Background: Although caffeine is widely consumed and has demonstrated neuroprotective effects, its role in age-related macular degeneration (AMD) remains unclear, particularly across disease subtypes and dietary sources such as tea and coffee.
Methods: We analyzed 2005-2008 NHANES data using weighted logistic regression and restricted cubic splines to assess the dose-response relationship between caffeine intake and the prevalence of early and late AMD. Two-sample Mendelian randomization (MR) using GWAS summary statistics was employed to evaluate causal effects of tea and coffee consumption on AMD subtypes. Furthermore, a two-step MR approach was utilized to identify potential immune-mediated pathways.
Results: NHANES data showed that caffeine intake was inversely associated with late AMD (fully adjusted OR = 0.65, 95% CI: 0.44-0.96). Dose-response modeling revealed an L-shaped nonlinear relationship (P for nonlinear = 0.046), indicating that the protective effect of caffeine plateaued once daily intake exceeded approximately 110-150 mg. MR analysis further supported a causal protective association between tea consumption and dry AMD, including geographic atrophy (OR = 0.44, 95% CI: 0.20-0.97), which may be partially attributable to immunological mechanisms, specifically the downregulation of secretory regulatory T cells (% of CD4 + Tregs) and CD45RA- CD4 + T cell (% of CD4 + T cell). In contrast, coffee consumption showed no significant effect.
Conclusions: Tea, a specific source of caffeine typically corresponding to moderate intake levels, may confer protection against dry AMD, including geographic atrophy, potentially through modulation of immune cell profiles. These findings suggest a potential preventive strategy and warrant further clinical investigation.
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