Li · Nature medicine 2026 · Randomized controlled trial (prespecified ancillary study) · n=958

Effects of daily multivitamin-multimineral and cocoa extract supplementation on epigenetic aging clocks in the COSMOS randomized clinical trial.

Cited 18 times in the scientific literature.

Level 2 - randomized trial

Individual randomized controlled trial evaluating 2-year biomarker outcomes.

PubMed 41803341 · doi:10.1038/s41591-026-04239-3 · record verified 2026-08-26

What was done

This prespecified ancillary study of the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) evaluated 958 participants (482 women and 476 men) randomized to receive daily multivitamin-multimineral (MVM; Centrum Silver), cocoa extract (500 mg cocoa flavanols including 80 mg (-)-epicatechin), or placebo for 2 years. Investigators measured changes across five DNA methylation measures of biological aging: PCHannum, PCHorvath, PCPhenoAge, PCGrimAge, and DunedinPACE.

What was found

Compared with placebo, daily MVM supplementation modestly slowed the annual rate of biological aging on two second-generation clocks: - PCGrimAge yearly change difference: -0.113 years (95% CI -0.205 to -0.020; P = 0.017). - PCPhenoAge yearly change difference: -0.214 years (95% CI -0.410 to -0.019; P = 0.032). - The MVM effect on PCGrimAge was greater in individuals with accelerated baseline biological aging (-0.236 years [95% CI -0.380 to -0.091]) compared to those with normal or decelerated aging (-0.013 years [95% CI -0.130 to 0.104]; P for interaction = 0.018). - Cocoa extract had no effect on the five epigenetic clocks tested.

Why it matters

These findings provide randomized trial evidence that daily multivitamin supplementation can directly slow epigenetic clocks of biological aging over 2 years, particularly in individuals with accelerated baseline aging.

Limits

The effect sizes were modest, and whether slowing these surrogate methylation clocks translates into reduced clinical morbidity or mortality is not established by these data. The abstract does not provide numerical values or detailed findings for PCHannum, PCHorvath, or DunedinPACE, and follow-up was limited to 2 years.

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