Supplements and Drugs Are Associated With Biological Age in a Cohort of Exceptionally Healthy Individuals.

In this cross-sectional cohort we analyzed data from 4260 "health enthusiasts" who purchased at least one saliva-based DNA epigenetic test between 2020 and 2025 and completed detailed lifestyle and supplement questionnaires. A proprietary 9-CpG clock with a mean absolute error of 5.4 years served as the primary biomarker of biological age. High prevalence (71%) of supplement use in this cohort increased our power to study the effects of supplements compared to earlier studies that focused on the general population. We tested the association between 84 commonly used supplements and biological age measured as Age Residual. In our cross-sectional analysis, a commercially available, delayed-release calcium-alpha-ketoglutarate (dAKG) + vitamin supplement ("Rejuvant") was associated with an average 1.8-year lower Age Residual. The difference remained significant in models adjusted for age, sex, smoking, health status and additional covariates. In contrast, participants who reported taking regular AKG showed a much smaller and statistically insignificant benefit. Among medications, there was a non-significant benefit of antihistamine use, although the analysis was sample-size limited. In a longitudinal subset, intake of coenzyme Q10 (CoQ10) and dAKG was associated with increased odds of a lower Age Residual, but the results were not significant after multivariate correction. In conclusion, this study underscores the utility of an inexpensive saliva-based epigenetic test for population-level aging research and the benefits of health enthusiast cohorts. It highlights AKG and CoQ10, among others, as promising supplements warranting further investigation. Limitations like healthy user and recruitment bias remain and will require future controlled trials to fully address.