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Myung SK, Ju W, Oh SW, et. al. Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: systematic review and meta-analysis of randomised controlled trials. BMJ 2013 Jan 18;346:f10.
Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev 2012;3:CD007176.
Martí-Carvajal AJ, Solà I, Lathyris D, Karakitsiou DE, Simancas-Racines D. Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev. 2013 Jan 31;1:CD006612.

Efficacy Endpoints

Decrease in major cardiovascular events (cardiovascular death, fatal/non-fatal MI, angina, sudden cardiac death, fatal/non-fatal stroke, and TIA)

Harm Endpoints

Increase in major cardiovascular events (see above)

Narrative

Cardiovascular disease is a major cause of morbidity and mortality worldwide, and there have been many conflicting studies regarding the efficacy of vitamin or antioxidant supplements for the prevention of cardiovascular disease and its related complications.

This review included 50 randomized-controlled trials enrolling 294,478 subjects and gives a comprehensive report regarding the efficacy of vitamin and antioxidant supplements on cardiovascular diseases. It found that the use of vitamin and antioxidant supplements was not associated with reduced risks of cardiovascular events (RR 1.00), 95% CI 0.98-1.02). However, in a subgroup meta-analysis by type of outcome, vitamin B6 and vitamin E were associated with a reduced risk of cardiovascular death (RR 0.91, 95% CI 0.83-0.99) and myocardial infarction (RR 0.77, 95% CI 0.65-0.91) respectively. Importantly, these benefits were found only in trials sponsored by industry, while further analysis by the review authors found no improvement in outcomes when analyzing trials not funded by industry.

Caveats

The authors note that their review investigated the use of synthetic vitamin and antioxidant compounds and that their results should not be directly applied to the use of fruits and vegetables (for which observational studies and some trials have suggested cardiovascular benefits). In addition, heterogeneity levels for the various meta-analyses in this paper are, in many cases, very high. This indicates that many of these studies should, arguably, not have been pooled together and should have instead been assessed on their individual merits and validity. The fact that the authors neither explain nor deal with this level of heterogeneity is an important, and unmentioned, point that weakens their conclusions.

Finally, the review again illustrates the difficulty of interpreting data from studies that receive funding or support from the pharmaceutical industry, with industry sponsored trials reporting a benefit often not replicated in trials without industry ties. Overall, however, we feel that this meta-analysis provides strong evidence for the assertion that vitamin and antioxidant supplements are likely ineffective for the primary prevention of cardiovascular disease.

Author

Manpreet Singh, MD and Dan Runde, MD

Published/Updated

April 10, 2013