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Homocysteine and vascular disease: review of published results of the homocysteine‐lowering trials
Abstract
Moderately elevated homocysteine levels have been associated with a higher risk of cardiovascular disease in observational studies, but whether these associations are causal is uncertain. Randomized trials of dietary supplementation with B vitamins were set up to assess whether lowering homocysteine levels could reduce the risk of vascular disease. This review is based on a meta‐analysis of published results of eight homocysteine‐lowering trials for preventing vascular disease. The eight trials comprised a total of 37,485 individuals and provided comparisons of the effects of B vitamins on 5,074 coronary heart disease (CHD) events, 1,483 stroke events, 2,692 incident cancer events, and 5,128 deaths. Our meta‐analysis assessed the effects of lowering homocysteine levels by about 25% for about 5 years. Allocation to B vitamins had no beneficial effects on any cardiovascular events, with hazard ratios (95% confidence intervals) of 1.01 (0.96–1.07) for CHD and 0.96 (0.87–1.07) for stroke. Moreover, allocation to B vitamins had no significant adverse effects on cancer [1.08 (0.99–1.17)], or for death from any cause [1.02 (0.97–1.07)]. Thus, supplementation with B vitamins had no statistically significant effects on the risks of cardiovascular events, total mortality rates, or cancer. A meta‐analysis based on individual participant data from all available trials will assess the effects of lowering homocysteine levels on a broader range of outcomes, overall and in all relevant subgroups. However, available evidence does not support the routine use of B vitamins to prevent cardiovascular disease.
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“In a study involving elderly individuals who were aged ≥ 85 years and had no history of cardiovascular disease, a high homocysteine concentration in the blood increased the relative risk for MI290).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [290]
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Metadata
- Authors
- Clarke, R., Halsey, J., Bennett, D., & Lewington, S.
- Affiliations
- University of Oxford (GB)
- Corresponding author
- Clarke, Robert
- Venue
- Journal of Inherited Metabolic Disease
- Publisher
- Wiley
- Published
- 2010-11-11
- Volume
- 34
- Issue
- 1
- Pages
- 83-91
- ISSN
- 0141-8955 (ISSN-L)
- 1573-2665
- OpenAlex
- W2005016697
- Cited by
- 104
- References
- 41
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1 · 2023: 3 · 2022: 5 · 2021: 6 · 2020: 3 · 2019: 4 · 2018: 3 · 2017: 6 · 2016: 8 · 2015: 12 · 2014: 10 · 2013: 17 · 2012: 15
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Inherited Metabolic Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- British Heart Foundation
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Folate and B Vitamins Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- homocysteine, B vitamins, folic acid, vitamin B12, vitamin B6, coronary artery disease, stroke, cancer risk, cardiovascular disease prevention, mortality
- MeSH terms
- Cause of Death, Clinical Trials as Topic, Folic Acid, Homocysteine, Humans, Neoplasms, Vascular Diseases, Vitamin B Complex, Down-Regulation, Dietary Supplements
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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