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Meta-Analysis
. 2013 Jan 18:346:f10.
doi: 10.1136/bmj.f10.

Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: systematic review and meta-analysis of randomised controlled trials

Seung-Kwon Myung  1 , Woong Ju, Belong Cho, Seung-Won Oh, Sang Min Park, Bon-Kwon Koo, Byung-Joo Park; Korean Meta-Analysis Study Group
Affiliations
Meta-Analysis

Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: systematic review and meta-analysis of randomised controlled trials

Seung-Kwon Myung et al. BMJ. .

Abstract

Objective: To assess the efficacy of vitamin and antioxidant supplements in the prevention of cardiovascular diseases.

Design: Meta-analysis of randomised controlled trials.

Data sources and study selection: PubMed, EMBASE, the Cochrane Library, Scopus, CINAHL, and ClinicalTrials.gov searched in June and November 2012. Two authors independently reviewed and selected eligible randomised controlled trials, based on predetermined selection criteria.

Results: Out of 2240 articles retrieved from databases and relevant bibliographies, 50 randomised controlled trials with 294,478 participants (156,663 in intervention groups and 137,815 in control groups) were included in the final analyses. In a fixed effect meta-analysis of the 50 trials, supplementation with vitamins and antioxidants was not associated with reductions in the risk of major cardiovascular events (relative risk 1.00, 95% confidence interval 0.98 to 1.02; I(2)=42%). Overall, there was no beneficial effect of these supplements in the subgroup meta-analyses by type of prevention, type of vitamins and antioxidants, type of cardiovascular outcomes, study design, methodological quality, duration of treatment, funding source, provider of supplements, type of control, number of participants in each trial, and supplements given singly or in combination with other supplements. Among the subgroup meta-analyses by type of cardiovascular outcomes, vitamin and antioxidant supplementation was associated with a marginally increased risk of angina pectoris, while low dose vitamin B(6) supplementation was associated with a slightly decreased risk of major cardiovascular events. Those beneficial or harmful effects disappeared in subgroup meta-analysis of high quality randomised controlled trials within each category. Also, even though supplementation with vitamin B(6) was associated with a decreased risk of cardiovascular death in high quality trials, and vitamin E supplementation with a decreased risk of myocardial infarction, those beneficial effects were seen only in randomised controlled trials in which the supplements were supplied by the pharmaceutical industry.

Conclusion: There is no evidence to support the use of vitamin and antioxidant supplements for prevention of cardiovascular diseases.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

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Fig 1 Flow diagram for identification of relevant clinical trials examining effect of vitamins and supplements in prevention of cardiovascular disease
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Fig 2 Efficacy of vitamin and antioxidant supplements in prevention of major cardiovascular events in meta-analysis of 50 randomised controlled trials sorted in ascending order of number of participants
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Fig 3 Efficacy of vitamin A supplements in prevention of major cardiovascular events in subgroup meta-analysis of randomised controlled trials
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Fig 4 Efficacy of vitamins B6 and B12 and folic acid supplements in prevention of major cardiovascular events in subgroup meta-analysis of randomised controlled trials
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Fig 5 Efficacy of vitamins C, D, and E supplements in prevention of major cardiovascular events in subgroup meta-analysis of randomised controlled trials. For subgroup meta-analysis of vitamin C and vitamin E, we used data from 2008 PHS2 article83 because data were not available in 2012 PHS article
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Fig 6 Efficacy of β carotene and selenium supplements in prevention of major cardiovascular events in subgroup meta-analysis of randomised controlled trials
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Fig 7 Efficacy of low dose vitamin B6 supplements in prevention of major cardiovascular events in subgroup meta-analysis of randomised controlled trials by study quality according to Jadad scale
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Fig 8 Efficacy of vitamin E supplements in prevention of myocardial infarction in subgroup meta-analysis of randomised controlled trials according to provider of supplements (pharmaceutical industry or other). For subgroup meta-analysis of vitamin E, we used data from 2008 PHS2 article83 because data were not available in 2012 PHS article
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Comment in

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