Dietary antioxidants: a challenge or an opportunity for asthma? Genetic insights from a Two-sample mendelian randomization study

Oxidative stress is crucial in the immune response and airway inflammatory process associated with asthma. While the relationship between dietary antioxidants and asthma remains debated in observational studies, this study uses two-sample Mendelian randomization (MR) to explore a potential causal link. We acquired six distinct categories of absolute circulating antioxidants and five different types of metabolic circulating antioxidants from the most recent genome-wide association study data of the European population, including vitamin A (retinol), vitamin C (ascorbic acid), vitamin E (tocopherol), β-carotene, lycopene, and urate. The latest data regarding asthma was obtained from the FinnGen database. We utilized single nucleotide polymorphisms as instrumental variables to conduct five MR methods. To confirm the accuracy of the results, additional sensitivity analyses were performed to eliminate any potential confounding factors, such as heterogeneity and pleiotropy. MR and sensitivity analyses revealed an association between circulating urate and asthma, suggesting a potential increase in asthma risk (OR = 1.090; 95% CI = 1.030–1.150; p = 0.004). No causal relationship was found for other antioxidants. This MR analysis suggested that genetically determined circulating urate may increase asthma risk. Further large-scale randomized controlled trials and mediated MR analysis are needed to explore underlying mechanisms.