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

Daily MVM supplementation modestly reduced the rate of increase of PCGrimAge compared with placebo.

• Between-group difference in yearly change was -0.113 years (95% CI -0.205 to -0.020; P = 0.017) for PCGrimAge.
• The supplement tested was Centrum Silver taken daily over 2 years.
• The study included 958 participants (482 women and 476 men) from the COSMOS randomized clinical trial.
• PCGrimAge is classified as a second-generation epigenetic clock based on DNA methylation measures.

Daily MVM supplementation modestly reduced the rate of increase of PCPhenoAge compared with placebo.

• Between-group difference in yearly change was -0.214 years (95% CI -0.410 to -0.019; P = 0.032) for PCPhenoAge.
• PCPhenoAge is classified as a second-generation epigenetic clock.
• The intervention duration was 2 years.

MVM supplementation had a stronger effect on PCGrimAge among participants with accelerated biological aging at baseline compared with those with normal or decelerated biological aging.

• Among those with accelerated biological aging at baseline, the between-group difference in yearly PCGrimAge change was -0.236 years (95% CI -0.380 to -0.091).
• Among those with normal or decelerated biological aging at baseline, the between-group difference was -0.013 years (95% CI -0.130 to 0.104).
• The P-value for interaction was 0.018.

Cocoa extract supplementation did not have a statistically significant effect on any of the five epigenetic clocks tested.

• The cocoa extract dose was 500 mg cocoa flavanols per day, including 80 mg (-)-epicatechin.
• The five DNA methylation measures evaluated were PCHannum, PCHorvath, PCPhenoAge, PCGrimAge, and DunedinPACE.
• No significant between-group differences were observed for cocoa extract versus placebo on any clock.

The study was a prespecified ancillary study of the COSMOS randomized clinical trial evaluating effects of MVM and cocoa extract on five DNA methylation-based biological aging measures.

• The five epigenetic clocks assessed were PCHannum, PCHorvath, PCPhenoAge, PCGrimAge, and DunedinPACE.
• The study sample comprised 958 participants, 482 women and 476 men.
• The intervention period was 2 years.
• The MVM supplement was Centrum Silver and the cocoa extract provided 500 mg cocoa flavanols per day including 80 mg (-)-epicatechin.

The authors conclude that additional studies are needed to determine the clinical relevance of MVM supplementation on epigenetic clocks and whether such effects can help explain the beneficial effects of MVM supplementation on aging-related chronic conditions.

• Large-scale randomized trials have previously found that MVM supplements and cocoa flavanols may benefit several age-related chronic conditions among older adults.
• The authors describe the statistically significant effects of MVM on slowing biological aging as 'statistically significant but small.'
• The authors note that it remains unclear whether these supplements 'directly slow the biological aging process.'