Randomised controlled trialindependent cross-checkfull text checked★ key study I-FAST-02 in-depth review
Alternate-day fasting vs eating less every day
Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial.
Overview
Trepanowski JF et al.. JAMA Intern Med 2017 · PMID 28459931 · DOI 10.1001/jamainternmed.2017.0936
Both approaches gave similar weight loss after a year; fasting had more dropouts and higher LDL.
Does the study support the specific claim? Partly · Methodological quality: moderate
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Alternate-day fasting vs daily calorie restriction on weight and CV risk
- How was the study done?
Single-centre RCT, 1 year
- How many people, animals or samples were studied?
100; Metabolically healthy obese adults, mean BMI 34
- What was actually found?
No superiority.
- How large was the observed effect?
-6.0% vs -5.3% weight
- What do the results mean in everyday life?
Choose what one can sustain.
- What are the study's limitations?
Small; 38% of fasting group dropped out; mostly healthy women; fast days still included ~500 kcal; lead author wrote a book on this diet.
- What does it say about Elawady's specific claim?
- Do the results apply to Germany and Europe?
US; transferable.
- What can explicitly not be concluded from this study?
Long-term disease outcomes.
Scientific in-depth review
1. Full reference
- Authors
- Trepanowski JF et al.
- Journal
- JAMA Intern Med
- Year
- 2017
- Identifier
- PMID 28459931 DOI 10.1001/jamainternmed.2017.0936
- Verification
- verified – PubMed efetch 2026-10-25 (this agent)
- Retracted
- no
- Corrections
- none
- Extent checked
- full text
- Conflicts of interest and funding
Funded by NIH/NHLBI (R01HL106228) and NIDDK (P30DK072476, F32DK107157); funders had no role. Senior author K. Varady received an advance for the book 'The Every-Other-Day Diet' (Hachette).
2. Research question
Alternate-day fasting vs daily calorie restriction on weight and CV risk
3. Study design and population
- Study design
- Randomised controlled trial – Single-centre, three-arm randomised clinical trial (NCT00960505), 1:1:1 stratified block randomisation; 6-month weight-loss phase plus 6-month weight-maintenance phase; intention-to-treat linear mixed models.
- Population
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.
- Country
USA (University of Illinois at Chicago)
- Period
1 October 2011 - 15 January 2015; 12 months per participant.
- Sample size
100 randomised (ADF 34, daily calorie restriction 35, control 31) of 222 screened; 69 completed (dropout 38%, 29%, 26%).
- Inclusion and exclusion criteria
Included 18-65 years, BMI 25.0-39.9, sedentary; excluded history of CVD or type 1/2 diabetes, interfering medication, unstable weight, perimenopause/irregular cycles, pregnancy, current smoking.
4. Methods and endpoints
- Exposure / intervention
Alternate-day fasting: 25% of energy needs as lunch on fast days and 125% on feast days (maintenance: 50%/150%); all meals provided for the first 3 months, then dietary counselling.
- Comparator
Daily calorie restriction (75% of energy needs every day; maintenance 100%); no-intervention control.
- Endpoints
Primary: change in body weight. Secondary: adherence (food records, doubly labelled water), body composition (DXA, MRI visceral fat), BP, heart rate, lipids, glucose, insulin, HOMA-IR, CRP, homocysteine.
- Statistical methods
ITT linear mixed models (missing at random) for all 100 randomised; sensitivity adjustment for sex and race; power reduced from 80% to 60% due to dropout.
5. Actual results
- Results
Weight vs control: month 6 ADF -6.8% (95% CI -9.1 to -4.5) vs CR -6.8% (-9.1 to -4.6); month 12 ADF -6.0% (-8.5 to -3.6) vs CR -5.3% (-7.6 to -3.0); ADF minus CR at 12 months -0.7% (-3.1 to 1.6). Energy restriction by doubly labelled water to month 6: 21% (ADF) vs 24% (CR). ADF participants ate more than prescribed on fast days and less on feast days; CR more often adherent. No between-diet differences in BP, heart rate, triglycerides, glucose, insulin, HOMA-IR, CRP, homocysteine, fat or visceral fat mass. HDL +6.2 mg/dL (0.1-12.4) with ADF vs CR at 6 months, not at 12 months; LDL +11.5 mg/dL (1.9-21.1) with ADF vs CR at 12 months.
- Absolute risks
Not applicable (continuous outcomes); dropout 38% vs 29% vs 26%.
- Authors' conclusion
Alternate-day fasting did not produce superior adherence, weight loss, weight maintenance or cardioprotection compared with daily calorie restriction; it may be less sustainable for most obese individuals.
6. Strengths
- Randomised with 1-year duration (longest ADF trial at the time)
- Objective adherence measures (doubly labelled water) and body composition by DXA/MRI
- ITT analysis of all randomised participants; registered with protocol available
- Investigator COI would favour ADF, yet result is null
7. Weaknesses
- 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
- Imperfect control group (less attention); maintenance phase only 6 months
- Mostly metabolically healthy women - limited generalisability
- Fast days were modified (~500 kcal), not complete fasting or one meal a day
- Many secondary outcomes; LDL finding may be chance
8. Risk of bias
- Orienting tool
- RoB 2
- Type of assessment
- structured assessment based on the full text by a single reviewer (no formal double review)
- Full formal assessment
- no
- Overall risk of bias
- some concerns
- Rationale
Single-reviewer RoB 2-oriented judgement from the full text; formal assessment requires two independent reviewers. Overall unchanged (some_concerns), mainly due to differential attrition and unblinded behavioural interventions.
| Domain | Judgement | Rationale |
|---|---|---|
| D1 randomisation process | low | Stratified block randomisation; balanced baseline (allocation concealment details not reported in main text). |
| D2 deviations from intended interventions | some concerns | Unblinded dietary interventions; poor adherence to ADF prescription (converted to de facto calorie restriction); ITT analysis appropriate. |
| D3 missing outcome data | some concerns | 31% dropout, highest with ADF; mixed models assume missing at random, but dropout related to diet dissatisfaction. |
| D4 measurement of the outcome | low | Weight measured on digital scale in gown; laboratory markers objective. |
| D5 selection of the reported result | low | Registered trial with published protocol; primary outcome reported as specified. |
Full-text review (25 October 2026): Eligibility, intervention details (meal provision, maintenance prescriptions), doubly labelled water energy restriction (21% vs 24%), between-diet difference with CI, body composition and full secondary results added; funding (NIH) and author COI (ADF book advance) added; RoB 2 domains added, overall unchanged; relevance refined (C-FAST-05 mixed, C-SRC-22 contradicted).
9. Assessment of the statistical interpretation
No meaningful difference between ADF and daily restriction (12-month difference -0.7%, CI -3.1 to 1.6); both achieved similar measured energy deficits, i.e. weight loss tracked calorie deficit, not meal timing. Wide CIs for secondary outcomes.
10. Relevance to the specific claim
Limits C-FAST-02 and C-FAST-04 (no special metabolic benefit of fasting beyond calorie deficit); mixed for C-FAST-05 (modified ADF works similarly to daily restriction but is harder to sustain; OMAD not tested); contradicts C-SRC-22 (weight loss followed measured calorie deficit).
11. Independent contrary findings
12. Transferability to Germany and Europe
US; transferable.
13. Overall methodological judgement
Modified alternate-day fasting is not superior to daily calorie restriction for weight, adherence or cardiometabolic markers and had more dropouts and a later LDL rise; supports energy balance (calories) as the driver of weight loss.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | moderate |
| Risk of bias | some concerns |
| Precision of results | low |
| Directness | direct |
| Reproducibility | replicated |
| Consistency with the overall evidence | consistent |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | not applicable |
14. Open questions
None beyond those stated.
15. Linked fact checks
- Fasting gives the liver and gut the chance to repair themselves and expel toxins; intermittent fasting is the only treatment for fatty liver and treats joint pain, autoimmune and allergy-like symptoms. – Studies contradicting or limiting the claim
- Health equals the ability to avoid toxic inputs: zero inputs means infinite health; complete abstinence from all inputs (fasting) keeps the body in a state that does not become ill, and not eating for three or four days makes the body strong. – Studies contradicting or limiting the claim
- Long daily intermittent fasting with one meal a day as the default eating pattern (and sometimes eating once every two days) is the healthy way to eat. – Studies with mixed or unclear results
- Calories are not a relevant concept ('there is no such thing as calories'); his system is based on high calorie intake, and people lose weight while eating sugar, juices, fats, potatoes and rice, because with 'zero insulin' no fat is formed (the passage continues: 'even if you drink oil, even if you swallow bags of sugar'). Elsewhere he says he drinks 6 litres of sugar-cane juice and eats baladi ghee, rice and potatoes every day. – Studies contradicting or limiting the claim