Linking Dietary Creatine to DNA Methylation-Based Predictors of Mortality in Individuals Aged 50 and above

Introduction: Creatine is a conditionally essential nutrient integral to cellular energy homeostasis, with emerging evidence suggesting its potential role in modulating biological aging. However, associations between dietary creatine intake and epigenetic biomarkers of mortality remain unexplored. This study investigates the relationship between dietary creatine intake and DNA methylation-derived mortality indices in US adults aged 50 years and older.

Data from the NHANES 1999-2002 cycles were analyzed, including dietary creatine intake estimated from 24-h recall interviews and DNA methylation profiles measured using the Illumina EPIC array. Epigenetic mortality predictors GrimAgeMort and GrimAge2Mort were examined in relation to creatine intake.

Among 4,983 participants (mean age 67.6 ± 10.7 years), a significant inverse correlation was observed between dietary creatine and both GrimAgeMort (r = -0.041, p = 0.045) and GrimAge2Mort (r = -0.047, p = 0.019), indicating that higher creatine consumption was associated with lower epigenetic mortality risk scores. These associations persisted as statistically significant after adjustment for demographic variables and pertinent dietary factors.

Higher dietary creatine intake is linked to reduced biological age acceleration and mortality risk as estimated by epigenetic biomarkers. These findings highlight creatine's potential as a modifiable dietary factor promoting healthy aging and longevity. Further research is warranted to elucidate underlying mechanisms.