Daily Multivitamin May Slow Ticking of Biological Aging Clock

A daily multivitamin-multimineral supplement may slow markers of biological aging in humans, a prespecified analysis of COSMOS trial data showed.

Older adults who took the daily vitamin and mineral supplement had a significant reduction in the yearly rate of increase in two epigenetic clocks developed to estimate mortality risk — PCPhenoAge and PCGrimAge — by about 2.6 months (0.214 years, P=0.032) and 1.4 months (0.113 years, P=0.017), respectively, reported Howard Sesso, ScD, MPH, of Mass General Brigham in Boston, and colleagues.

The daily supplement had a stronger effect in people with accelerated biological aging at baseline on PCGrimAge (-0.236 years) compared with those who had normal or decelerated biological aging (-0.013 years, P=0.018 for interaction), the researchers wrote in Nature Medicine.

Patterns were similar for three other DNA methylation clocks (PCHannum, PCHorvath, and DunedinPACE), but trends were not significant.

COSMOS tested the effects of two daily interventions — a vitamin and mineral supplement or cocoa extract – versus placebo on older adults. This analysis looked at the 2-year results of the interventions on five epigenetic clocks that measure DNA patterns in blood to estimate the biological aging process.

Cocoa extract had no effect on any epigenetic clocks tested.

The findings are “a major advance for the supplement field” but whether a daily vitamin can increase a healthy lifespan is an open question, noted Daniel Belsky, PhD, and Calen Ryan, PhD, both of the Columbia University Mailman School of Public Health in New York City, in an accompanying editorial.

“The ‘geroscience hypothesis’ proposes that interventions to slow or reverse cellular-level processes of aging can delay or prevent chronic diseases and increase healthy lifespan (healthspan),” Belsky and Ryan wrote.

The best validated biomarkers to quantify the pace of biological processes of aging are epigenetic clocks, the editorialists observed. “There is now abundant evidence from observational studies that some of these clocks — in particular, GrimAge 3 and DunedinPACE 4 — are reliably predictive of both healthspan and lifespan,” they wrote.

“Evidence that simple multivitamin supplementation can slow aging, even slightly, would have substantial implications, including for public health guidelines,” Belsky and Ryan pointed out. “The data reported from COSMOS brings the field one step closer to that evidence, but uncertainties remain.”

The results complement findings seen in similar analyses of other trial data, including the DO-HEALTH study that showed that omega-3 supplementation may slow epigenetic clocks in healthy older Swiss adults.

The original COSMOS trial reported that cocoa extract decreased cardiovascular disease death by 27%, but a later study found that cocoa had no effect on age-related macular degeneration.

The ancillary COSMOS-Mind trial showed that daily vitamin and mineral supplementation improved global cognition in older adults, notably for participants with cardiovascular disease.

COSMOS included 21,442 older adults and its COSMOS Blood subcohort included 6,867 participants. Sesso and colleagues analyzed DNA methylation data from blood samples of 958 randomly selected healthy participants with a mean chronological age of 70 who remained free of chronic disease throughout the trial. Most (89.1%) were white; 482 participants were women and 476 were men.

The researchers evaluated the 2-year effect of a daily multivitamin-multimineral supplement (Centrum Silver) or cocoa extract (500 mg cocoa flavanols per day, including 80 mg (−)-epicatechin) on five DNA methylation measures.

The effect of a daily multivitamin varied on each of the five epigenetic clocks, “although the directions were quite consistent,” Sesso and co-authors noted.

“Although these epigenetic clocks have each been identified as valid biomarkers of aging, they are composed of distinct methylation sites and designed to estimate different age-related measures, suggesting that they likely reflect unique aspects of aging processes,” they added.

A post-hoc analysis of 166 participants revealed that lower baseline levels of nutritional biomarkers were linked to faster biological aging, while greater increases in nutritional biomarkers during follow-up were associated with slower epigenetic aging.

A daily vitamin and mineral supplement may significantly increase folate and lutein levels in people with accelerated biological aging at baseline, and there may be a tendency for other biomarkers like zeaxanthin, vitamin B12, and vitamin D to increase, Sesso and co-authors noted.

Further work is needed to understand how improvements in biological aging explain reductions in clinical outcomes, they added. The researchers plan to investigate how the effects of daily multivitamin-multimineral supplementation extend to different outcomes they’ve seen, including improvements in cognition.