Dietary supplements and risk of cause-specific death, cardiovascular disease, and cancer: a systematic review and meta-analysis of primary prevention trials
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Our aim was to assess the efficacy of dietary supplements in the primary prevention of cause-specific death, cardiovascular disease (CVD), and cancer by using meta-analytical approaches. Electronic and hand searches were performed until August 2016. Inclusion criteria were as follows: 1) minimum intervention period of 12 mo; 2) primary prevention trials; 3) mean age ≥18 y; 4) interventions included vitamins, fatty acids, minerals, supplements containing combinations of vitamins and minerals, protein, fiber, prebiotics, and probiotics; and 5) primary outcome of all-cause mortality and secondary outcomes of mortality or incidence from CVD or cancer. Pooled effects across studies were estimated by using random-effects meta-analysis. Overall, 49 trials (69 reports) including 287,304 participants met the inclusion criteria. Thirty-two trials were judged as low risk-, 15 trials as moderate risk-, and 2 trials as high risk-of-bias studies. Supplements containing vitamin E (RR: 0.88; 95% CI: 0.80, 0.96) significantly reduced cardiovascular mortality risk, whereas supplements with folic acid reduced the risk of CVD (RR: 0.81; 95% CI: 0.70, 0.94). Vitamins D, C, and K; selenium; zinc; magnesium; and eicosapentaenoic acid showed no significant risk reduction for any of the outcomes. On the contrary, vitamin A was linked to an increased cancer risk (RR: 1.16; 95% CI: 1.00, 1.35). Supplements with β-carotene showed no significant effect; however, in the subgroup with β-carotene given singly, an increased risk of all-cause mortality by 6% (RR: 1.06; 95% CI: 1.02, 1.10) was observed. Taken together, we found insufficient evidence to support the use of dietary supplements in the primary prevention of cause-specific death, incidence of CVD, and incidence of cancer. The application of some supplements generated small beneficial effects; however, the heterogeneous types and doses of supplements limit the generalizability to the overall population.
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Supplementation of ≥30 mg/d β-carotene is linked to increased all-cause mortality.
“consistent with previous work linking supplementation of ≥30 mg/d β-carotene to increased all-cause mortality.”
From Micronutrient Supplementation to Reduce Cardiovascular Risk (2022) · cites this paper as [29]
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- Authors
- Schwingshackl, L., Boeing, H., Stelmach-Mardas, M., Gottschald, M., Dietrich, S., Hoffmann, G., & Chaimani, A.
- Affiliations
- German Institute of Human Nutrition (DE)
- Poznan University of Medical Sciences (PL)
- University of Vienna (AT)
- University of Ioannina (GR)
- Corresponding author
- Schwingshackl, Lukas
- ORCID
- Venue
- Advances in Nutrition
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 8
- Issue
- 1
- Pages
- 27-39
- ISSN
- 2156-5376 (ISSN-L)
- 2161-8313
- PMC
- PMC5227980
- OpenAlex
- W2576285435
- Cited by
- 165
- References
- 119
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 9 · 2023: 25 · 2022: 22 · 2021: 32 · 2020: 14 · 2019: 15 · 2018: 28 · 2017: 7
- FWCI
- 2.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Advances in Nutrition (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutrition and Health Studies
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- dietary supplements, primary prevention, cause-specific mortality, cardiovascular disease, cancer incidence, vitamin E, folic acid, vitamin A, beta-carotene, cardiovascular mortality, selenium, zinc, magnesium, eicosapentaenoic acid, prebiotics, probiotics, all-cause mortality
- MeSH terms
- Cardiovascular Diseases, Diet, Humans, Neoplasms, Primary Prevention, Nutrition Assessment, Incidence, Randomized Controlled Trials as Topic, Micronutrients, Dietary Supplements, Observational Studies as Topic
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