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Vitamin and Mineral Supplements for the Primary Prevention of Cardiovascular Disease and Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force

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O’Connor, Elizabeth A., Evans, Corinne V., Ivlev, Ilya, Rushkin, Megan C., Thomas, Rachel G., Martin, Allea, Lin, Jennifer S.·2022·JAMA
DOI 10.1001/jama.2021.15650PMC PMC13207626
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Abstract

Importance: Cardiovascular disease and cancer are the 2 leading causes of death in the US, and vitamin and mineral supplementation has been proposed to help prevent these conditions. Objective: To review the benefits and harms of vitamin and mineral supplementation in healthy adults to prevent cardiovascular disease and cancer to inform the US Preventive Services Task Force. Data Sources: MEDLINE, PubMed (publisher-supplied records only), Cochrane Library, and Embase (January 2013 to February 1, 2022); prior reviews. Study Selection: English-language randomized clinical trials (RCTs) of vitamin or mineral use among adults without cardiovascular disease or cancer and with no known vitamin or mineral deficiencies; observational cohort studies examining serious harms. Data Extraction and Synthesis: Single extraction, verified by a second reviewer. Quantitative pooling methods appropriate for rare events were used for most analyses. Main Outcomes and Measures: Mortality, cardiovascular disease events, cancer incidence, serious harms. Results: Eighty-four studies (N=739 803) were included. In pooled analyses, multivitamin use was significantly associated with a lower incidence of any cancer (odds ratio [OR], 0.93 [95% CI, 0.87-0.99]; 4 RCTs [n=48 859]; absolute risk difference [ARD] range among adequately powered trials, -0.2% to -1.2%) and lung cancer (OR, 0.75 [95% CI, 0.58-0.95]; 2 RCTs [n=36 052]; ARD, 0.2%). However, the evidence for multivitamins had important limitations. Beta carotene (with or without vitamin A) was significantly associated with an increased risk of lung cancer (OR, 1.20 [95% CI, 1.01-1.42]; 4 RCTs [n=94 830]; ARD range, -0.1% to 0.6%) and cardiovascular mortality (OR, 1.10 [95% CI, 1.02-1.19]; 5 RCTs [n=94 506] ARD range, -0.8% to 0.8%). Vitamin D use was not significantly associated with all-cause mortality (OR, 0.96 [95% CI, 0.91-1.02]; 27 RCTs [n=117 082]), cardiovascular disease (eg, composite cardiovascular disease event outcome: OR, 1.00 [95% CI, 0.95-1.05]; 7 RCTs [n=74 925]), or cancer outcomes (eg, any cancer incidence: OR, 0.98 [95% CI, 0.92-1.03]; 19 RCTs [n=86 899]). Vitamin E was not significantly associated with all-cause mortality (OR, 1.02 [95% CI, 0.97-1.07]; 9 RCTs [n=107 772]), cardiovascular disease events (OR, 0.96 [95% CI, 0.90-1.04]; 4 RCTs [n=62 136]), or cancer incidence (OR, 1.02 [95% CI, 0.98-1.08]; 5 RCTs [n=76 777]). Evidence for benefit of other supplements was equivocal, minimal, or absent. Limited evidence suggested some supplements may be associated with higher risk of serious harms (hip fracture [vitamin A], hemorrhagic stroke [vitamin E], and kidney stones [vitamin C, calcium]). Conclusions and Relevance: Vitamin and mineral supplementation was associated with little or no benefit in preventing cancer, cardiovascular disease, and death, with the exception of a small benefit for cancer incidence with multivitamin use. Beta carotene was associated with an increased risk of lung cancer and other harmful outcomes in persons at high risk of lung cancer.

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  1. Murphy SL, Xu J, Kochanek KD, Arias E, Tejada-Vera B. Deaths: final data for 2018. Natl Vital Stat Rep. 2021;69(13):1-83.
  2. US Preventive Services Task Force. US Preventive Services Task Force Procedure Manual. Published May 2021. https://www. uspreventiveservicestaskforce.org/uspstf/about- uspstf/methods-and-processes/procedure-manual 10. US Preventive Services Task Force. Final research plan: vitamin, mineral, and multivitamin supplementation to prevent cardiovascular disease and cancer. Published 2019. Accessed May 9, 2022. https://www.uspreventiveservicestaskforce.org/ uspstf/document/final-research-plan/vitamin- supplementation-to-prevent-cvd-and-cancer- preventive-medication 11. O'Connor EA, Evans CV, Ivlev I, et al. Vitamin, Mineral, and Multivitamin Supplements for the Primary Prevention of Cardiovascular Disease and Cancer: A Systematic Evidence Review for the US Preventive Services Task Force. Evidence Synthesis No. 209. Agency for Healthcare Research and Quality; 2022. AHRQ publication 21-05278-EF-1.
  3. Moon TE, Levine N, Cartmel B, et al; Southwest Skin Cancer Prevention Study Group. Effect of retinol in preventing squamous cell skin cancer in moderate-risk subjects: a randomized, double-blind, controlled trial. Cancer Epidemiol Biomarkers Prev. 1997;6(11):949-956.

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Authors
O’Connor, E. A., Evans, C. V., Ivlev, I., Rushkin, M. C., Thomas, R. G., Martin, A., & Lin, J. S.
Affiliations
Kaiser Permanente (US)
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2022-06-21
Volume
327
Issue
23
Pages
2334
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.2021.15650
PMC
PMC13207626
OpenAlex
W4283215237
Cited by
151
References
100
Citations by year
2026: 27 · 2025: 31 · 2024: 40 · 2023: 37 · 2022: 16
FWCI
6.16
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
Funders
Agency for Healthcare Research and Quality (HHSA 290-2015-00007-I)
Topics
  • 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
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords
vitamin supplementation, mineral supplementation, multivitamins, beta-carotene, vitamin A, vitamin D, cardiovascular disease prevention, cancer prevention, lung cancer, cardiovascular mortality, all-cause mortality, serious harm, healthy adults, USPSTF recommendations, primary prevention, cancer incidence, cardiovascular events, risk-benefit assessment
MeSH terms
Adult, Cardiovascular Diseases, Humans, Lung Neoplasms, Minerals, Neoplasms, Primary Prevention, United States, Vitamin A, Vitamins, beta Carotene, Dietary Supplements, Advisory Committees

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