Copper-to-zinc ratio predicts incident sarcopenia and adverse health outcomes: Results from I-Lan Longitudinal Aging Study.

INTRODUCTION

The copper-to‑zinc (Cu/Zn) ratio is linked to inflammation and aging, but longitudinal evidence for sarcopenia remains limited. We examined associations of serum copper (Cu), zinc (Zn), and Cu/Zn ratio with adverse health outcomes and sarcopenia.

METHODS

Cu, Zn, and the Cu/Zn ratio were analyzed as continuous variables and by tertiles. The study included (1) a 5-year survival analysis assessing associations with adverse outcomes (falls, hospital admissions, emergency department visits, mortality, and a composite outcome); and (2) cross-sectional and 3-year longitudinal analysis examining their associations with prevalent and incident sarcopenia. Sarcopenia was defined based on the Asian Working Group for Sarcopenia 2019 criteria.

RESULTS

Over five years, 357 of 2015 participants experienced adverse events; 311 of 1474 non-sarcopenic participants developed incident sarcopenia over three years. Each standard deviation increase in the Cu/Zn ratio was associated with higher risks of adverse outcomes (aHR 1.18, 95 % CI 1.04-1.33, p = 0.008), hospitalization (aHR 1.23, 95 % CI 1.02-1.49, p = 0.030), mortality (aHR 1.50, 95 % CI 1.06-2.13, p = 0.021), and incident sarcopenia (aOR 1.39, 95 % CI 1.13-1.73, p < 0.001). Higher Cu levels predicted low muscle mass (aOR 1.18, 95 % CI 1.05-1.33, p = 0.005), while higher Zn levels were protective against muscle weakness (aOR 0.84, 95 % CI 0.73-0.97, p = 0.015). Importantly, the association between the Cu/Zn ratio and incident sarcopenia remained significant after additional adjustment for cardiometabolic risk factors and inflammatory biomarkers.

CONCLUSIONS

Elevated serum Cu/Zn ratio predicts adverse outcomes and sarcopenia, highlighting its value as a biomarker for clinical risk in older adults.