Association between serum Copper-Zinc-Selenium mixture and multiple health outcomes.

Background: Metallic biomaterials have transformed modern medicine, with copper (Cu), zinc (Zn), and selenium (Se) emerging as critical components in medical applications. The study of the single and synergistic effects of serum metal concentrations on human health can provide valuable insights for future clinical transformation of biodegradable alloys. Methods: We evaluated 2381 NHANES 2011-2016 participants to study individual and combined effects of these metals on health outcomes. Multivariable logistic regression, restricted cubic splines, and piecewise linear regression were used to examine linear, nonlinear, and threshold relationships. Overall metal mixture effects were assessed using weighted quantile sum (WQS) and Bayesian kernel-machine regression (BKMR). Results: Elevated serum Cu levels were significantly associated with an increased risk of osteoarthritis. When Serum Cu ≥ 99.48 μg/dL, each 1-unit increase in Ln Cu raised diabetes risk 4.55-fold. For Se ≥ 122.74 μg/L, each 1-unit increase in Ln Se led to a 29.96-fold rise in diabetes prevalence, for Se < 157.56 μg/L it increased heart attack risk 165.19-fold. Furthermore, mixtures of Cu, Se, and Zn were positively associated with diabetes, hypertension, and heart attack risks; each unit increase in the mixture corresponded to a 23 % rise in diabetes and a 15 % rise in hypertension prevalence. Conclusions: Serum Cu levels ≥99.48 μg/dL are significantly linked to diabetes risk, while serum Se levels ≥122.74 μg/L are associated with diabetes risk and levels <157.56 μg/L with elevated heart attack risk. Serum metal mixtures containing Cu, Se and Zn were significantly and positively associated with risk of diabetes, hypertension and heart attack.