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 MI.
“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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- 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 › Medicine › Rheumatology › Folate and B Vitamins Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Health Sciences › Medicine › Surgery › 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
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