Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: systematic review and meta-analysis of randomised controlled trials
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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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The impact of vitamin E supplementation on cardiovascular mortality or prostate cancer is still not settled and clinical intervention studies have shown no benefit.
“Nonetheless, the impact of vitamin E supplementation on cardiovascular mortality or prostate cancer is still not settled and clinical intervention studies have shown no bene fi t.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [370]
The Introduction (page unavailable) reports a prior meta-analysis finding no cardiovascular-death benefit from vitamin E, and the Results (page unavailable) find no overall cardiovascular benefit from vitamin or antioxidant supplements. The paper does not address whether vitamin E’s effect on prostate cancer is unsettled or whether intervention studies show no prostate-cancer benefit (searched: prostate cancer, prostate). (LLM, conf=0.86)
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Tacke, F., Horn, P., Wai-Sun Wong, V., Ratziu, V., Bugianesi, E., Francque, S., Zelber-Sagi, S., Valenti, L., Roden, M., Schick, F., et al. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.04.031 · Cited by 2,210 · see citing works
Theodoratou, E., Tzoulaki, I., Zgaga, L., & Ioannidis, J. P. A. (2014) · BMJ · doi:10.1136/bmj.g2035 · Cited by 956 · see citing works
Mendelian Randomization: Concepts and Scope
Richmond, R. C., & Davey Smith, G. (2022) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a040501 · Cited by 841 · see citing works
Mendelian randomization in cardiometabolic disease: challenges in evaluating causality
Holmes, M. V., Ala-Korpela, M., & Smith, G. D. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2017.78 · Cited by 679 · see citing works
Vitamin D supplementation for prevention of mortality in adults
Bjelakovic, G., Gluud, L. L., Nikolova, D., Whitfield, K., Wetterslev, J., Simonetti, R. G., Bjelakovic, M., & Gluud, C. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007470.pub3 · Cited by 695 · see citing works
Ageing, age-related diseases and oxidative stress: What to do next?
Luo, J., Mills, K., le Cessie, S., Noordam, R., & van Heemst, D. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2019.100982 · Cited by 581 · see citing works
Does nutrition play a role in the prevention and management of sarcopenia?
Robinson, S. M., Reginster, J. Y., Rizzoli, R., Shaw, S. C., Kanis, J. A., Bautmans, I., Bischoff-Ferrari, H., Bruyère, O., Cesari, M., Dawson-Hughes, B., et al. (2018) · Clinical Nutrition · doi:10.1016/j.clnu.2017.08.016 · Cited by 491 · see citing works
Wang, Y., Xue, H., Huang, Y., Huang, L., & Zhang, D. (2017) · Advances in Nutrition · doi:10.3945/an.116.014100 · Cited by 310 · see citing works
Effects of the Mediterranean Diet on Cardiovascular Outcomes—A Systematic Review and Meta-Analysis
Liyanage, T., Ninomiya, T., Wang, A., Neal, B., Jun, M., Wong, M. G., Jardine, M., Hillis, G. S., & Perkovic, V. (2016) · PLOS ONE · doi:10.1371/journal.pone.0159252 · Cited by 210 · see citing works
Bjelakovic, G., Nikolova, D., & Gluud, C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0074558 · Cited by 183 · see citing works
Schwingshackl, L., Boeing, H., Stelmach-Mardas, M., Gottschald, M., Dietrich, S., Hoffmann, G., & Chaimani, A. (2017) · Advances in Nutrition · doi:10.3945/an.116.013516 · Cited by 165 · see citing works
Targeting inflammation to reduce cardiovascular disease risk: A realistic clinical prospect?
Welsh, P., Grassia, G., Botha, S., Sattar, N., & Maffia, P. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13818 · Cited by 164 · see citing works
Mechanisms of Sudden Cardiac Death: Oxidants and Metabolism
Yang, K.-C., Kyle, J. W., Makielski, J. C., & Dudley, S. C. (2015) · Circulation Research · doi:10.1161/circresaha.116.304691 · Cited by 127 · see citing works
Mao, Y., Lin, W., Wen, J., & Chen, G. (2020) · BMJ Open Diabetes Research & Care · doi:10.1136/bmjdrc-2020-001225 · Cited by 108 · see citing works
Varadharaj, S., Kelly, O. J., Khayat, R. N., Kumar, P. S., Ahmed, N., & Zweier, J. L. (2017) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2017.00064 · Cited by 101 · see citing works
Ashor, A. W., Brown, R., Keenan, P. D., Willis, N. D., Siervo, M., & Mathers, J. C. (2019) · Nutrition Research · doi:10.1016/j.nutres.2018.08.005 · Cited by 66 · see citing works
Jones, C. W., Keil, L. G., Weaver, M. A., & Platts-Mills, T. F. (2014) · Systematic Reviews · doi:10.1186/2046-4053-3-126 · Cited by 61 · see citing works
Skin Redox Balance Maintenance: The Need for an Nrf2-Activator Delivery System
Ben-Yehuda Greenwald, M., Ben-Sasson, S., Bianco-Peled, H., & Kohen, R. (2016) · Cosmetics · doi:10.3390/cosmetics3010001 · Cited by 49 · see citing works
Treatment of Oxidative Stress with Exosomes in Myocardial Ischemia
Liu, Y., Wang, M., Liang, Y., Wang, C., Naruse, K., & Takahashi, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041729 · Cited by 42 · see citing works
Yanamala, N., Kapralov, A. A., Djukic, M., Peterson, J., Mao, G., Klein-Seetharaman, J., Stoyanovsky, D. A., Stursa, J., Neuzil, J., & Kagan, V. E. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.601377 · Cited by 19 · see citing works
Hsieh, C., Hsiao, G., Hsu, M., Wang, Y., & Sheu, J. (2014) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12277 · Cited by 15 · see citing works
Pei, R., Mah, E., Leonard, S. W., Traber, M. G., & Bruno, R. S. (2015) · Free Radical Research · doi:10.3109/10715762.2015.1040788 · Cited by 14 · see citing works
- Authors
- Myung, S.-K., Ju, W., Cho, B., Oh, S.-W., Park, S. M., Koo, B.-K., Park, B.-J., & for the Korean Meta-Analysis (KORMA) Study Group
- Affiliations
- Seoul National University (KR)
- Ewha Womans University (KR)
- Corresponding author
- Cho, B.
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2013-01-18
- Volume
- 346
- Issue
- jan18 1
- Pages
- f10-f10
- ISSN
- 1756-1833 (ISSN-L)
- PMC
- PMC3548618
- OpenAlex
- W2095592188
- Cited by
- 467
- References
- 96
- Citations by year
- 2026: 18 · 2025: 17 · 2024: 27 · 2023: 22 · 2022: 29 · 2021: 37 · 2020: 39 · 2019: 41 · 2018: 37 · 2017: 42 · 2016: 38 · 2015: 41 · 2014: 49 · 2013: 30
- FWCI
- 5.14
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- BMJ (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutrition and Health Studies
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Keywords
- vitamin supplements, antioxidant supplements, cardiovascular disease prevention, vitamin B6, vitamin E, major cardiovascular events, angina pectoris, cardiovascular mortality, myocardial infarction, pharmaceutical industry funding, supplement quality
- MeSH terms
- Antioxidants, Cardiovascular Diseases, Humans, Vitamins, Randomized Controlled Trials as Topic, Dietary Supplements
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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