1:3 to obese and 1:10 to non-obese controls | Fractures were about 38% more frequent than in obese controls, clearly so only after biliopancreatic diversion. | Obese controls not BMI-matched; bariatric group had more comorbidities and baseline fractures (authors); Administrative data; no information on medications, physical activity, smoking, alcohol, trauma level, weight loss (authors) | moderate | C-BAR-06 |
| I-BAR-08 | Fracture Risk After Gastric Bypass Surgery: A Retrospective Cohort Study. Axelsson KF et al. | 2018 | PMID 30011091 DOI 10.1002/jbmr.3553 | Cohort study | Swedish obese patients | Fracture risk was about 26-32% higher than in similar people without surgery. | Median follow-up 3.1 years | moderate | C-BAR-06 C-BAR-14 |
| I-BAR-09 | Clinical Practice Guidelines for the Perioperative Nutrition, Metabolic, and Nonsurgical Support of Patients Undergoing Bariatric Procedures - 2019 Update (Executive Summary). Mechanick JI et al. | 2019 | PMID 31682518 DOI 10.4158/GL-2019-0406 | Guideline / position statement | Nutrition and metabolic follow-up is a mandatory part of bariatric care. | Many low-grade recommendations; Detailed supplement doses not in abstract | moderate | C-BAR-05 | |
| I-BAR-10 | Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. Global BMI Mortality Collaboration | 2016 | PMID 27423262 DOI 10.1016/S0140-6736(16)30175-1 | Meta-analysis | Adults aged 20-90 years, BMI 15-<60, in 32 countries (Asia, Australia/New Zealand, Europe, North America); primary analysis restricted to never-smokers without known chronic disease at baseline who survived 5 years | Severe obesity (BMI 40+) was linked to nearly 3 times the death risk of normal weight. | Observational; BMI is the only adiposity measure (authors); Study results generally not adjusted for ethnicity or socioeconomic status (authors) | high | C-BAR-01 C-BAR-09 |
| I-BAR-11 | 2022 American Society of Metabolic and Bariatric Surgery (ASMBS) and International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) Indications for Metabolic and Bariatric Surgery. Eisenberg D et al. | 2023 | PMID 36336720 DOI 10.1007/s11695-022-06332-1 | Guideline / position statement | Surgical societies recommend it for BMI above 35 and consider it from BMI 30 with metabolic disease. | Surgical societies (professional interest); Abstract only | moderate | C-BAR-10 | |
| I-BAR-12 | Ursodeoxycholic acid for the prevention of gallstones and subsequent cholecystectomy after bariatric surgery: a meta-analysis of randomized controlled trials. Mulliri A et al. | 2022 | PMID 35704084 DOI 10.1007/s00535-022-01886-4 | Meta-analysis | Bariatric patients | A bile-acid drug cut new gallstones by about 75% after surgery, including sleeve. | Control incidence not in abstract | moderate | C-BAR-11 |
| I-CAN-01 | Mortality in relation to smoking: 50 years' observations on male British doctors. Doll R et al. | 2004 | PMID 15213107 DOI 10.1136/bmj.38142.554479.AE | Cohort study | Male British doctors | Smoking tripled death rates; stopping at 30 avoided almost all the excess risk. | Men, doctors only | high | C-CAN-02 C-CAN-01 C-SYS-01 C-SYS-03 C-SRC-62 |
| I-CAN-02 | Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States, 2019. Islami F et al. | 2024 | PMID 38990124 DOI 10.3322/caac.21858 | Risk assessment | US adults >=30 y | Smoking accounted for 19% of cancers and 29% of cancer deaths; excess weight and alcohol followed. | Assumes causal RRs; US-specific prevalence | moderate | C-CAN-02 C-CAN-01 C-CAN-07 C-CAN-08 C-CAN-06 C-SYS-03 C-SRC-62 |
| I-CAN-03 | The global burden of cancer attributable to risk factors, 2010-19: a systematic analysis for the Global Burden of Disease Study 2019. GBD 2019 Cancer Risk Factors Collaborators | 2022 | PMID 35988567 DOI 10.1016/S0140-6736(22)01438-6 | Risk assessment | Global population; 204 countries and territories, by age, sex, region and Socio-demographic Index (SDI) | 44% of cancer deaths worldwide in 2019 were attributable to known risk factors, smoking first; diet accounted for about 5-6% of cancer burden. | Model-based; sparse registry and exposure data in many low-SDI countries, with greater uncertainty (authors); Residual exposure measurement bias likely despite adjustment; exposure model performance not formally assessed (authors) | moderate | C-CAN-01 C-CAN-02 C-CAN-07 C-CAN-08 C-SYS-02 C-SRC-62 |
| I-CAN-04 | Familial Risk and Heritability of Cancer Among Twins in Nordic Countries. Mucci LA et al. | 2016 | PMID 26746459 DOI 10.1001/jama.2015.17703 | Cohort study | Same-sex monozygotic and dizygotic twins from the national twin registries of Denmark, Finland, Norway and Sweden (birth cohorts 1870-2004) | Heritability of cancer overall was 33% in 200,000 Nordic twins. | Equal-environment assumption of twin models cannot be tested (authors); Incomplete registry coverage and survival-to-age-6 requirement in early birth cohorts (selection) | high | C-CAN-01 C-SYS-03 |
| I-CAN-05 | Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. de Martel C et al. | 2020 | PMID 31862245 DOI 10.1016/S2214-109X(19)30488-7 | Risk assessment | Global | H. pylori, HPV and hepatitis B/C viruses cause most infection-related cancers. | Model-based fractions | moderate | C-CAN-01 C-SYS-03 |
| I-CAN-06 | Definition and classification of cancer cachexia: an international consensus. Fearon K et al. | 2011 | PMID 21296615 DOI 10.1016/S1470-2045(10)70218-7 | Guideline / position statement | Cancer patients | Experts define cachexia as muscle loss driven by the tumour's effects on metabolism and appetite, not fully reversible by food. | Expert opinion | moderate | C-CAN-05 C-SYS-01 C-SRC-32 |
| I-CAN-07 | Dietary sugar consumption and health: umbrella review. Huang Y et al. | 2023 | PMID 37019448 DOI 10.1136/bmj-2022-071609 | Systematic review | Humans free of disease at baseline | Evidence for weight gain is moderate; links with cancers are mostly low quality. | Mostly observational, low-quality evidence for cancer outcomes | moderate | C-CAN-06 |
| I-CHK-01 | Restricting the use of antibiotics in food-producing animals and its associations with antibiotic resistance in food-producing animals and human beings: a systematic review and meta-analysis. Tang KL et al. | 2017 | PMID 29387833 DOI 10.1016/S2542-5196(17)30141-9 | Meta-analysis | Food-producing animals; humans | Restricting antibiotics in livestock reduced resistant bacteria in animals and, in fewer studies, in people. | Underlying studies mostly cross-sectional with few adjusting for confounders; Extreme heterogeneity (I2 up to 99.4%; human 97.4%) | high | C-CHK-05 |
| I-CHK-02 | Regulation (EC) No 1831/2003 on additives for use in animal nutrition (original text, Article 11 and recitals 25-26) European Parliament and Council | 2003 | Guideline / position statement | EU animal feed | Since 2006, antibiotics may not be used as growth-promoting feed additives in the EU. | Therapeutic and prophylactic veterinary use regulated separately (not covered) | not applicable | C-CHK-05 C-CHK-07 | |
| I-CHK-03 | Arsenic-based Animal Drugs and Poultry (FDA web page, last updated 29 April 2022) US Food and Drug Administration | 2022 | Guideline / position statement | US poultry | Arsenic-based poultry drugs were withdrawn in the US between 2013 and 2015. | Page does not cover other countries | not applicable | C-CHK-07 | |
| I-CHK-04 | The European Union summary report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food in 2021-2022. EFSA, ECDC | 2024 | PMID 38419967 DOI 10.2903/j.efsa.2024.8583 | Other | EU MSs | Resistance in poultry-linked bacteria is common and varies by country, but key indicators improved in several countries. | Country variation in sampling | high | C-CHK-05 |
| I-CHK-05 | Update and review of control options for Campylobacter in broilers at primary production. EFSA BIOHAZ Panel | 2020 | PMID 32874298 DOI 10.2903/j.efsa.2020.6090 | Risk assessment | EU broiler production | Farm measures could reduce human Campylobacter infections from chicken meat substantially. | Wide, overlapping probability intervals make ranking uncertain; Relies on risk-factor studies with Nordic over-representation and on an outdated 2008 baseline survey | high | C-CHK-09 C-CHK-08 |
| I-CHK-06 | Carcinogenicity of consumption of red and processed meat. Bouvard V et al. | 2015 | PMID 26514947 DOI 10.1016/S1470-2045(15)00444-1 | Guideline / position statement | Human evidence base | Processed meat causes cancer and red meat probably does; poultry was not evaluated; cooking method evidence was insufficient. | Poultry not evaluated | high | C-CHK-01 C-CHK-10 |
| I-CHK-07 | Meat consumption and risk of 25 common conditions: outcome-wide analyses in 475,000 men and women in the UK Biobank study. Papier K et al. | 2021 | PMID 33648505 DOI 10.1186/s12916-021-01922-9 | Cohort study | UK Biobank participants aged ~40-69 at recruitment (2006-2010) from 22 assessment centres, excluding prevalent cancer | More poultry was linked to slightly more reflux, gastritis and diabetes, partly explained by body weight, and to less anaemia. | Residual confounding, especially by adiposity and energy intake (total energy not measured); Meat types not mutually adjusted | high | C-CHK-01 C-CHK-04 |
| I-CHK-08 | Association between total, processed, red and white meat consumption and all-cause, CVD and IHD mortality: a meta-analysis of cohort studies. Abete I et al. | 2014 | PMID 24932617 DOI 10.1017/S000711451400124X | Meta-analysis | 13 cohorts | Processed and red meat were linked to higher death risk, white meat (including poultry) was not. | High heterogeneity; Older | moderate | C-CHK-01 |
| I-CHK-09 | Antimicrobial resistance profiles and virulence genotyping of Salmonella enterica serovars recovered from broiler chickens and chicken carcasses in Egypt. Elkenany R et al. | 2019 | PMID 31029108 DOI 10.1186/s12917-019-1867-z | Cross-sectional study | Five small-scale broiler farms (birds at 3 weeks of the growing cycle; farm environment incl. water, feed, litter, fans, workers' hands) and five retail shops (freshly dressed whole carcasses, outer skin) | About 29% of retail chicken carcasses and 32% of farm chickens in one Egyptian province had Salmonella, mostly multidrug-resistant. | Only 5 farms and 5 shops in one province, single summer season; small clusters (34 carcasses per shop) not accounted for; Selection of farms and shops not described | moderate | C-CHK-05 C-CHK-08 C-CHK-09 |
| I-CHK-10 | Avian Influenza A(H5N1) Virus in Egypt. Kayali G et al. | 2016 | PMID 26886164 DOI 10.3201/eid2203.150593 | Narrative review | Poultry in commercial/semicommercial farms, abattoirs, backyard flocks and live bird markets across Egyptian governorates; human H5N1 cases in Egypt | Bird flu is established in Egyptian poultry and has caused many human infections. | Non-random bird selection; uneven sampling across governorates; Human case data from official reports; true burden uncertain | moderate | C-CHK-13 |
| I-CHK-11 | Breast muscle myopathies: twists and turns in modern broilers. Greene ES et al. | 2025 | PMID 40658058 DOI 10.1080/03079457.2025.2533454 | Narrative review | Modern broilers | Muscle disorders such as woody breast are widespread in fast-growing broilers. | Narrative | moderate | C-CHK-03 C-CHK-06 |
| I-CHK-12 | Health risk assessment of enrofloxacin, oxytetracycline, and sulfadimidine residues in broiler chicken carcasses marketed in Mit Ghamr, Egypt. Noah SM et al. | 2026 | PMID 42527435 DOI 10.1038/s41598-026-63227-2 | Measurement / residue study | Broiler carcass tissues (breast, thigh, liver; carcass ~1.25 kg) purchased from poultry shops in Mit Ghamr City, Dakahlia, Egypt | Many chicken samples had antibiotic residues above legal limits, especially in liver, but estimated health risk was low. | One city; number of shops and sampling procedure unclear; small n per tissue (60); HPLC-PDA without confirmatory LC-MS/MS (acknowledged by authors) | moderate | C-EGG-10 C-CHK-05 C-CHK-12 |
| I-CHK-13 | Overview of Colistin Resistance in the Middle East and North Africa (MENA) Region. Saniour R et al. | 2026 | PMID 42655038 DOI 10.3390/microorganisms14081693 | Narrative review | Humans, animals, food, environment | Resistance to the last-resort antibiotic colistin is reported in Egypt and other countries, including in poultry. | Narrative; heterogeneous sources | low | C-CHK-05 |
| I-CHK-14 | Dietary Intake of Meat Cooking-Related Mutagens (HCAs) and Risk of Colorectal Adenoma and Cancer: A Systematic Review and Meta-Analysis. Chiavarini M et al. | 2017 | PMID 28524104 DOI 10.3390/nu9050514 | Meta-analysis | Observational studies | Higher intake of cooking-related mutagens was linked to more colorectal polyps and cancer. | Mutagen intake estimated from questionnaires; Heterogeneity | moderate | C-CHK-10 |
| I-CHK-15 | Salmonella enterica serotypes isolated from squabs reveal multidrug resistance and a distinct pathogenicity gene repertoire. Osman KM et al. | 2014 | PMID 25812222 DOI 10.20506/rst.33.3.2336 | Cross-sectional study | Squabs (young pigeons) | About one in eight squabs carried Salmonella, often multidrug-resistant. | Small sample | low | C-CHK-12 |
| I-CHM-01 | Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. EBCTCG | 2012 | PMID 22152853 DOI 10.1016/S0140-6736(11)61625-5 | Meta-analysis | Women with early breast cancer | In 123 trials with 100,000 women, modern regimens cut breast-cancer deaths by about one-third, and overall deaths fell too. | Chemotherapy-vs-none trials are old (median start 1986), half without endocrine therapy, suboptimal supportive care; 3 taxane trials (n~7000) unavailable; taxane follow-up short (mostly <=8 years) | high | C-CHM-09 C-CHM-10 C-CHM-12 C-CHM-13 C-SYS-06 |
| I-CHM-02 | Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. EBCTCG | 2011 | PMID 22019144 DOI 10.1016/S0140-6736(11)61629-2 | Meta-analysis | Women after breast-conserving surgery | Recurrence within 10 years fell from 35% to 19%, and breast-cancer deaths within 15 years from 25% to 21%. | Older radiotherapy, surgery, pathology and systemic therapy (trials 1976-99); margins would differ with modern pathology (authors); Risk-prediction categories derived from the same data, not externally validated (authors) | high | C-CHM-09 C-CHM-02 C-CHM-10 C-CHM-12 C-CHM-13 |
| I-CHM-03 | Use of Alternative Medicine for Cancer and Its Impact on Survival. Johnson SB et al. | 2018 | PMID 28922780 DOI 10.1093/jnci/djx145 | Cohort study | Nonmetastatic breast, prostate, lung or colorectal cancer | Risk of death was 2.5 times higher overall and 5.7 times higher for breast cancer. | Small AM group; Observational; residual confounding | moderate | C-CHM-09 C-CHM-10 C-CHM-12 C-CAN-04 C-SYS-01 C-SYS-06 C-SRC-32 C-SRC-45 |
| I-CHM-04 | Complementary Medicine, Refusal of Conventional Cancer Therapy, and Survival Among Patients With Curable Cancers. Johnson SB et al. | 2018 | PMID 30027204 DOI 10.1001/jamaoncol.2018.2487 | Cohort study | Nonmetastatic breast, prostate, lung, colorectal cancer 2004-2013 | Users of complementary medicine refused chemotherapy or radiotherapy far more often and had about twice the risk of death. | Observational; CM recording incomplete | moderate | C-CHM-12 C-CHM-09 C-CAN-04 C-SRC-32 |
| I-CHM-05 | Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the children's oncology group. Hunger SP et al. | 2012 | PMID 22412151 DOI 10.1200/JCO.2011.37.8018 | Cohort study | Children/adolescents 0-22 y with ALL | 5-year survival in childhood ALL rose to 90.4% by 2000-2005. | Trial participants only | high | C-CHM-06 C-CHM-09 C-CHM-11 C-CHM-12 C-CHM-13 C-SYS-06 |
| I-CHM-06 | Estimating the Risks of Breast Cancer Radiotherapy: Evidence From Modern Radiation Doses to the Lungs and Heart and From Previous Randomized Trials. Taylor C et al. | 2017 | PMID 28319436 DOI 10.1200/JCO.2016.72.0722 | Meta-analysis | Women randomised to RT vs no RT | About 0.3% risk of radiation-related heart death or lung cancer in non-smokers, higher in smokers. | Smoking status unavailable in trials (modelled) | high | C-CHM-02 C-CHM-01 C-CHM-03 C-CAN-02 |
| I-CHM-07 | Mortality due to cancer treatment delay: systematic review and meta-analysis. Hanna TP et al. | 2020 | PMID 33148535 DOI 10.1136/bmj.m4087 | Meta-analysis | Patients receiving curative, neoadjuvant or adjuvant surgery, systemic treatment or radiotherapy for bladder, breast, colon, rectum, lung, cervix, head and neck cancer | For example, every 4-week delay of breast surgery was linked to 8% higher mortality. | All primary studies retrospective observational: residual confounding by comorbidity/performance status (authors' main limitation); Single database (Medline) plus reference lists/Google; English only; no registered protocol reported | moderate | C-CHM-10 C-CHM-12 C-CAN-04 |
| I-CHM-08 | Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. Larkin J et al. | 2019 | PMID 31562797 DOI 10.1056/NEJMoa1910836 | Randomised controlled trial | Previously untreated advanced melanoma | 5-year survival 52% with combined immunotherapy vs 26% with the older drug. | Industry funded; Active comparator | high | C-CAN-03 C-CHM-13 C-CAN-01 |
| I-CHM-09 | Adriamycin, 14-hydroxydaunomycin, a new antitumor antibiotic from S. peucetius var. caesius. Arcamone F et al. | 1969 | PMID 5365804 DOI 10.1002/bit.260110607 | Other | not applicable | The 1969 discovery paper names Streptomyces peucetius as the source. | Only title read | moderate | C-CHM-14 |
| I-CHM-10 | Platinum compounds: a new class of potent antitumour agents. Rosenberg B et al. | 1969 | PMID 5782119 DOI 10.1038/222385a0 | Other | not applicable | Its anticancer action was discovered in platinum compounds, not fungi. | Only title read | moderate | C-CHM-14 |
| I-CHM-11 | Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Olive KP et al. | 2009 | PMID 19460966 DOI 10.1126/science.1171362 | Animal study | KPC mice with autochthonous pancreatic ductal adenocarcinoma; mice with transplanted (xenograft, orthotopic, syngeneic) tumours; 18 human PDA specimens vs normal pancreas (5) and chronic pancreatitis (5) | Reducing the tumour's supporting tissue briefly let more drug reach the tumour. | Mouse model; one tumour type (PDA); Small groups; randomisation, blinding and sample-size planning not reported | moderate | C-CHM-11 |
| I-CHM-12 | Cancer statistics, 2024. Siegel RL et al. | 2024 | PMID 38230766 DOI 10.3322/caac.21820 | Other | US population | More than 4 million cancer deaths averted since 1991 thanks to less smoking, earlier detection and better treatment. | Attribution to causes is not quantified per cause in abstract | moderate | C-CHM-09 C-CHM-13 C-CAN-02 |
| I-DRY-01 | Associations of dairy intake with risk of mortality in women and men: three prospective cohort studies. Ding M et al. | 2019 | PMID 31776125 DOI 10.1136/bmj.l6204 | Cohort study | 168,153 women (NHS 74,805; NHS II 93,348) and 49,602 men (HPFS), US health professionals (~95% European ancestry), free of CVD and cancer at baseline (1984 NHS, 1989 NHS II, 1986 HPFS) | Only the highest intake (about 4.2 servings/day) showed 7% higher mortality. | Observational; residual confounding acknowledged (whole milk may mark unhealthy lifestyle); Mostly white US health professionals; limited generalisability | high | C-DRY-03 C-DRY-04 |
| I-DRY-02 | Milk and dairy consumption and risk of cardiovascular diseases and all-cause mortality: dose-response meta-analysis of prospective cohort studies. Guo J et al. | 2017 | PMID 28374228 DOI 10.1007/s10654-017-0243-1 | Meta-analysis | 938,465 participants in 29 cohorts | No association for milk or total dairy; fermented dairy slightly inverse. | Dairy-industry funding/COI declared by several authors; High heterogeneity (I2 up to 94%) | moderate | C-DRY-03 |
| I-DRY-03 | Dairy product consumption and risk of hip fracture: a systematic review and meta-analysis. Bian S et al. | 2018 | PMID 29357845 DOI 10.1186/s12889-018-5041-5 | Meta-analysis | Adults in cohort and case-control studies | Yogurt RR 0.75 and cheese RR 0.68 in 3 cohort studies each; milk RR 0.91 (not significant), though the cohort dose curve rose up to about 600 g/day. | Yogurt and cheese estimates rest on only 3 cohort studies each, cream on 1; no subgroup or heterogeneity analysis possible for them; High heterogeneity for milk (I2 75-87%) | moderate | C-DRY-03 C-DRY-11 |
| I-DRY-04 | Milk A1 β-casein and health-related outcomes in humans: a systematic review. Küllenberg de Gaudry D et al. | 2019 | PMID 30722004 DOI 10.1093/nutrit/nuy063 | Systematic review | Humans in 15 RCTs, 2 case-control, 8 ecological studies | Moderate certainty for digestive symptoms; low/very low for other outcomes. | Few, small, often industry-funded primary trials; Ecological data weak | high | C-DRY-07 C-DRY-10 |
| I-DRY-05 | Systematic Review of the Gastrointestinal Effects of A1 Compared with A2 β-Casein. Brooke-Taylor S et al. | 2017 | PMID 28916574 DOI 10.3945/an.116.013953 | Systematic review | Rodents and humans (39 studies) | Human evidence limited to a few studies. | Authors consulted for / received support from A2 companies; Mainly animal data | low | C-DRY-07 |
| I-DRY-06 | A Meta-analysis of Individual Participant Data Reveals an Association between Circulating Levels of IGF-I and Prostate Cancer Risk. Travis RC et al. | 2016 | PMID 26921328 DOI 10.1158/0008-5472.CAN-15-1551 | Meta-analysis | Men in 19 studies | Top vs bottom fifth: OR 1.29. | Does not address diet; Observational | high | C-DRY-04 C-DRY-06 |
| I-DRY-07 | Dairy foods intake and risk of Parkinson's disease: a dose-response meta-analysis of prospective cohort studies. Jiang W et al. | 2014 | PMID 24894826 DOI 10.1007/s10654-014-9921-4 | Meta-analysis | 304,193 subjects; 1,083 PD cases | Absolute risk: 2-4 extra cases per 100,000 person-years per 200 g milk a day. | Few studies; Observational | moderate | C-DRY-09 C-DRY-11 |
| I-DRY-08 | Dairy intake and acne development: A meta-analysis of observational studies. Aghasi M et al. | 2019 | PMID 29778512 DOI 10.1016/j.clnu.2018.04.015 | Meta-analysis | Observational study participants | Total milk OR 1.48. | Observational, heterogeneous; Sample sizes not in abstract | moderate | C-DRY-08 C-DRY-11 |
| I-DRY-09 | Dairy Intake and Acne Vulgaris: A Systematic Review and Meta-Analysis of 78,529 Children, Adolescents, and Young Adults. Juhl CR et al. | 2018 | PMID 30096883 DOI 10.3390/nu10081049 | Meta-analysis | Children, adolescents, young adults | Any dairy OR 1.25; cheese 1.22; yogurt 1.36. | Publication bias; Unadjusted estimates | moderate | C-DRY-08 |
| I-DRY-10 | Dairy consumption and risk of type 2 diabetes: 3 cohorts of US adults and an updated meta-analysis. Chen M et al. | 2014 | PMID 25420418 DOI 10.1186/s12916-014-0215-1 | Cohort study | US men (HPFS) and women (NHS, NHS II) | Each daily serving of yogurt: about 18% lower risk of type 2 diabetes in the meta-analysis. | Observational; residual confounding acknowledged, especially for yogurt (marker of healthy lifestyle); Health professionals of mainly European ancestry (91-99% white); limited generalisability | high | C-DRY-11 |
| I-DRY-11 | Dairy products and colorectal cancer risk: a systematic review and meta-analysis of cohort studies. Aune D et al. | 2012 | PMID 21617020 DOI 10.1093/annonc/mdr269 | Meta-analysis | Adults in 19 cohorts | Total dairy RR 0.83 per 400 g/day. | Observational | high | C-DRY-04 |
| I-DRY-12 | Milk consumption and multiple health outcomes: umbrella review of systematic reviews and meta-analyses in humans. Zhang X et al. | 2021 | PMID 33413488 DOI 10.1186/s12986-020-00527-y | Systematic review | Humans in included meta-analyses | Milk was linked more often to benefits (heart, stroke, bowel cancer, diabetes, bones) than to harms (prostate cancer, Parkinson's, acne); most evidence was rated low certainty. | No registered protocol reported; English-language only; screening process by two reviewers not clearly described; list of excluded studies not given; Only one (newest/largest) meta-analysis per outcome selected; overlap of primary studies between meta-analyses not assessed | low | C-DRY-01 C-DRY-03 C-DRY-04 C-DRY-11 |
| I-DRY-13 | Lactose Residual Content in PDO Cheeses: Novel Inclusions for Consumers with Lactose Intolerance. Facioni MS et al. | 2021 | PMID 34574346 DOI 10.3390/foods10092236 | Measurement / residue study | 25 PDO soft, semi-hard and hard cheeses bought in Italian supermarkets (incl. Cheddar, Brie, Emmentaler, Le Gruyere); Mozzarella di Bufala Campana PDO as positive control. Survey: 1,398 lactose-intolerant consumers (91.2% female, mean age 35) recruited via the AILI patients' association on Facebook; 57 nutrition professionals. | All but one of 25 PDO cheeses (even some aged only 20-35 days) had lactose below 10 mg/kg; fresh mozzarella had about 3,500 mg/kg. | Industry funding and authors' financial interest in lactose-free certification; conclusions promote the authors' trademark; Fresh cheeses, yogurt, processed cheese and Egyptian products (romi, processed triangles) not analysed | moderate | C-DRY-10 C-DRY-11 |
| I-DRY-14 | Nutritional management of lactose intolerance: the importance of diet and food labelling. Facioni MS et al. | 2020 | PMID 32590986 DOI 10.1186/s12967-020-02429-2 | Narrative review | Lactose-intolerant people | Most adults worldwide produce less lactase, but most lactose-intolerant people tolerate small amounts of lactose and usually yogurt; avoiding all dairy may harm bones. | Narrative review without search strategy, selection criteria or quality appraisal; Funded by and partly authored by a lactose-free certification company; promotes its own trademark (Lfree) | low | C-DRY-02 C-DRY-10 C-DRY-11 |
| I-DRY-15 | Cheese consumption and risk of cardiovascular disease: a meta-analysis of prospective studies. Chen GC et al. | 2017 | PMID 27517544 DOI 10.1007/s00394-016-1292-z | Meta-analysis | Adults in 15 prospective studies | High vs low cheese: CVD RR 0.90. | Observational; Erratum published | moderate | C-DRY-11 |
| I-DRY-16 | The prevalence of aflatoxin M1 in milk of Middle East region: A systematic review, meta-analysis and probabilistic health risk assessment. Rahmani J et al. | 2018 | PMID 29902498 DOI 10.1016/j.fct.2018.06.016 | Risk assessment | Milk samples from Middle-East countries | Egyptian raw milk: 38% of samples positive; estimated hazard index 0.84 for children. | Heterogeneous sampling; Hazard-index approach for a genotoxic carcinogen is debatable | moderate | C-DRY-01 |
| I-DRY-17 | Hormones in Dairy Foods and Their Impact on Public Health - A Narrative Review Article. Malekinejad H et al. | 2015 | PMID 26258087 | Narrative review | n/a | Milk contains small amounts of hormones (more in butter and cream than in milk); the authors raise a cancer concern but provide no new human outcome data. | Narrative, non-systematic; no selection or appraisal of evidence; Abstract conclusion ('important risk factor for various cancers') is stronger than the body text, which calls the cancer evidence 'very controversial' and notes low bioavailability for several hormones | very low | C-DRY-01 C-DRY-11 |
| I-DRY-18 | Effects of dairy products consumption on inflammatory biomarkers among adults: A systematic review and meta-analysis of randomized controlled trials. Moosavian SP et al. | 2020 | PMID 32409275 DOI 10.1016/j.numecd.2020.01.011 | Meta-analysis | 663 participants in 11 RCTs | CRP slightly lower (-0.24 mg/L) with more dairy; no effect in cross-over trials. | Small trials, short duration; Surrogate markers | moderate | C-DRY-02 |
| I-DRY-19 | Dairy products and inflammation: A review of the clinical evidence. Bordoni A et al. | 2017 | PMID 26287637 DOI 10.1080/10408398.2014.967385 | Systematic review | Participants of 52 trials | Overall anti-inflammatory score; pro-inflammatory only in allergic people. | Ad hoc scoring method; Heterogeneous trials | moderate | C-DRY-02 C-DRY-10 |
| I-EGG-01 | Egg consumption and risk of cardiovascular disease: three large prospective US cohort studies, systematic review, and updated meta-analysis. Drouin-Chartier JP et al. | 2020 | PMID 32132002 DOI 10.1136/bmj.m513 | Meta-analysis | US women and men free of CVD, diabetes and cancer; meta-analysis of global cohorts | Eating up to one egg a day was not linked to heart disease or stroke. | Observational data; higher egg eaters were less healthy (higher BMI, more red meat, more T2D), so residual confounding possible; Health-professional cohorts may limit generalisability | high | C-EGG-02 C-EGG-04 C-EGG-05 C-EGG-11 |
| I-EGG-02 | Association of egg intake with blood lipids, cardiovascular disease, and mortality in 177,000 people in 50 countries. Dehghan M et al. | 2020 | PMID 31965140 DOI 10.1093/ajcn/nqz348 | Cohort study | PURE general population (21 countries) and patients with vascular disease (ONTARGET/TRANSCEND) | Eating an egg a day was not linked to cholesterol levels, heart disease or death. | Single FFQ; Few very high consumers | high | C-EGG-02 C-EGG-04 C-EGG-05 C-EGG-11 |
| I-EGG-03 | Associations of egg consumption with cardiovascular disease in a cohort study of 0.5 million Chinese adults. Qin C et al. | 2018 | PMID 29785957 DOI 10.1136/heartjnl-2017-312651 | Cohort study | Adults 30-79 from 10 regions, free of cancer, CVD, diabetes | Daily egg eaters had a lower risk of heart disease and stroke. | Low intake range; Reverse causation possible | high | C-EGG-04 |
| I-EGG-04 | Egg consumption and cardiovascular risk: a dose-response meta-analysis of prospective cohort studies. Godos J et al. | 2021 | PMID 32865658 DOI 10.1007/s00394-020-02345-7 | Meta-analysis | 39 studies, ~2 million individuals | Moderate egg intake was not linked to more heart disease; a possible higher heart failure risk at 1+ egg/day. | Overlap with other meta-analyses; Low certainty | moderate | C-EGG-04 |
| I-EGG-05 | Egg Consumption and Risk of All-Cause and Cause-Specific Mortality: A Systematic Review and Dose-Response Meta-analysis of Prospective Studies. Mousavi SM et al. | 2022 | PMID 35396834 DOI 10.1093/advances/nmac040 | Meta-analysis | General population | Egg intake was not linked to overall or heart deaths; a small link with cancer deaths was found. | Overlap with other meta-analyses; Heterogeneity | moderate | C-EGG-02 C-EGG-04 C-EGG-11 |
| I-EGG-06 | Dietary Cholesterol and Cardiovascular Risk: A Science Advisory From the American Heart Association. Carson JAS et al. | 2020 | PMID 31838890 DOI 10.1161/CIR.0000000000000743 | Guideline / position statement | General population | Studies do not show a clear link between dietary cholesterol and heart disease, but high intakes can raise LDL; focus on overall diet. | Not a formal systematic review | moderate | C-EGG-04 C-EGG-11 C-SRC-05 |
| I-EGG-07 | Meta-regression analysis of the effects of dietary cholesterol intake on LDL and HDL cholesterol. Vincent MJ et al. | 2019 | PMID 30596814 DOI 10.1093/ajcn/nqy273 | Meta-analysis | Trial participants | More dietary cholesterol modestly raises LDL cholesterol. | Surrogate endpoint | moderate | C-EGG-04 |
| I-EGG-08 | Egg consumption and risk of type 2 diabetes: findings from 3 large US cohort studies of men and women and a systematic review and meta-analysis of prospective cohort studies. Drouin-Chartier JP et al. | 2020 | PMID 32453379 DOI 10.1093/ajcn/nqaa115 | Meta-analysis | US cohorts; global cohorts | No overall link; higher risk only in US studies. | Heterogeneity | high | C-EGG-07 |
| I-EGG-09 | Egg intake and cancers of the breast, ovary and prostate: a dose-response meta-analysis of prospective observational studies. Keum N et al. | 2015 | PMID 26293984 DOI 10.1017/S0007114515002135 | Meta-analysis | Participants of prospective cohorts, nested case-control/case-cohort and pooled cohort studies (North America, Europe, Asia) | A possible link with fatal prostate cancer, but small studies may exaggerate it; no link with prostate cancer overall. | Fatal prostate estimate based on only 4 studies and 609 cases, with small-study effects (P Egger 0.04); Fatal prostate association loses significance under the alternative serving-size assumption (RR 1.23, 0.97-1.55) | low | C-EGG-06 |
| I-EGG-10 | Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial. Wilcox J et al. | 2021 | PMID 33872583 DOI 10.1016/j.amjmed.2021.03.016 | Randomised controlled trial | Healthy volunteers from the Cleveland, Ohio area with normal renal function (median age 28.0 [IQR 24.0-38.8]; 41.5% male; 81.7% Caucasian; median BMI 26.9) | Eating four eggs a day for four weeks did not raise fasting TMAO; choline pills did. | Small arms (10-20); no power calculation; non-significance for eggs (P=0.20) does not exclude a small rise; Fifth (PC) arm enrolled later, i.e. not concurrently randomised | moderate | C-EGG-05 |
| I-EGG-11 | Prevalence estimates of eight big food allergies in Europe: Updated systematic review and meta-analysis. Spolidoro GCI et al. | 2023 | PMID 37405695 DOI 10.1111/all.15801 | Meta-analysis | European populations, all ages | Confirmed egg allergy affects about 0.8% of people; 2.4% believe they have it. | Most studies moderate risk of bias | high | C-EGG-01 C-SRC-05 |
| I-EGG-12 | Dreams of the Rarebit Fiend: food and diet as instigators of bizarre and disturbing dreams. Nielsen T, Powell RA | 2015 | PMID 25741294 DOI 10.3389/fpsyg.2015.00047 | Cross-sectional study | Undergraduate students in first-year psychology courses at a Canadian university, receiving partial course credit; 130 males (mean age 21.6), 264 females (mean age 21.4), 2 unspecified | About one in six students thought food affected their dreams, mostly dairy. | Convenience sample of young psychology students receiving course credit; Self-reported, retrospective perceptions; in-house unvalidated dream and food items | low | C-EGG-01 C-CHK-02 |
| I-EGG-13 | More dreams of the rarebit fiend: food sensitivity and dietary correlates of sleep and dreaming. Nielsen T et al. | 2025 | PMID 40667395 DOI 10.3389/fpsyg.2025.1544475 | Cross-sectional study | Undergraduate psychology students at MacEwan University, Canada (mean age 20.3 +/- 3.68, range 17-54; 721 women, 338 men, 23 other/undisclosed; 46.4% White, 22.2% Asian, 7.9% Black, 6.3% Arab); course credit (2% of final grade) | Only 5.5% of students thought food affected their dreams, mostly sweets and dairy; eggs were rarely named. People with food allergy or lactose intolerance reported more nightmares. | Student convenience sample with course credit; All exposures and outcomes self-reported; food sensitivities not clinically verified | low | C-EGG-01 C-CHK-02 |
| I-EGG-14 | The European Union One Health 2024 Zoonoses Report. EFSA, ECDC | 2025 | PMID 41377167 DOI 10.2903/j.efsa.2025.9759 | Other | 27 EU Member States, UK (NI), 8 non-MS | Campylobacter and Salmonella are the most common food-borne infections in the EU; about 5% of fresh chicken samples and 0.3% of egg samples had Salmonella. | Reporting differences between countries; Operator vs official sampling differ | high | C-EGG-09 C-CHK-08 C-CHK-09 |
| I-EGG-15 | Salmonella control in poultry flocks and its public health impact. EFSA BIOHAZ Panel | 2019 | PMID 32626222 DOI 10.2903/j.efsa.2019.5596 | Risk assessment | EU poultry flocks | Overall, laying-hen flocks kept outside cages tend to have less Salmonella, but studies conflict; crowding, large farms and stress clearly increase it. | Housing evidence largely from studies before the 2012 EU ban on conventional cages; Cage effect confounded by flock size, stocking density, cleaning and infection history (EFSA states the cause is unclear) | high | C-EGG-09 |
| I-EGG-16 | Risk to human health related to the presence of perfluoroalkyl substances in food. EFSA CONTAM Panel | 2020 | PMID 32994824 DOI 10.2903/j.efsa.2020.6223 | Risk assessment | European population | EFSA set a safe weekly intake for PFAS and named fish, fruit and eggs as main dietary sources. | Lower-bound vs upper-bound uncertainty | high | C-EGG-08 |
| I-EGG-17 | Council Directive 1999/74/EC laying down minimum standards for the protection of laying hens (as summarised by the European Commission) European Commission | 1999 | Guideline / position statement | EU laying hens | The EU banned barren battery cages in 2012; enriched cages and cage-free systems remain. | Enriched cages still permitted | not applicable | C-EGG-09 | |
| I-FAST-01 | Fuel metabolism in starvation. Cahill GF | 2006 | PMID 16848698 DOI 10.1146/annurev.nutr.26.061505.111258 | Narrative review | Humans in starvation (historical studies) | During long fasting the brain uses ketones from fat, which allows survival. | Narrative; No quantitative data in abstract | moderate | C-FAST-01 C-FAST-02 C-FAST-03 C-FAST-04 C-SYS-04 |
| I-FAST-02 | Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial. Trepanowski JF et al. | 2017 | PMID 28459931 DOI 10.1001/jamainternmed.2017.0936 | Randomised controlled trial | Sedentary obese/overweight adults aged 18-65 (BMI 25.0-39.9; mean 34), 86% women, mean age 44; primarily metabolically healthy; excluded CVD, diabetes, smokers, weight-affecting medication. | Both approaches gave similar weight loss after a year; fasting had more dropouts and higher LDL. | Small sample (100); power fell to 60% for the primary comparison; High and differential dropout (38% ADF), more ADF withdrawals for diet dissatisfaction - possible selection bias | moderate | C-FAST-02 C-FAST-04 C-FAST-05 C-SRC-22 |
| I-FAST-03 | Calorie Restriction with or without Time-Restricted Eating in Weight Loss. Liu D et al. | 2022 | PMID 35443107 DOI 10.1056/NEJMoa2114833 | Randomised controlled trial | Adults with obesity | Adding an 8-hour eating window to calorie restriction did not significantly improve weight loss. | Single country | high | C-FAST-02 C-FAST-04 C-FAST-05 C-SRC-22 |
| I-FAST-04 | Effects of Time-Restricted Eating on Weight Loss and Other Metabolic Parameters in Women and Men With Overweight and Obesity: The TREAT Randomized Clinical Trial. Lowe DA et al. | 2020 | PMID 32986097 DOI 10.1001/jamainternmed.2020.4153 | Randomised controlled trial | Adults with BMI 27-43 | No more weight loss than three meals a day, and slightly more muscle-related lean mass loss. | Short; Self-reported adherence | moderate | C-FAST-02 C-FAST-05 |
| I-FAST-05 | Metabolic Effects of Intermittent Fasting. Patterson RE et al. | 2017 | PMID 28715993 DOI 10.1146/annurev-nutr-071816-064634 | Narrative review | Rodent models (mostly male mice) and adults in small human trials (n=8-107) and observational studies. | Fasting regimens seem to help weight loss and may improve metabolism; much is still hypothesis. | Non-systematic narrative review: single database, no protocol, no risk-of-bias assessment, no pooling; Human evidence consists of small, short trials, many uncontrolled; much mechanistic reasoning extrapolated from male rodents | low | C-FAST-01 C-FAST-02 C-FAST-05 |
| I-FAST-06 | Similar weight loss with low-energy food combining or balanced diets. Golay A et al. | 2000 | PMID 10805507 DOI 10.1038/sj.ijo.0801185 | Randomised controlled trial | Obese patients | Separating food groups did not add weight loss. | Short; Small | moderate | C-FAST-06 |
| I-FAST-07 | Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study Group. Bauer J et al. | 2013 | PMID 23867520 DOI 10.1016/j.jamda.2013.05.021 | Guideline / position statement | Adults >65 | People over 65 should eat at least 1.0-1.2 g protein per kg body weight every day. | Expert consensus | moderate | C-FAST-04 C-FAST-05 C-FAST-07 C-FAST-08 |
| I-FAST-08 | "Drink at least eight glasses of water a day." Really? Is there scientific evidence for "8 x 8"? Valtin H | 2002 | PMID 12376390 DOI 10.1152/ajpregu.00365.2002 | Narrative review | Healthy adults | No proof for 8 glasses in healthy adults in mild climates, but more is needed in heat, hard work and some diseases. | Narrative; Old | moderate | C-FAST-09 C-FAST-10 C-GUT-08 |
| I-FAST-09 | Urinary volume, water and recurrences in idiopathic calcium nephrolithiasis: a 5-year randomized prospective study. Borghi L et al. | 1996 | PMID 8583588 | Randomised controlled trial | First-episode idiopathic calcium stone formers (plus 101 controls) | Over five years, stones came back in 12% of those drinking a lot vs 27% without advice. | Not blinded; Single centre | moderate | C-FAST-09 C-FAST-10 C-GUT-08 |
| I-FAST-10 | A population-based study of diabetes and its characteristics during the fasting month of Ramadan in 13 countries: results of the epidemiology of diabetes and Ramadan 1422/2001 (EPIDIAR) study. Salti I et al. | 2004 | PMID 15451892 DOI 10.2337/diacare.27.10.2306 | Cross-sectional study | Muslims with type 1 or type 2 diabetes | Severe low blood sugar was 4.7 times (type 1) and 7.5 times (type 2) more common during Ramadan. | Retrospective, recall | moderate | C-FAST-03 C-FAST-05 C-FAST-07 |
| I-FAST-11 | Diabetes and Ramadan: Practical guidelines 2021. Hassanein M et al. | 2022 | PMID 35016991 DOI 10.1016/j.diabres.2021.109185 | Guideline / position statement | People with diabetes who fast | People with diabetes who fast need individual risk assessment and medical guidance. | Abstract only read | moderate | C-FAST-03 C-FAST-10 |
| I-FAST-12 | Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lean ME et al. | 2018 | PMID 29221645 DOI 10.1016/S0140-6736(17)33102-1 | Randomised controlled trial | Age 20-65, T2D <6 years, BMI 27-45, not on insulin | 46% of people in the programme were free of diabetes and medication after one year. | Open-label; Selected population | high | C-INS-10 C-DIAB-03 C-INS-01 |
| I-FAST-13 | Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial. Lean MEJ et al. | 2019 | PMID 30852132 DOI 10.1016/S2213-8587(19)30068-3 | Randomised controlled trial | As DiRECT | 36% were still in remission after two years. | Open-label | high | C-DIAB-03 |
| I-FAST-14 | 5-year follow-up of the randomised Diabetes Remission Clinical Trial (DiRECT) of continued support for weight loss maintenance in the UK: an extension study. Lean ME et al. | 2024 | PMID 38423026 DOI 10.1016/S2213-8587(23)00385-6 | Randomised controlled trial | Adults aged 20-65 with type 2 diabetes diagnosed within 6 years (mean duration 3.0 years), BMI 27-45 kg/m2 (mean ~34-35), NOT receiving insulin, in Scotland and Tyneside. | Only 13% of those continuing support were still in remission at 5 years; people with long diabetes or on insulin were not studied. | Extension group self-selected (engaged participants) - non-randomised comparison; Large missing data, especially controls (45% without year-5 weight) | moderate | C-DIAB-03 |
| I-FAT-01 | Reduction in saturated fat intake for cardiovascular disease. Hooper L et al. | 2020 | PMID 32827219 DOI 10.1002/14651858.CD011737.pub3 | Meta-analysis | Adults with or without CVD (15 RCTs, 16 comparisons) | 17% fewer combined cardiovascular events (RR 0.83); no clear effect on deaths. | Old trials with heterogeneous interventions; Heterogeneity (I2 67%) | high | C-FAT-01 C-FAT-02 C-MEAT-04 |
| I-FAT-02 | Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Ference BA et al. | 2017 | PMID 28444290 DOI 10.1093/eurheartj/ehx144 | Guideline / position statement | Totality of evidence (>2 million participants) | Genetic studies, cohorts and drug trials agree: more LDL over time means more atherosclerosis. | Not a systematic review: no protocol, selection of meta-analyses partly by panel discussion, no formal risk-of-bias or GRADE assessment; Extensive financial ties of panel members to manufacturers of LDL-lowering drugs; meeting logistics funded by MSD and Amgen | moderate | C-FAT-01 C-FAT-02 C-FAT-05 |
| I-FAT-03 | Is Butter Back? A Systematic Review and Meta-Analysis of Butter Consumption and Risk of Cardiovascular Disease, Diabetes, and Total Mortality. Pimpin L et al. | 2016 | PMID 27355649 DOI 10.1371/journal.pone.0158118 | Meta-analysis | Adults (mean age 44-71 years) in general-population cohorts in the USA, Netherlands, Sweden, Finland (incl. one cohort of male smokers, ATBC) and 8 European EPIC countries. | Per tablespoon/day: CVD RR 1.00; mortality RR 1.01. | Observational only; no RCTs; residual confounding acknowledged (butter eaters have worse diets/lifestyles); Few independent cohorts per outcome (CVD 4, CHD 3, mortality 2 publications); subgroup analyses not possible; Egger's test underpowered | moderate | C-FAT-01 |
| I-FAT-04 | Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. Estruch R et al. | 2018 | PMID 29897866 DOI 10.1056/NEJMoa1800389 | Randomised controlled trial | 7,447 adults aged 55-80 at high CV risk | HR 0.69; events 3.8% vs 4.4%. | Randomisation irregularities at some sites (corrected analysis); Whole-diet intervention, not olive oil alone | moderate | C-FAT-03 C-FAT-04 |
| I-FAT-05 | Dietary linoleic acid and risk of coronary heart disease: a systematic review and meta-analysis of prospective cohort studies. Farvid MS et al. | 2014 | PMID 25161045 DOI 10.1161/CIRCULATIONAHA.114.010236 | Meta-analysis | 310,602 individuals; 12,479 CHD events | CHD events RR 0.85 highest vs lowest intake. | Observational | moderate | C-FAT-04 |
| I-FAT-06 | Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73). Ramsden CE et al. | 2016 | PMID 27071971 DOI 10.1136/bmj.i1246 | Randomised controlled trial | 9,423 institutionalised women and men aged 20-97 | No mortality benefit; HR 1.22 death per 30 mg/dL cholesterol drop. | Institutionalised population; short exposure for many; Control diet contained trans-fat margarines | low | C-FAT-04 |
| I-FAT-07 | Saturated Fats and Health: A Reassessment and Proposal for Food-Based Recommendations: JACC State-of-the-Art Review. Astrup A et al. | 2020 | PMID 32562735 DOI 10.1016/j.jacc.2020.05.077 | Narrative review | n/a | Claims whole-fat dairy and unprocessed meat are not linked to more CVD. | Narrative, non-systematic; Possible COI | low | C-FAT-01 |
| I-FAT-08 | Saturated fatty acid and trans-fatty acid intake for adults and children: WHO guideline World Health Organization | 2023 | Guideline / position statement | Adults and children | Replace with plant oils rich in unsaturated fats. | Population-level guidance | high | C-FAT-01 C-FAT-03 C-FAT-04 | |
| I-FRU-01 | Fruit consumption and risk of type 2 diabetes: results from three prospective longitudinal cohort studies. Muraki I et al. | 2013 | PMID 23990623 DOI 10.1136/bmj.f5001 | Cohort study | 66,105 + 85,104 women, 36,173 men | Blueberries, grapes and apples linked to lower diabetes risk; juice and cantaloupe to slightly higher risk; glycaemic load did not explain the differences. | US health professionals; Watermelon not regularly measured | high | C-FRU-01 C-FRU-03 C-FRU-04 C-FRU-05 |
| I-FRU-02 | Consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice and incidence of type 2 diabetes: systematic review, meta-analysis, and estimation of population attributable fraction. Imamura F et al. | 2015 | PMID 26199070 DOI 10.1136/bmj.h3576 | Meta-analysis | Adults aged >=18 years free of diabetes in 17 prospective cohorts (USA, Finland, Japan, France, Singapore, 8 EPIC countries); PAF in NHANES 2009-10 (n=4729, representing 189.1 million) and UK NDNS 2008-12 (n=1932, representing 44.7 million) | Sugary drinks were linked to more type 2 diabetes. Fruit juice showed at most a small, unstable link (low-quality evidence), so juice is not a proven healthy alternative. | Observational cohorts: residual confounding and reverse causation (health-conscious or high-risk people changing beverages); Protocol not registered; title/abstract screening by one author | high | C-FRU-03 |
| I-FRU-03 | Fruit and vegetable consumption and the risk of type 2 diabetes: a systematic review and dose-response meta-analysis of prospective studies. Halvorsen RE et al. | 2021 | PMID 35028521 DOI 10.1136/bmjnph-2020-000218 | Meta-analysis | Adults free of T2D at baseline in 23 prospective cohort, case-cohort or nested case-control studies (42 publications): 10 from America, 5 Europe, 5 Asia, 3 Australia; follow-up 4-30 years | Eating more fruit was linked to about 7% lower diabetes risk. Grapes/raisins and apples looked favourable; cantaloupe and sweetened fruit drinks were linked to higher risk, but in very few studies. 100% fruit juice showed no clear link. | No registered protocol (stated by authors); Subtype analyses based on 2-6 studies, many from the same US cohorts (NHS, NHS II, HPFS); possible selective reporting | moderate | C-FRU-01 C-FRU-03 C-FRU-05 |
| I-FRU-04 | Glycemic indices of five varieties of dates in healthy and diabetic subjects. Alkaabi JM et al. | 2011 | PMID 21619670 DOI 10.1186/1475-2891-10-59 | Other | 13 healthy volunteers (7 F, 6 M; mean age 40.2 years, BMI 27.4) and 10 adults with type 2 diabetes controlled on diet with or without metformin (HbA1c <=8%; mean HbA1c 6.6%, age 40.8 years, BMI 30.7), recruited by poster advertisement in Al Ain | Five date varieties had GI 46-55. | Very small sample (13 + 10); wide SEMs (up to 8.6 GI units); Test order not randomised (authors' limitation); reference tests all before test foods | moderate | C-FRU-05 C-FRU-01 |
| I-FRU-05 | [Food poisoning by cucurbitacines]. Jung C et al. | 2020 | PMID 32668470 DOI 10.1055/a-1163-9741 | Case series / case report | 1 woman, 66 y | A woman developed severe diarrhoea after eating bitter zucchini; bitter taste is the warning sign. | Single case | low | C-FRU-02 |
| I-FRU-06 | WHO calls on countries to reduce sugars intake among adults and children (news release on WHO Guideline: Sugars intake for adults and children, 2015). World Health Organization | 2015 | Guideline / position statement | Adults and children | WHO advises less than 10% of energy from free sugars, which include fruit juice and honey but not whole fruit. | Press release; full PDF not read | high | C-FRU-03 C-FRU-05 | |
| I-FSH-01 | Impact of sustainable feeds on omega-3 long-chain fatty acid levels in farmed Atlantic salmon, 2006-2015. Sprague M et al. | 2016 | PMID 26899924 DOI 10.1038/srep21892 | Measurement / residue study | Farmed Scottish Atlantic salmon (standard quality cuts supplied year-round by producers and feed manufacturers); comparators: 21 wild (mainly Pacific) salmon from supermarkets and retail mackerel, cod, tuna, sardines, beef, chicken, lamb, pork (2014/2015) | Omega-3 in farmed Scottish salmon roughly halved from 2006 to 2015 (2.74 to 1.36 g per 100 g), but it still had more omega-3 per 100 g than the wild salmon tested (0.76 g) and most other foods. | Convenience samples submitted by industry; representativeness not verified; Wild salmon n=21, mostly Pacific species from supermarkets (not wild Atlantic) | high | C-FSH-04 C-FSH-05 C-FSH-11 C-FSH-13 |
| I-FSH-02 | Lower levels of Persistent Organic Pollutants, metals and the marine omega 3-fatty acid DHA in farmed compared to wild Atlantic salmon (Salmo salar). Lundebye AK et al. | 2017 | PMID 28189073 DOI 10.1016/j.envres.2017.01.026 | Measurement / residue study | Wild and farmed Atlantic salmon | Wild salmon had more dioxins, PCBs and mercury than farmed salmon; both were good omega-3 sources. | Norwegian government institute authors (no COI stated); Sample size not in abstract | moderate | C-FSH-01 C-FSH-02 C-FSH-03 C-FSH-04 C-FSH-05 C-FSH-13 C-FSH-14 |
| I-FSH-03 | Fish intake, contaminants, and human health: evaluating the risks and the benefits. Mozaffarian D & Rimm EB | 2006 | PMID 17047219 DOI 10.1001/jama.296.15.1885 | Systematic review | Adults, women of childbearing age | For adults, the benefits of eating fish 1-2 times a week outweigh risks from contaminants. | Not fully systematic; Observational basis for many outcomes | moderate | C-FSH-02 C-FSH-03 C-FSH-05 C-FSH-14 |
| I-FSH-04 | Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood (ALSPAC study): an observational cohort study. Hibbeln JR et al. | 2007 | PMID 17307104 DOI 10.1016/S0140-6736(07)60277-3 | Cohort study | Pregnant women and children | Children of mothers who ate more seafood in pregnancy had better developmental scores. | Observational; FFQ | moderate | C-FSH-14 |
| I-FSH-05 | Evidence on the human health effects of low-level methylmercury exposure. Karagas MR et al. | 2012 | PMID 22275730 DOI 10.1289/ehp.1104494 | Narrative review | General populations (excluding very high consumers) | Methylmercury is a nerve toxin; at low levels possible effects on babies' early development, unclear effects on heart and immune system. | Not a systematic review: limited search (two databases, keywords), no protocol, no duplicate selection, no study-quality assessment, no quantitative synthesis; Excludes the most informative moderate-exposure cohorts by design | low | C-FSH-14 |
| I-FSH-06 | Global trends in antimicrobial use in aquaculture. Schar D et al. | 2020 | PMID 33318576 DOI 10.1038/s41598-020-78849-3 | Systematic review | Aquaculture species groups | About 10,000 tonnes were used in 2017, mostly in Asia; salmon had the lowest use per kg. | Only 25 surveys from 12 countries; China and carp under-represented; Extremely wide UIs (e.g. catfish 9-2,751 mg/kg) | moderate | C-FSH-08 |
| I-FSH-07 | Occurrence and human health risks of pesticides and antibiotics in Nile tilapia along the Rosetta Nile branch, Egypt. Eissa F et al. | 2020 | PMID 33384941 DOI 10.1016/j.toxrep.2020.03.004 | Measurement / residue study | Wild Nile tilapia (Oreochromis niloticus) caught with local fishermen 1 km upstream of the El-Rahawy (Giza), Sabal (Minoufiya) and Tala (Gharbiya) drain outlets on the Rosetta branch | Most wild river tilapia sampled near drains had pesticide traces (chlorpyrifos above the EU limit in 45%) and a fifth had antibiotic traces, including EU-banned drugs; estimated non-cancer risk was low. | Wild river fish sampled close to drain outlets (worst-case locations), not market or farmed fish; Small n per site-season; antibiotic findings driven by one site-season (Sabal, spring) | moderate | C-FSH-12 C-FSH-16 C-RES-01 C-RES-02 |
| I-FSH-08 | Potential health risk assessment of some bioaccumulated metals in Nile tilapia (Oreochromis niloticus) cultured in Kafr El-Shaikh farms, Egypt. Shaaban NA et al. | 2021 | PMID 34043970 DOI 10.1016/j.envres.2021.111358 | Measurement / residue study | 200 farmed tilapia from 3 farms | Metal levels in muscle were judged safe, though fish tissues showed damage at drainage-water farms. | No mercury; Three farms | moderate | C-FSH-12 |
| I-FSH-09 | Heavy Metals Assessment and Health Risk to Consumers of Two Commercial Fish Species from Polyculture Fishponds in El-Sharkia and Kafr El-Sheikh, Egypt: Physiological and Biochemical Study. Abbas MMM et al. | 2024 | PMID 38129339 DOI 10.1007/s12011-023-04007-1 | Measurement / residue study | Tilapia (bolti) and mullet (topara) | Mostly safe, but cadmium in tilapia from one governorate was a cancer-risk warning for children. | Sample size not in abstract | moderate | C-FSH-12 |
| I-FSH-10 | One health risk assessment of heavy-metal contamination in Nile tilapia (Oreochromis niloticus) from contrasting aquaculture systems in Egypt. Farahat Abdelmawla M et al. | 2026 | PMID 42662802 DOI 10.1016/j.toxrep.2026.102331 | Measurement / residue study | Nile tilapia, 4 sites | Even at a heavily polluted drain, tilapia muscle stayed within limits, but lead margins were narrow. | Few sites | moderate | C-FSH-12 |
| I-FSH-11 | Hysterical tetracycline in intensive poultry farms accountable for substantial gene resistance, health and ecological risk in Egypt- manure and fish. Mahmoud MAM & Abdel-Mohsein HS | 2019 | PMID 31521994 DOI 10.1016/j.envpol.2019.113039 | Measurement / residue study | Poultry litter/droppings; tilapia from Nile and aquaculture | Farmed tilapia had more tetracycline residues than river tilapia; poultry litter may spread resistance. | Sample sizes not in abstract; Risk statement for fish not quantified in abstract | moderate | C-FSH-12 |
| I-FSH-12 | Comparative analysis of virulence genes, antibiotic resistance and gyrB-based phylogeny of motile Aeromonas species isolates from Nile tilapia and domestic fowl. Abu-Elala N et al. | 2015 | PMID 26280543 DOI 10.1111/lam.12484 | Other | Nile tilapia, domestic fowl isolates | Integrated fish farms often use poultry droppings as feed and fertiliser. | Small microbiological study | low | C-FSH-12 |
| I-FSH-13 | Systems-thinking approach to identify and assess feasibility of potential interventions to reduce antibiotic use in tilapia farming in Egypt. Desbois AP et al. | 2021 | PMID 34276104 DOI 10.1016/j.aquaculture.2021.736735 | Other | Aquaculture stakeholders | Antibiotics enter farms via medicated feed and drainage water. | Qualitative | low | C-FSH-08 C-FSH-12 |
| I-FSH-14 | Carcinogenic and non-carcinogenic health risks associated with heavy metal exposure in commonly consumed marine fish in Egypt. Elshebrawy HA et al. | 2026 | PMID 42632867 DOI 10.1038/s41598-026-67201-w | Measurement / residue study | Flathead grey mullet (Mugil cephalus, n=50), round sardinella (Sardinella aurita, n=100) and Atlantic mackerel (Scomber scombrus, n=100; imported frozen, mainly from Norway and the Netherlands per vendors) from six retail outlets in East Mansoura | Up to a fifth of mullet, sardine and mackerel samples exceeded mercury limits; heavy eaters could exceed safe intake for mercury and lead (arsenic risk is probably overestimated). | Total arsenic used for cancer risk; authors state more than 90% of As in marine fish is organic and only 0.02-11% inorganic, so cancer risk is substantially overestimated; Hg measured as total Hg (treated as MeHg) | moderate | C-FSH-14 |
| I-FSH-15 | Toxic trace elements in fish and seafood from North African coasts: A systematic review and meta-analysis of contamination levels and health risk assessment. Nahal A & Mehouel F | 2026 | PMID 42250752 DOI 10.1016/j.yrtph.2026.106156 | Meta-analysis | Fish and seafood | Mercury and cadmium in seafood signalled potential concern in Egypt and Tunisia. | Heterogeneous studies; Mixed farmed/wild | moderate | C-FSH-14 |
| I-FSH-16 | Prevalence of fish and shellfish allergy: A systematic review. Moonesinghe H et al. | 2016 | PMID 27613460 DOI 10.1016/j.anai.2016.07.015 | Systematic review | General populations | With proper food challenges, under 1% of people were allergic to shellfish. | Heterogeneous diagnostic methods | moderate | C-FSH-15 |
| I-FSH-17 | Risk for animal and human health related to the presence of dioxins and dioxin-like PCBs in feed and food. EFSA Panel on Contaminants in the Food Chain (CONTAM) et al. | 2018 | PMID 32625737 DOI 10.2903/j.efsa.2018.5333 | Risk assessment | EU population; farm animals | EFSA set a stricter weekly limit for dioxins (2 pg TEQ/kg/week), which many Europeans exceed from their whole diet. | Single critical study | high | C-FSH-02 C-FSH-03 |
| I-FSH-18 | Risk to human health related to the presence of perfluoroalkyl substances in food. EFSA Panel on Contaminants in the Food Chain (EFSA CONTAM Panel) et al. | 2020 | PMID 32994824 DOI 10.2903/j.efsa.2020.6223 | Risk assessment | EU population | Fish meat, fruit and eggs were the main dietary PFAS sources; EFSA set a weekly limit of 4.4 ng/kg body weight, which parts of the population exceed. Freshwater fish such as eel had the highest levels; salmon/trout were low. | 92% of results left-censored; large LB-UB gap; Occurrence data concentrated in 3 countries | high | C-FSH-14 |
| I-FSH-19 | Risk to human health related to the presence of perfluorooctane sulfonic acid and perfluorooctanoic acid in food. EFSA Panel on Contaminants in the Food Chain (CONTAM) et al. | 2018 | PMID 32625773 DOI 10.2903/j.efsa.2018.5194 | Risk assessment | EU population | Fish and seafood were important dietary sources of PFOS and PFOA; many Europeans exceeded EFSA's 2018 weekly limits (13 and 6 ng/kg). | High left-censoring and insensitive methods; large LB-UB gap; Data dominated by Germany (62%) | high | C-FSH-14 |
| I-FSH-20 | Scientific Opinion on the risk for public health related to the presence of mercury and methylmercury in food (EFSA press release: 'Mercury in food - EFSA updates advice on risks for public health', 20 December 2012) EFSA CONTAM Panel | 2012 | DOI 10.2903/j.efsa.2012.2985 | Risk assessment | EU population | EFSA set a weekly safety limit for methylmercury; tuna, swordfish and pike are among the main sources. | Only the press release was read | high | C-FSH-14 |
| I-FSH-21 | Statement on the benefits of fish/seafood consumption compared to the risks of methylmercury in fish/seafood (EFSA press release 'Fish: scenarios indicate benefits versus risks', 22 January 2015) EFSA Scientific Committee | 2015 | DOI 10.2903/j.efsa.2015.3982 | Risk assessment | EU population groups | Eating fish 1-4 times a week brings benefits; children and women of childbearing age should choose low-mercury species. | Only press release read | high | C-FSH-14 |
| I-GRN-01 | Fructan, Rather Than Gluten, Induces Symptoms in Patients With Self-Reported Non-Celiac Gluten Sensitivity. Skodje GI et al. | 2018 | PMID 29102613 DOI 10.1053/j.gastro.2017.10.040 | Randomised controlled trial | 59 adults on self-instituted gluten-free diet, coeliac excluded | In people who think they react to gluten, a wheat sugar (fructan) caused more symptoms than gluten. | Small; short challenges | high | C-GRN-01 C-WHT-09 |
| I-GRN-02 | European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders. Al-Toma A et al. | 2019 | PMID 31210940 DOI 10.1177/2050640619844125 | Guideline / position statement | Adults and children with coeliac disease (CD), dermatitis herpetiformis, non-coeliac gluten sensitivity (NCGS), gluten ataxia and other gluten-related disorders | Coeliac disease needs a strict lifelong gluten-free diet; gluten is in wheat, rye and barley (not in uncontaminated rice, maize or oats); non-coeliac gluten sensitivity is recognised after coeliac disease and wheat allergy are excluded. | Literature search in PubMed only; no systematic review, evidence tables or explicit study selection criteria; Consensus by a small board (8 authors); no patient, dietitian or methodologist involvement reported | moderate | C-GRN-01 C-GRN-02 C-GRN-03 C-WHT-02 |
| I-GRN-03 | White Rice Intake and Incident Diabetes: A Study of 132,373 Participants in 21 Countries. Bhavadharini B et al. | 2020 | PMID 32873587 DOI 10.2337/dc19-2335 | Cohort study | PURE participants aged 35-70 years without baseline diabetes, with complete diet data and >=1 follow-up visit (148,858 with diet data minus 16,485 with baseline diabetes); mean age 50 years; South Asia n=26,419, China n=41,727, rest of world n=64,227 | Very high white rice intake (>=3 cups/day) linked to 20% higher diabetes risk. | Diet measured once at baseline by FFQ; no rice type data (parboiled, basmati, etc.); Residual confounding possible (authors list unmeasured alcohol, air pollution, pesticides; South Asian high consumers differ markedly: lower BMI, fibre 10.8 vs 24.2 g/day, 71% energy from carbohydrate) | high | C-GRN-05 C-SRC-18 |
| I-GRN-04 | Total and specific potato intake and risk of type 2 diabetes: results from three US cohort studies and a substitution meta-analysis of prospective cohorts. Mousavi SM et al. | 2025 | PMID 40769531 DOI 10.1136/bmj-2024-082121 | Cohort study | US female nurses (NHS n=72,712; NHS II n=90,232) and male health professionals (HPFS n=42,163), free of diabetes, CVD and cancer at baseline; >90% of European ancestry. Meta-analysis: 13 cohorts (5 US, 4 Europe, 2 Asia, 2 Australia), 587,081 participants | Eating fries 3 more times a week was linked to 20% higher diabetes risk; boiled, baked or mashed potatoes and potato/corn chips showed no clear link. Swapping potatoes for whole grains was linked to lower risk, swapping for white rice to higher risk. | Observational: residual confounding (high potato/fries consumers had lower diet quality and activity); Health professionals, >90% European ancestry; effect modification by race and BMI | high | C-GRN-07 C-GRN-05 |
| I-GRN-05 | Fried potato consumption is associated with elevated mortality: an 8-y longitudinal cohort study. Veronese N et al. | 2017 | PMID 28592612 DOI 10.3945/ajcn.117.154872 | Cohort study | 4440 adults 45-79 y | Fried potatoes 3+ times/week linked to about double the death risk in a small cohort. | Small number of deaths; Subgroup finding | low | C-GRN-07 |
| I-GRN-06 | Update of the risk assessment of inorganic arsenic in food. EFSA CONTAM Panel | 2024 | PMID 38239496 DOI 10.2903/j.efsa.2024.8488 | Risk assessment | EU population | Arsenic exposure from food, mainly rice, is a health concern; the EU limits arsenic in rice. | Uncertainties acknowledged | high | C-GRN-06 |
| I-GRN-07 | International tables of glycemic index and glycemic load values 2021: a systematic review. Atkinson FS et al. | 2021 | PMID 34258626 DOI 10.1093/ajcn/nqab233 | Systematic review | Foods tested | Fruits usually have a low GI; most potatoes have a high GI. | Abstract only; food-specific values not extracted | high | C-FRU-01 C-GRN-07 C-SRC-18 |
| I-GUT-01 | Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Malfertheiner P et al. | 2022 | PMID 35944925 DOI 10.1136/gutjnl-2022-327745 | Guideline / position statement | Global | H. pylori is an infectious disease; infected people should be treated. | Industry COI of several authors; Abstract only read | moderate | C-GUT-06 C-SRC-50 |
| I-GUT-02 | Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive people. Ford AC et al. | 2016 | PMID 27092708 DOI 10.1002/14651858.CD003840.pub5 | Meta-analysis | H. pylori-positive ulcer patients | Duodenal ulcer recurrence fell from 64% without treatment to 13% with eradication. | Low/very low GRADE for some outcomes (older trials) | high | C-GUT-06 |
| I-GUT-03 | Helicobacter pylori eradication therapy to prevent gastric cancer: systematic review and meta-analysis. Ford AC et al. | 2020 | PMID 32205420 DOI 10.1136/gutjnl-2020-320839 | Meta-analysis | Healthy H. pylori-positive adults; patients after endoscopic resection | Eradication nearly halved gastric cancer incidence in trials. | Mostly East Asian; COI of one author | high | C-GUT-06 |
| I-GUT-04 | Fructan, Rather Than Gluten, Induces Symptoms in Patients With Self-Reported Non-Celiac Gluten Sensitivity. Skodje GI et al. | 2018 | PMID 29102613 DOI 10.1053/j.gastro.2017.10.040 | Randomised controlled trial | Adults on self-instituted gluten-free diet, coeliac disease excluded | In people who felt gluten-sensitive, fructans (wheat sugars) increased bloating and symptoms; gluten did not. | Small; Selected population | moderate | C-GUT-01 |
| I-GUT-05 | ACG Clinical Guideline: Management of Irritable Bowel Syndrome. Lacy BE et al. | 2021 | PMID 33315591 DOI 10.14309/ajg.0000000000001036 | Guideline / position statement | Patients with IBS | A low-FODMAP diet trial is recommended, along with drugs and psychotherapy. | Abstract only | high | C-GUT-01 C-GUT-02 |
| I-GUT-06 | Intra-abdominal hypertension and the abdominal compartment syndrome: updated consensus definitions and clinical practice guidelines from the World Society of the Abdominal Compartment Syndrome. Kirkpatrick AW et al. | 2013 | PMID 23673399 DOI 10.1007/s00134-013-2906-z | Guideline / position statement | Critically ill patients | Harmful pressure starts at ≥12 mmHg sustained, in critically ill patients. | Low-quality evidence base | moderate | C-GUT-04 C-UPF-10 |
| I-GUT-07 | Carbohydrate quality and human health: a series of systematic reviews and meta-analyses. Reynolds A et al. | 2019 | PMID 30638909 DOI 10.1016/S0140-6736(18)31809-9 | Meta-analysis | Adults without chronic disease | People eating the most fibre had 15–30% lower risk of death and major chronic diseases. | Observational main outcomes; Erratum | high | C-GUT-05 |
| I-GUT-08 | Gut-microbiota-targeted diets modulate human immune status. Wastyk HC et al. | 2021 | PMID 34256014 DOI 10.1016/j.cell.2021.06.019 | Randomised controlled trial | Healthy adults | Fermented foods increased gut bacterial diversity and lowered inflammation markers in a small trial. | Very small; Primary outcome null | low | C-GUT-05 |
| I-GUT-09 | Dietary interventions for multiple sclerosis-related outcomes. Parks NE et al. | 2020 | PMID 32428983 DOI 10.1002/14651858.CD004192.pub4 | Systematic review | Adults with MS | No reliable evidence that diet changes relapses or disability in MS. | Low-certainty evidence; Author COI | high | C-AUTO-01 |
| I-GUT-10 | EULAR recommendations for the management of systemic lupus erythematosus: 2023 update. Fanouriakis A et al. | 2024 | PMID 37827694 DOI 10.1136/ard-2023-224762 | Guideline / position statement | Patients with SLE (incl. lupus nephritis, cutaneous, neuropsychiatric, haematological disease, SLE-associated APS) | Hydroxychloroquine for all patients; immunosuppressants and biologics to control disease. | Extensive industry relationships of panel members relevant to recommended biologics; SLR limited to two databases and English language | high | C-AUTO-01 C-EGG-03 |
| I-INS-01 | Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. ADVANCE Collaborative Group; Patel A et al. | 2008 | PMID 18539916 DOI 10.1056/NEJMoa0802987 | Randomised controlled trial | Type 2 diabetes diagnosed at >=30 years, age >=55 (mean 66), with history of major macro- or microvascular disease or >=1 other vascular risk factor; mean diabetes duration 7.9 years, mean HbA1c 7.5%; 91% on oral agents, ~1.5% on insulin; definite indication for long-term insulin excluded. | Fewer kidney complications and no extra deaths, but more severe hypoglycaemia. | Open-label glucose comparison; more visits in intensive arm (31 vs 11) - co-intervention (e.g. lower BP); Mid-trial protocol amendment adding joint primary outcome (stated as blinded to results) | high | C-INS-04 C-ODD-11 |
| I-INS-02 | 10-year follow-up of intensive glucose control in type 2 diabetes. Holman RR et al. | 2008 | PMID 18784090 DOI 10.1056/NEJMoa0806470 | Randomised controlled trial | Newly diagnosed type 2 diabetes from UKPDS | People treated intensively early with sulfonylureas or insulin had 15% fewer heart attacks and 13% fewer deaths years later. | Post-trial therapy not controlled; Questionnaire follow-up | high | C-INS-03 C-INS-04 C-INS-05 C-ODD-01 C-ODD-11 C-DIAB-01 |
| I-INS-03 | The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. Diabetes Control and Complications Trial Research Group; Nathan DM et al. | 1993 | PMID 8366922 DOI 10.1056/NEJM199309303291401 | Randomised controlled trial | Insulin-dependent (type 1) diabetes | Intensive insulin cut the risk of eye damage by three-quarters and nerve damage by 60%, with more low-sugar episodes. | Open-label; Selected young population | high | C-INS-02 C-INS-04 C-INS-07 C-INS-09 C-INS-10 C-ODD-03 C-DIAB-01 C-DIAB-03 |
| I-INS-04 | Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. Stratton IM et al. | 2000 | PMID 10938048 DOI 10.1136/bmj.321.7258.405 | Cohort study | UKPDS patients (white, Asian Indian, Afro-Caribbean) | Each 1% lower HbA1c was linked to 21% fewer diabetes deaths and 37% fewer eye/kidney complications. | Observational | moderate | C-INS-09 C-ODD-06 C-DIAB-01 C-DIAB-02 |
| I-INS-05 | The association of basal insulin glargine and/or n-3 fatty acids with incident cancers in patients with dysglycemia. Bordeleau L et al. | 2014 | PMID 24574355 DOI 10.2337/dc13-1468 | Randomised controlled trial | Dysglycaemia with high CV risk, mean age 63.5 | Cancer rates were identical with glargine and standard care (1.32 per 100 person-years each). | Industry funding; 6 years may be short for some cancers | high | C-INS-05 C-INS-06 |
| I-INS-06 | Insulin glargine and cancer risk in patients with diabetes: a meta-analysis. Tang X et al. | 2012 | PMID 23284776 DOI 10.1371/journal.pone.0051814 | Meta-analysis | Diabetes patients | Glargine was not linked to more cancer, including breast cancer. | Very high heterogeneity (I2 = 93% overall cancer; ~80% breast cancer); No study-level risk-of-bias tool; 3 of 11 studies unadjusted for confounders; few adjusted for metformin or diabetes type | low | C-INS-06 |
| I-INS-07 | Hyperglycemic Crises in Adults With Diabetes: A Consensus Report. Umpierrez GE et al. | 2024 | PMID 39052901 DOI 10.2337/dci24-0032 | Guideline / position statement | Adults with diabetes | Insulin, fluids and potassium are the core treatment; with this, fewer than 1% of adults die. | Consensus, not trial | high | C-INS-02 C-INS-07 C-INS-08 C-INS-09 C-INS-10 C-FAST-03 C-FAST-10 C-DIAB-02 |
| I-INS-08 | Diabetic ketoacidosis. Dhatariya KK et al. | 2020 | PMID 32409703 DOI 10.1038/s41572-020-0165-1 | Narrative review | Adults and children with diabetes | DKA is an emergency that can kill; it is treated with fluids, insulin and salts, and insulin must not be stopped in type 1 diabetes even when not eating. | Narrative review without systematic search, selection or appraisal methods; Epidemiological figures are cited from heterogeneous primary studies, not pooled | moderate | C-INS-02 C-INS-07 C-INS-08 C-INS-10 C-ODD-03 C-FAST-01 C-FAST-03 C-DIAB-02 |
| I-INS-09 | Calorie for Calorie, Dietary Fat Restriction Results in More Body Fat Loss than Carbohydrate Restriction in People with Obesity. Hall KD et al. | 2015 | PMID 26278052 DOI 10.1016/j.cmet.2015.07.021 | Randomised controlled trial | Adults with obesity (BMI >30; mean 35.9 +/- 1.1 kg/m2), 10 men and 9 women, weight-stable, non-diabetic per exclusion of interfering disease/medication | Cutting fat led to more fat loss than cutting carbs, even though cutting carbs lowered insulin more. | Very short (6-day) diet periods; long-term inference rests on model simulation; Small sample (19 randomised, 17 complete crossovers) | high | C-INS-01 C-SRC-22 |
| I-INS-10 | 6. Glycemic Goals, Hypoglycemia, and Hyperglycemic Crises: Standards of Care in Diabetes-2026. American Diabetes Association Professional Practice Committee for Diabetes* | 2026 | PMID 41358894 DOI 10.2337/dc26-S006 | Guideline / position statement | People with diabetes | Most adults should aim for HbA1c below 7%, avoid low sugar, and measure ketones when at risk. | US-centred; Partially read | high | C-INS-04 C-INS-08 C-INS-11 C-ODD-01 C-ODD-02 C-FAST-01 C-FAST-03 C-DIAB-02 |
| I-INTA-01 | Association between tea consumption and gastroesophageal reflux disease: A meta-analysis. Cao H et al. | 2019 | PMID 30681584 DOI 10.1097/MD.0000000000014173 | Meta-analysis | Participants of 23 observational studies (30 estimates) published 2004-2017: 17 estimates from East Asia, 5 Europe, 5 Middle East, 2 North America, 1 South Asia | Across 30 studies, tea drinkers did not have significantly more reflux disease overall (OR 1.12, 0.98-1.27). | Mostly cross-sectional and case-control data; only 3 cohort estimates (all null); Majority of included studies did not adjust for confounders (authors' statement) | low | C-SRC-24 |
| I-INTA-02 | Tea consumption and risk of all-cause, cardiovascular disease, and cancer mortality: a meta-analysis of thirty-eight prospective cohort data sets. Kim Y et al. | 2024 | PMID 38938012 DOI 10.4178/epih.e2024056 | Meta-analysis | General adult populations in prospective cohorts (studies restricted to patients with a specific disease excluded); cohorts from Asia, Europe, USA and Oceania; mean follow-up 12.3 years (5-23 years) | Across nearly 2 million people, tea drinkers had about 10% lower death rates than non-drinkers. | Observational cohorts: residual confounding and healthy-user effects; adjustment sets vary; High heterogeneity (I2 75-82%) | moderate | C-SRC-24 |
| I-INTA-03 | Tea Consumption and Health Outcomes: Umbrella Review of Meta-Analyses of Observational Studies in Humans. Yi M et al. | 2019 | PMID 31216091 DOI 10.1002/mnfr.201900389 | Systematic review | All human populations in included meta-analyses | Across 96 meta-analyses, tea showed more benefits than harms; only very hot tea (>55-60 °C) was linked to oesophageal and gastric cancer. | Observational evidence only; Overlapping meta-analyses | moderate | C-SRC-24 |
| I-INTA-04 | The effect of tea on iron absorption. Disler PB et al. | 1975 | PMID 1168162 DOI 10.1136/gut.16.3.193 | Other | Human volunteers | Tea taken with meals reduced absorption of plant (non-haem) iron in volunteers. | Old study; Sample size not given in abstract | moderate | C-SRC-24 |
| I-INTA-05 | Analysis of oxytocin in milk samples and intake pattern in different age groups of Indian population. Mishra M et al. | 2014 | PMID 24712660 DOI 10.3109/15376516.2014.910851 | Measurement / residue study | Milk samples from Lucknow, India; consumers of different age groups | In 55 milk samples from an Indian city, oxytocin was found in milkman samples; the authors report indiscriminate injection of cattle. | Small sample, one city; No health outcomes | low | C-SRC-29 |
| I-INTA-06 | Induction of milk ejection and milk removal in different production systems. Bruckmaier RM et al. | 2008 | PMID 17709779 DOI 10.2527/jas.2007-0335 | Narrative review | Dairy cows | Oxytocin releases the milk stored in the udder during milking; long-term injections make cows respond less to their own oxytocin. | Narrative review; Abstract only | moderate | C-SRC-29 |
| I-INTA-07 | Endocrinology of milk production. Svennersten-Sjaunja K et al. | 2005 | PMID 15876512 DOI 10.1016/j.domaniend.2005.03.006 | Narrative review | Dairy cows | Pregnancy hormones, growth hormone and prolactin build and run milk production; oxytocin only releases the milk. | Narrative review; Abstract only | moderate | C-SRC-29 |
| I-INTA-08 | Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial. de Groot S et al. | 2020 | PMID 32576828 DOI 10.1038/s41467-020-16138-3 | Randomised controlled trial | Women >=18 years with HER2-negative stage II/III breast cancer receiving neoadjuvant AC-T or FEC-T chemotherapy at 11 Dutch centres; BMI >19 kg/m2, no diabetes, WHO 0-2, adequate organ function; median age 49-51 years, median BMI about 26 | In 131 women with breast cancer, a fasting-mimicking diet around chemotherapy did not reduce severe side effects or increase complete tumour disappearance (the main outcomes); tumour shrinkage on imaging was more frequent, but this was a secondary result. | Primary endpoint (grade III/IV toxicity) not met; pCR (planned phase III primary) not different; Positive findings are secondary endpoints with P values near 0.05 and wide CIs; pathological benefit only in per-protocol analysis (selection bias acknowledged by authors) | moderate | C-SRC-32 |
| I-INTA-09 | ESPEN guidelines on nutrition in cancer patients. Arends J et al. | 2017 | PMID 27637832 DOI 10.1016/j.clnu.2016.07.015 | Guideline / position statement | Adult cancer patients | European guidelines say cancer patients should be screened for malnutrition and should get enough energy and protein. | Abstract only read; Evidence gaps acknowledged | high | C-SRC-32 |
| I-INTA-10 | Impact of intermittent fasting on patients with cancer undergoing chemotherapy and/or targeted therapies: a systematic review of the literature. Maes J et al. | 2025 | PMID 40970988 DOI 10.1007/s00520-025-09907-7 | Systematic review | Cancer patients undergoing chemotherapy or targeted therapy (mostly breast cancer) | Nine small studies found fasting feasible and safe under supervision but showed no proven effect on treatment results or side effects. | Few, small studies; Mostly breast cancer | moderate | C-SRC-32 |
| I-INTA-11 | Growth, efficiency, and yield of commercial broilers from 1957, 1978, and 2005. Zuidhof MJ et al. | 2014 | PMID 25260522 DOI 10.3382/ps.2014-04291 | Other | Broiler chicks: University of Alberta control strains unselected since 1957 and 1978, and Ross 308 (2005) | Modern broilers grew over four times faster than 1957 birds on the same feed, showing the role of breeding. | Single experiment; Abstract does not mention antibiotic use | moderate | C-RES-05 |
| I-INTA-12 | Aetiology and associations of halitosis: A systematic review. Memon MA et al. | 2023 | PMID 35212093 DOI 10.1111/odi.14172 | Systematic review | Studies on people with halitosis | 80-90% of bad breath comes from the mouth itself (tongue coating, gum disease, poor hygiene). | Narrative synthesis; Limited time window | moderate | C-SRC-05 |
| I-INTA-13 | Egg intake and cognitive function in healthy adults: A systematic review of the literature. Sultan N et al. | 2025 | PMID 41061594 DOI 10.1016/j.jnha.2025.100696 | Systematic review | Adults >=18 years without diagnosed chronic metabolic/cardiovascular disease, or cohorts statistically adjusted for chronic disease; mostly older adults; 11 studies (1 pre-post, 6 prospective cohorts, 3 cross-sectional, 1 case-control) from China (6), USA (3), Thailand (1), Finland (1) | Eleven mostly observational studies did not show that eggs cause dementia; several found no link, some found better results with moderate intake, and one cross-sectional study found more mild cognitive impairment at the highest intake. | English-only; small number of heterogeneous studies; no meta-analysis; Mostly observational (cross-sectional and case-control included); residual confounding and reverse causation (cognitive decline may change diet) | moderate | C-SRC-05 |
| I-INTA-14 | Effect of different cooking methods on glycaemic index of Indian and Pakistani basmati rice varieties. Gunathilaka MD et al. | 2015 | PMID 26132185 DOI 10.4038/cmj.v60i2.7545 | Randomised controlled trial | Healthy adults aged 20-30, BMI 18.5-23.5 | Two basmati rices had low (Indian) and medium (Pakistani) glycaemic index in 10 volunteers. | n = 10; Large SD | low | C-SRC-18 |
| I-INTA-15 | Rice variety and processing: contribution to glycaemic response. Nisanka T U et al. | 2016 | PMID 28076944 DOI 10.4038/cmj.v61i4.8381 | Randomised controlled trial | Healthy volunteers | In 11 volunteers, a basmati variety had a high GI (73), while parboiled rice had a low GI (40). | n = 11; Local varieties | low | C-SRC-18 |
| I-INTA-16 | Relationship between Physicochemical and Cooking Quality Parameters with Estimated Glycaemic Index of Rice Varieties. Pereira CL et al. | 2023 | PMID 38201163 DOI 10.3390/foods13010135 | Laboratory / cell study | Commercial rice types | In laboratory tests, basmati and a long-grain rice had the lowest estimated glycaemic index. | In vitro estimate, not human GI | low | C-SRC-18 |
| I-INTA-17 | The Glycemic Index of Rice and Rice Products: A Review, and Table of GI Values. Kaur B et al. | 2016 | PMID 25590950 DOI 10.1080/10408398.2012.717976 | Narrative review | Not applicable | No: the effect of rice on blood sugar depends on the variety, how it is processed and what it is eaten with. | Narrative; Abstract gives no specific values | moderate | C-SRC-18 |
| I-INTA-18 | Impact of Peptide Structure on Colonic Stability and Tissue Permeability. Taherali F et al. | 2023 | PMID 37514143 DOI 10.3390/pharmaceutics15071956 | Laboratory / cell study | Not applicable | Peptide hormones like oxytocin are broken down in the gut and poorly absorbed; that is why they are usually injected. | In vitro/ex vivo; Colon model, not whole-gut digestion of milk | low | C-SRC-29 |
| I-INTB-01 | Mechanisms of Insulin Action and Insulin Resistance. Petersen MC, Shulman GI | 2018 | PMID 30067154 DOI 10.1152/physrev.00063.2017 | Narrative review | Human and animal physiology literature | Insulin resistance in muscle, liver and fat is a central process in type 2 diabetes; some mechanisms are still debated. | Narrative, not systematic; Abstract only read | moderate | C-SRC-37 |
| I-INTB-02 | Slow glucose removal rate and hyperinsulinemia precede the development of type II diabetes in the offspring of diabetic parents. Warram JH et al. | 1990 | PMID 2240915 DOI 10.7326/0003-4819-113-12-909 | Cohort study | 155 normoglycaemic offspring of two parents with type 2 diabetes and 186 controls without family history, aged 16-60 | In high-risk offspring, slow glucose clearance with high insulin levels predicted diabetes one to two decades later. | Selected high-risk population (both parents diabetic); IVGTT is an indirect index of insulin sensitivity | moderate | C-SRC-37 |
| I-INTB-03 | Insulin resistance and hyperinsulinemia: is hyperinsulinemia the cart or the horse? Shanik MH et al. | 2008 | PMID 18227495 DOI 10.2337/dc08-s264 | Narrative review | Animal and human studies | Evidence suggests high insulin can be both a result and a driver of insulin resistance. | Narrative, selective; Mainly animal and indirect human data | low | C-SRC-37 |
| I-INTB-04 | Neoadjuvant chemotherapy induces breast cancer metastasis through a TMEM-mediated mechanism. Karagiannis GS et al. | 2017 | PMID 28679654 DOI 10.1126/scitranslmed.aan0026 | Animal study | Mice with early-stage mammary carcinomas (~11 per group planned; up to 25% removed per panel); 20 patients with ER+/HER2- breast cancer and residual disease (RCB 2-3) after neoadjuvant weekly paclitaxel followed by 4 cycles of doxorubicin plus cyclophosphamide; separate fine-needle aspirates from 5 patients before and 1 week after the second paclitaxel dose | In mice and in residual human tumours, chemotherapy increased markers of cancer-cell dissemination. | Primarily animal data; dosing schedules differ from clinical practice; Human analysis: only 20 selected patients with residual disease (non-responders), unblinded TMEM scoring, surrogate markers only, no recurrence or survival analysis (follow-up insufficient) | moderate | C-CHM-10 |
| I-INTB-05 | Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. Fisher B et al. | 2002 | PMID 12192016 DOI 10.1056/NEJMoa020128 | Randomised controlled trial | 1079 women with clinically node-negative and 586 with clinically node-positive breast cancer | Over 25 years, women without routine axillary dissection survived as long as those with radical mastectomy. | Older surgical and systemic-therapy context; Abstract only read | high | C-SRC-45 |
| I-INTB-06 | Effect of Axillary Dissection vs No Axillary Dissection on 10-Year Overall Survival Among Women With Invasive Breast Cancer and Sentinel Node Metastasis: The ACOSOG Z0011 (Alliance) Randomized Clinical Trial. Giuliano AE et al. | 2017 | PMID 28898379 DOI 10.1001/jama.2017.11470 | Randomised controlled trial | Women with clinical T1-T2 invasive breast cancer, no palpable adenopathy, 1-2 positive sentinel nodes, treated with lumpectomy, whole-breast irradiation and systemic therapy | In women with 1-2 positive sentinel nodes, skipping full axillary dissection did not worsen 10-year survival. | Closed early: 891 of 1900 planned patients and 110 of 500 planned deaths, so underpowered; wide non-inferiority margin (HR 1.3); Adjusted HR upper bound (1.28) close to the margin | high | C-SRC-45 |
| I-INTB-07 | Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma. Faries MB et al. | 2017 | PMID 28591523 DOI 10.1056/NEJMoa1613210 | Randomised controlled trial | Patients aged 18-75 years with clinically localised cutaneous melanoma, ECOG 0-1, non-melanoma life expectancy >=10 years and a tumour-positive sentinel node (by standard pathology or multimarker RT-PCR assay); low nodal tumour burden (median largest deposit 0.61-0.67 mm) | Completion dissection did not improve melanoma-specific survival but caused more lymphoedema. | Short median follow-up (43 months) for melanoma-specific survival; results released at an interim analysis; Main text reports per-protocol rather than ITT analysis; 140 patients in dissection group declined surgery (differed in prognostic factors) | high | C-SRC-45 |
| I-INTB-08 | Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis. DiSipio T et al. | 2013 | PMID 23540561 DOI 10.1016/S1470-2045(13)70076-7 | Meta-analysis | Breast-cancer survivors | About 1 in 5 survivors develop arm lymphoedema; risk is about four times higher after full axillary dissection. | Heterogeneous diagnostic methods; Observational studies | moderate | C-SRC-45 |
| I-INTB-09 | Frequency and impact of nonadherence to immunosuppressants after renal transplantation: a systematic review. Butler JA et al. | 2004 | PMID 15021846 DOI 10.1097/01.tp.0000110408.83054.88 | Meta-analysis | Adult kidney-transplant recipients | Not taking immunosuppressants was linked to about seven times higher odds of graft failure. | Adherence measurement mostly self-report; Older studies | moderate | C-SRC-46 |
| I-INTB-10 | A prospective, randomized, double-blind, placebo-controlled multicenter trial comparing early (7 day) corticosteroid cessation versus long-term, low-dose corticosteroid therapy. Woodle ES et al. | 2008 | PMID 18936569 DOI 10.1097/SLA.0b013e318187d1da | Randomised controlled trial | Adult deceased and living donor kidney-transplant recipients without delayed graft function, on tacrolimus/MMF/antibody induction | With continued tacrolimus and MMF, early steroid withdrawal gave similar 5-year graft survival but more mild rejection. | Selected low-risk recipients; Abstract only read | high | C-SRC-46 |
| I-INTB-11 | KDIGO clinical practice guideline for the care of kidney transplant recipients. KDIGO Transplant Work Group | 2009 | PMID 19845597 DOI 10.1111/j.1600-6143.2009.02834.x | Guideline / position statement | Adults and children after kidney transplantation | Gives recommendations on immunosuppression and monitoring after kidney transplant. | Abstract only read; specific recommendation text not verified here; 2009 | moderate | C-SRC-46 |
| I-INTB-12 | Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. GBD Chronic Kidney Disease Collaboration | 2020 | PMID 32061315 DOI 10.1016/S0140-6736(20)30045-3 | Risk assessment | Populations of 195 countries and territories (GBD 2017), all ages, both sexes | About 9% of the world's population (698 million people) had CKD in 2017, about 7.1 million of them in Egypt; diabetes caused almost a third of the burden. | Many countries lack primary population-based CKD data; estimates rely on covariates and neighbouring countries; Single eGFR/ACR measurement may overestimate prevalence by 25-50% (authors) | moderate | C-SRC-47 |
| I-INTB-13 | Vaccines for preventing influenza in healthy adults. Demicheli V et al. | 2018 | PMID 29388196 DOI 10.1002/14651858.CD001269.pub6 | Meta-analysis | Healthy adults 16-65 years incl. pregnant women | Vaccination roughly halves confirmed influenza (2.3% to 0.9%); absolute benefit is modest. | Old trials; Seasonal variability | high | C-SRC-47 C-SRC-56 |
| I-INTB-14 | Non-invasive diagnostic tests for Helicobacter pylori infection. Best LM et al. | 2018 | PMID 29543326 DOI 10.1002/14651858.CD012080.pub2 | Meta-analysis | People suspected of H. pylori infection | Breath tests are highly accurate; blood and stool tests somewhat less so; about 46 false positives per 1000 tested in a model scenario. | Indirect comparisons; Variable thresholds | high | C-SRC-50 |
| I-INTB-15 | Contribution of vaccination to improved survival and health: modelling 50 years of the Expanded Programme on Immunization. Shattock AJ et al. | 2024 | PMID 38705159 DOI 10.1016/S0140-6736(24)00850-X | Risk assessment | Populations of 194 WHO member states, all ages | Vaccines against 14 diseases averted an estimated 154 million deaths since 1974 (about 94 million by measles vaccine alone), mostly in young children. | Counterfactual (no vaccination) cannot be observed; results depend on model structure and assumptions; No interpretable uncertainty intervals for final estimates (authors' statement) | moderate | C-SRC-56 |
| I-INTB-16 | Vaccines for measles, mumps, rubella, and varicella in children. Di Pietrantonj C et al. | 2021 | PMID 34806766 DOI 10.1002/14651858.CD004407.pub5 | Systematic review | Healthy children up to 15 years | One dose prevents about 95% of measles; serious side effects are rare and no link to autism was found. | Mostly observational for effectiveness; Abstract only read | high | C-SRC-56 |
| I-INTB-17 | Vaccines are not associated with autism: an evidence-based meta-analysis of case-control and cohort studies. Taylor LE, Swerdfeger AL, Eslick GD | 2014 | PMID 24814559 DOI 10.1016/j.vaccine.2014.04.085 | Meta-analysis | Children | In over 1.2 million children, vaccination was not linked to autism. | Observational data; Abstract only read | moderate | C-SRC-56 |
| I-INTB-18 | Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. CTT Collaboration, Baigent C et al. | 2010 | PMID 21067804 DOI 10.1016/S0140-6736(10)61350-5 | Meta-analysis | Participants of 26 randomised statin trials: 5 trials of more vs less intensive statin (8,659 acute coronary syndrome and 30,953 stable coronary disease patients) and 21 trials of statin vs control (incl. primary prevention, diabetes, haemodialysis, heart failure, coronary disease) | Each 1 mmol/L LDL reduction cut major vascular events by about a fifth and deaths by 10%, without more cancer. | Most trials industry-funded; IPD missing for 3 eligible trials (11,342 patients); including their published haemorrhagic stroke data gives a significant excess | high | C-SRC-60 |
| I-INTB-19 | Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials. Cholesterol Treatment Trialists' Collaboration | 2022 | PMID 36049498 DOI 10.1016/S0140-6736(22)01545-8 | Meta-analysis | Participants of 19 double-blind statin vs placebo trials (mean age 63 years, 27.9% women, 48.1% previous vascular disease, 18.5% diabetes) and 4 double-blind trials of more vs less intensive statin (all with vascular disease, mean age 62) | Statins cause a small excess of mild muscle pain, mostly in year 1; most muscle complaints are not caused by the statin. | Heterogeneous ascertainment of muscle symptoms across trials (first-year reporting 1.0% to 60.5%); CK measured in <6.2% of symptom reports | high | C-SRC-60 |
| I-INTB-20 | Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Sattar N et al. | 2010 | PMID 20167359 DOI 10.1016/S0140-6736(09)61965-6 | Meta-analysis | Participants of statin endpoint trials | About one extra diabetes case per 255 people treated for 4 years. | Diabetes was not a primary endpoint of trials; Abstract only read | high | C-SRC-60 |
| I-INTB-21 | Low cigarette consumption and risk of coronary heart disease and stroke: meta-analysis of 141 cohort studies in 55 study reports. Hackshaw A et al. | 2018 | PMID 29367388 DOI 10.1136/bmj.j5855 | Meta-analysis | Generally healthy adults in prospective cohorts (high-risk-only cohorts excluded); for CHD in men about 3.07 million participants and >75,000 cases; stroke in men about 3.53 million and >73,000 cases; CHD in women about 2.56 million and >36,000 cases; stroke in women about 3.78 million and 62,000 cases | One cigarette a day carries about half the heart-disease risk of 20 a day. | Single database (Medline), English only; no registered protocol; Aggregate data only; log-linear modelling of category midpoints; within-study correlation not fully modelled | moderate | C-SRC-62 |
| I-INTB-22 | A longitudinal study of plasma and urinary cortisol in pregnancy and postpartum. Jung C et al. | 2011 | PMID 21367926 DOI 10.1210/jc.2010-2395 | Cohort study | 20 pregnant women, 12 OCP users, 15 controls | Total cortisol rose about threefold and free cortisol 1.6-fold by the third trimester. | Small sample; Abstract only read | moderate | C-SRC-65 |
| I-INTB-23 | Intra-abdominal pressure, intra-abdominal hypertension, and pregnancy: a review. Chun R, Kirkpatrick AW | 2012 | PMID 22873421 DOI 10.1186/2110-5820-2-S1-S5 | Narrative review | Pregnant and peripartum women, particularly critically ill parturients; case of a 16-year-old at about 32 weeks with influenza A ARDS | Abdominal pressure is probably raised near term, but most women adapt to it; any role in pre-eclampsia is only a hypothesis. Cortisol is not discussed. | Narrative review without systematic search or appraisal; Evidence for IAH-pre-eclampsia link limited to hypotheses, two case reports and historical/animal data | low | C-SRC-65 |
| I-INTC-01 | Water, hydration, and health. Popkin BM et al. | 2010 | PMID 20646222 DOI 10.1111/j.1753-4887.2010.00304.x | Narrative review | General population (review) | Water is a critical nutrient; without it a person dies within days. Long-term trials on ideal intake are missing. | Narrative, non-systematic review; Funded by a bottled-water company (Nestlé Waters), with company staff advice | moderate | C-SYS-04 C-SYS-05 C-GUT-08 |
| I-INTC-02 | Risk-benefit analysis of micronutrients. Renwick AG et al. | 2004 | PMID 15500928 DOI 10.1016/j.fct.2004.07.013 | Narrative review | Not applicable (method paper) | Nutrient risk assessment weighs the risk of deficiency against the risk of excess. | Methodological proposal; no empirical outcome data; Micronutrients only | moderate | C-SYS-04 C-SYS-05 |
| I-INTC-03 | 5. Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes: Standards of Care in Diabetes-2026. American Diabetes Association Professional Practice Committee | 2026 | PMID 41358898 DOI 10.2337/dc26-S005 | Guideline / position statement | People with prediabetes or diabetes | There is no single diet for diabetes; meals should be individualised with a dietitian, and medicines may need adjustment when the diet changes. | US-focused; Only the nutrition passages quoted here were read in detail | high | C-SYS-08 |
| I-INTC-04 | Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus Nephritis. Rovin BH et al. | 2024 | PMID 38182299 DOI 10.1016/j.kint.2023.09.001 | Guideline / position statement | Patients with lupus nephritis | Kidney involvement in lupus is treated with specific medicines; the guideline was updated in 2024 after two new drugs were approved. | Only the abstract was read; recommendations themselves not audited | high | C-EGG-03 |
| I-INTC-05 | Bologna guidelines for diagnosis and management of adhesive small bowel obstruction (ASBO): 2017 update of the evidence-based guidelines from the world society of emergency surgery ASBO working group. Ten Broek RPG et al. | 2018 | PMID 29946347 DOI 10.1186/s13017-018-0185-2 | Guideline / position statement | Patients with small bowel obstruction | A blocked bowel is an emergency with pain, vomiting and swelling; it is usually caused by scar tissue after surgery, hernias or tumours. | Some recommendations based on limited evidence | high | C-GUT-03 C-GUT-09 C-UPF-10 |
| I-INTC-06 | Incretin hormones: Their role in health and disease. Nauck MA et al. | 2018 | PMID 29364588 DOI 10.1111/dom.13129 | Narrative review | Humans (physiology and clinical studies) | After eating, gut hormones and rising blood sugar make the pancreas release insulin; oral glucose triggers 2-3 times more insulin than glucose given into a vein. | Narrative review; Abstract only | moderate | C-GUT-03 |
| I-INTC-07 | Saliva and gastrointestinal functions of taste, mastication, swallowing and digestion. Pedersen AM et al. | 2002 | PMID 12108756 DOI 10.1034/j.1601-0825.2002.02851.x | Narrative review | Humans | Chewing and saliva start digestion and help form a swallowable bolus. | Narrative; Abstract without quantitative data | moderate | C-GUT-09 |
| I-INTC-08 | Review of the diagnosis and management of gastrointestinal bezoars. Iwamuro M et al. | 2015 | PMID 25901212 DOI 10.4253/wjge.v7.i4.336 | Narrative review | Patients with bezoars | Bezoars cause 0.4-4.8% of intestinal blockages, mostly in people with stomach surgery or slow stomach emptying. | Narrative; based partly on own small case series | low | C-GUT-09 |
| I-INTC-09 | Bariatric surgery and the incidence of rheumatoid arthritis - a Swedish Obese Subjects study. Maglio C et al. | 2020 | PMID 31321442 DOI 10.1093/rheumatology/kez275 | Cohort study | Adults aged 37-60 years with obesity (BMI >=34 men, >=38 women) without prevalent RA, recruited at 25 surgical departments and 480 primary care centres | Over a median of 21 years, people who had weight-loss surgery did not develop rheumatoid arthritis more often than matched controls. | Not randomised (ethics boards did not allow randomisation in 1987); surgery group had higher BMI, CRP and smoking at baseline; RA was not a predefined SOS endpoint; authors state the study may be underpowered (92 events) | moderate | C-BAR-13 |
| I-INTC-10 | Systematic review: Outcomes of bariatric surgery in patients with inflammatory bowel disease and de-novo IBD development after bariatric surgery. Mian A et al. | 2023 | PMID 35660070 DOI 10.1016/j.surge.2022.04.008 | Systematic review | Patients with or without IBD undergoing bariatric surgery | Some studies report new inflammatory bowel disease after weight-loss surgery, but how often and whether surgery causes it is unknown. | Mostly case reports/series and observational data; No incidence comparison in abstract | low | C-BAR-13 |
| I-INTC-11 | Fibromyalgia and obesity: A comprehensive systematic review and meta-analysis. D'Onghia M et al. | 2021 | PMID 33676126 DOI 10.1016/j.semarthrit.2021.02.007 | Meta-analysis | Patients with fibromyalgia | About one in three people with fibromyalgia has obesity; early studies suggest weight loss, including surgery, may ease symptoms. | High risk of bias in included studies; Few weight-loss studies | moderate | C-BAR-13 |
| I-INTC-12 | Does breast feeding provide protection against acute appendicitis? A case-control study. Alves JG et al. | 2008 | PMID 18820196 DOI 10.1258/td.2008.070404 | Case-control study | Children with histologically confirmed appendicitis and their siblings | Children breastfed for longer had appendicitis less often than their siblings in one small study. | Small; Recall of breastfeeding | low | C-ORG-02 |
| I-INTC-13 | Risk factors of obstructive sleep apnea syndrome in children. Xu Z et al. | 2020 | PMID 32131901 DOI 10.1186/s40463-020-0404-1 | Cross-sectional study | Children aged 2-15 years with snoring undergoing polysomnography at Beijing Children's Hospital sleep centre, mostly referred by ENT or respiratory specialists | Enlarged tonsils and adenoids, obesity and male sex were linked to sleep apnoea; breastfeeding was too, probably due to other factors. | Highly selected referral population (snoring children, 64% OSAS); not generalisable to the general population; Cross-sectional; exposure recalled by parents years later | low | C-ORG-02 |
| I-INTC-14 | Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect. Victora CG et al. | 2016 | PMID 26869575 DOI 10.1016/S0140-6736(15)01024-7 | Meta-analysis | Children and mothers worldwide | Breastfeeding protects children against infections and has other benefits; it is not shown here to prevent tonsil or appendix surgery. | Observational evidence for many outcomes; Tonsil, adenoid and appendicitis outcomes not mentioned in abstract | high | C-ORG-02 |
| I-INTC-15 | Instant noodle intake and dietary patterns are associated with distinct cardiometabolic risk factors in Korea. Shin HJ et al. | 2014 | PMID 24966409 DOI 10.3945/jn.113.188441 | Cross-sectional study | Adults 19-64 years | Women who ate instant noodles twice a week or more had metabolic syndrome more often (OR 1.68). | Cross-sectional; FFQ-based | moderate | C-UPF-10 |
| I-LEG-01 | Legume Consumption and Risk of All-Cause and Cause-Specific Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies. Zargarzadeh N et al. | 2023 | PMID 36811595 DOI 10.1016/j.advnut.2022.10.009 | Meta-analysis | General adult populations (aged >=18 y) without prior disease; 5 US, 14 European, 10 Asian, 1 Australian and 2 international cohorts | People eating more legumes had about 6% lower risk of death from any cause. | Observational data: residual confounding and healthy-user effects possible; Substantial heterogeneity (I2 ~65% for all-cause) | moderate | C-LEG-01 C-LEG-02 C-LEG-04 C-LEG-07 C-LEG-13 C-VEG-16 |
| I-LEG-02 | Effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction: a systematic review and meta-analysis of randomized controlled trials. Ha V et al. | 2014 | PMID 24710915 DOI 10.1503/cmaj.131727 | Meta-analysis | Adults in RCTs | About one serving of pulses daily lowered LDL cholesterol in randomised trials. | Short trials; Quality variable | moderate | C-LEG-01 C-LEG-04 C-LEG-07 C-LEG-13 C-VEG-16 |
| I-LEG-03 | Effects of non-soy legume consumption on C-reactive protein: a systematic review and meta-analysis. Salehi-Abargouei A et al. | 2015 | PMID 25837205 DOI 10.1016/j.nut.2014.10.018 | Meta-analysis | Adults in RCTs | Trials found no increase in CRP from eating legumes; levels tended to fall. | Small; Overall not significant | moderate | C-LEG-01 C-LEG-02 |
| I-LEG-04 | Consumption of nuts and legumes and risk of incident ischemic heart disease, stroke, and diabetes: a systematic review and meta-analysis. Afshin A et al. | 2014 | PMID 24898241 DOI 10.3945/ajcn.113.076901 | Meta-analysis | Adults | Eating legumes regularly was linked to 14% lower heart-disease risk. | Few legume studies (5 for IHD) | moderate | C-LEG-01 C-LEG-04 C-LEG-13 |
| I-LEG-05 | Study of Glucose-6-Phosphate Dehydrogenase Deficiency: 5 Years Retrospective Egyptian Study. Hagag AA et al. | 2018 | PMID 28982343 DOI 10.2174/1871530317666171003160350 | Case series / case report | Children with G6PD deficiency anaemia, Tanta University Hospital | In 1,000 Egyptian children with G6PD deficiency, haemolysis was most often triggered by fava beans and falafel. | Retrospective; precipitants from history; Single centre | low | C-LEG-03 C-LEG-05 |
| I-LEG-06 | Prevalence of glucose-6-phosphate dehydrogenase deficiency in jaundiced Egyptian neonates. Abo El Fotoh WM et al. | 2016 | PMID 26866975 DOI 10.3109/14767058.2016.1148133 | Cross-sectional study | Neonates with indirect hyperbilirubinaemia | About 9% of jaundiced newborns had G6PD deficiency. | Selected (jaundiced) sample; not population prevalence | low | C-LEG-03 |
| I-LEG-07 | Glucose-6-phosphate dehydrogenase deficiency and sulfadimidin acetylation phenotypes in Egyptian oases. Hussein L et al. | 1992 | PMID 1590743 DOI 10.1007/BF02399702 | Cross-sectional study | Males from two oases | 5.9% of 1,315 men screened in two oases had G6PD deficiency. | Oases only; old | low | C-LEG-03 |
| I-LEG-08 | Glucose-6-phosphate dehydrogenase deficiency. Luzzatto L et al. | 2020 | PMID 32702756 DOI 10.1182/blood.2019000944 | Narrative review | Global | About 500 million people carry G6PD deficiency; fava beans, some drugs and infections trigger haemolysis. | Narrative | moderate | C-LEG-03 C-LEG-05 |
| I-LEG-09 | The global prevalence of glucose-6-phosphate dehydrogenase deficiency: a systematic review and meta-analysis. Nkhoma ET et al. | 2009 | PMID 19233695 DOI 10.1016/j.bcmd.2008.12.005 | Meta-analysis | Populations in 88 countries | About 400 million people have G6PD deficiency worldwide; highest in sub-Saharan Africa. | Heterogeneity; Country figures not in abstract | moderate | C-LEG-03 |
| I-LEG-10 | Exposure to soy-based formula in infancy and endocrinological and reproductive outcomes in young adulthood. Strom BL et al. | 2001 | PMID 11497534 DOI 10.1001/jama.286.7.807 | Cohort study | Adults aged 20-34 | No major health differences in young adulthood; slightly longer menstrual bleeding in women. | Self-report; Many outcomes (multiple testing) | moderate | C-LEG-10 |
| I-LEG-11 | Randomized trial of peanut consumption in infants at risk for peanut allergy. Du Toit G et al. | 2015 | PMID 25705822 DOI 10.1056/NEJMoa1414850 | Randomised controlled trial | Infants aged 4 to <11 months with severe eczema, egg allergy or both; skin-prick wheal 0 mm (n=542) or 1-4 mm (n=98); infants with wheals >4 mm (76/834 screened, 9.1%) excluded | Babies at high risk who ate peanut early developed far less peanut allergy than those who avoided it. | Open-label; no placebo; Only high-risk infants; those with SPT >4 mm excluded | high | C-LEG-11 |
| I-LEG-12 | Food anaphylaxis in the United Kingdom: analysis of national data, 1998-2018. Baseggio Conrado A et al. | 2021 | PMID 33597169 DOI 10.1136/bmj.n251 | Ecological study | Whole UK population (England, Scotland, Wales, Northern Ireland) | Peanut/tree nut caused at least 46% of food-anaphylaxis deaths; cow's milk is now the top single cause in school children. | Administrative coding errors (trigger and diagnosis); ED-only cases excluded; Admissions are a poor surrogate for anaphylaxis incidence (authors) | moderate | C-LEG-11 |
| I-LEG-13 | Efficacy of a low FODMAP diet in irritable bowel syndrome: systematic review and network meta-analysis. Black CJ et al. | 2022 | PMID 34376515 DOI 10.1136/gutjnl-2021-325214 | Meta-analysis | IBS patients | Across 13 trials, a low-FODMAP diet was the most effective diet for IBS symptoms. | Blinding issues; No reintroduction data | moderate | C-LEG-12 |
| I-MEAT-01 | IARC Monographs Volume 114: Red Meat and Processed Meat (with IARC Q&A and Press Release No. 240) International Agency for Research on Cancer (IARC) | 2018 (evaluation 2015) | Risk assessment | Epidemiological and mechanistic literature | About 18% higher risk per 50 g processed meat a day; red meat about 17% per 100 g if causal. | Hazard identification, not risk magnitude; Red meat evidence limited | high | C-MEAT-01 C-MEAT-04 | |
| I-MEAT-02 | Carcinogenicity of consumption of red and processed meat. Bouvard V et al. | 2015 | PMID 26514947 DOI 10.1016/S1470-2045(15)00444-1 | Risk assessment | n/a | Same conclusions as I-MEAT-01 (no abstract available). | No abstract; full text not accessed | moderate | C-MEAT-01 |
| I-MEAT-03 | Red and processed meat and colorectal cancer incidence: meta-analysis of prospective studies. Chan DS et al. | 2011 | PMID 21674008 DOI 10.1371/journal.pone.0020456 | Meta-analysis | Adults in 24 prospective studies: 12 North American, EPIC (10 European countries), Finland, Netherlands, Japan (2 each), Australia, Canada, Sweden, China, Singapore; 13 mixed-sex, 3 male, 8 female cohorts. | Fresh red meat RR 1.17 per 100 g/day; processed meat RR 1.18 per 50 g/day. | Observational studies; residual confounding cannot be ruled out (authors); association attenuated in some better-adjusted analyses (e.g. NHS/HPFS); No formal risk-of-bias/quality assessment of included studies | moderate | C-MEAT-01 |
| I-MEAT-04 | Reduction of Red and Processed Meat Intake and Cancer Mortality and Incidence: A Systematic Review and Meta-analysis of Cohort Studies. Han MA et al. | 2019 | PMID 31569214 DOI 10.7326/M19-0699 | Meta-analysis | >6 million participants (56 cohorts) | Very small absolute reductions; low certainty. | Methodological choices debated (comments in literature); Article corrected | high | C-MEAT-01 |
| I-MEAT-05 | Unprocessed Red Meat and Processed Meat Consumption: Dietary Guideline Recommendations From the Nutritional Recommendations (NutriRECS) Consortium. Johnston BC et al. | 2019 | PMID 31569235 DOI 10.7326/M19-1621 | Guideline / position statement | Adults | Weak recommendation to continue current intake. | Controversial; contradicts most guideline bodies; Article corrected | moderate | C-MEAT-01 |
| I-MEAT-06 | Teratogenicity of high vitamin A intake. Rothman KJ et al. | 1995 | PMID 7477116 DOI 10.1056/NEJM199511233332101 | Cohort study | Pregnant women undergoing AFP screening or amniocentesis | Above 15,000 IU/day: 3.5-fold more defects of head/face structures. | Dietary vitamin A self-reported; Few exposed cases | moderate | C-MEAT-03 |
| I-MEAT-07 | Foods to avoid in pregnancy (NHS) NHS (UK National Health Service) | accessed 2026 | Guideline / position statement | Pregnant women | Liver has high vitamin A, which can harm the baby. | UK-specific; no evidence summary on page | high | C-MEAT-03 | |
| I-MEAT-08 | Purine-rich foods, dairy and protein intake, and the risk of gout in men. Choi HK et al. | 2004 | PMID 15014182 DOI 10.1056/NEJMoa035700 | Cohort study | 47,150 men without gout | Meat RR 1.41; dairy RR 0.56. | Men only; health professionals; Offal not analysed separately in abstract | moderate | C-MEAT-03 |
| I-MEAT-09 | Heme iron from meat and risk of colorectal cancer: a meta-analysis and a review of the mechanisms involved. Bastide NM et al. | 2011 | PMID 21209396 DOI 10.1158/1940-6207.CAPR-10-0113 | Meta-analysis | 566,607 individuals; 4,734 cases | Highest vs lowest heme intake RR 1.18. | Observational; heme estimates from FFQ | moderate | C-MEAT-01 |
| I-MEAT-10 | Well-done meat intake, heterocyclic amine exposure, and cancer risk. Zheng W et al. | 2009 | PMID 19838915 DOI 10.1080/01635580802710741 | Narrative review | Epidemiological studies | Studies suggest higher cancer risk with well-done meat and HCAs. | Narrative; exposure assessment of doneness uncertain | low | C-MEAT-04 |
| I-ODD-01 | Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. UKPDS Group | 1998 | PMID 9742977 | Randomised controlled trial | Overweight newly diagnosed type 2 diabetes, mean age 53 | Metformin reduced deaths from any cause by about a third over 10 years. | Small arms; Open-label | moderate | C-INS-11 C-ODD-01 C-ODD-05 C-ODD-06 C-ODD-07 C-ODD-11 |
| I-ODD-02 | Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. Zinman B et al. | 2015 | PMID 26378978 DOI 10.1056/NEJMoa1504720 | Randomised controlled trial | Type 2 diabetes with high CV risk | Deaths fell from 8.3% to 5.7% over about 3 years. | Industry funded; Selected high-risk population | high | C-ODD-02 C-ODD-05 C-ODD-06 |
| I-ODD-03 | Dapagliflozin in Patients with Chronic Kidney Disease. Heerspink HJL et al. | 2020 | PMID 32970396 DOI 10.1056/NEJMoa2024816 | Randomised controlled trial | Adults with CKD (eGFR 25-75 ml/min/1.73 m2, urinary albumin-to-creatinine ratio 200-5000 mg/g) on stable ACE inhibitor/ARB unless intolerant; 67.5% with type 2 diabetes; mean age 61.8 years; 33.1% female; mean eGFR 43.1; median UACR 949 | Forxiga reduced kidney failure and deaths; the trial was stopped early because the benefit was clear. | Stopped early for benefit (408 of planned 681 events), which can overestimate effect size and reduces power for secondary outcomes; Industry sponsored with sponsor employees among authors | high | C-ODD-02 C-ODD-05 C-ODD-06 |
| I-ODD-04 | Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. McMurray JJV et al. | 2019 | PMID 31535829 DOI 10.1056/NEJMoa1911303 | Randomised controlled trial | HFrEF NYHA II-IV, EF <=40%, with/without diabetes | Fewer heart failure worsenings and deaths with Forxiga. | Industry funded; Selected high-risk population | high | C-ODD-02 C-ODD-05 C-ODD-06 |
| I-ODD-05 | Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. Perkovic V et al. | 2019 | PMID 30990260 DOI 10.1056/NEJMoa1811744 | Randomised controlled trial | Adults >=30 years with type 2 diabetes (HbA1c 6.5-12.0%), eGFR 30 to <90 ml/min/1.73 m2 and UACR >300-5000 mg/g on stable maximum-tolerated ACEi/ARB; mean age 63.0 years, 33.9% women, mean HbA1c 8.3%, mean eGFR 56.2, median UACR 927; 50.4% with cardiovascular disease; 5.3% prior amputation | Kidney failure and heart problems fell by about a third; amputations and fractures were not increased, but rare ketoacidosis was more common (11 vs 1 cases). | Stopped early at interim analysis (may overestimate effect size; reduced power for secondary outcomes), as authors acknowledge; Industry sponsorship and author financial ties | high | C-ODD-05 C-ODD-06 C-ODD-02 |
| I-ODD-06 | Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. Marso SP et al. | 2016 | PMID 27295427 DOI 10.1056/NEJMoa1603827 | Randomised controlled trial | Type 2 diabetes, HbA1c >=7.0%, age >=50 with established CVD/CKD stage >=3/heart failure NYHA II-III, or age >=60 with >=1 CV risk factor; 81.3% had established CVD and/or CKD; mean diabetes duration 12.8 years; mean HbA1c 8.7% | Fewer heart deaths and deaths overall; pancreatitis not increased, but more gallstone disease and a small, non-significant excess of pancreatic cancer. | Industry sponsored; sponsor co-analysed data and four authors are sponsor employees with patents; High-risk population (HbA1c >=7%, mostly established CVD); limited applicability to lower-risk patients | high | C-ODD-04 C-ODD-05 C-ODD-06 |
| I-ODD-07 | Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. Marso SP et al. | 2016 | PMID 27633186 DOI 10.1056/NEJMoa1607141 | Randomised controlled trial | Type 2 diabetes, 83% with CVD/CKD | Fewer heart attacks/strokes, but more diabetic eye complications and stomach side effects. | Industry funded; Selected high-risk population | high | C-ODD-05 C-ODD-06 |
| I-ODD-08 | Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Salpeter SR et al. | 2010 | PMID 20393934 DOI 10.1002/14651858.CD002967.pub4 | Systematic review | Type 2 diabetes in trials/cohorts >=1 month | No lactic acidosis cases in about 70,000 patient-years of metformin use. | Trials often excluded high-risk patients | high | C-ODD-01 |
| I-ODD-09 | Sodium-Glucose Cotransporter-2 Inhibitors and the Risk for Diabetic Ketoacidosis : A Multicenter Cohort Study. Douros A et al. | 2020 | PMID 32716707 DOI 10.7326/M20-0289 | Cohort study | Type 2 diabetes new users | About 2 per 1,000 users per year developed ketoacidosis, nearly 3 times more than with DPP-4 drugs. | No lab data; Unmeasured confounding | high | C-ODD-02 C-FAST-03 |
| I-ODD-10 | Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium-Glucose Cotransporter 2 Inhibition. Peters AL et al. | 2015 | PMID 26078479 DOI 10.2337/dc15-0843 | Case series / case report | 9 patients (8 women, 1 man; age 26-64) on canagliflozin: 7 with type 1 diabetes (off-label use, insulin pump or MDI) and 2 with type 2 diabetes (both postoperative) | Several patients developed ketoacidosis with near-normal sugar, so it was recognised late. | Incidental, non-systematic case collection; no denominator, so incidence cannot be estimated; 7 of 9 patients used the drug off-label in type 1 diabetes; frequent insulin reduction/omission, alcohol and illness as co-factors | very low | C-ODD-02 C-ODD-03 C-FAST-03 |
| I-ODD-11 | Glucagon-like peptide-1 receptor agonists and risk of acute pancreatitis in patients with type 2 diabetes. Storgaard H et al. | 2017 | PMID 28105738 DOI 10.1111/dom.12885 | Meta-analysis | Type 2 diabetes | In large blinded trials, pancreatitis was not more frequent with GLP-1 drugs than placebo. | Only 3 trials; Rare outcome | high | C-ODD-04 |
| I-ODD-12 | Fournier's gangrene and sodium-glucose co-transporter-2 inhibitors: A meta-analysis of randomized controlled trials. Silverii GA et al. | 2020 | PMID 31637829 DOI 10.1111/dom.13900 | Meta-analysis | Type 2 diabetes in RCTs | Across 84 trials Fournier gangrene was not more frequent, but cases were too few to be sure. | Very few events; FG not systematically adjudicated | moderate | C-ODD-05 C-ODD-08 |
| I-ODD-13 | Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Home PD et al. | 2009 | PMID 19501900 DOI 10.1016/S0140-6736(09)60953-3 | Randomised controlled trial | Type 2 diabetes on metformin or SU, HbA1c 7.9% | Overall heart outcomes were not worse, but heart failure doubled; heart-attack effect unclear. | Open-label; Manufacturer funded | moderate | C-ODD-05 C-ODD-09 |
| I-ODD-14 | Semaglutide and the Risk of Nonarteritic Ischemic Optic Neuropathy: A Systematic Review and Certainty of Evidence Meta-Analysis. Abdelaal A et al. | 2026 | PMID 41692115 DOI 10.1016/j.ophtha.2026.02.013 | Meta-analysis | Adults on semaglutide or comparators | No consistent overall increase found; possible increase in diabetes patients; evidence weak. | Observational inputs; Extreme heterogeneity | moderate | C-ODD-10 |
| I-ODD-15 | Glucagon-like Peptide-1 Receptor Agonists and Risk of Nonarteritic Anterior Ischemic Optic Neuropathy: Systematic Review and Meta-Analysis. Dhivagaran T et al. | 2026 | PMID 42060879 DOI 10.1212/WNL.0000000000214864 | Meta-analysis | GLP-1 RA users vs non-users | Risk about 2.5 times higher, but absolute risk about 1 per 1,000 users. | Observational inputs; Heterogeneous incidence | moderate | C-ODD-10 |
| I-ODD-16 | 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2026. American Diabetes Association Professional Practice Committee for Diabetes* | 2026 | PMID 41358900 DOI 10.2337/dc26-S009 | Guideline / position statement | People with type 1 and type 2 diabetes | Insulin is essential in type 1 diabetes; SGLT2/GLP-1 drugs are recommended for heart and kidney protection; side effects listed. | Partially read | high | C-INS-07 C-INS-10 C-INS-11 C-ODD-04 C-ODD-07 C-ODD-08 C-ODD-10 C-DIAB-03 |
| I-ODD-17 | Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Davies MJ et al. | 2022 | PMID 36148880 DOI 10.2337/dci22-0034 | Guideline / position statement | Adults with type 2 diabetes | Weight management plus heart- and kidney-protective drugs are central to type 2 diabetes care. | Abstract only read | high | C-INS-11 C-ODD-06 |
| I-ORG-01 | Korea's thyroid-cancer "epidemic"--screening and overdiagnosis. Ahn HS, Kim HJ, Welch HG | 2014 | PMID 25372084 DOI 10.1056/NEJMp1409841 | Other | Title indicates screening-driven overdiagnosis; content not verified here. | Content not verified by this project beyond metadata | moderate | C-ORG-14 | |
| I-ORG-02 | Thyroid Cancer Screening in South Korea Increases Detection of Papillary Cancers with No Impact on Other Subtypes or Thyroid Cancer Mortality. Ahn HS et al. | 2016 | PMID 27627550 DOI 10.1089/thy.2016.0075 | Ecological study | Regions that screened more found far more small papillary cancers, without any effect on thyroid cancer deaths. | Ecological fallacy | moderate | C-ORG-14 C-ORG-15 | |
| I-ORG-03 | Screening for Thyroid Cancer: US Preventive Services Task Force Recommendation Statement. US Preventive Services Task Force | 2017 | PMID 28492905 DOI 10.1001/jama.2017.4011 | Guideline / position statement | Screening does more harm than good because it finds many harmless cancers. | Indirect evidence | high | C-ORG-14 C-ORG-15 | |
| I-ORG-04 | Tonsillectomy or adenotonsillectomy versus non-surgical treatment for chronic/recurrent acute tonsillitis. Burton MJ et al. | 2014 | PMID 25407135 DOI 10.1002/14651858.CD001802.pub3 | Systematic review | Surgery reduced sore throats modestly in the first year (about 0.6 episodes fewer in children); many children get better without surgery. | Short follow-up; Few adult data | high | C-ORG-01 C-ORG-03 | |
| I-ORG-05 | Conservative management versus tonsillectomy in adults with recurrent acute tonsillitis in the UK (NATTINA): a multicentre, open-label, randomised controlled trial. Wilson JA et al. | 2023 | PMID 37209706 DOI 10.1016/S0140-6736(23)00519-6 | Randomised controlled trial | Adults >=16 years newly referred to secondary-care ENT with recurrent acute tonsillitis meeting UK (SIGN) criteria (>=7 episodes in 1 year, >=5/year for 2 years, or >=3/year for 3 years); median age 23, 78% female, 90% White | Surgery roughly halved sore-throat days over 2 years, but 19% had bleeding complications. | Open label; self-reported primary outcome without swab confirmation; High crossover/non-adherence (35% did not receive allocated intervention) | high | C-ORG-01 C-ORG-15 |
| I-ORG-06 | Clinical Practice Guideline: Tonsillectomy in Children (Update). Mitchell RB et al. | 2019 | PMID 30798778 DOI 10.1177/0194599818801757 | Guideline / position statement | Watchful waiting is recommended unless infections are very frequent; surgery is recommended for documented sleep apnea. | US-specific | high | C-ORG-01 C-ORG-15 C-ORG-02 | |
| I-ORG-07 | A Randomized Trial Comparing Antibiotics with Appendectomy for Appendicitis. CODA Collaborative; Flum DR et al. | 2020 | PMID 33017106 DOI 10.1056/NEJMoa2014320 | Randomised controlled trial | Antibiotics worked about as well for overall health at 30 days, but 29% still needed surgery within 90 days. | Unblinded; Short primary endpoint | high | C-ORG-15 C-ORG-17 | |
| I-ORG-08 | Five-Year Follow-up of Antibiotic Therapy for Uncomplicated Acute Appendicitis in the APPAC Randomized Clinical Trial. Salminen P et al. | 2018 | PMID 30264120 DOI 10.1001/jama.2018.13201 | Randomised controlled trial | About 61% treated with antibiotics never needed their appendix removed in 5 years. | Open appendectomy (not laparoscopic) | high | C-ORG-17 | |
| I-ORG-09 | Laparoscopic cholecystectomy versus conservative management for adults with uncomplicated symptomatic gallstones: the C-GALL RCT. Innes K et al. | 2024 | PMID 38943314 DOI 10.3310/MNBY3104 | Randomised controlled trial | Adults with symptomatic uncomplicated gallstone disease (biliary colic or acute cholecystitis) referred to secondary care; mean age 51, predominantly female, 86% white | Over 18 months general pain scores were similar, but about 30% of the 'wait' group needed surgery, 11.5% had gallstone complications before surgery, and gallstone-specific quality of life was better after surgery. | Unblinded participants and surgeons; all outcomes patient-reported or unblinded (authors); Substantial crossover (29.5% conservative had surgery; 29.5% of surgery group not operated by 24 months) | high | C-ORG-01 C-ORG-07 |
| I-ORG-10 | Long-term outcomes of hysterectomy with bilateral salpingo-oophorectomy: a systematic review and meta-analysis. Hassan H et al. | 2024 | PMID 37364803 DOI 10.1016/j.ajog.2023.06.043 | Meta-analysis | Women with hysterectomy plus BSO for benign indications (excluding cancer treatment, gender affirmation, high ovarian-cancer risk); studies from USA, Europe, Australia, Canada, Asia | Linked to less breast cancer but more heart disease, dementia and other conditions in younger women; effect on death was inconsistent. | Fixed-effect pooling despite substantial heterogeneity for several outcomes (I2 up to 92%); No formal per-study risk-of-bias tool (only GRADE) | moderate | C-ORG-09 C-ORG-11 |
| I-ORG-11 | Risk of infection and death among post-splenectomy patients. Bisharat N et al. | 2001 | PMID 11798256 DOI 10.1053/jinf.2001.0904 | Systematic review | About 3% developed serious infections and 1.4% died of them over about 7 years in older studies. | Old literature 1966-96; Pre-modern vaccination | low | C-ORG-12 | |
| I-PPI-01 | Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin. Moayyedi P et al. | 2019 | PMID 31152740 DOI 10.1053/j.gastro.2019.05.056 | Randomised controlled trial | Adults with stable coronary or peripheral artery disease (aged >=65, or younger with additional criteria) without a clinical need for long-term PPI; mean age 67.6, 78% male; excluded high bleeding risk, severe heart failure, significant renal impairment (GFR <15), dementia, severe COPD | Over three years, only gut infections were more common with pantoprazole (1.4% vs 1.0%). | Not powered for safety outcomes; rare events (C. difficile, gastric atrophy) underpowered; Non-CV outcomes self-reported without adjudication (non-differential misclassification biases to null) | high | C-PPI-01 C-PPI-02 C-PPI-04 C-PPI-05 C-PPI-09 |
| I-PPI-02 | Proton pump inhibitors and risk of all-cause and cause-specific mortality: A cohort study. Brown JP et al. | 2021 | PMID 33393677 DOI 10.1111/bcp.14728 | Cohort study | Adults newly prescribed a PPI or H2RA in CPRD GOLD practices eligible for linkage; secondary cohort of PPI users and age/sex/year/practice-matched non-users of acid suppression | The link between PPIs and death shrank with better adjustment and appeared even for causes PPIs could not plausibly cause. | Observational; unmeasured frailty/disease severity likely; Prescription-based exposure; OTC use and non-adherence unrecorded | high | C-PPI-01 |
| I-PPI-03 | The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Freedberg DE et al. | 2017 | PMID 28257716 DOI 10.1053/j.gastro.2017.01.031 | Guideline / position statement | Long-term PPI users | PPIs are justified for defined indications; risks do not require routine monitoring. | Expert opinion; Abstract only | moderate | C-PPI-01 C-PPI-02 C-PPI-03 C-PPI-05 C-PPI-10 C-PPI-11 |
| I-PPI-04 | AGA Clinical Practice Update on De-Prescribing of Proton Pump Inhibitors: Expert Review. Targownik LE et al. | 2022 | PMID 35183361 DOI 10.1053/j.gastro.2021.12.247 | Guideline / position statement | Ambulatory PPI users | Stop PPIs without a definite indication; keep them in Barrett's, severe oesophagitis and high bleeding risk; expect temporary rebound. | Not a systematic review; no formal evidence grading | moderate | C-PPI-01 C-PPI-06 C-PPI-07 C-PPI-10 C-PPI-11 |
| I-PPI-05 | Deprescribing proton pump inhibitors: Evidence-based clinical practice guideline. Farrell B et al. | 2017 | PMID 28500192 | Guideline / position statement | Adults on PPIs ≥4 weeks for heartburn/mild–moderate GERD/oesophagitis with resolved symptoms | PPIs can be reduced or stopped in many patients, but not in Barrett's, severe oesophagitis or after bleeding ulcers. | Abstract only read | moderate | C-PPI-07 C-PPI-10 C-PPI-11 |
| I-PPI-06 | Systematic review: symptoms of rebound acid hypersecretion following proton pump inhibitor treatment. Lødrup AB et al. | 2013 | PMID 23311977 DOI 10.3109/00365521.2012.746395 | Systematic review | Volunteers and reflux patients | Volunteers often get mild symptoms for up to 4 weeks; patients' studies show no clear rebound. | Only PubMed; 5 studies; Authors include Reimer (A-PPI-14) – not independent | moderate | C-PPI-06 C-PPI-07 |
| I-PPI-07 | Effect of Oral Ranitidine on Urinary Excretion of N-Nitrosodimethylamine (NDMA): A Randomized Clinical Trial. Florian J et al. | 2021 | PMID 34180947 DOI 10.1001/jama.2021.9199 | Randomised controlled trial | Healthy adults | Ranitidine did not raise NDMA in urine compared with placebo. | Small; Urinary NDMA is an indirect marker | moderate | C-PPI-08 |
| I-PPI-08 | Clopidogrel with or without omeprazole in coronary artery disease. Bhatt DL et al. | 2010 | PMID 20925534 DOI 10.1056/NEJMoa1007964 | Randomised controlled trial | Patients with indication for aspirin + clopidogrel | GI events fell from 2.9% to 1.1% with omeprazole. | Stopped early (loss of funding); Industry-funded (Cogentus) | high | C-PPI-10 |
| I-PPI-09 | Esomeprazole and aspirin in Barrett's oesophagus (AspECT): a randomised factorial trial. Jankowski JAZ et al. | 2018 | PMID 30057104 DOI 10.1016/S0140-6736(18)31388-6 | Randomised controlled trial | Adults with histologically proven Barrett's oesophagus >=1 cm without high-grade dysplasia or adenocarcinoma and not on NSAIDs; ~80% men (women capped at ~500); median age 58-59; predominantly white | Over about 9 years, high-dose esomeprazole improved a composite of death, cancer and severe dysplasia. | Open-label; no placebo or no-PPI arm (compares doses only); Benefit driven by all-cause mortality and dysplasia; no effect on adenocarcinoma itself | high | C-PPI-10 |
| I-PPI-10 | ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease. Katz PO et al. | 2022 | PMID 34807007 DOI 10.14309/ajg.0000000000001538 | Guideline / position statement | Patients with GERD | Weight loss, avoiding late meals and trigger foods help; PPIs are best for erosive oesophagitis. | Some recommendations low-quality evidence | high | C-PPI-10 C-GUT-01 C-GUT-02 C-GUT-07 |
| I-RES-01 | Commission Regulation (EU) No 37/2010 of 22 December 2009 on pharmacologically active substances and their classification regarding maximum residue limits in foodstuffs of animal origin European Commission | 2010 | Guideline / position statement | The EU sets residue limits (e.g. emamectin 100 µg/kg in fish) and bans some drugs such as chloramphenicol and nitrofurans. | As-adopted version; later amendments not checked | high | C-FSH-10 C-RES-03 C-MEAT-02 | ||
| I-RES-02 | Council Directive 96/22/EC concerning the prohibition on the use in stockfarming of certain substances having a hormonal or thyrostatic action and of beta-agonists Council of the EU | 1996 | Guideline / position statement | The EU prohibits hormonal growth promoters in farm animals. | Only title/contents page read | high | C-FSH-16 C-RES-04 | ||
| I-RES-03 | Regulation (EC) No 396/2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin European Parliament and Council | 2005 | Guideline / position statement | EU law sets maximum pesticide residue levels for all foods. | Only title page read | high | C-RES-01 | ||
| I-RES-04 | Regulation (EC) No 1831/2003 on additives for use in animal nutrition, Article 11 European Parliament and Council | 2003 | Guideline / position statement | Since 1 January 2006, antibiotics may not be used as growth promoters in EU animal feed. | high | C-RES-04 C-RES-05 | |||
| I-RES-05 | The 2023 European Union report on pesticide residues in food (EFSA news: 'Pesticides residues in food: what's the situation in the EU?') EFSA | 2025 | DOI 10.2903/j.efsa.2025.9398 | Measurement / residue study | Food samples | About 98% of samples complied with EU limits; EFSA judged consumer risk low. | Risk-based sampling not representative of average diet (MANCP) | high | C-RES-01 C-RES-02 |
| I-RES-06 | The 2024 European Union report on pesticide residues in food (summary: 'EFSA's 2024 pesticide residue report finds 98.8% of tested EU foods compliant') EFSA | 2026 | DOI 10.2903/j.efsa.2026.10054 | Measurement / residue study | Food samples | 98.8% of tested common foods complied with EU limits. | Secondary EU summary page, not EFSA report itself | high | C-RES-01 C-RES-02 |
| I-RES-07 | Report for 2023 on the results from the monitoring of veterinary medicinal product residues and other substances in live animals and animal products (EFSA news: 'Veterinary drug residues in food - non-compliance stays low in 2023') EFSA | 2025 | Measurement / residue study | Animals and animal products | Only 0.11% of over half a million samples were non-compliant. | Aquaculture not separately reported on the page read | high | C-FSH-09 C-FSH-16 C-RES-02 C-RES-04 C-MEAT-02 | |
| I-RES-08 | Health risk assessment of enrofloxacin, oxytetracycline, and sulfadimidine residues in broiler chicken carcasses marketed in Mit Ghamr, Egypt. Noah SM et al. | 2026 | PMID 42527435 DOI 10.1038/s41598-026-63227-2 | Measurement / residue study | Broiler chicken breast, thigh and liver from different poultry shops in Mit Ghamr City, Egypt | Most chicken samples had antibiotic residues, often above legal limits, but estimated intake was far below harmful levels. | One town; shop-level sampling without documented farm origin; No confirmatory LC-MS/MS (authors' stated limitation); PDA identification by retention time and spectrum only | moderate | C-FSH-16 C-RES-01 C-RES-02 C-RES-03 |
| I-RES-09 | Hormonal residues in chicken and cattle meat: A risk threat the present and future consumer health. Kamaly HF & Sharkawy AA | 2023 | PMID 37956705 DOI 10.1016/j.fct.2023.114172 | Measurement / residue study | 92 chicken, 56 beef samples | A small study reported high hormone levels, but its method cannot tell natural from added hormones. | ELISA cannot distinguish endogenous from administered hormones; Small | low | C-RES-04 C-MEAT-02 |
| I-SOD-01 | Systematic review: the effects of carbonated beverages on gastro-oesophageal reflux disease. Johnson T et al. | 2010 | PMID 20055784 DOI 10.1111/j.1365-2036.2010.04232.x | Systematic review | Not stated in abstract | Fizzy drinks briefly lower acidity in the food pipe, but there is no direct evidence that they cause reflux disease. | Old (2010); Limited primary evidence | moderate | C-SOD-12 C-SOD-13 C-SOD-14 |
| I-SOD-02 | Effects of carbonated water on functional dyspepsia and constipation. Cuomo R et al. | 2002 | PMID 12352219 DOI 10.1097/00042737-200209000-00010 | Randomised controlled trial | Patients with dyspepsia and secondary constipation | In a small trial, sparkling water improved indigestion and constipation compared with tap water. | Very small; Short | low | C-SOD-12 C-SOD-14 |
| I-SOD-03 | Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Suez J et al. | 2022 | PMID 35987213 DOI 10.1016/j.cell.2022.07.016 | Randomised controlled trial | Healthy adults | Saccharin and sucralose worsened glucose responses in some people; aspartame and stevia did not significantly. | Short (2 weeks); Clinical relevance unknown | high | C-SOD-07 |
| I-SOD-04 | Effect of fructose on markers of non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of controlled feeding trials. Chiu S et al. | 2014 | PMID 24569542 DOI 10.1038/ejcn.2014.8 | Meta-analysis | Healthy participants | Fructose raised liver fat only when it added large amounts of extra calories. | Few, small, short, poor-quality trials | moderate | C-SOD-04 |
| I-SOD-05 | Fructose intake and risk of gout and hyperuricemia: a systematic review and meta-analysis of prospective cohort studies. Jamnik J et al. | 2016 | PMID 27697882 DOI 10.1136/bmjopen-2016-013191 | Meta-analysis | Predominantly white health professionals | High fructose intake was linked with 62% higher gout risk in two cohorts; certainty low. | Only 2 cohorts; Indirect population | moderate | C-SOD-05 |
| I-SOD-06 | Artificially Sweetened Beverages and Stroke, Coronary Heart Disease, and All-Cause Mortality in the Women's Health Initiative. Mossavar-Rahmani Y et al. | 2019 | PMID 30802187 DOI 10.1161/STROKEAHA.118.023100 | Cohort study | Postmenopausal women 50-79 | Women drinking two or more diet drinks daily had 31% more ischaemic strokes; far less than the 'triple' figure. | Reverse causation; Single population | high | C-SOD-06 |
| I-SOD-07 | Sugar-sweetened beverage consumption and bone health: a systematic review and meta-analysis. Ahn H, Park YK | 2021 | PMID 33952276 DOI 10.1186/s12937-021-00698-1 | Meta-analysis | Children and adults | Higher sugary and fizzy drink intake was linked with lower bone density in adults. | Observational; Small meta-analysed sample | moderate | C-SOD-08 |
| I-SOD-08 | WHO advises not to use non-sugar sweeteners for weight control in newly released guideline (Use of non-sugar sweeteners: WHO guideline, 2023) — news release World Health Organization | 2023 | Guideline / position statement | All people except those with pre-existing diabetes | WHO advises not to use sweeteners for weight control, because no long-term benefit was shown; possible harms may be confounded. | Conditional; observational evidence for harms | high | C-SOD-06 C-SOD-10 | |
| I-SOD-09 | Aspartame hazard and risk assessment results released (IARC and WHO/FAO JECFA, 14 July 2023) — news release WHO / IARC / JECFA | 2023 | Risk assessment | General population | IARC said 'possibly carcinogenic' on limited evidence; JECFA kept the safe daily limit of 40 mg/kg. | Limited evidence base | high | C-UPF-07 C-UPF-08 | |
| I-SUG-01 | Dietary sugars and body weight: systematic review and meta-analyses of randomised controlled trials and cohort studies. Te Morenga L et al. | 2012 | PMID 23321486 DOI 10.1136/bmj.e7492 | Meta-analysis | Adults and children | Eating more sugar increased body weight and eating less reduced it, through extra calories. | Heterogeneity in one analysis; Child trials low compliance | high | C-SOD-02 C-SUG-01 |
| I-SUG-02 | Dietary sugar consumption and health: umbrella review. Huang Y et al. | 2023 | PMID 37019448 DOI 10.1136/bmj-2022-071609 | Systematic review | Humans free of acute or chronic disease (children and adults) | Across 73 meta-analyses, high sugar intake was linked to 45 adverse outcomes; authors advise under 25 g/day of added sugar. | Evidence dominated by SSB (58/73 meta-analyses); few data on solid sugars, honey or sugars in foods; Mostly observational; nearly all outcomes low or very low quality; no class I evidence | high | C-SOD-01 C-SOD-03 C-SOD-05 C-SUG-01 |
| I-SUG-03 | Tolerable upper intake level for dietary sugars. EFSA NDA Panel et al. | 2022 | PMID 35251356 DOI 10.2903/j.efsa.2022.7074 | Risk assessment | General European population (children, adults, pregnant women) | EFSA found no safe intake level and advises keeping added and free sugars as low as possible. | RCT evidence on surrogate endpoints only, mostly at intakes >=10% of energy; Cohort analyses mostly isocaloric, which limits detection of energy-mediated effects | high | C-SOD-01 C-SUG-01 C-SUG-05 C-SRC-22 C-SOD-03 C-SOD-05 C-SOD-11 |
| I-SUG-04 | Systematic Review of the Effect on Caries of Sugars Intake: Ten-Year Update. Moores CJ et al. | 2022 | PMID 35302414 DOI 10.1177/00220345221082918 | Systematic review | Children and adults | Most studies link more sugar with more tooth decay; keeping sugar below 10% of energy lowers decay. | Vote counting; Mostly observational | moderate | C-SOD-11 C-SUG-01 |
| I-SUG-05 | WHO calls on countries to reduce sugars intake among adults and children (Guideline: Sugars intake for adults and children, 2015) — news release World Health Organization | 2015 | Guideline / position statement | Adults and children | WHO recommends keeping free sugars, including honey and juice sugars, below 10% of energy. | Conditional recommendation for <5% | high | C-SOD-02 C-SOD-11 C-SUG-01 C-SUG-02 C-SUG-05 C-SUG-06 | |
| I-SUG-06 | USDA FoodData Central: Honey (FDC 169640) and Sugars, granulated (FDC 169655), SR Legacy US Department of Agriculture | SR Legacy | Measurement / residue study | Not applicable | Honey is about 82% sugar and 17% water; white sugar is almost 100% sugar. | US samples; honey composition varies by origin | high | C-SUG-02 C-SUG-03 | |
| I-SUG-07 | Enteroendocrine hormonal response after the ingestion of cola beverages with sucrose and non-nutritive sweeteners in healthy adults: A randomized crossover trial. Galicia-Ayala C et al. | 2026 | PMID 41016269 DOI 10.1016/j.nut.2025.112938 | Randomised controlled trial | Healthy adults | Sugar-sweetened cola raised blood sugar and insulin most; diet cola and sparkling water did not. | Small; Acute only | moderate | C-SUG-04 C-SUG-07 |
| I-SUP-01 | Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. MRC Vitamin Study Research Group | 1991 | PMID 1677062 | Randomised controlled trial | Women with a previous NTD-affected pregnancy | Folic acid cut neural tube defects by 72%. | High-risk population (recurrence, not first occurrence); Folic acid dose not given in abstract | high | C-SUP-10 |
| I-SUP-02 | Effects and safety of periconceptional oral folate supplementation for preventing birth defects. De-Regil LM et al. | 2015 | PMID 26662928 DOI 10.1002/14651858.CD007950.pub3 | Meta-analysis | Women of reproductive age | Folic acid lowered neural tube defects by about 69%. | Only one trial low risk of bias; Author COI (NGO) | high | C-SUP-10 |
| I-SUP-03 | Folic Acid Supplementation to Prevent Neural Tube Defects: US Preventive Services Task Force Reaffirmation Recommendation Statement. US Preventive Services Task Force et al. | 2023 | PMID 37526713 DOI 10.1001/jama.2023.12876 | Guideline / position statement | Persons planning or able to become pregnant | All who could become pregnant should take 400–800 µg folic acid daily (grade A). | US context | high | C-SUP-10 |
| I-SUP-04 | Daily oral iron supplementation during pregnancy. Peña-Rosas JP et al. | 2015 | PMID 26198451 DOI 10.1002/14651858.CD004736.pub5 | Meta-analysis | Pregnant women | Daily iron reduced anaemia at term by 70%. | Heterogeneity; Low-quality evidence for main outcomes | high | C-SUP-09 C-SUP-10 |
| I-SUP-05 | Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline. Demay MB et al. | 2024 | PMID 38828931 DOI 10.1210/clinem/dgae290 | Guideline / position statement | General population by age group, pregnancy, prediabetes | Suggests vitamin D for children, pregnancy, people ≥75 and high-risk prediabetes. | Conditional recommendations; Errata | high | C-SUP-07 C-SUP-10 |
| I-SUP-06 | Calcium Intake and Cardiovascular Disease Risk: An Updated Systematic Review and Meta-analysis. Chung M et al. | 2016 | PMID 27776363 DOI 10.7326/M16-1165 | Meta-analysis | Generally healthy adults | No link between calcium intake within upper limits and heart disease. | CVD secondary outcomes; Funded by National Osteoporosis Foundation (potential interest) | moderate | C-SUP-04 |
| I-SUP-07 | Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50,000 individuals. Vollset SE et al. | 2013 | PMID 23352552 DOI 10.1016/S0140-6736(12)62001-7 | Meta-analysis | Participants of 10 cardiovascular-prevention trials (n=46,969; people with or at high risk of CVD, incl. one renal trial) and 3 colorectal-adenoma trials (n=2652); two-thirds men, mean age 64 | No significant effect of folic acid on cancer over about 5 years. | Only in-trial follow-up (~5 years); late effects not addressed; Search limited to PubMed and reference lists | high | C-SUP-06 |
| I-SUP-08 | Vitamin and Mineral Supplements for the Primary Prevention of Cardiovascular Disease and Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. O'Connor EA et al. | 2022 | PMID 35727272 DOI 10.1001/jama.2021.15650 | Systematic review | Adults without CVD, cancer or known deficiency | Supplements gave little or no protection; beta-carotene harmful; multivitamins slightly fewer cancers. | Excludes deficiency, pregnancy | high | C-SUP-01 C-SUP-02 C-SUP-03 C-SUP-06 |
| I-SUP-09 | Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. Bhatt DL et al. | 2019 | PMID 30415628 DOI 10.1056/NEJMoa1812792 | Randomised controlled trial | Statin-treated with CVD or diabetes + risk factors, TG 135–499 mg/dL | High-dose purified EPA reduced cardiovascular events by 25% in high-risk patients; more AF. | Industry-funded (Amarin); Placebo choice debated (not in abstract) | high | C-SUP-01 C-SUP-05 |
| I-SUP-10 | Liver injury from herbal and dietary supplements. Navarro VJ et al. | 2017 | PMID 27677775 DOI 10.1002/hep.28813 | Narrative review | US cases of hepatotoxicity | Mainly bodybuilding steroids, green tea extract and multi-ingredient products. | Narrative review without systematic search, selection or appraisal methods; Case-series/registry proportions only; no denominator of users, so no risk per user | moderate | C-SUP-08 |
| I-SUP-11 | International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. Kreider RB et al. | 2017 | PMID 28615996 DOI 10.1186/s12970-017-0173-z | Narrative review | Athletes and patient groups | Creatine reported safe up to 30 g/day for 5 years in healthy people. | Narrative; Authors with industry links (sports nutrition) | low | C-SUP-08 |
| I-SYS-01 | Health effects of dietary risks in 195 countries, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. GBD 2017 Diet Collaborators | 2019 | PMID 30954305 DOI 10.1016/S0140-6736(19)30041-8 | Risk assessment | Adults >=25 y, 195 countries | 11 million deaths in 2017 were attributed to dietary risks, mainly too much salt and too few whole grains and fruits. | Mostly observational RR inputs; Mixed dietary data sources | moderate | C-SYS-02 C-SYS-03 C-CAN-08 C-CAN-07 |
| I-SYS-02 | Global burden of 87 risk factors in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. GBD 2019 Risk Factors Collaborators | 2020 | PMID 33069327 DOI 10.1016/S0140-6736(20)30752-2 | Risk assessment | Global | In 2019, high blood pressure was linked to 10.8 million and tobacco to 8.7 million deaths. | Model-based; sparse and self-reported exposure data in many locations (authors); Uncertainty intervals do not reflect differences in evidence strength or risk of bias across risk-outcome pairs (authors) | moderate | C-SYS-02 C-SYS-03 C-SYS-07 |
| I-SYS-03 | Sleep duration and all-cause mortality: a systematic review and meta-analysis of prospective studies. Cappuccio FP et al. | 2010 | PMID 20469800 DOI 10.1093/sleep/33.5.585 | Meta-analysis | General populations | Short sleepers had 12% and long sleepers 30% higher death risk. | Self-reported sleep; Observational; reverse causation possible for long sleep | moderate | C-LIFE-04 C-LIFE-03 |
| I-SYS-04 | Dose-response associations between accelerometry measured physical activity and sedentary time and all cause mortality: systematic review and harmonised meta-analysis. Ekelund U et al. | 2019 | PMID 31434697 DOI 10.1136/bmj.l4570 | Meta-analysis | Middle-aged and older adults | The most active quarter had about a quarter of the death risk of the least active. | Observational; reverse causation | moderate | C-LIFE-03 C-LIFE-02 |
| I-SYS-05 | Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin Secretion: The DIETFITS Randomized Clinical Trial. Gardner CD et al. | 2018 | PMID 29466592 DOI 10.1001/jama.2018.0245 | Randomised controlled trial | Adults 18-50, BMI 28-40, no diabetes | After a year, weight loss was 5.3 kg vs 6.0 kg - no real difference. | Free-living adherence variation | high | C-LIFE-01 C-SRC-22 |
| I-SYS-06 | Isolated aerobic exercise and weight loss: a systematic review and meta-analysis of randomized controlled trials. Thorogood A et al. | 2011 | PMID 21787904 DOI 10.1016/j.amjmed.2011.02.037 | Meta-analysis | Overweight/obese adults | 6-12 months of aerobic exercise reduced weight by about 1.6-1.7 kg. | Few trials; Moderate exercise doses | moderate | C-LIFE-02 |
| I-SYS-07 | Constrained Total Energy Expenditure and Metabolic Adaptation to Physical Activity in Adult Humans. Pontzer H et al. | 2016 | PMID 26832439 DOI 10.1016/j.cub.2015.12.046 | Cross-sectional study | Adults aged 25-45 years (55% female) from five populations: Ghana, South Africa, Seychelles, Jamaica, United States. | Daily energy use levels off at higher activity. | Cross-sectional (authors' main limitation); between-person comparison cannot show within-person adaptation over time; Accelerometry is an imperfect measure of activity energy cost | moderate | C-LIFE-02 C-SRC-22 |
| I-SYS-08 | How Breath-Control Can Change Your Life: A Systematic Review on Psycho-Physiological Correlates of Slow Breathing. Zaccaro A et al. | 2018 | PMID 30245619 DOI 10.3389/fnhum.2018.00353 | Systematic review | Healthy subjects | Small studies show more relaxation and heart-rate variability. | Few small studies; Healthy subjects; no hard outcomes | low | C-LIFE-05 C-LIFE-03 |
| I-UPF-01 | Ultraprocessed or minimally processed diets following healthy dietary guidelines on weight and cardiometabolic health: a randomized, crossover trial. Dicken SJ et al. | 2025 | PMID 40760353 DOI 10.1038/s41591-025-03842-0 | Randomised controlled trial | Adults in England with BMI >=25 to <40 kg/m2 and habitual UPF intake >=50% of energy (mean 67.4%); mean age 43.2 years; 90.9% women; mostly NHS staff (e.g. 43.6% nurses); mean BMI 32.7 | Both diets led to weight loss, but about twice as much on minimally processed food. | Modest sample (50 ITT, 43 PP), 91% women, mostly health-care staff; Observed difference (1.01%) much smaller than the 2.7% the trial was powered for; P=0.024 with CI close to zero | high | C-UPF-02 |
| I-UPF-02 | Ultra-processed foods: how functional is the NOVA system? Braesco V et al. | 2022 | PMID 35314769 DOI 10.1038/s41430-022-01099-1 | Other | French food and nutrition specialists | Experts often disagreed when sorting foods into NOVA groups, though typical UPF were mostly classified alike. | French experts only; Authors with industry links | moderate | C-UPF-01 |
| I-UPF-03 | Ultra-processed foods in human health: a critical appraisal. Gibney MJ et al. | 2017 | PMID 28793996 DOI 10.3945/ajcn.117.160440 | Narrative review | Not applicable | Critics argue the UPF category is too broad and adds little beyond nutrients. | Opinion piece; predates RCTs (Hall 2019, Dicken 2025) | low | C-UPF-01 C-UPF-03 |
| I-UPF-04 | Food additive emulsifiers and risk of cardiovascular disease in the NutriNet-Santé cohort: prospective cohort study. Sellem L et al. | 2023 | PMID 37673430 DOI 10.1136/bmj-2023-076058 | Cohort study | French adults without prevalent CVD; mean age 43.1 (SD 14.5); 79.0% women; more educated and health-conscious than the general population | Higher intake of some emulsifiers, including CMC, was linked with slightly more heart disease. | Single volunteer cohort (79% women, health-conscious); limited generalisability (authors); Very small per-SD HRs (1.03-1.11); absolute risks not reported | moderate | C-UPF-06 C-UPF-11 |
| I-UPF-05 | Food additive emulsifiers and the risk of type 2 diabetes: analysis of data from the NutriNet-Santé prospective cohort study. Salame C et al. | 2024 | PMID 38663950 DOI 10.1016/S2213-8587(24)00086-X | Cohort study | Adults, 79% women | Several emulsifiers were linked with slightly higher diabetes risk. | Single cohort; Multiple testing | moderate | C-UPF-06 C-UPF-11 |
| I-UPF-06 | European Commission: Re-evaluation of food additives (incl. Q&A on titanium dioxide, Regulation (EU) 2022/63) and EU rules on food additives (Regulation (EC) No 1333/2008) European Commission (DG SANTE) | 2026 (accessed) | Guideline / position statement | Not applicable | EU additives need authorisation, are re-evaluated, and E171 was banned in 2022. | Regulatory status may change | high | C-UPF-09 C-UPF-11 | |
| I-VEG-01 | Carbohydrate quality and human health: a series of systematic reviews and meta-analyses. Reynolds A et al. | 2019 | PMID 30638909 DOI 10.1016/S0140-6736(18)31809-9 | Meta-analysis | Adults without chronic disease | High fibre intake is linked to 15-30% lower death and disease rates; trials show better weight, blood pressure and cholesterol. | Observational for hard endpoints | high | C-LEG-09 C-VEG-01 C-VEG-02 C-VEG-16 |
| I-VEG-02 | Fruit and vegetable intake and the risk of cardiovascular disease, total cancer and all-cause mortality-a systematic review and dose-response meta-analysis of prospective studies. Aune D et al. | 2017 | PMID 28338764 DOI 10.1093/ije/dyw319 | Meta-analysis | Adult general-population prospective cohorts: 44 from Europe, 26 USA, 20 Asia, 5 Australia; no cohorts from Africa, West Asia or Latin America | Each extra 200 g of fruit and vegetables a day was linked to 10% lower death risk; green leafy vegetables and salads were also protective. | Observational: residual confounding by healthy lifestyle and healthcare access possible (acknowledged); High heterogeneity for all-cause mortality and stroke | high | C-VEG-01 C-VEG-08 C-VEG-10 C-VEG-13 C-VEG-15 C-VEG-16 |
| I-VEG-03 | From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites. Koh A et al. | 2016 | PMID 27259147 DOI 10.1016/j.cell.2016.05.041 | Narrative review | Not applicable | Gut bacteria turn fibre into short-chain fatty acids that act as fuel and signals for the body. | Mechanistic; much animal data | moderate | C-LEG-09 C-VEG-01 C-VEG-02 |
| I-VEG-04 | Attribution of foodborne illnesses, hospitalizations, and deaths to food commodities by using outbreak data, United States, 1998-2008. Painter JA et al. | 2013 | PMID 23622497 DOI 10.3201/eid1903.111866 | Other | US outbreak data | Leafy vegetables caused the most outbreak illnesses (22%), poultry the most deaths. | Outbreak data may not represent sporadic illness | moderate | C-VEG-03 |
| I-VEG-05 | Oxalate intake and the risk for nephrolithiasis. Taylor EN, Curhan GC | 2007 | PMID 17538185 DOI 10.1681/ASN.2007020219 | Cohort study | US health professionals | Highest oxalate intake raised stone risk only modestly (about 20%) in some groups; authors: not a major risk factor. | FFQ oxalate estimates imprecise; Self-reported stones | high | C-VEG-05 |
| I-VEG-06 | DASH-style diet associates with reduced risk for kidney stones. Taylor EN et al. | 2009 | PMID 19679672 DOI 10.1681/ASN.2009030276 | Cohort study | US health professionals | People with a diet rich in vegetables, fruit and legumes had about 40-45% fewer kidney stones. | Observational | high | C-LEG-13 C-VEG-05 C-VEG-16 |
| I-VEG-07 | Contribution of Dietary Oxalate and Oxalate Precursors to Urinary Oxalate Excretion. Crivelli JJ et al. | 2020 | PMID 33379176 DOI 10.3390/nu13010062 | Narrative review | Not applicable | Dietary oxalate contributes to urinary oxalate, modified by gut bacteria and calcium. | Narrative; Industry consulting | moderate | C-VEG-05 |
| I-VEG-08 | Infant methemoglobinemia: the role of dietary nitrate in food and water. Greer FR, Shannon M | 2005 | PMID 16140723 DOI 10.1542/peds.2005-1497 | Guideline / position statement | Infants | Babies can be poisoned by nitrate mainly from well water or home-made vegetable foods; breastfed babies are not at risk. | Not systematic | moderate | C-VEG-07 |
| I-VEG-09 | Inorganic nitrate and beetroot juice supplementation reduces blood pressure in adults: a systematic review and meta-analysis. Siervo M et al. | 2013 | PMID 23596162 DOI 10.3945/jn.112.170233 | Meta-analysis | Adults | Nitrate from beetroot juice lowered systolic blood pressure by about 4 mm Hg in short trials. | Small, short (2 h - 15 d) | moderate | C-VEG-08 |
| I-VEG-10 | Poisoning by non-edible squash: retrospective series of 353 patients from French Poison Control Centers. Le Roux G et al. | 2018 | PMID 29323540 DOI 10.1080/15563650.2018.1424891 | Case series / case report | Exposures reported to French PCCs | 353 cases, usually mild, no deaths; discard bitter squash. | Passive reporting | moderate | C-VEG-09 |
| I-VEG-11 | Pesticide Residues in Vegetables and Fruits from Farmer Markets and Associated Dietary Risks. El-Sheikh EA et al. | 2022 | PMID 36432173 DOI 10.3390/molecules27228072 | Measurement / residue study | Composite vegetable and fruit samples (3 kg each from 3 sellers) from three farmers' markets | About 4 in 10 detected residues exceeded legal limits; some may pose risks. | Small sample (120 composites) from one governorate; not nationally representative; Exceedance expressed per residue finding, not per sample | moderate | C-VEG-14 |
| I-VEG-12 | Monitoring of pesticide residues in Egyptian fruits and vegetables during 1997. Dogheim SM et al. | 2002 | PMID 12456272 DOI 10.1080/02652030210157655 | Measurement / residue study | 2,318 domestic samples from 8 markets | Most samples had no detectable residues; 1.9% exceeded limits. | Old (1997) | moderate | C-VEG-14 |
| I-VEG-13 | Effect of increased potassium intake on cardiovascular risk factors and disease: systematic review and meta-analyses. Aburto NJ et al. | 2013 | PMID 23558164 DOI 10.1136/bmj.f1378 | Meta-analysis | Apparently healthy adults and children without impaired renal potassium handling; acutely ill, hospitalised and HIV-positive people excluded | More potassium lowered blood pressure in people with hypertension and was linked to 24% lower stroke risk. | Most RCTs tested supplements, so food-based evidence for vegetables is indirect; High heterogeneity in overall BP analysis (reduced by excluding outliers) | high | C-VEG-16 |
| I-VEG-14 | Commission Regulation (EU) 2023/915 on maximum levels for certain contaminants in food (Annex I, section 6.1 Nitrates) European Commission | 2023 | Guideline / position statement | Not applicable | The EU caps nitrate in spinach, lettuce and rocket and sets a much lower limit for baby food. | Not peer-reviewed study | moderate | C-VEG-07 C-VEG-08 | |
| I-VEG-15 | Pesticide residues in food: what's the situation in the EU? (EFSA news on the 2023 EU report) EFSA | 2025 | Risk assessment | Not applicable | Only about 2% of random EU samples exceeded legal limits; EFSA judged consumer risk low. | Not peer-reviewed study | moderate | C-VEG-13 | |
| I-VEG-16 | EFSA Task Force report on tracing seeds in relation to the STEC O104:H4 2011 outbreaks (press release 5 July 2011) EFSA | 2011 | Risk assessment | Not applicable | EFSA traced the outbreak to fenugreek seeds from Egypt used for sprouts. | Not peer-reviewed study | moderate | C-VEG-04 | |
| I-VEG-17 | Vorsicht beim Verzehr von bitteren Zucchini (Mitteilung Nr. 027/2015) BfR (German Federal Institute for Risk Assessment) | 2015 | Guideline / position statement | Not applicable | Bitter zucchini should be discarded; cultivated zucchini is bred to lack the toxin; poisonings are rare and usually mild. | Not peer-reviewed study | moderate | C-VEG-09 | |
| I-WHT-01 | Carbohydrate quality and human health: a series of systematic reviews and meta-analyses. Reynolds A et al. | 2019 | PMID 30638909 DOI 10.1016/S0140-6736(18)31809-9 | Meta-analysis | Adults without chronic disease | High fibre/whole grain intake linked to 15-30% lower risk of several diseases; GI/GL evidence weaker. | Observational core | high | C-WHT-04 C-WHT-05 C-WHT-03 C-GRN-08 |
| I-WHT-02 | Refined grain intake and cardiovascular disease: Meta-analyses of prospective cohort studies. Gaesser GA | 2024 | PMID 36075506 DOI 10.1016/j.tcm.2022.08.002 | Meta-analysis | Cohort participants | Pooled cohorts showed no clear link between refined grains and heart disease. | Single author; Likely industry links | low | C-WHT-03 C-WHT-04 C-GRN-05 |
| I-WHT-03 | Dietary intake and the risk of gastro-oesophageal reflux disease: a cross sectional study in volunteers. El-Serag HB et al. | 2005 | PMID 15591498 DOI 10.1136/gut.2004.040337 | Cross-sectional study | Employees of Houston VAMC | More fibre linked to fewer reflux symptoms; more fat to more symptoms. | Small, cross-sectional; Volunteers | low | C-WHT-01 C-WHT-08 |
| I-WHT-04 | Global Prevalence of Celiac Disease: Systematic Review and Meta-analysis. Singh P et al. | 2018 | PMID 29551598 DOI 10.1016/j.cgh.2017.06.037 | Meta-analysis | General populations | About 1 in 70 have coeliac antibodies and about 1 in 140 biopsy-confirmed disease worldwide. | Heterogeneous sources | moderate | C-WHT-02 C-GRN-01 C-GRN-03 |
| I-WHT-05 | Food groups and the likelihood of non-alcoholic fatty liver disease: a systematic review and meta-analysis. He K et al. | 2020 | PMID 32138796 DOI 10.1017/S0007114520000914 | Meta-analysis | Observational study participants | Refined grains were not linked to fatty liver; soft drinks and red meat were. | No prospective studies | low | C-WHT-07 |
| I-WHT-06 | Associations between types and sources of dietary carbohydrates and liver fat: a UK Biobank study. Orliacq J et al. | 2023 | PMID 37968623 DOI 10.1186/s12916-023-03135-8 | Cohort study | UK Biobank adults without diabetes/liver/CVD | Refined-grain starch linked to liver fat in one analysis but not on MRI; free sugars linked on MRI. | Diet measured by 24-h recall; Inconsistent between analyses | moderate | C-WHT-07 |
| I-WHT-07 | Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study. Lebwohl B et al. | 2017 | PMID 28465308 DOI 10.1136/bmj.j1892 | Cohort study | 64,714 female nurses (NHS) and 45,303 male health professionals (HPFS) without CHD, stroke, CABG, cancer or self-reported coeliac disease, with plausible energy intake on the 1986 FFQ | Eating more gluten was not linked to more heart disease over 26 years. | Gluten estimated indirectly from FFQ with a fixed 75% protein conversion; not validated directly; Could not identify people following gluten-free diets or eating gluten-free substitutes; undiagnosed coeliac disease not excluded | high | C-WHT-09 C-GRN-01 |
Sources of the case study EU/Germany – Egypt
- Regulation (EC) No 178/2002 laying down the general principles and requirements of food law, establishing EFSA (General Food Law); consolidated version 01.01.2026 (CELEX 02002R0178-20260101) – European Parliament and Council, 2002. https://eur-lex.europa.eu/eli/reg/2002/178/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force (Cellar flag in_force=true). Art. 14(1): 'Food shall not be placed on the market if it is unsafe.' Establishes EFSA and the rapid alert system (RASFF). - Regulation (EU) 2017/625 on official controls (Official Controls Regulation); consolidated version 05.01.2025 – European Parliament and Council, 2017. https://eur-lex.europa.eu/eli/reg/2017/625/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Governs official controls on food and feed in Member States and on entry of goods from third countries; legal basis for third-country lists (Art. 127) and increased import controls. - Regulation (EC) No 396/2005 on maximum residue levels of pesticides in or on food and feed – European Parliament and Council, 2005. https://eur-lex.europa.eu/eli/reg/2005/396/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Art. 18(1)(b): default MRL of 0,01 mg/kg for products for which no specific MRL is set; recital: MRLs set at the lower level of analytical determination where uses are not authorised. - Commission Regulation (EU) No 37/2010 on pharmacologically active substances and their classification regarding maximum residue limits in foodstuffs of animal origin; consolidated 16.08.2026 – European Commission, 2010. https://eur-lex.europa.eu/eli/reg/2010/37/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Lists allowed substances with MRLs and prohibited substances (Table 2) for food-producing animals. - Regulation (EU) 2019/6 on veterinary medicinal products; consolidated 28.01.2022 – European Parliament and Council, 2019. https://eur-lex.europa.eu/eli/reg/2019/6/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Art. 107(1): antimicrobials 'shall not be applied routinely nor used to compensate for poor hygiene, inadequate animal husbandry'; Art. 107(2): not to be used 'for the purpose of promoting growth nor to increase yield'; Art. 107(3): prophylaxis only in exceptional cases, antibiotic prophylaxis limited to an individual animal; Art. 107(4): metaphylaxis only when risk of spread is high and no appropriate alternatives exist. Art. 105: a veterinary prescription for antimicrobials 'shall be valid for five days from the date of its issue'. Art. 118(1): growth-promotion and reserved-antimicrobial prohibitions extended to imports. - Council Directive 96/22/EC concerning the prohibition on the use in stockfarming of certain substances having a hormonal or thyrostatic action and of beta-agonists; consolidated 18.12.2008 – Council of the EU, 1996. https://eur-lex.europa.eu/eli/dir/1996/22/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Art. 3: Member States prohibit administering listed substances to farm or aquaculture animals. Art. 4/5 allow narrowly defined therapeutic/zootechnical veterinary use by a veterinarian; Art. 4 text: 'young fish may be treated for the first three months for the purpose of sex inversion with veterinary medicinal products that have an androgenous action' (authorised products only). - Commission Regulation (EU) 2023/915 on maximum levels for certain contaminants in food (repealing Reg. 1881/2006); consolidated 19.08.2026 – European Commission, 2023. https://eur-lex.europa.eu/eli/reg/2023/915/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force (1881/2006 not in force since 2023-05-24). Values as read in Annex I: aflatoxin M1 in raw/heat-treated milk 0,050 µg/kg; groundnuts for direct consumption B1 2,0 / sum 4,0 µg/kg (8,0/15,0 before sorting); eggs (except goose) sum dioxins 2,5 pg WHO-TEQ/g fat, dioxins+dl-PCBs 5,0 pg/g fat, ndl-PCBs 40 ng/g fat; PFAS in eggs PFOS 1,0, PFOA 0,30, PFNA 0,70, PFHxS 0,30, sum of 4 PFAS 1,7 µg/kg; lead in fish muscle 0,30 mg/kg; cadmium in fish muscle (most species) 0,050 mg/kg; mercury in fish muscle (most species) 0,50 mg/kg; nitrate in fresh spinach 3 500 mg/kg, fresh lettuce 2 000–5 000 mg/kg depending on type/season/cover, rucola up to 7 000 mg/kg. - Commission Regulation (EC) No 2073/2005 on microbiological criteria for foodstuffs; consolidated 01.07.2026 – European Commission, 2005. https://eur-lex.europa.eu/eli/reg/2005/2073/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Food safety criterion 1.28: fresh poultry meat – Salmonella Typhimurium and S. Enteritidis 'Not detected in 25 g' (n=5, c=0). Process hygiene criteria for Salmonella/Campylobacter on poultry carcases (neck skin). Criteria for egg products and RTE foods containing raw egg. - Regulation (EC) No 2160/2003 on the control of salmonella and other specified food-borne zoonotic agents; consolidated 21.04.2021 – European Parliament and Council, 2003. https://eur-lex.europa.eu/eli/reg/2003/2160/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Obliges Member States to run national Salmonella control programmes in poultry populations with Union reduction targets. - Commission Regulation (EU) No 517/2011 – Union target for reduction of Salmonella serotypes in laying hens; and Commission Regulation (EU) No 200/2012 – Union target for S. Enteritidis and S. Typhimurium in broiler flocks – European Commission, 2011/2012. https://eur-lex.europa.eu/eli/reg/2011/517/oj ; https://eur-lex.europa.eu/eli/reg/2012/200/oj (Type: regulation; verified: yes; accessed 2026-10-25)
Both in force. Laying hens: reduction to '2 % or less of positive flocks of adult laying hens' (target serovars S. Enteritidis/Typhimurium). Broilers: maximum percentage of flocks positive for S. Enteritidis/Typhimurium 'equal to 1% or less'. - Regulation (EU) No 1169/2011 on the provision of food information to consumers; consolidated 01.04.2025 – European Parliament and Council, 2011. https://eur-lex.europa.eu/eli/reg/2011/1169/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Mandatory food information (ingredients, allergens, nutrition declaration, origin rules). EFSA's 2024 pesticide report cites it as part of the obligation to report country of origin. - Directive (EU) 2020/2184 on the quality of water intended for human consumption (recast) – European Parliament and Council, 2020. https://eur-lex.europa.eu/eli/dir/2020/2184/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. EU drinking water quality parameters, risk-based approach; transposed in Germany by TrinkwV 2023. - Trinkwasserverordnung (TrinkwV) vom 20. Juni 2023 (BGBl. 2023 I Nr. 159) – Bundesministerium für Gesundheit (Germany), 2023. https://www.gesetze-im-internet.de/trinkwv_2023/BJNR09F0B0023.html (Type: regulation; verified: yes; accessed 2026-10-25)
Transposes Directive (EU) 2020/2184. Values read: nitrate 50 mg/l (with nitrate/50 + nitrite/3 ≤ 1); pesticides 0,00010 mg/l per substance; 'Summe PFAS-20' 0,00010 mg/l applicable from 12 January 2026; 'Summe PFAS-4' 0,000020 mg/l applicable from 12 January 2028. - Commission Implementing Regulation (EU) 2019/1793 on the temporary increase of official controls and emergency measures governing the entry of certain goods from certain third countries; consolidated text 30.06.2026 – European Commission, 2019. https://eur-lex.europa.eu/eli/reg_impl/2019/1793/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Annex I (increased identity/physical checks) entries for Egypt (EG), hazard 'pesticide residues': sweet and other Capsicum peppers 30 %; oranges 10 %; sugar apple 30 %; vine leaves 50 %; mango 20 %; strawberries (fresh, chilled or frozen) 20 %. Annex II (special conditions incl. official certificate): Egypt groundnuts (peanuts), peanut butter and preparations, groundnut oilcake/flours – aflatoxins, 30 %. - Regulation (EC) No 1831/2003 on additives for use in animal nutrition; consolidated 27.03.2021 – European Parliament and Council, 2003. https://eur-lex.europa.eu/eli/reg/2003/1831/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. 'Antibiotics, other than coccidiostats or histomonostats, shall not be authorised as feed additives'; transitional Art. 11(2): such antibiotics 'may be marketed and used as feed additives only until 31 December 2005; as from 1 January 2006, those substances shall be deleted from the Register'. - Commission Delegated Regulation (EU) 2023/905 on the application of the prohibition of use of certain antimicrobial medicinal products in animals or products of animal origin exported from third countries into the Union – European Commission, 2023. https://eur-lex.europa.eu/eli/reg_del/2023/905/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Art. 3: animals/products exported to the EU shall not have been administered antimicrobials for growth promotion/yield increase, nor antimicrobials reserved for humans (Implementing Reg. 2022/1255). Conditions apply 24 months after the implementing list act; per Implementing Reg. 2026/1189 this is 3 September 2026. - Commission Implementing Regulation (EU) 2026/1189 amending Implementing Regulation (EU) 2021/405 as regards the restrictions on the use of certain antimicrobial medicinal products (repealing Implementing Reg. 2024/2598) – European Commission, 2026. https://eur-lex.europa.eu/eli/reg_impl/2026/1189/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force; Art. 1 applies from 3 September 2026. New Annex XVIa of 2021/405 lists third countries with guarantees of compliance with Art. 3 of 2023/905. Egypt's row has an 'X' only in the column 'Casings' (no entry for bovine, poultry, aquaculture, milk, eggs, honey). Recital 17: Brazil's entries for poultry, aquaculture etc. deleted for lack of guarantees. - Commission Implementing Regulation (EU) 2021/405 laying down the lists of third countries authorised for entry into the Union of certain animals and goods intended for human consumption; consolidated 03.09.2026 – European Commission, 2021. https://eur-lex.europa.eu/eli/reg_impl/2021/405/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Annex -I (approved residue control plans): Egypt marked 'X' only for 'Casings' (no approved plan for bovine, poultry, aquaculture, milk, eggs, honey). Annex IX (fishery products): Egypt 'Only wild catch'. Annex XI: Egypt 'Only frogs' legs'. - Council Directive 1999/74/EC laying down minimum standards for the protection of laying hens; and Commission Delegated Regulation (EU) 2023/2465 on marketing standards for eggs – Council of the EU / European Commission, 1999/2023. https://eur-lex.europa.eu/eli/dir/1999/74/oj ; https://eur-lex.europa.eu/eli/reg_del/2023/2465/oj (Type: regulation; verified: yes; accessed 2026-10-25)
Both in force. 1999/74: rearing in unenriched cages 'prohibited with effect from 1 January 2012'. 2023/2465: eggs marked with a producer code identifying farming method and production site; meaning of the producer code must be explained on or inside the pack. - The 2024 European Union report on pesticide residues in food – EFSA, 2026. https://pubmed.ncbi.nlm.nih.gov/42095190/ (Type: monitoring_data; verified: yes; accessed 2026-10-25)
Abstract: EU-coordinated programme 9842 samples, 1.2 % non-compliant; national programmes 86,449 samples, 1.8 % non-compliant; increased import control programme 39,433 samples, 3.6 % non-compliant; 'the estimated dietary risk was found to be low for most of the EU subpopulation groups'. Full text (Europe PMC): EU MACP 97.6 % within legal limits; 46.6 % domestic, 29.3 % other reporting countries, 20.1 % third countries; a pesticide quantified in 14.1 % of 759 samples 'Most of the quantifications were in oranges ... coming from Egypt' (0.01–0.13 mg/kg, none non-compliant); imidacloprid findings in 'pomegranate from Peru and Egypt, potato from Egypt'. For authorised uses non-compliance shares were similar for EU and third-country origin ('very similar independently of the country of origin'). - The European Union One Health 2024 Zoonoses Report – EFSA and ECDC, 2025. https://pubmed.ncbi.nlm.nih.gov/41377167/ (Type: monitoring_data; verified: yes; accessed 2026-10-25)
Full text (Europe PMC PMC12686834): adult laying-hen flocks 2024 EU Salmonella flock prevalence 4.0 % (3.9 % 2023), target serovars 1.6 %; broiler flocks Salmonella 4.3 %, target serovars 0.29 %; 'Fourteen MSs and the United Kingdom (Northern Ireland) met all targets'; Salmonella in 'eggs and egg products' the agent/food pair of most concern; official FSC verification samples: 4.9 % positive at manufacturing vs 2.3 % at distribution. Travel-associated salmonellosis acquired outside the EU (n=5473): Türkiye 25.5 %, Egypt 11.5 % (628/5473). - EFSA news 'Veterinary drug residues in food: what's the latest in the EU?' (report on 2024 monitoring data; technical report doi 10.2903/sp.efsa.2026.EN-9913) – EFSA, 2026. https://www.efsa.europa.eu/en/news/veterinary-drug-residues-food-whats-latest-eu (Type: monitoring_data; verified: yes; accessed 2026-10-25)
News of 10 February 2026: 2024 data from EU MS plus Iceland and Norway; '0.13% (629 of 493,664 samples)' non-compliant (0.11 % previous year); risk-based production plan 0.16 %, randomised surveillance plan 0.22 %, risk-based third-country import plan 0.2 %. - European Sales and Use of Antimicrobials for Veterinary Medicine (ESUAvet) – Annual surveillance report for 2024 (EMA/CVMP/ESUAVET/376993/2025) – European Medicines Agency, 2025. https://www.ema.europa.eu/en/documents/report/european-sales-use-antimicrobials-veterinary-medicine-annual-surveillance-report-2024_en.pdf (Type: monitoring_data; verified: yes; accessed 2026-10-25)
2018 baseline 118.3 mg/PCU, 2030 target 59.2 mg/PCU (50 % reduction, Farm to Fork). 'In 2024, aggregated sales in the EU were 89.6 mg/PCU, a reduction of 24.3% compared to 2018.' - BVL Pressemitteilung 'Antibiotikaabgabe in der Tiermedizin weiter auf niedrigem Niveau' (data year 2025) – Bundesamt für Verbraucherschutz und Lebensmittelsicherheit (BVL), 2026. https://www.bvl.bund.de/SharedDocs/Pressemitteilungen/05_tierarzneimittel/2026/PM_Antibiotika-Abgabemengen.html (Type: monitoring_data; verified: yes; accessed 2026-10-25)
Dated 06.10.2026: 562 t antibiotics dispensed in veterinary medicine in Germany in 2025 (−0.3 t vs 2024); 67 % lower than 2011 (1,706 t); colistin 31 t (2024) → 26 t (2025); fluoroquinolones +~18 % to 6.3 t. - BfR Stellungnahme 031/2024: Ergebnisse des Nationalen Rückstandskontrollplans und des Einfuhrüberwachungsplans 2022 – Bundesinstitut für Risikobewertung (BfR), 2024. https://bfr.bund.de/cm/343/ergebnisse-des-nationalen-rueckstandskontrollplans-und-des-einfuhrueberwachungsplans-2022.pdf (Type: official_report; verified: yes; accessed 2026-10-25)
NRKP 2022: 53.267 Planproben, 191 (0,36 %) non-compliant (2021: 0,32 %); EÜP 2022: 1.055 import samples, 2 (0,19 %) non-compliant. Group A (anabolic/unauthorised substances): 38.585 samples, 1 non-compliant. Dioxins/PCBs: 'nur eine von etwa 180 Eierproben' exceeded maximum levels. BfR: health impairment 'nicht zu erwarten' for most samples; some antibacterial residues could select less-susceptible bacteria. - Nationale Berichterstattung 'Pflanzenschutzmittelrückstände in Lebensmitteln' – Zusammenfassung der Ergebnisse des Jahres 2024 – BVL, 2026. https://www.bvl.bund.de/SharedDocs/Downloads/01_Lebensmittel/nbpsm/00_Berichte/NBPSMR_2024.pdf?__blob=publicationFile&v=2 (Type: monitoring_data; verified: yes; accessed 2026-10-25)
Dated 15 January 2026: 16.423 samples. Origin: 6.668 Germany, 4.368 other EU, 2.694 third countries, 2.629 unknown. MRL exceedances (surveillance sampling): Germany 1,0 %, other EU 1,5 %, third countries 6,7 % (2023: 8,5 %); Beanstandungen 0,4 % / 0,4 % / 4,3 %. No quantifiable residues: Germany 57,8 %, other EU 38,3 %, third countries 40,1 %. Egypt-specific: sweet potatoes from Egypt Beanstandungsquote 10,9 % (5 of 46 samples, mainly mepiquat); one mango sample from Egypt objected for four substances; vine leaves from Egypt listed as frequently conspicuous (hence in Reg. 2019/1793). - Bericht des BMG und des UBA an die Verbraucherinnen und Verbraucher über die Qualität von Wasser für den menschlichen Gebrauch (Trinkwasser) in Deutschland (2020–2022), Reihe Umwelt & Gesundheit 03/2025 – Bundesministerium für Gesundheit / Umweltbundesamt, 2025. https://www.umweltbundesamt.de/publikationen/bericht-des-bundesministeriums-fuer-gesundheit-des-5 (Type: official_report; verified: yes; accessed 2026-10-25)
Period 1.1.2020–31.12.2022; 2 507 large supply areas serving 74.1 million people (88.6 %) in 2022; 'Bei den meisten mikrobiologischen und chemischen Qualitätsparametern erfüllten über 99 % der untersuchten Proben' the TrinkwV requirements. - Risk to human health related to the presence of perfluoroalkyl substances in food – EFSA CONTAM Panel, 2020. https://pubmed.ncbi.nlm.nih.gov/32994824/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
TWI 4.4 ng/kg bw per week for sum of PFOA, PFNA, PFHxS, PFOS; 'Fish meat', 'Fruit and fruit products' and 'Eggs and egg products' contributed most to exposure; 'parts of the European population exceed this TWI, which is of concern.' - Risk for animal and human health related to the presence of dioxins and dioxin-like PCBs in feed and food – EFSA CONTAM Panel, 2018. https://pubmed.ncbi.nlm.nih.gov/32625737/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
TWI 2 pg TEQ/kg bw/week; mean and P95 intake of adolescents/adults/elderly 2.1–10.5 and 5.3–30.4 pg TEQ/kg bw/week, 'implying a considerable exceedance of the TWI'; PCDD/Fs and DL-PCBs transfer to milk and eggs. - National Food Safety Authority (NFSA) of Egypt – official website (Law No. 1 of 2017) – National Food Safety Authority, Egypt, 2017. https://www.nfsa.gov.eg/ (Type: official_report; verified: yes; accessed 2026-10-25)
Law No. 1 of 2017 establishing NFSA published in the Official Gazette on 10 January 2017; NFSA created as a single body because more than 17 bodies under several ministries previously shared food-safety duties. - NFSA legislation index (القوانين والتشريعات والقرارات الغذائية) – National Food Safety Authority, Egypt, 2017-2023. https://nfsa.gov.eg/ar-eg/SitePages/Index/%D8%A7%D9%84%D9%82%D9%88%D8%A7%D9%86%D9%8A%D9%86%20%D9%88%D8%A7%D9%84%D8%AA%D8%B4%D8%B1%D9%8A%D8%B9%D8%A7%D8%AA%20%D9%88%D8%A7%D9%84%D9%82%D8%B1%D8%A7%D8%B1%D8%A7%D8%AA%20%D8%A7%D9%84%D8%BA%D8%B0%D8%A7%D8%A6%D9%8A%D8%A92 (Type: regulation; verified: yes; accessed 2026-10-25)
Lists e.g.: Executive regulations (Cabinet Decision 412/2019); Decision 13/2020 binding technical rules on maximum limits of veterinary drug residues in food; Decision 6/2021 on permitted pesticide residues; Decision 6/2022 on maximum limits of chemical contaminants; Decision 1/2021 microbiological criteria; Decision 4/2020 food additives; Decision 11/2020 food-safety requirements in food establishments; Decision 16/2022 traceability (amended 3/2023); Decision 1/2022 technical requirements for fish exports to the EU; Decision 7/2020 risk-based import control. - DG SANTE audit CT-2025-0205, Egypt, October 2025: Pesticides (controls of pesticide residues in food of plant origin intended for export to the EU); published 26-02-2026 – European Commission, DG SANTE, 2026. https://ec.europa.eu/food/audits-analysis/audit-report/details/4976 (Type: audit_report; verified: yes; accessed 2026-10-25)
Read in full (PDF download 17197). Scope: oranges, sugar apples, peppers, vine leaves, strawberries. 2023 EFSA data: Egypt-origin food non-compliance 4.61 %, MRL exceedance 8.14 %, vs 3.4 % and 6.2 % average for non-EU exporters. Orange non-compliance at EU import fell from 15 % (2nd half 2022) to 1.41 % (1st half 2025); peppers ~8 % (4.59–13.16 %); all sampled vine-leaf consignments rejected. 3 408 PPP formulations on 296 active substances registered in Egypt; 118 substances in Egyptian-registered PPPs not approved in the EU; chlorpyrifos banned in Egypt June 2022; Egyptian MRL list referenced primarily to Codex, some higher than EU. National monitoring 'shows relatively low non-compliance rates ... But since the benchmarks for compliance are different, the results are not fully comparable.' Export controls (registration, traceability, pre-export sampling) are additional programmes for the export chain; frozen/processed products can come from non-registered growers; 'From January 2026 the mandate will include the domestic market' (NFSA). 'the potential trade of illegal PPPs is still a matter of concern'. - DG SANTE audit 2024-8055, Egypt, November 2024: Food of non-animal origin intended for export to the EU (microbiological risks); published 22-04-2025 – European Commission, DG SANTE, 2025. https://ec.europa.eu/food/audits-analysis/audit-report/details/4863 (Type: audit_report; verified: yes; accessed 2026-10-25)
Executive summary: official control system for export FNAO covers farms, processors, exporters; GAP inspection/certification for nine main commodities incl. strawberries; for herbs and spices farm controls generally limited to random inspections; post-harvest system 'well-established, comprehensive and efficient'; 'The report contains no recommendations to Egypt.' - DG SANTE audit 2024-8106, Egypt, May–June 2024: Fishery products intended for export to the EU; published 23-09-2024 – European Commission, DG SANTE, 2024. https://ec.europa.eu/food/audits-analysis/audit-report/details/4800 (Type: audit_report; verified: yes; accessed 2026-10-25)
After the 2021 audit Egypt withdrew all establishments from the EU list and suspended certification; 'no exports of fishery products have taken place' since 2021; no RASFF notifications on Egyptian fishery products since then. 2023 sampling plan: heavy metals 22 samples (all compliant), dioxins/PCBs 14 samples; PFAS 'not subject to control' at the time (not in line with Reg. 2019/627); histamine reference method not used. Deficiencies weaken guarantees. - DG SANTE audit 2022-7391, Egypt, September 2022: Contaminants (aflatoxin in peanuts for export to the EU); published 17-02-2023 – European Commission, DG SANTE, 2023. https://ec.europa.eu/food/audits-analysis/audit-report/details/4574 (Type: audit_report; verified: yes; accessed 2026-10-25)
Egypt has the necessary legal/organisational framework; accredited laboratories perform well; but official controls at primary producers do not verify GAP for aflatoxin prevention; packing houses allowed to export even if not complying with all certificate conditions ('raises concerns about the reliability of the certification system'); increase in RASFF notifications possibly related to strongly increased export volume; a small number of operators account for most rejections. - DG SANTE audit 2021-7328, Egypt, May–June 2021 (remote): Fishery products; published 04-01-2022 – European Commission, DG SANTE, 2022. https://ec.europa.eu/food/audits-analysis/audit-report/details/4439 (Type: audit_report; verified: yes; accessed 2026-10-25)
Remote audit; 'important shortcomings in virtually all of the areas relevant to this audit' (legislation, written procedures, training, controls of primary production, landing sites, additives). - DG SANTE audit 2019-6697, Egypt, Jan–Feb 2019: Microbiological contamination in food of non-animal origin; published 03-07-2019 – European Commission, DG SANTE, 2019. https://ec.europa.eu/food/audits-analysis/audit-report/details/4148 (Type: audit_report; verified: yes; accessed 2026-10-25)
Control system for microbiological risks in export FNAO 'in a phase of transition and reforms'; hygiene practices at visited farms/exporters in line with EU requirements; background cites the 2011 STEC O104:H4 outbreak in Germany (about 4,000 ill, more than 56 deaths). - DG SANTE audit 2011-6265, Egypt, August 2011: trace back the source of infection of the recent E. coli O104:H4 strain outbreaks in the EU (detail page) – European Commission, DG SANTE, 2011. https://ec.europa.eu/food/audits-analysis/audit-report/details/2769 (Type: audit_report; verified: yes; accessed 2026-10-25)
Detail page confirms an EU audit in Egypt in August 2011 to trace back the source of the O104:H4 outbreaks (published 26-10-2011). - RASFF Window – public notification search (consolidated), queried for notifications with 'Egypt' in the subject and origin country EG, validation years 2023–2025 – European Commission (RASFF), 2026. https://webgate.ec.europa.eu/rasff-window/screen/search (Type: database; verified: yes; accessed 2026-10-25)
Own query of the public backend (POST .../rasff-window/backend/public/notification/search/consolidated/) on 2026-10-25: 2023: 113 notifications; 2024: 153; 2025: 119. Keyword-based classification of subjects (approximate): pesticide residues 73 / 70 / 82; aflatoxins 15 / 47 / 14; microbiological 11 / 13 / 4; other (additives, pyrrolizidine alkaloids, foreign bodies, certificates etc.) 14 / 23 / 19. Product categories 2023–2025: fruits and vegetables 217, nuts/nut products/seeds 86, herbs and spices 41; only one animal-product notification (lead in salted beef casings, 2023); none for poultry, eggs, milk or fish. - Pesticide Residues in Egyptian Strawberries Inspected at the EU Border (2021-2024) – Sikorska-Zimny KM et al., 2025. https://pubmed.ncbi.nlm.nih.gov/41471804/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Egyptian strawberries inspected at the Polish border: detection rates rose from 63 % (2022) to over 90 % (2023–2024); some samples with no residues each year; eleven MRL exceedances; up to eleven pesticides in a single sample. - Pesticide Residues in Vegetables and Fruits from Farmer Markets and Associated Dietary Risks – El-Sheikh EA et al., 2022. https://pubmed.ncbi.nlm.nih.gov/36432173/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Farmers' markets, Sharkia Governorate, Egypt; LC-MS/MS and GC-MS/MS; 40 pesticides detected; 35 (40.7 %) of 86 residues detected in vegetables and 35 (38.9 %) of 90 residues in fruits exceeded MRLs; acute/chronic risk flagged for lambda-cyhalothrin (spinach), fipronil (zucchini), dimethoate (kaki), omethoate (strawberry). - Assessment of antibiotic residues in chicken meat – Kamouh HM et al., 2024. https://pubmed.ncbi.nlm.nih.gov/38633178/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
100 chicken meat samples (breast, thigh, gizzard, liver; 25 each) retailed in Egypt; microbial inhibition assay + HPLC; 23 % positive for oxytetracycline, 21 % gentamicin, 17 % ciprofloxacin; boiling 30 min reduced residues by 88.2 %, 95.2 %, 31.3 %. - Health risk assessment of enrofloxacin, oxytetracycline, and sulfadimidine residues in broiler chicken carcasses marketed in Mit Ghamr, Egypt – Noah SM et al., 2026. https://pubmed.ncbi.nlm.nih.gov/42527435/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
180 tissue samples (60 breast, 60 thigh, 60 liver) from poultry shops; HPLC; detected enrofloxacin 51.67 %, oxytetracycline 71.67 %, sulfadimidine 16.67 %; of positives 54.84 %, 55.81 %, 70 % exceeded MRLs; hazard quotients 0.0002–0.050 – 'no significant health risk for either adults or children'. - Antibiotic residues correlate with antibiotic resistance of Salmonella typhimurium isolated from edible chicken meat – Ali HR et al., 2025. https://pubmed.ncbi.nlm.nih.gov/40307359/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Chilled chicken meat, Fayoum province: 22.2 % of meat/liver contaminated with S. Typhimurium, all isolates drug-resistant; residues of tylosin, chloramphenicol, oxytetracycline (and 4-epi-OTC) detected; isolates from samples above MRL resistant to the same antibiotic. - Antimicrobial use in animal farms in Egypt: rates, patterns, and determinants – ElSayed N et al., 2025. https://pubmed.ncbi.nlm.nih.gov/39828782/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Survey, 111 of 150 farms (74 %) in 15 governorates: all used antimicrobials; 65 % reported non-therapeutic use; penicillins 81 %, macrolides 78 %, tetracyclines 72 %; half used colistin, 55 % of those non-therapeutically; non-therapeutic use had no impact on feed conversion ratio; authors: 'Egyptian guidelines for AMU in livestock are urgently needed'. - Hormonal residues in chicken and cattle meat: A risk threat the present and future consumer health – Kamaly HF et al., 2023. https://pubmed.ncbi.nlm.nih.gov/37956705/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
92 chicken and 56 cattle meat samples, Assiut City 2022; ELISA for estradiol, progesterone, testosterone; authors report estimated intake of estradiol exceeding ADI in nearly all samples and HI >1; 'in Egypt ... no safe limits have been set till now'. - Antimicrobial Resistance of Salmonella enteritidis and Salmonella typhimurium Isolated from Laying Hens, Table Eggs, and Humans ... – Abou Elez RMM et al., 2021. https://pubmed.ncbi.nlm.nih.gov/34944331/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Sharkia Governorate: Salmonella in 19.3 % of tested samples; laying hens 33.1 %; S. Enteritidis 5.8 %, S. Typhimurium 2.8 %; MDR 83.8 % of isolates. - Prevalence of Non-typhoidal Salmonellae in the Retail Chicken Meat in Alexandria, Egypt – Barac D et al., 2024. https://pubmed.ncbi.nlm.nih.gov/39678989/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
60 raw chicken carcass samples from six markets: 33.3 % Salmonella; liver and gizzard 60 %; one supermarket showed no Salmonella; authors attribute contamination largely to market handling. - Ecological prevalence, genetic diversity, and multidrug resistance of Salmonella enteritidis recovered from broiler and layer chicken farms – Elsayed MM et al., 2024. https://pubmed.ncbi.nlm.nih.gov/38215504/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Salmonella in 20 (17 %) of 117 samples from small-scale broiler flocks; isolates MDR. - A Public Health Insight into Salmonella in Poultry in Africa: A Review of the Past Decade: 2010-2020 – Ramtahal MA et al., 2022. https://pubmed.ncbi.nlm.nih.gov/35696336/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
PRISMA-guided narrative review; MDR Salmonella prevalence ranged from 12.1 % (Zimbabwe) to 100 % in Egypt, Ethiopia, Nigeria, Senegal, South Africa; AMU described in only 11.5 % of studies. - Dietary intake of dioxins and dioxin-like PCBs, due to the consumption of dairy products, fish/seafood and meat from Ismailia city, Egypt – Loutfy N et al., 2006. https://pubmed.ncbi.nlm.nih.gov/16806402/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
HRGC/HRMS; intake 6.04–6.68 pg WHO-TEQ/kg bw/day incl. DL-PCBs from dairy, fish/seafood, meat; dairy (mainly cheese) contributed 89 % of PCDD/F intake; 'higher than the maximum WHO TDI of 4 pg TEQ/kg bw/day'. Eggs were not measured (EU data used for estimation). - Aflatoxin M1 in Africa: Exposure Assessment, Regulations, and Prevention Strategies - A Review – Zinedine A et al., 2021. https://pubmed.ncbi.nlm.nih.gov/34611756/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Egypt, Kenya and Nigeria have the most AFM1 investigations in Africa; some reports showed 100 % of samples exceeding the EU limit (50 ng/kg), e.g. in Egypt; AFM1 up to 8,000 ng/kg reported in milk from Egypt. - The prevalence of aflatoxin M1 in milk of Middle East region: A systematic review, meta-analysis and probabilistic health risk assessment – Rahmani J et al., 2018. https://pubmed.ncbi.nlm.nih.gov/29902498/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
49 articles, 7484 data (1995–2017); raw-milk AFM1 prevalence Egypt 38 %; country ranking for raw-milk concentration Syria > Turkey > Iran > Egypt > Lebanon > Palestine; hazard index for Egyptian raw milk 0.18 (adults), 0.84 (children). - A Comprehensive Systematic Review and Meta-Analysis on the Prevalence of Aflatoxin M1 in Dairy Products in Selected Middle East Countries – Arghavan B et al., 2025. https://pubmed.ncbi.nlm.nih.gov/39840829/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
193 studies, 297,530 samples (to Aug 2023); AFM1 in 87 % of dairy products overall; ranking by prevalence Iran > Jordan > Turkey > Kuwait > Lebanon > Syria > Egypt > Cyprus > UAE. - Assessment of some chemical residues in Egyptian raw milk and traditional cheese – Ibrahim AA et al., 2024. https://pubmed.ncbi.nlm.nih.gov/38549581/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Raw milk: elevated lead in 46 % and cadmium in 4 % of samples; p,p'-DDE in 45 % of raw milk and 29 % of Ras cheese; AFM1 exceeded acceptable limits in only 7 % of milk and 2.9 % of Ras cheese samples (ELISA). - Heavy Metal Residues in Some Fishes from Manzala Lake, Egypt, and Their Health-Risk Assessment – Sallam KI et al., 2019. https://pubmed.ncbi.nlm.nih.gov/31242536/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
600 fish (200 each Nile tilapia, flathead grey mullet, African catfish); mean Pb 0.704, 0.635, 0.64 µg/g; Hg 0.045, 0.0145, 0.017 µg/g; Cd 0.024, 0.006, 0.020 µg/g wet weight; health-risk indices suggest potential hazard. - Carcinogenic and non-carcinogenic health risks associated with the consumption of fishes contaminated with heavy metals from Manzala Lake, Egypt – Abd-Elghany SM et al., 2024. https://pubmed.ncbi.nlm.nih.gov/38657491/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Mean Pb 1.01, 0.87, 0.95 mg/kg; Cd 0.05, 0.12, 0.06 mg/kg; Hg 0.01, 0.15, 0.29 mg/kg; As 3.16–4.74 mg/kg (tilapia, mullet, catfish); 'levels ... exceeded their maximum permissible limits in most samples'; THQ >1 for Hg and Cd. - Exposure assessment of pesticide residues, heavy metals, and veterinary drugs through consumption of Egyptian fish samples – Ghuniem MM et al., 2024. https://pubmed.ncbi.nlm.nih.gov/39309634/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
48 fish samples, Kafr El-Sheikh governorate; LC-MS/MS, ICP-MS, GC-MS; mean Cd 0.02, Hg 0.051, Pb 0.031 mg/kg; 'All levels of cadmium, mercury, and lead ... significantly lower than the maximum permissible limits set by Egyptian and European standards'; antibiotics and pesticide residues not detected in any sample. - One health risk assessment of heavy-metal contamination in Nile tilapia (Oreochromis niloticus) from contrasting aquaculture systems in Egypt – Farahat Abdelmawla M et al., 2026. https://pubmed.ncbi.nlm.nih.gov/42662802/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Aquaculture relying on agricultural drainage water; Kitchener Drain water Pb, Cd, Cr, Hg exceeded WHO limits 5–54-fold; liver Pb up to 4.90 mg/kg; 'Muscle remained within FAO/WHO limits'; all THQ <1; narrow Pb margin (0.28 vs 0.3 mg/kg). - Systems-thinking approach to identify and assess feasibility of potential interventions to reduce antibiotic use in tilapia farming in Egypt – Desbois AP et al., 2021. https://pubmed.ncbi.nlm.nih.gov/34276104/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Full text (Europe PMC PMC8164158): 'Egypt produces more fish from aquaculture than the rest of Africa combined ... 1.56 million tonnes in 2018 (FAO, 2020)'; grow-out ponds supplied mainly by agricultural drainage water (ca. 70 % of farms), Nile ca. 20 %, groundwater ca. 10 %; antibiotics enter via medicated feed/pond water and via drainage water; ponds stocked with mono-sex fry. - World Bank World Development Indicators API – SH.H2O.SMDW.ZS, SH.H2O.BASW.ZS, SH.STA.SMSS.ZS (source: WHO/UNICEF JMP) – World Bank / WHO-UNICEF Joint Monitoring Programme, 2026. https://api.worldbank.org/v2/country/EGY;DEU/indicator/SH.H2O.SMDW.ZS?format=json (Type: database; verified: yes; accessed 2026-10-25)
Safely managed drinking water 2024: Egypt 78.94 %, Germany 99.92 %; at least basic drinking water 2024: Egypt 97.30 %, Germany 100 %; safely managed sanitation 2024: Egypt 57.34 %. - Prevalence of glucose-6-phosphate dehydrogenase deficiency in neonates in Egypt – Elella SA et al., 2017. https://pubmed.ncbi.nlm.nih.gov/28988250/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Full text (Europe PMC PMC6074198): infants born 2015 at a university hospital screened by quantitative fluorometric assay; G6PD deficiency in 119 (4.3 %) newborns; 6.2 % (91/1453) of males and 2.1 % (28/1329) of females. - Prevalence of and mothers' knowledge, attitude and practice towards glucose-6-phosphate dehydrogenase deficiency among neonates with jaundice: a cross-sectional study – Kasemy ZA et al., 2020. https://pubmed.ncbi.nlm.nih.gov/32102818/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
487 Egyptian neonates with indirect hyperbilirubinaemia (2018–2019): G6PD deficiency 10.10 %; risk factors male sex, family history, consanguinity. - The global prevalence of glucose-6-phosphate dehydrogenase deficiency: a systematic review and meta-analysis – Nkhoma ET et al., 2009. https://pubmed.ncbi.nlm.nih.gov/19233695/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
~400 million affected worldwide; 280 prevalence estimates from 88 countries; highest prevalence in sub-Saharan Africa; high heterogeneity largely due to differing assessment methods. - [Increase in genetically determined anemia as a result of migration in Germany] – Zur B et al., 2016. https://pubmed.ncbi.nlm.nih.gov/26899228/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Haemoglobinopathies and G6PD deficiency 'are no longer rare diseases in Germany' because of migration from endemic regions where prevalence of 40 % and higher has been found. - Favism: Clinical Features at Different Ages – Beretta A et al., 2023. https://pubmed.ncbi.nlm.nih.gov/36678214/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Favism = haemolysis after fava-bean ingestion in G6PD-deficient individuals; wide inter-/intra-individual variability; most severe in youngest children and pregnant women; deaths reported in infants. - Analysis of Reported Aflatoxin Levels in EU's Rapid Alert System for Food and Feed (RASFF) Notifications – Kow R et al., 2025. https://pubmed.ncbi.nlm.nih.gov/41008222/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
RASFF aflatoxin notifications 2010–2023: peanuts 34.4 %, pistachios 17.3 %, figs 12.5 % of notifications; country-specific patterns. - German outbreak of Escherichia coli O104:H4 associated with sprouts – Buchholz U et al., 2011. https://pubmed.ncbi.nlm.nih.gov/22029753/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Sprouts identified as most likely vehicle (restaurant cohort RR 14.2; sprout consumption explained 100 % of cases); trace-back to producer A; outbreak strain not found on seeds of implicated lot. - Outbreak of Shiga toxin-producing Escherichia coli (STEC) O104:H4 infection in Germany causes a paradigm shift ... – Beutin L et al., 2012. https://pubmed.ncbi.nlm.nih.gov/22289607/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
3,842 cases; 'Epidemiological investigations revealed fenugreek seeds as the source of entry ... however, microbiological analysis of seeds for this pathogen produced negative results.' - Digitale-Dienste-Gesetz (DDG) vom 6. Mai 2024 (BGBl. 2024 I Nr. 149), § 5 Allgemeine Informationspflichten; § 7 Beschränkte Verantwortlichkeit – Bundesrepublik Deutschland, 2024. https://www.gesetze-im-internet.de/ddg/__5.html ; https://www.gesetze-im-internet.de/ddg/__7.html (Type: regulation; verified: yes; accessed 2026-10-25)
§ 5(1): providers of 'geschäftsmäßige, in der Regel gegen Entgelt angebotene digitale Dienste' must keep available name and address, rapid electronic contact incl. e-mail, register data, VAT ID etc., 'leicht erkennbar, unmittelbar erreichbar ... ständig verfügbar'. § 7(1): Articles 4–8 of Regulation (EU) 2022/2065 apply to all service providers. Fassung last amended by Art. 1 G v. 12.5.2026. - Leitfaden zur Impressumspflicht im Internet (2024) – Niedersächsische Landesmedienanstalt (NLM), 2024. https://www.nlm.de/fileadmin/dateien/pdf/leitfaden_impressumspflicht_2024.pdf (Type: official_report; verified: yes; accessed 2026-10-25)
Impressum duty arises from § 18 MStV and § 5 DDG; journalistic-editorial offers must additionally name a 'Verantwortlicher' (name, address; permanent residence in Germany, full legal capacity etc.) under § 18 Abs. 2 MStV; other telemedia not exclusively personal/family purposes need a simple Impressum under § 18 Abs. 1 MStV (name, ladungsfähige Anschrift); purely private use 'sehr eng ausgelegt', in doubt an Impressum is recommended; reachable within max. two clicks; fines up to 50.000 EUR (§ 115 MStV / § 33 DDG). - Regulation (EU) 2016/679 (General Data Protection Regulation) – European Parliament and Council, 2016. https://eur-lex.europa.eu/eli/reg/2016/679/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Art. 6(1)(f) (text read): processing lawful where 'necessary for the purposes of the legitimate interests pursued by the controller or by a third party, except where such interests are overridden by the interests or fundamental rights and freedoms of the data subject'; Art. 13: information to be provided where data are collected from the data subject. Relevant for server logs containing IP addresses. - Telekommunikation-Digitale-Dienste-Datenschutz-Gesetz (TDDDG, formerly TTDSG) § 25 Schutz der Privatsphäre bei Endeinrichtungen – Bundesrepublik Deutschland, 2021/2024. https://www.gesetze-im-internet.de/ttdsg/__25.html (Type: regulation; verified: yes; accessed 2026-10-25)
§ 25(1): storing/accessing information in the end user's terminal equipment only with consent; § 25(2) Nr. 2: no consent needed if 'unbedingt erforderlich' to provide a digital service explicitly requested by the user. - Urheberrechtsgesetz (UrhG) § 51 Zitate; § 62 Änderungsverbot; § 63 Quellenangabe – Bundesrepublik Deutschland, 1965 (current). https://www.gesetze-im-internet.de/urhg/__51.html ; https://www.gesetze-im-internet.de/urhg/__62.html ; https://www.gesetze-im-internet.de/urhg/__63.html (Type: regulation; verified: yes; accessed 2026-10-25)
§ 51: quotation of a published work permitted 'sofern die Nutzung in ihrem Umfang durch den besonderen Zweck gerechtfertigt ist', esp. passages in an independent work. § 62(1): no changes; § 62(2): translations and excerpts allowed where the purpose requires. § 63(1): 'ist stets die Quelle deutlich anzugeben'. - UrhG § 44b Text und Data Mining; Directive (EU) 2019/790 Art. 4 – Bundesrepublik Deutschland / European Union, 2019/2021. https://www.gesetze-im-internet.de/urhg/__44b.html ; https://eur-lex.europa.eu/eli/dir/2019/790/oj (Type: regulation; verified: yes; accessed 2026-10-25)
§ 44b(3): TDM uses only allowed if the rightholder has not reserved them; a reservation for online works is effective only if machine-readable. Dir. 2019/790 Art. 4(3) equivalent. - eltayebat.com robots.txt (Content-Signal declarations) – Operator of eltayebat.com (Cloudflare-managed content block), 2026. https://eltayebat.com/robots.txt (Type: database; verified: yes; accessed 2026-10-25)
'Content-Signal: search=yes,ai-train=no,use=reference'; states restrictions are 'EXPRESS RESERVATIONS OF RIGHTS UNDER ARTICLE 4 OF ... DIRECTIVE 2019/790'; disallows training crawlers incl. ClaudeBot, GPTBot, Google-Extended, CCBot. - eltayebat.com 'About the archive' page (حول الأرشيف) – Operator of eltayebat.com, 2026. https://eltayebat.com/about/ (Type: database; verified: yes; accessed 2026-10-25)
Arabic text: 'حقوق النشر الحقوق الأدبية للراحل ولورثته. الأرشيف غير ربحي ولا يحتوي إعلانات. أرشيف تعليمي يحفظ محتوى الراحل د. ضياء العوضي بإذن من الورثة. لا يتحمل الأرشيف مسؤولية المحتوى الطبي.' (moral/copyright rights belong to the deceased and his heirs; non-profit, no ads; with permission of the heirs; no responsibility for medical content). - Heilmittelwerbegesetz (HWG) § 1 Anwendungsbereich – Bundesrepublik Deutschland, 1965 (current). https://www.gesetze-im-internet.de/heilmwerbg/__1.html (Type: regulation; verified: yes; accessed 2026-10-25)
§ 1(1): applies to 'Werbung' for medicinal products, medical devices, and other means/procedures/treatments where the advertising statement relates to recognising, eliminating or alleviating diseases. - Regulation (EU) 2022/2065 (Digital Services Act) – European Parliament and Council, 2022. https://eur-lex.europa.eu/eli/reg/2022/2065/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Arts. 4–8: liability exemptions for intermediary services (mere conduit, caching, hosting); referenced by § 7 DDG.