The effects of multivitamin–multimineral and cocoa extracts on aging

Large-scale randomized trials have found that multivitamin–multimineral (MVM) supplements and cocoa flavanols may benefit several age-related chronic conditions among older adults, but it remains unclear whether these two supplements directly slow the biological aging process. This prespecified ancillary study evaluated the 2-year effect of a daily MVM (Centrum Silver) and cocoa extract (500 mg cocoa flavanols per day, including 80 mg (−)-epicatechin) on five DNA methylation measures of biological aging (PCHannum, PCHorvath, PCPhenoAge, PCGrimAge and DunedinPACE) among 958 participants (482 women and 476 men) in the Cocoa Supplement and Multivitamin Outcomes Study (COSMOS).

Compared with placebo, daily MVM supplementation modestly reduced the rate of increase of second-generation epigenetic clocks, with a between-group difference in yearly change of −0.113 years (95% confidence interval (CI) −0.205 to −0.020; P = 0.017) for PCGrimAge and −0.214 years (−0.410 to −0.019; P = 0.032) for PCPhenoAge. MVM had a stronger effect on PCGrimAge among those with accelerated biological aging at baseline (−0.236 [−0.380 to −0.091]).

Compared with those with normal or decelerated biological aging (−0.013 [−0.130 to 0.104]; P = 0.018 for interaction). Cocoa extract did not have an effect on the five epigenetic clocks tested. Although the statistically significant but small effects of daily MVM supplementation on slowing biological aging are encouraging, additional studies are needed to determine the clinical relevance of daily MVM supplementation on epigenetic clocks and whether such effects can help explain the beneficial effects of MVM supplementation on aging-related chronic conditions.

Experts who were not involved in the new study urged caution. While the researchers saw an effect with two epigenetic clocks, three other epigenetic clocks included in the study showed no statistically significant change to their speed. “The multivitamin produced small favorable changes in two epigenetic aging markers, but not across all the clocks that were measured,” says José Ordovás, a professor of nutrition and genetics at Tufts University. “That makes the finding interesting, but it is still far from showing that multivitamins broadly slow aging or improve longevity.”

One of the study’s strengths is that the researchers carefully matched the characteristics of people in the vitamin group to those in the placebo group, says Zachary Clayton, an assistant professor of medicine at the University of Colorado Anschutz, who was also not involved with the research. “However, the magnitude of the observed differences was modest, and their clinical significance remains uncertain,” he says. The study doesn’t take a person’s exact diet or physical activity during the two-year period into account, and those factors can’t be ruled out as having an effect on biological aging, he adds.

Still, in nutrition science, randomized clinical trials of this kind are rare. They aren’t generally required to sell supplements like multivitamins, even if the makers claim specific health benefits. Additional trials, the authors note, “are needed to confirm these findings and determine the role of [multivitamins] in extending healthy aging not only among older adults, but also across the lifespan.”

In addition to these criticisms, I would add a few further points:

• Scientists emphasize that “biological age” as measured by DNA methylation is a biomarker, a surrogate endpoint, but not a direct health outcome. It is currently unknown if a 2-month reduction in an epigenetic clock actually translates into a lower risk of disease, disability, or a longer life.
• The 2-year duration of the study is a great achievement for such a trial; yet it still is considered relatively short for assessing biological aging, which is a process that accumulates over decades. Longer-term data is needed to see if these small changes persist or lead to meaningful health differences.
• The fact that those study participants who started “biologically older” saw the most benefit could be a statistical artifact known as “regression to the mean” rather than a true systemic effect of the supplements.
• The study participants were primarily of Caucasian descent and over the age of 60. This limits the ability to generalize the findings to younger populations or diverse ethnic groups.
• Epigenetic alterations are only one of several “hallmarks of aging.” Because the study did not measure other factors like DNA damage, protein stability, or cellular communication, it provides only a very narrow “snapshot” of the aging process.
• The multivitamin might not have “slowed aging” in a general sense, but could have corrected minor, undiagnosed nutrient deficiencies in some participants, which then reflected positively on their biomarkers. If that were true, supplementation of non-deficient volunteers would have no effect.