Multivitamins

What it is

A multivitamin-multimineral (MVM) pill combines many vitamins and minerals in one daily dose. Multivitamin preparations are the most common dietary supplement, taken by at least one-third of US adults [1]. The COSMOS trials tested one product, Centrum Silver, taken once a day [2].

What the research says

Memory and thinking. In COSMOS-Mind, 2,262 older adults took a daily multivitamin-mineral or placebo for three years; global cognition improved slightly more on the multivitamin (0.07 standard units, 95% CI 0.02 to 0.12) [3]. A meta-analysis of three COSMOS cognitive substudies found a benefit for global cognition and for episodic memory; the authors said the global cognition effect was about equal to two years of slower cognitive aging [4]. In the Physicians' Health Study II, 5,947 male physicians aged 65 and older took a multivitamin for up to 12 years and showed no difference in cognitive change [5].

Cancer. In 14,641 male physicians followed for 11 years, a daily multivitamin modestly reduced total cancer (hazard ratio 0.92, 95% CI 0.86 to 0.998), but not prostate or colorectal cancer individually [1]. In COSMOS-Web, 21,442 adults took it for 3.6 years and total invasive cancer was not significantly reduced (hazard ratio 0.97, 95% CI 0.86 to 1.09) [6]. A systematic review of trials for the US Preventive Services Task Force found a small reduction in cancer incidence with multivitamin use, while noting the limits of the evidence [7].

Heart disease. In the Physicians' Health Study II, 14,641 men were followed for about 11 years, and the multivitamin did not reduce major cardiovascular events (hazard ratio 1.01, 95% CI 0.91 to 1.10) [8]. COSMOS-Web found the same for its combined heart outcome (hazard ratio 0.98) [6]. A 2018 meta-analysis of trials and cohorts found no association with cardiovascular death (relative risk 1.00) [9].

Biological aging. In a prespecified two-year substudy of 958 COSMOS participants, the multivitamin slowed the rise of two epigenetic clocks, PCGrimAge and PCPhenoAge [2]. A smaller metabolomic analysis of 399 people found small rises in omega-3 fatty acids and DHA, but its aging clocks were not statistically significant [10].

Doses used in studies

The COSMOS trials used one daily multivitamin-mineral pill (Centrum Silver) against placebo [2]. Trial length ranged from two years for the aging clocks [2] to 3.6 years in COSMOS-Web [6], three years in COSMOS-Mind [3] and about 11 to 12 years in the Physicians' Health Study II [8][5].

Safety and interactions

• Side effects: COSMOS-Web reported no safety concerns with the daily multivitamin [6].
• Beta carotene: separate beta carotene supplements were linked to more lung cancer in people at high risk of it, and to more cardiovascular deaths [7].
• Single vitamins: the same review linked vitamin A to hip fracture, vitamin E to hemorrhagic stroke, and vitamin C and calcium to kidney stones [7].
• Upper limits, pregnancy and medicine interactions: the trial abstracts read for this page did not report upper intake limits, pregnancy data or interactions with medicines. Ask a doctor or pharmacist, especially if you take medicines or have kidney disease.

Caveats and open questions

The trials mostly enrolled healthy, well-nourished older adults, and the authors of the Physicians' Health Study II noted that doses may be too low, or the population too well-nourished, to benefit [5]. Cancer and cognition results disagree between trials [1][6][3][5]. The aging clocks are surrogate markers, and their clinical meaning is unknown [2]. Manufacturers donated pills and packaging for the COSMOS trials [2].