Abstract
OBJECTIVE: To investigate the relationship between theobromine and age-related macular degeneration (AMD) using a nationwide representative sample of adults and in vitro experiments. METHODS: We analyzed data from the 2005-2008 years of the National Health and Nutrition Examination Survey (NHANES), which included 5485 participants with available data on dietary theobromine intake and AMD. Multivariable logistic regression and smoothing curve fitting were used to examine the potential correlations. The inflection point was determined using a two-piecewise linear regression. Interaction tests and subgroup analyses were also conducted. In vitro experiments were conducted to investigate the effects of theobromine on cell proliferation, intracellular reactive oxygen species (ROS) levels, and the expression of heme oxygenase-1 (HO-1) and superoxide dismutase-1 (SOD-1) in a sodium iodate (NaIO(3))-induced ARPE-19 cell injury model. RESULTS: After controlling for potential confounding variables, the multivariate logistic regression model revealed an odds ratio of 0.73 (95% confidence interval: 0.56-0.98) for the association between dietary theobromine and AMD. The usage of smoothing curve fitting revealed a non-linear relationship, with an inflection point observed at 60 mg/d (adjust OR 0.31;95% CI 0.14-0.66). The negative correlation remained consistent across various demographic scenarios in subgroup analyses and interaction tests. In the NaIO(3)-induced ARPE-19 cell injury model, theobromine enhanced cell proliferation, reduced the expression of HO-1, and increased the expression of SOD-1. CONCLUSIONS: A non-linear negative correlation between dietary theobromine and AMD was observed, and the antioxidant activity of theobromine was observed in vitro. Our findings suggest a potential association between higher theobromine intake and lower odds of AMD prevalence, which warrants further investigation of its therapeutic implications.