Vitamin, Mineral, and Multivitamin Supplements for the Primary Prevention of Cardiovascular Disease and Cancer

Background In the United States, dietary supplements are commonly used to prevent chronic diseases, including cardiovascular disease (CVD) and cancer. Purpose To systematically review evidence for the use of multivitamins or single nutrients and functionally related nutrient pairs for the prevention of CVD and cancer in the general population (primary prevention). Methods We searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, and Cochrane Central Register of Controlled Trials to identify literature that was published between 2005 and January 29, 2013. We also examined the references from the previous reviews and other relevant reviews to identify additional studies; we also searched Web sites of government agencies and other organizations for grey literature. Two investigators independently reviewed identified abstracts and full-text articles against a set of a priori inclusion and quality criteria. One investigator abstracted data into an evidence table and a second investigator checked these data. We qualitatively and quantitatively synthesized the results for the four key questions and grouped the included studies by study supplement. We conducted meta-analyses using Mantel-Haenzel fixed effects models for overall cancer incidence, CVD incidence, and all-cause mortality. Results We included 103 articles representing 26 unique studies. Very few studies examined the use of multivitamin supplements. Two trials showed a protective effect against cancer in men; only one of these trials included women and found no effect. No effects of treatment were seen on CVD or all-cause mortality. Beta-carotene showed a negative effect on lung cancer incidence and mortality among individuals at high risk for lung cancer at baseline (i.e., smokers and asbestos-exposed workers); this effect was persistent even when combined with vitamin A or E. Trials of vitamin E supplementation showed mixed results and altogether had no overall effect on cancer, CVD, or all-cause mortality. Only one of two included selenium trials showed a beneficial effect for colorectal and prostate cancer; however, this trial included a small sample size. The few studies addressing folic acid, vitamin C, and vitamin A showed no effect on CVD, cancer, and mortality. Vitamin D and/or calcium supplementation also showed no overall effect on CVD, cancer, and mortality. Harms were infrequently reported and aside from limited paradoxical effects for some supplements, were not considered serious. Conclusions There are a limited number of trials examining the effects of dietary supplements on the primary prevention of CVD and cancer; the majority showed no effect in healthy populations. Clinical heterogeneity of included studies limits generalizability of results to the general primary care population. Results from trials in at-risk populations discourage additional studies for particular supplements (e.g., beta-carotene); however, future research in general primary care populations and on other supplements is required to address research gaps.