Lycopene was the only dietary supplement that remained associated with lower diabetes prevalence after full covariate adjustment and false discovery rate correction, with epigenetic aging biomarkers explaining only a small proportion of this association.
Key Findings
Results
Lycopene supplementation was associated with significantly lower diabetes prevalence after full covariate adjustment and false discovery rate correction.
Odds ratio of 0.092 (95% CI: 0.033–0.256) for lycopene use versus non-use
False discovery rate-adjusted P value = 0.003
Lycopene was the only supplement to remain statistically significant after FDR correction
Analysis was conducted among 2381 adult NHANES participants from 1999–2002
Survey-weighted logistic regression was used to estimate associations with diabetes prevalence
Results
Calcium, iodine, and molybdenum showed inverse associations with diabetes prevalence before false discovery rate correction, but these did not survive correction.
These three supplements showed inverse associations in unadjusted or partially adjusted models
Associations were no longer statistically significant after false discovery rate correction
These findings were considered preliminary and not robust
The study analyzed supplement use as binary (use vs. non-use) during the previous 30 days
Results
Epigenetic aging biomarkers mediated only a small proportion of the lycopene-diabetes association.
Twelve epigenetic aging biomarkers derived from DNA methylation were evaluated
The largest mediation signals were observed for GrimAgeMort, DunedinPoAm, and HorvathTelo
The mediated proportions were described as 'only a small proportion' of the total lycopene-diabetes association
DNA methylation data were available for the 2381 participants drawn from NHANES 1999–2002
Results
Exploratory mediation effects through GrimAgeMort were observed for calcium, iodine, and molybdenum supplements.
Several corrected indirect effects were observed for calcium, iodine, and molybdenum
The primary mediation pathway for these supplements was through GrimAgeMort
These findings were explicitly characterized as 'exploratory'
Mediation analyses assessed indirect effects of epigenetic aging biomarkers in the supplement-diabetes pathway
Methods
The study used a cross-sectional design with diabetes status defined by multiple criteria including self-report, medication use, fasting glucose, and hemoglobin A1c.
Data were drawn from the National Health and Nutrition Examination Survey (NHANES) 1999–2002
Diabetes status was defined using self-reported diagnosis, use of glucose-lowering medication, fasting glucose, or hemoglobin A1c
Supplement use was captured as use versus non-use during the previous 30 days
Subgroup analyses were conducted across demographic, lifestyle, and clinical strata
Total analytic sample included 2381 participants with available data on supplements, diabetes, and DNA methylation
Conclusions
The authors concluded that longitudinal studies with detailed exposure assessment and repeated DNA methylation measurements are needed to confirm these findings.
The cross-sectional design precludes causal inference
Supplement use was measured as binary (use vs. non-use), limiting dose-response analysis
Repeated DNA methylation measurements were not available in this dataset
The authors identified the lycopene finding as 'the most robust supplement-related finding'
What This Means
This research suggests that among a wide range of dietary supplements examined, lycopene — a compound found naturally in tomatoes and other red fruits — was the only supplement consistently linked to a lower likelihood of having diabetes in a large U.S. adult population survey. The researchers analyzed data from nearly 2,400 adults who participated in the National Health and Nutrition Examination Survey between 1999 and 2002, looking at whether people who reported taking specific supplements in the past 30 days were less likely to have diabetes. After applying rigorous statistical corrections to reduce the chance of false-positive findings, only lycopene supplementation showed a robust and statistically significant association with lower diabetes prevalence. Three other supplements — calcium, iodine, and molybdenum — showed suggestive associations but did not hold up after those corrections.
The study also explored whether biological aging processes, specifically 'epigenetic aging' measured from DNA, might help explain the link between lycopene and diabetes. Epigenetic aging refers to chemical modifications on DNA that can reflect how quickly a person's cells are aging beyond their chronological age. The researchers found that while certain epigenetic aging markers (GrimAgeMort, DunedinPoAm, and HorvathTelo) showed some mediation of the lycopene-diabetes relationship, they explained only a small fraction of the overall association, meaning other mechanisms are likely involved.
Because this was a cross-sectional study — meaning it captured a single snapshot in time rather than following people over years — it cannot prove that taking lycopene supplements causes lower diabetes risk. Supplement use was also measured simply as 'yes or no,' without capturing dosage or duration. The authors emphasize the need for future long-term studies that track supplement use over time alongside repeated biological measurements to better understand whether and how lycopene and other supplements might affect diabetes risk.
Wang J, Lv C, Pei B, Shi Y, Yu Y, Jia Y, et al.. (2026). Dietary supplements, epigenetic aging, and diabetes status: A cross-sectional NHANES study.. Maturitas. https://doi.org/10.1016/j.maturitas.2026.109092