Copper exposure association with prevalence of non-alcoholic fatty liver disease and insulin resistance among US adults (NHANES 2011-2014)

Background: Excessive copper (Cu) has risky effect on insulin resistance (IR), oxidative stress and inflammation. Instead, some studies reported serum Cu to be protective for non-alcoholic fatty liver disease (NAFLD). The aim of this study was to reevaluate the evidence for a potential risky correlation of serum Cu to NAFLD in large-scale and non-institutionalized American subjects. Methods: A cross-sectional study of 3211 subjects was from the National Health and Nutrition Examination Survey (NHANES). Logistic regression and cubic spline-based curve-fitting analyses were used to estimate the independent risky effect of Cu to hepatic steatosis index (HSI), US fatty liver index (USFLI) and NAFLD and their dose-effect relationship. Moreover, this association was analyzed in stratification of HOMA-IR, Metabolic syndrome (MetS) and severity of NAFLD, besides age and gender. Results: The average level of serum Cu was 18.67 mu mol/L and the prevalence of NAFLD was 54.53% and 32.60%, respectively defined by HSI and USFLI. Generally, the level of Cu was higher in females than males. Serum Cu was positively associated with higher HSI, USFLI index and risk of NAFLD. In fully adjusted models, compared with the lowest quartile, the risk of NAFLD increased 97% in the highest quartile of Cu. Interestingly, stratified analysis showed that the risky effect of Cu to NAFLD was more prominent in the middle-aged, females and subjects with improved status of IR (lower HOMA-IR and non-Mets) compared with their counterparts. Moreover, we further found that circulating copper was correlated to severity of NAFLD only in males. Conclusion: Excess serum Cu is significantly associated with risk of NAFLD, which is prominent in females, middle-aged and subjects with improved status of IR, and seems to be related to the severity of NAFLD, additionally. It is necessary to be cautious of the toxic effect of Cu and prospective cohort and mechanism studies are needed to verify the causal effect of Cu to NAFLD.

Automated summary

Excessive serum copper is significantly associated with the risk of NAFLD, particularly in females, middle-aged individuals, and those with improved status of insulin resistance. Further research is needed to verify the causal effect of copper on NAFLD.