Relation of elevated serum alanine aminotransferase activity with iron and antioxidant levels in the United States

Background & Aims: Oxidative stress is thought to play a role In liver injury. Hepatic iron may promote liver injury, whereas antioxidant vitamins and minerals may inhibit it, but few clinical studies have examined such relationships. We analyzed the associations of serum iron measures and antioxidant concentrations with abnormal serum alanine transaminase (ALT) activity in a large, national, population-based study. Methods: A total of :13,605 adult participants in the third U.S. National Health and Nutrition Examination Survey (NHANES III), 1988-1994, underwent phlebotomy. Exclusions included excessive alcohol consumption, hepatitis B and C, and iron overload. Results: Elevated ALT levels were found in 3.1% of the population. In univariate analysis, factors associated with abnormal ALT levels (P < 0.05) included higher transferrin saturation and iron and selenium concentrations, and lower vitamin C, alpha and P carotene, and lutein/zeaxanthin concentrations. In multivariate logistic regression analyses, elevated ALT level was associated positively with increasing deciles of transferrin saturation (odds ratio [OR] per decile, :1.1.0; 95% confidence interval [CI], 1.03-1.18) and iron concentration (OR, 1.13; 95% CI,1.06-1.21). Abnormal ALT level was associated negatively with increasing deciles of a carotene (OR, 0.82; 95% Cl, 0.72-0.94), P carotene (OR, 0.91; 95% CI, 0.86-0.96), P cryptoxanthin (OR, 0.91; 95% CI, 0.84-0.99), lute! n/zeaxanth in (OR, 0.90; 95% CI, 0.84-0.96), and a variable combining the 5 carotenoid measures (OR, 0.89; 95% CI, 0.83-0.95). Vitamin C was associated inversely, but only at the highest concentrations. Conclusions: In this large, national, population-based study, the risk for apparent liver injury was associated with increased iron and decreased antioxidants, particularly carotenoids.