Systematic reviewcited by the Tayebat archivefull text checked★ key study A-VEG-17 in-depth review
Vitamin K foods and warfarin
Interaction Between Dietary Vitamin K Intake and Anticoagulation by Vitamin K Antagonists: Is It Really True?: A Systematic Review.
Overview
Violi F et al.. Medicine (Baltimore) 2016 · PMID 26962786 · DOI 10.1097/MD.0000000000002895
Review found no good evidence that patients on warfarin should restrict leafy greens; stable intake matters.
Does the study support the specific claim? No · Methodological quality: low
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Assess diet-warfarin interaction
- How was the study done?
Systematic review
- How many people, animals or samples were studied?
11 studies
- What was actually found?
Conflicting; no basis for restriction
- How large was the observed effect?
Effect possibly >150 µg/day
- What do the results mean in everyday life?
Keep intake stable.
- What are the study's limitations?
Few studies
- What does it say about Elawady's specific claim?
Contradicts archive
- Do the results apply to Germany and Europe?
High
- What can explicitly not be concluded from this study?
Cannot show greens must be avoided.
Scientific in-depth review
1. Full reference
- Authors
- Violi F, Lip GY, Pignatelli P, Pastori D
- Journal
- Medicine (Baltimore)
- Year
- 2016
- Identifier
- PMID 26962786 DOI 10.1097/MD.0000000000002895 · PMC4998867
- Verification
- verified – PubMed E-utilities efetch, 2026-10-25
- Retracted
- no
- Corrections
- none
- Extent checked
- full text
- Conflicts of interest and funding
Authors declare no conflicts of interest; funding not stated in full text.
2. Research question
Does dietary vitamin K affect INR in VKA users?
3. Study design and population
- Study design
- Systematic review – Systematic review (PRISMA-reported) with narrative synthesis; no meta-analysis
- Population
Patients treated with vitamin K antagonists (mostly warfarin; also phenprocoumon, acenocoumarol) for AF, prosthetic valves or VTE
- Country
Multiple
- Period
Up to October 2015
- Sample size
11 studies (2 dietary interventional trials with 37 and 12 patients; 9 observational studies, sample sizes ~40 to 1157) from 14,865 records
- Inclusion and exclusion criteria
Original interventional or observational studies of real-life dietary vitamin K intake and any coagulation measure in VKA users; studies of vitamin supplementation or single supplemented foods excluded
4. Methods and endpoints
- Exposure / intervention
Dietary vitamin K (phylloquinone) intake, habitual or experimentally changed
- Comparator
Lower or different vitamin K intake
- Endpoints
INR/PT, INR variability (CV), warfarin sensitivity or dose, incident over- or under-anticoagulation
- Statistical methods
Narrative synthesis; study quality graded with American Academy of Neurology classes I-IV; two independent screeners
5. Actual results
- Results
Conflicting evidence. In one trial (n=37), some patients eating vitamin-K-rich vegetables (median 1100 ug/day) for 1-2 days left the therapeutic INR range; in another (n=12), both vitamin-K-depleted and -enriched diets caused INR instability. Observational: some inverse associations (e.g. phylloquinone vs INR r=-0.23); a nested case-control study (300 vs 302) found no association with INR >=6; others found higher intake associated with more stable INR (Leiden, n=1157: 20% lower risk of subtherapeutic INR with >300 ug/day, 33% higher with <100 ug/day). Median intakes 76-217 ug/day; effects reported only at >150 ug/day (~118 g raw lettuce, 106 g cooked broccoli or 30 g cooked spinach). No study reached AAN class I.
- Absolute risks
not reported in full text
- Authors' conclusion
Evidence does not support advising patients to change dietary habits when starting VKAs; restricting vitamin K intake does not seem valid; maintaining stable habits and avoiding wide changes in vitamin K intake may be more relevant; the authors suggest removing the putative food-VKA interaction from guidelines until controlled studies show it.
6. Strengths
- Explicit eligibility focused on real diets rather than supplements
- Duplicate screening
- Quality grading of included studies
7. Weaknesses
- Only MEDLINE and Cochrane searched
- No protocol registration; no meta-analysis
- Few, small and low-quality primary studies with heterogeneous outcomes
- Internal inconsistencies (text mentions both 2 and 3 interventional trials)
- Funding not reported
- Conclusion to remove the interaction from guidelines goes somewhat beyond the evidence, which does show INR effects of large intake changes
8. Risk of bias
- Orienting tool
- AMSTAR 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
- high
- Rationale
Single-reviewer structured AMSTAR 2 appraisal from full text; not formal (needs two independent reviewers). Multiple critical weaknesses (no protocol, no excluded-studies list, limited search) correspond to low/critically low confidence; bias judgement raised from some_concerns to high.
| Domain | Judgement | Rationale |
|---|---|---|
| Item 1 PICO components | low | Population, exposure and outcomes defined. |
| Item 2 Protocol registered a priori (critical) | high | No protocol mentioned. |
| Item 3 Explanation of included designs | low | Both interventional and observational designs included by rationale. |
| Item 4 Comprehensive search (critical) | some concerns | Two databases plus related-articles and reference checks; no grey literature or Embase. |
| Item 5 Duplicate selection | low | Two physicians screened independently, third resolved disagreements. |
| Item 6 Duplicate extraction | some concerns | Not stated as duplicate. |
| Item 7 Excluded studies justified (critical) | high | Only aggregate exclusion counts; no list of excluded full texts. |
| Item 8 Description of included studies | low | Tables of study characteristics. |
| Item 9 RoB of included studies (critical) | some concerns | AAN classification used, not a domain-based RoB tool. |
| Item 10 Funding of included studies | high | Not reported. |
| Item 11 Meta-analytic methods (critical) | not applicable | No meta-analysis (justified by heterogeneity). |
| Item 12 Impact of RoB on results | not applicable | No pooled estimate. |
| Item 13 RoB considered in interpretation (critical) | some concerns | Low quality acknowledged, yet strong recommendation to drop guideline statements. |
| Item 14 Heterogeneity discussed | low | Heterogeneity of outcomes and populations discussed. |
| Item 15 Publication bias (critical) | not applicable | No quantitative synthesis. |
| Item 16 Conflicts of interest | low | Declared none. |
Full-text review (25 October 2026): Added individual study findings (trial n=37 and n=12, Leiden n=1157 stability data), the >150 ug/day threshold in food amounts, quality grading method, search limitations, missing funding statement; AMSTAR 2 item-level appraisal raised bias from some_concerns to high (methodological quality low). Nuanced that large abrupt intake changes can shift INR.
9. Assessment of the statistical interpretation
Narrative; underlying studies show that abrupt large changes in vitamin K intake (in either direction) can shift INR, whereas habitual moderate or higher stable intake is not associated with instability and may be associated with greater stability.
10. Relevance to the specific claim
Contradicts C-VEG-12.
11. Independent contrary findings
Itself.
12. Transferability to Germany and Europe
High.
13. Overall methodological judgement
Misrepresented by the archive.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | low |
| Risk of bias | high |
| Precision of results | low |
| Directness | direct |
| Reproducibility | partly replicated |
| Consistency with the overall evidence | mixed |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | not supported by the study |
14. Open questions
Controlled trials of realistic dietary changes on time in therapeutic range; relevance with DOACs (not VKA-dependent).
15. Linked fact checks
- Vitamin K in leafy greens destabilises warfarin therapy (archive citing a Medicine (Baltimore) review). – Studies contradicting or limiting the claim
Use by the Tayebat archive
Note: according to the archive, the studies were compiled by the archive operators. Whether Dr. Elawady himself cited this study is not established.
- What the archive says about the study
Narrative: 'the Medicine (Baltimore) review even shows their vitamin K destabilises warfarin therapy'.
- A. What was actually studied?
Diet-VKA interaction.
- B. What did the authors find?
Conflicting, low-quality evidence; abrupt large changes in vitamin K intake can shift INR, but habitual or higher stable intake is not harmful and may be associated with more stable INR; effects only above ~150 ug/day.
- C. What conclusions do the authors themselves draw?
No support for dietary restriction; stable habits.
- D. What does the archive derive from it?
Greens destabilise warfarin.
- E. Is this derivation scientifically justified?
Not justified as stated: the review's message is that greens need not be restricted and that intake should be kept stable; only large abrupt changes affect INR. The archive presents it as showing that greens destabilise warfarin.
- Adequacy of the interpretation (by the archive)
- not supported by the study