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

BMJ 2013; 346 doi: (Published 18 January 2013) Cite this as: BMJ 2013;346:f10
  1. Seung-Kwon Myung, senior scientist12,
  2. Woong Ju, associate professor3,
  3. Belong Cho, professor1,
  4. Seung-Won Oh, assistant professor4,
  5. Sang Min Park, associate professor1,
  6. Bon-Kwon Koo, associate professor5,
  7. Byung-Joo Park, professor6
  8. for the Korean Meta-Analysis (KORMA) Study Group
  1. 1Department of Family Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
  2. 2Carcinogenesis Research Branch and Department of Family Medicine, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea
  3. 3Department of Obstetrics and Gynecology and Medical Research Institute, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
  4. 4Healthcare Research Institute and Department of Family Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Republic of Korea
  5. 5Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
  6. 6Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
  1. Correspondence to: B Cho, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of Korea belong{at}, and S-K Myung, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do, 410-769, Republic of Korea msk{at}
  • Accepted 19 December 2012


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 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; I2=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 B6 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 B6 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.


  • Contributors: BC and S-KM were responsible for the initial plan, study design, conducting the study, data interpretation, and manuscript drafting. S-KM was responsible for statistical analysis. S-KM, WJ, and S-WO were responsible for data collection, data extraction, and data interpretation. SMP, B-KK, and B-J P were responsible for data interpretation and manuscript drafting. BC and S-KM are guarantors.

  • Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at (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.

  • Ethical approval: Not required.

  • Data sharing: No additional data available.

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