Benefits
Reduced total cancer incidence in older men (PHS II)
A large RCT in male physicians aged 50+ found a daily multivitamin reduced total cancer incidence by 8%. The effect was driven by cancers other than prostate, with no effect on prostate cancer, and was a 27% reduction in men with a prior cancer history. The first major RCT to show cancer prevention from a multivitamin.
Lung cancer protection in COSMOS
A large trial in older men and women found a daily multivitamin reduced lung cancer risk by 38%. Total cancer and CVD showed no significant effect, but trial duration may have been too short for the total cancer endpoint.
Slowing of cognitive decline (COSMOS-Mind)
A trial in adults aged 65+ found a daily multivitamin produced a statistically significant improvement in global cognition versus placebo, with effects equivalent to slowing cognitive aging by about 2 years. Episodic memory and executive function also improved, and the effect was stronger in participants with prior CVD.
Filling micronutrient gaps in suboptimal diets
NHANES data show ~30–50% of US adults have inadequate intake of vitamins D, E, K, calcium, magnesium, and potassium. A daily multivitamin provides insurance against subclinical deficiencies, particularly relevant for older adults, restrictive dieters, and those with impaired absorption. Multivitamin users had significantly higher nutrient intake adequacy across the population.
Mechanism of action
Replenishing micronutrient cofactors for hundreds of enzymatic reactions
B vitamins serve as cofactors for energy metabolism (B1, B2, B3, B5), one-carbon metabolism (B6, B9, B12), and DNA synthesis. Magnesium, zinc, and selenium serve as cofactors for hundreds of enzymes including those involved in DNA repair, antioxidant defense (superoxide dismutase, glutathione peroxidase), and immune function. Even subclinical deficiencies impair enzymatic function and may accelerate aging-related decline.
Antioxidant defense (vitamins C, E, selenium, zinc)
Vitamins C and E and the trace minerals selenium, zinc, and copper support cellular antioxidant defense. Selenium-dependent glutathione peroxidase, copper/zinc-dependent superoxide dismutase, and vitamin C/E recycling all require adequate micronutrient status. May explain modest but real benefit in cancer endpoints (DNA damage from oxidative stress is mechanistically linked to carcinogenesis).
Immune support and DNA integrity
Multiple micronutrients (vitamins A, D, E, B6, B12, folate, zinc, selenium, iron, copper) are essential for innate and adaptive immune function. Folate and B12 support DNA methylation patterns and chromosome stability. The combination of these mechanisms likely explains the modest cancer reduction observed in PHS II — DNA repair fidelity improvement compounding over years of supplementation.
Clinical trials
Large-scale randomized, double-blind, placebo-controlled trial (Gaziano JM, Sesso HD, Christen WG, Bubes V, Smith JP, MacFadyen J, Schvartz M, Manson JE, Glynn RJ, Buring JE 2012, JAMA 308(18):1871-1880, doi:10.1001/jama.2012.14641).
14,641 male U.S. physicians initially aged ≥50 (mean age 64.3). Including 1,312 men with cancer history. Randomized to daily Centrum Silver multivitamin or placebo. Treatment and follow-up 1997-2011 (median 11.2 years).
Total cancer incidence significantly reduced: 17.0 vs 18.3 events per 1,000 person-years (HR 0.92, 95% CI 0.86-0.998, p=0.04) — an 8% reduction. No significant effect on prostate cancer (HR 0.98), colorectal cancer (HR 0.89), or lung cancer (HR 0.84). Effect stronger in men with cancer history (HR 0.73) and men ≥70 (HR 0.82). 1,732 cancer deaths during follow-up — no significant difference in cancer mortality between groups. The first large clinical trial to demonstrate cancer prevention from a multivitamin.
Randomized, double-blind, placebo-controlled trial (Sesso HD, Rist PM, Aragaki AK, Rautiainen S, Johnson LG, Friedenberg G, Copeland T, Clar A, Mora S, Moorthy MV, Sarkissian A, Wactawski-Wende J, Tinker LF, Carrick WR, Anderson GL, Manson JE for the COSMOS Research, Am J Clin Nutr 115(6):1501-1510, doi:10.1093/ajcn/nqac056).
21,442 U.S. adults (men ≥60 years, women ≥65 years). Randomized to daily Centrum Silver or placebo. Median follow-up 3.6 years.
Primary outcome (total invasive cancer): HR 0.97 (95% CI 0.86-1.09, p=0.57) — no significant overall effect. Secondary: Lung cancer significantly reduced (HR 0.62, 95% CI 0.42-0.92). No significant effect on breast (HR 1.06), colorectal (HR 1.30), CVD composite (HR 0.98), or all-cause mortality (HR 0.93). Authors concluded 3.6 years may be too short to detect total cancer effect; longer follow-up needed. The lung cancer signal is consistent with mechanisms involving B vitamins, folate, and antioxidants in cellular DNA repair.
Ancillary study to COSMOS evaluating cognitive function (Baker LD, Manson JE, Rapp SR, Sesso HD, Gaussoin SA, Shumaker SA, Espeland MA 2023, Alzheimers Dement 19(4):1308-1319, doi:10.1002/alz.12767).
2,262 COSMOS participants ≥65 years (subset of larger trial). 3-year follow-up with annual cognitive assessments via telephone interview using composite of 5 tests covering global cognition, episodic memory, and executive function.
Daily multivitamin produced statistically significant improvement in global cognition vs placebo (effect size 0.07 SD, p=0.007), corresponding to slowing of cognitive aging by approximately 2 years (60% slowing of expected age-related decline over 3 years). Significant improvements also in episodic memory and executive function. Effect was stronger in participants with cardiovascular disease history. The largest, most rigorous trial to date showing cognitive benefit from a multivitamin.