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Effects of folic acid supplementation on homocysteine level as primary prevention of heart disease: a systematic review

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Supplements are commonly used to prevent cardiovascular diseases. Unfortunately, studies on folic acid supplementation have failed to support its benefit with pre-existing cardiovascular disease. Observational data suggest the benefit may be greater for healthy and at-risk individuals, but clinical trials have yet to be presented. The purpose of this paper is to systematically review evidence regarding the effectiveness of folic acid supplementation on homocysteine levels among healthy people who are at risk regarding the primary prevention of heart disease.


PubMed, Science Direct, COCHRANE Library, and Clinical were searched from the year 2000 to 2015, with manual searches of references list and gray literature. Two investigators were selected to review fair- and good-quality trials that included healthy participants or healthy with risk, measurements of homocysteine levels and trials reporting at least one of the coronary heart diseases as an outcome. Dual quality assessments and data abstraction protocols were established.


There are limited new trials that have been published to show the effectiveness in primary prevention of cardiovascular disease. This limited evidence has given a strong association regarding the effects of folic acid supplementation in reducing homocysteine levels. However, the effectiveness for its role in the primary prevention of a cardiovascular event is still not proven as being beneficial.


Limited evidence supports any benefit from folic acid supplementation for the primary prevention of coronary heart disease. Studies of the combined effect of folic acid with another preventative method of cardiovascular disease will help determine if folic acid supplementation causally reduces the cardiovascular event from the primary level. To prove its effectiveness, future clinical trials need to be performed.

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We would like to express our special thanks of gratitude to those involved directly and indirectly with the completion of this manuscript, which was undertaken with the hope it can contribute to future knowledge on the subject.

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The authors declare that they have no conflict of interest.

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Correspondence to Mohd Ihsani Mahmood.

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Mahmood, M.I., Rosli, N.M., Shukor, M.F.A. et al. Effects of folic acid supplementation on homocysteine level as primary prevention of heart disease: a systematic review. J Public Health 23, 387–394 (2015).

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