Background & aims: Based on experimental and epidemiologic studies, we investigated whether coffee and caffeine consumption reduced the risk of elevated alanine aminotransferase (ALT) activity in persons at high risk for liver injury in a national, population-based study.

Methods: Participants were 5944 adults in the Third US National Health and Nutrition Examination Survey, 1988-1994, with excessive alcohol consumption, viral hepatitis, iron overload, overweight, or impaired glucose metabolism. Liver injury was indicated by abnormal serum ALT activity (>43 U/L).

Results: Elevated ALT activity was found in 8.7% of this high-risk population. In unadjusted analysis, lower ALT activity was associated with increasing consumption of coffee ( P = .001) and caffeine ( P = .001). Multivariate logistic regression analyses showed that the risk of elevated ALT activity declined with increasing intake of coffee ( P for trend = .034) and caffeine ( P < .001). Comparing persons who drank more than 2 cups per day with noncoffee drinkers, the odds ratio was .56 (95% confidence interval, .31-1.0). Comparing persons in the highest caffeine quintile with the lowest, the odds ratio was .31 (95% confidence interval, .16-.61). These relationships were consistent across subgroups at risk for liver injury and were relatively unchanged when analyses included the entire population or when limited to persons without impaired liver function or right upper quadrant pain. Fasting insulin concentrations did not mediate the effects.

Conclusions: In this large, national, population-based study, among persons at high risk for liver injury, consumption of coffee and especially caffeine was associated with lower risk of elevated ALT activity.