Supplements and Drugs Are Associated With Biological Age in a Cohort of Exceptionally Healthy Individuals
Large but self-selected, non-randomised cohort finding that delayed-release calcium alpha-ketoglutarate showed the strongest association with lower epigenetic Age Residual among 84 supplements tested — a 1.8-year difference, substantially smaller than the ~8-year reduction claimed in the 2021 Rejuvant report.
Evidence
3/10
Emerging Evidence
Sample
4,260
subjects
Duration
2020-2025 (cross-sectional sampling)
study period
Journal
Aging Cell
Jan 2026
Full Abstract
Cross-sectional analysis of 4,260 health-enthusiast individuals who purchased saliva-based DNA methylation tests between 2020 and 2025 and completed lifestyle and supplement questionnaires. Associations between 84 commonly used supplements and an Age Residual derived from a proprietary 9-CpG epigenetic clock (mean absolute error 5.4 years) were tested. Delayed-release calcium alpha-ketoglutarate plus vitamins was associated with an average 1.8-year lower Age Residual, significant in models adjusted for age, sex, smoking, health status and additional covariates.
Key Findings
- 01
4,260 participants; 71% supplement users; 84 supplements tested
- 02
Delayed-release calcium alpha-ketoglutarate plus vitamins associated with 1.8-year lower Age Residual
- 03
Association persisted after adjustment for age, sex, smoking and health status
- 04
Outcome was a proprietary 9-CpG clock with 5.4-year mean absolute error
- 05
Effect size markedly smaller than the ~8-year reduction reported in the earlier 2021 Rejuvant analysis
Structured Methods
- Study Design
- Observational cross-sectional cohort
- Sample Size
- 4,260 subjects
- Study Duration
- 2020-2025 (cross-sectional sampling)
- Methodology
- Cross-sectional questionnaire-linked analysis of commercial saliva methylation test purchasers, proprietary 9-CpG epigenetic clock, multivariable adjustment
- Limitations
- Not randomised or blinded; self-selected supplement-buying cohort with unquantified healthy-user and reverse-causation bias; outcome is a proprietary, commercially owned epigenetic clock with a 5.4-year error rather than function or clinical events; cross-sectional design cannot establish that taking the supplement lowers biological age. Randomised AKG trials remain the evidence that would matter.
Citations & References
Pabis K (2026). Supplements and Drugs Are Associated With Biological Age in a Cohort of Exceptionally Healthy Individuals. Aging Cell. https://doi.org/10.1111/acel.70517
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