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.