Randomised controlled trialindependent cross-checkabstract checked★ key study I-VEG-101 in-depth review
Changing vitamin K intake shifts warfarin effect
Role of dietary vitamin K intake in chronic oral anticoagulation: prospective evidence from observational and randomized protocols.
Overview
Franco V et al.. Am J Med 2004 · PMID 15121490 · DOI 10.1016/j.amjmed.2003.12.036
In 12 patients, a diet low in vitamin K raised INR from 2.6 to 3.3 within a week, and a vitamin K-rich diet lowered it from 3.1 to 2.8.
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?
To test whether dietary vitamin K changes anticoagulation.
- How was the study done?
Observational follow-up plus a randomized crossover feeding trial.
- How many people, animals or samples were studied?
39 clinic patients; 12 in the trial.
- What was actually found?
Vitamin K intake was linked to both over- and under-anticoagulation; both diet changes moved INR.
- How large was the observed effect?
INR +0.7 (depleted), -0.3 (enriched).
- What do the results mean in everyday life?
Large sudden changes in greens intake can change how strongly warfarin works.
- What are the study's limitations?
Tiny sample, 4-day diets, extreme changes.
- What does it say about Elawady's specific claim?
Supports that greens can affect warfarin, but the problem is CHANGE in intake; stopping greens is also a change.
- Do the results apply to Germany and Europe?
Applies to all vitamin K antagonists.
- What can explicitly not be concluded from this study?
Cannot show that a stable intake of greens is harmful.
Scientific in-depth review
1. Full reference
- Authors
- Franco V et al.
- Journal
- Am J Med
- Year
- 2004
- Identifier
- PMID 15121490 DOI 10.1016/j.amjmed.2003.12.036
- Verification
- verified – PubMed efetch 2026-10-26; Crossref 2026-10-26
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
not stated in abstract
2. Research question
Does dietary vitamin K intake affect anticoagulation stability in patients on long-term oral anticoagulation?
3. Study design and population
- Study design
- Randomised controlled trial – Prospective observational protocol (39 outpatients, 230 visits) plus randomized crossover dietary intervention (12 stable patients, 4-day in-hospital diets)
- Population
Outpatients on chronic oral anticoagulation (coumarin) at an anticoagulation clinic
- Country
Brazil (Porto Alegre; from author affiliation in the PubMed record)
- Period
not stated in abstract
- Sample size
39 (observational) + 12 (randomized crossover)
- Inclusion and exclusion criteria
not stated in abstract
4. Methods and endpoints
- Exposure / intervention
Vitamin K-enriched diet (about 500% increase) or vitamin K-depleted diet (about 80% decrease) relative to baseline
- Comparator
Baseline diet / crossover
- Endpoints
INR; over- and under-anticoagulation
- Statistical methods
Univariate and multivariate logistic regression (observational); paired comparison of INR (crossover)
5. Actual results
- Results
Observational: vitamin K intake score inversely associated with anticoagulation level and independently associated with both over- and under-coagulation. Crossover: INR rose from 2.6 +/- 0.5 to 3.3 +/- 0.9 at day 7 on the vitamin K-depleted diet (P = 0.005) and fell from 3.1 +/- 0.8 to 2.8 +/- 0.6 at day 4 on the vitamin K-enriched diet (P = 0.04).
- Absolute risks
not reported
- Authors' conclusion
The interaction between vitamin K and coumarin is a clinically relevant, major independent factor that interferes with anticoagulation stability.
6. Strengths
- Randomized crossover with controlled in-hospital diets
- Tests both directions (more and less vitamin K)
7. Weaknesses
- Very small (n = 12 in the trial)
- Short exposure (4 days)
- Extreme dietary changes (+500% / -80%)
- Semiquantitative intake score in observational part
8. Risk of bias
- Orienting tool
- RoB 2
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- some concerns
- Rationale
Small crossover, open dietary intervention; outcome (INR) is objective.
9. Assessment of the statistical interpretation
Recalculated relative changes: +27% INR with depletion, -10% with enrichment (stats/C-VEG-12_warfarin.py). Direction consistent with pharmacology.
10. Relevance to the specific claim
Direct: shows that large changes of dietary vitamin K in either direction shift INR. Removing vitamin K raised INR (bleeding direction).
11. Independent contrary findings
Schurgers 2004 found food-borne vitamin K had a short-lived effect; Sconce 2007 and Dentali 2016 link LOW intake to instability.
12. Transferability to Germany and Europe
Pharmacology is universal; applies to warfarin and phenprocoumon users in Europe and Egypt.
13. Overall methodological judgement
Small but direct controlled evidence that large changes in vitamin K intake alter INR; supports advice for consistent intake, not avoidance.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | moderate |
| Risk of bias | some concerns |
| 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 applicable |
14. Open questions
Effect size of realistic day-to-day changes in leafy-green intake.
15. Linked fact checks
- Vitamin K in leafy greens destabilises warfarin therapy (archive citing a Medicine (Baltimore) review). – Studies supporting the claim