(P22-035-25) Effects of Multivitamin Supplementation on Metabolomic Profiles: 2-Year Findings From the COSMOS Randomized Clinical Trial

Objectives: To evaluate the effects of randomized multivitamin-multimineral (MVM) supplementation on metabolomic profiles among older adults.

Methods: COSMOS is a 2x2 factorial, placebo-controlled, double-blinded, randomized clinical trial testing the effects of a daily MVM (Centrum Silver) and cocoa extract in US older adults. We randomly selected 399 participants with plasma samples collected at baseline, 1-year, and 2-year follow-up (mean age, 70.3±5.7 years; 200 [50.1%] women). Metabolomics profiles were quantified using the Nightingale Health nuclear magnetic resonance biomarker platform. This study tested the effects of MVM versus placebo on 325 metabolites, 7 metabolomic risk scores (MRS; estimated using published algorithms) for biological aging, and 24 MRSs for chronic diseases based upon the intention-to-treat principle.

Results: Daily MVM favorably changed 21 metabolites at a nominal level, including docosahexaenoic acid, chylomicrons and extremely large VLDL subclasses, creatinine, glycoprotein acetyls, relative triglycerides concentrations in lipoproteins, and isoleucine, but effects were not significant after adjusting for multiple testing (P < 0.05; false positive rate [FDR] >0.05). MVM significantly reduced 5 of 7 MRSs for biological aging, with the strongest effect for Zhang clock, the MRS with the highest predictive value for mortality (yearly change for MVM versus placebo, -1.03 [95% CI, -1.76 to -0.30] years; P=0.006; FDR=0.024). MVM also reduced MRSs for 16 of 24 chronic diseases, including cardiometabolic, dementia, and cancer outcomes, only at a nominal level (P < 0.05; FDR >0.05). In pre-specified stratified analyses, MVM had stronger effects for all significantly changed MRSs among obese participants. For example, MVM reduced Zhang clock by -2.39 [-4.07 to -0.72] years among those with BMI≥30 compared with -0.47 [-1.27 to 0.33] years among those with BMI < 30 (FDR=0.046 for interaction).

Conclusions: The COSMOS trial provides novel evidence that daily MVM supplementation may favorably change metabolomic profiles for older adults, especially among obese individuals, that potentially translate to longer-term health benefits and slowing biological aging.

Funding Sources: Massachusetts Life Sciences Center and Biogen, Nightingale Health, Mars Edge, Pfizer Consumer Healthcare (now Haleon), and National Institutes of Health.