The study, led by researchers from the Healthy Longevity Translational Research Programme housed in the Yong Loo Lin School of Medicine, National University of Singapore, assessed the association between 84 commonly used supplements and biological age measured as Age Residual.
Cross-sectional analysis also showed that supplement users had significantly younger Age Residual than non-users. A non-significant benefit of taking supplements was also seen in the longitudinal analysis.
Study method
Researchers analyzed data from over 4,200 individuals who had taken at least one saliva-based DNA epigenetic test commercially available as TruMe between 2020 and 2025.
Seven out of 10 (71%) also reported using supplements, which researchers said has allowed them to study correlations between supplement consumption and the impact on biological age.
Multivitamins and minerals were the most commonly used supplements, with a user rate of 34.3%, followed by vitamin D at 8.5%, omega-3 fatty acids at 6.5% and joint support formulas at 5.4%.
The remaining supplements included nicotinamide adenine dinucleotide (NAD+) precursors, including nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), as well as berberine, carotenoids, creatine, trimethylglycine, resveratrol and AKG in both delayed-release and regular forms.
Using the epigenetic and supplement use data, researchers ran both cross-sectional analysis and longitudinal analysis.
dAKG’s benefits seen in cross-sectional analysis
Notably, Rejuvant, a commercially available, proprietary and delayed-release calcium-alpha-ketoglutarate (dAKG) product, was associated with the lowest Age Residual in both men and women.
Through a cross-sectional analysis involving 143 Rejuvant users, researchers found an average 1.8-year reduction in biological age. Aside from dAKG, Rejuvant also contains vitamin A and vitamin D3.
The difference remained significant in models adjusted for age, sex, smoking, health status and additional covariates.
“Additionally, we found that dAKG was associated with lower Age Residual regardless of weight, weekly exercise volume or alcohol intake, with slightly larger benefits seen in those who exercise more often,” researchers wrote in Aging Cell.
Participants on a dAKG subscription were also more likely to show a reversal in biological age, as opposed to those who used dAKG intermittently,
“Participants who were on a dAKG subscription, a much larger group than self-declared dAKG users, were significantly more likely to show a reduction in biological age over time in our unadjusted analysis,” they wrote.
However, researchers also acknowledged that no significant improvement was seen in dAKG supplementation in longitudinal analysis, which they said could be due to a limited sample size of only 26 participants.
Still, as an intermediate in the citric acid cycle and a metabolic precursor for the synthesis of certain amino acids and a cofactor in collagen synthesis and epigenetic modifying enzymes, researchers pointed out that AKG’s role in biological age reversal is plausible.
“A benefit on biological age is certainly plausible. Plasma AKG declines with aging in mice. AKG extends fly lifespan on a low protein diet and Ca-AKG supplementation late in life decreases frailty and extends mouse lifespan, although a later mouse study did not confirm this, highlighting the need for further research,” they wrote.
Aside from AKG, other supplements, such as carotenoids, calcium, CoQ10, curcumin, vitamin D3, and NAD+ booster supplements were associated with a lower Age Delta - another biological age clock - after correction for multiple testing.
Source: Aging Cell, Volume 25, Issue 6. doi: 10.1111/acel.70517. “Supplements and Drugs Are Associated With Biological Age in a Cohort of Exceptionally Healthy Individuals.” Authors: Brian K. Kennedy et al.
