Geroscience. 2026 Mar 30. doi: 10.1007/s11357-026-02197-9. Online ahead of print.
ABSTRACT
Despite widespread use in the USA, little is known about the impact of multivitamin-multimineral (MVM) supplementation on metabolomic profiles and how this may translate to biological aging and long-term risk of age-related chronic diseases. The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is a 2 × 2 factorial, placebo-controlled, double-blinded, randomized clinical trial testing daily MVM (Centrum Silver®) in US older adults. In 399 participants with metabolomics profiles quantified using the Nightingale Health nuclear magnetic resonance platform at baseline, year 1, and year 2 (70.3 ± 5.7 years; 50.1% female), we evaluate the effects of MVM versus placebo on 168 metabolites, 7 metabolomics clocks of biological aging, and 24 metabolomic risk scores (MRS) for chronic diseases. Compared with placebo, 2-year daily MVM supplementation increased the concentrations of docosahexaenoic acid (Cohen's d for between-group differences in changes from baseline to 2 years, 0.212 [95% CI, 0.02 to 0.404]) and omega-3 fatty acids (0.193 [0.003 to 0.382]) as well as delayed the increase in concentrations of creatinine (-0.222 [-0.424 to -0.019]). MVM also reduced MRS for 16 chronic diseases, including major cardiovascular events, renal disease, all-cause dementia, asthma, cataracts, glaucoma, liver disease, non-melanoma skin cancer, and prostate cancer (Cohen's d range, -0.206 to -0.277). However, all these effects were only significant at nominal levels, not after multiple-testing correction (p < 0.05; FDR > 0.05). Additionally, MVM led to a non-significant decrease across all metabolomic aging clocks, ranging from 0.496 to 1.054 years. Despite the limited sample size, COSMOS provides preliminary evidence that daily MVM supplementation may modestly improve metabolomic profiles in older adults. Further expansion within COSMOS is still warranted to confirm whether these alterations contribute to the benefits of MVM supplementation for healthy aging. Trial registration number: NCT02422745.
PMID:41910928 | DOI:10.1007/s11357-026-02197-9