Elevated Serum Gamma-Glutamyl Transferase as a Risk Factor for Frailty in Older Men: A Nationwide Population-Based Study

Abstract

Background: Oxidative stress is a key driver of accelerated ageing, and gamma-glutamyl transferase (GGT), an essential enzyme involved in the metabolism of glutathione, a major antioxidant, plays a pivotal role in the generation of free radical species. This study aimed to explore the potential utility of circulating GGT as a biomarker of frailty, which reflects biological ageing and overall health status.

Methods: This cross-sectional, population-based study included 2526 community-dwelling adults aged 65 years and older, using data from the Korea National Health and Nutrition Examination Survey. Frailty was assessed using a deficit accumulation frailty index (FI) derived from 36 items encompassing physical, cognitive, psychological, and social domains. Participants were categorised as nonfrail (FI ≤ 0.15), prefrail (0.15 < FI ≤ 0.25), or frail (FI > 0.25). Serum GGT levels were determined using an enzymatic activity assay.

Results: After adjusting for potential confounders including age, body mass index, socioeconomic status, lifestyle factors, and medical history, serum GGT levels were 26.0% higher in frail men than in nonfrail men (p = 0.010). Amongst men, serum GGT concentrations were positively correlated with the FI (p = 0.001), and each standard deviation increase in serum GGT was associated with a 1.36-fold higher odds of frailty (p = 0.001). Additionally, older men in the highest GGT quartile exhibited a significantly higher FI and a 2.08-fold increased odds of frailty compared to those in the lowest quartile (p = 0.010 and p = 0.019, respectively). In women, however, no significant association was observed between serum GGT levels and frailty.

Conclusion: Elevated serum GGT levels were significantly associated with frailty in older men, suggesting their potential as a biomarker of biological ageing. Nonetheless, the cross-sectional design precludes causal inference, and longitudinal studies are warranted to explore whether elevated GGT contributes to the onset or progression of frailty over time.

Keywords: biomarker; frailty index; gamma‐glutamyl transferase; oxidative stress.