Rautiainen S, Rist PM, Glynn RJ, Buring JE, Gaziano JM, Sesso HD. Multivitamin use and the risk of cardiovascular disease in men. J Nutr. 2016;146(6):1235-1240.
To investigate how multivitamin use is associated with the risk of cardiovascular disease (CVD) in initially healthy men at baseline
Prospective cohort; investigators followed a group of male physicians over a 12-year period. The men provided a wide range of self-reported lifestyle and clinical factors plus intake of selected foods and dietary supplements, including multivitamin use.
The study included 18,530 male physicians, aged 40 and older, from the Physicians’ Health Study I (PHS I) cohort; all of the men were free of cancer and CVD at baseline (1982).
The Physicians’ Health Study was originally designed as a 2x2 factorial randomized controlled trial to test the effects of aspirin and beta carotene on cancer and CVD. From 1982 to 1995 the PHS I tracked 22,071 male physicians aged 40 to 84 who were free of cancer and CVD at baseline (1982). This follow-up prospective cohort study by Rautiainen et al included only 18,530 men in the analysis because participants were excluded if there was missing information on dietary supplement use or selected lifestyle, clinical, and dietary factors.
Incidence of CVD events, including nonfatal myocardial infarction (MI), nonfatal stroke, and cardiac revascularization (coronary artery bypass grafting and/or percutaneous transluminal coronary angioplasty) were determined from self-reports on annual questionnaires. Reported CVD events were confirmed by an endpoints committee of physicians. Deaths were identified and tracked based on reports from family members, postal authorities, and the National Death Index. Further details pertaining to the criteria used to confirm study parameters is well-documented in the section titled “Ascertainment of CVD cases.”
Primary Outcome Measures
Incidence of CVD events including nonfatal MI, nonfatal stroke, and cardiac revascularization (coronary artery bypass grafting and/or percutaneous transluminal coronary angioplasty).
Investigators found no association between baseline multivitamin use and the risk of major CVD events, MI, stroke, or CVD death. However, multivitamin use was significantly associated with a 14% lower risk of cardiac revascularization and an 11% lower risk of ischemic heart diseases, defined as incident MI or cardiac revascularization. Self-reported use of multivitamins over a long duration (>20 years) was significantly associated with 44% lower risk of major cardiovascular disease.
Dietary supplement use in the United States is prevalent, with recent survey data showing that 68% of American adults take dietary supplements.1 Vitamins and minerals are the most prevailing category of supplements, and the “multivitamin” continues to be the top product consumed.1 Dietary supplement users report taking such products for overall health and wellness, as well as for specific health and nutrient benefits.1 When speaking with patients about why they take a multivitamin, most respond that they are taking it as an insurance policy to fill nutrient gaps that are not met by diet alone.
For nutrition-oriented practitioners this study reinforces existing practice, which is to assess an individual’s diet and recommend supplementation where nutrient shortfalls exist.
Consumers take multivitamins to augment the nutrient density of their diet. However, the scientific and medical communities often evaluate the benefits of taking a multivitamin based on its ability to reduce the risk of serious chronic diseases, such as cancer, cardiovascular disease, and others. Studying the benefits of supplemental nutrients on the incidence of long-latency chronic diseases is a scientific challenge that is not well-suited for drug-like randomized control trials—the scientific framework developed to evaluate the efficacy of drugs.2
Relying solely on pharmaceutical clinical trials to evaluate the impact of nutrient supplementations leads to erroneous overgeneralizations, such as the infamous Annals of Internal Medicine editorial, “Enough is Enough: Stop Wasting Money on Vitamin and Mineral Supplements.”3 This editorial discussed the results of 2 clinical trials and a US Preventive Service Task Force (USPSTF) report, which all came to the same conclusions: null. The editorial categorically dismissed any possible benefits of vitamin and mineral supplementation, without balancing the discussion with scientifically supported health benefits that carry real-world implications, such as folic acid and iodine for preventing neural tube defects or cognitive deficits in newborns;4-5 improving B12 status in the elderly;6 correcting iron deficiency in children;7 or providing missing nutrients for at-risk populations.8 Instead, in a high-impact medical journal, the authors characterized all vitamin and mineral supplementation as a “waste of money.” It is noteworthy that the USPSTF report, one of the 3 studies that served as the basis for the editorial, acknowledged that their systematic review of the scientific literature was “a review of trials, a study design used primarily to evaluate drug therapy. This design might not be ideally suited to evaluate nutrients. The control group in a placebo-controlled trial of medications is not exposed to the medication. In a nutrient supplementation study, however, the control group is exposed to some level of the nutrient…”9 This important consideration was lost in the catchy headline: “…Stop Wasting Your Money.”
The take-home message from the current study (Rautiainen et al) should be no surprise. A daily multivitamin is not a panacea for preventing cardiovascular disease. However, there was evidence of benefit in select outcomes such as a significant 14% lower risk of cardiac revascularization and an 11% lower risk of ischemic heart disease. There was also a significant “home run” finding of a statistically significant 44% lower risk for CVD in men who self-reported taking a multivitamin for 20 or more years. However, the authors wisely encourage readers to interpret this finding with caution because (a) this is an observational study; (b) there were a low number of participants who reported 20 or more years of multivitamin consumption; and (c) we already know that multivitamin use is positively associated with other healthy lifestyle and dietary factors that reduce your risk for CVD.10
Patients with perfect diets that provide optimal levels of all nutrients may not need a multivitamin. However, the 2015-2020 Dietary Guidelines for Americans identified potassium, dietary fiber, choline, magnesium, calcium, and vitamins A, D, E, and C as shortfall nutrients for Americans.6 In a clinician’s mind, this translates to the understanding that the typical American diet has meaningful nutrient shortfalls. For the majority of Americans, taking a multivitamin is a prudent recommendation that fills nutrient gaps that are not met through diet alone.