Genetic predisposition to raised circulating levels of dietary antioxidants and the association with respiratory health in high-risk populations

BackgroundObservational studies of raised dietary antioxidants suggest a beneficial effect on health, but the results from interventional studies generally show no effect. There are no robust studies targeting people exposed to high levels of environmental oxidants where any effects of raised antioxidants are plausibly stronger. ObjectivesTo examine whether people genetically predisposed to raised dietary serum antioxidants have improved respiratory health. MethodsWe identified single-nucleotide polymorphisms (SNPs) associated with serum ascorbate (vitamin C), retinol (vitamin A), and {beta}-carotene from external data sources. Outcome data on forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), were derived from individual-level data from over 285,000 UK Biobank participants. We used linear regression to explore relationships between the SNPs and lung function. To quantify any relationships, we instrumented the association using exposure beta coefficient from published literature and genome wide association studies (Mendelian randomization). ResultsWe found no consistent relationship between genetically raised serum antioxidant levels and respiratory health measures. There was no evidence of effect modification by exposures linked to oxidative stress including cigarette smoke, air pollution and poor diet. ConclusionsOur findings support interventional studies showing no causal relationship between dietary antioxidants and respiratory disease outcomes. Further, our results do not support interventions to increase serum levels of ascorbate, retinol, or {beta}-carotene in people exposed to high levels of environmental oxidants (Wellcome Grant ID: 209207/Z/17/Z and 225195/Z/22/Z).