Dietary supplements, epigenetic aging, and diabetes status: A cross-sectional NHANES study.

OBJECTIVES: To investigate associations between the use of dietary supplements and diabetes status, and to examine whether epigenetic aging biomarkers derived from DNA methylation statistically mediates these associations. STUDY DESIGN: Cross-sectional analysis of adults participating in the National Health and Nutrition Examination Survey 1999-2002 with available data on use of dietary supplements, diabetes, and DNA methylation. MAIN OUTCOME MEASURES: Diabetes status was defined using self-reported diagnosis, use of glucose-lowering medication, fasting glucose, or hemoglobin A1c. Use of particular dietary supplements during the previous 30 days was analyzed as use versus non-use. Twelve epigenetic aging biomarkers derived from DNA methylation were evaluated. Survey-weighted logistic regression estimated associations with diabetes prevalence, and mediation analyses assessed indirect effects. Subgroup analyses were conducted across demographic, lifestyle, and clinical strata. RESULTS: Among 2381 participants, lycopene was the only supplement that remained associated with lower diabetes prevalence after full covariate adjustment and false discovery rate correction (odds ratio 0.092; 95% confidence interval 0.033-0.256; false discovery rate-adjusted P value = 0.003). Calcium, iodine, and molybdenum showed inverse associations before false discovery rate correction, but these associations were no longer significant after correction. Epigenetic aging biomarkers explained only a small proportion of the lycopene-diabetes association, with the largest mediation signals observed for GrimAgeMort, DunedinPoAm, and HorvathTelo. Several corrected indirect effects were also observed for calcium, iodine, and molybdenum, particularly through GrimAgeMort, but these findings were exploratory. CONCLUSIONS: The most robust supplement-related finding was that concerning the use of lycopene. Longitudinal studies with detailed exposure assessment and repeated DNA methylation measurements are needed.