Genetically Raised Circulating Levels of Dietary Antioxidants and the Association With Respiratory Health in...

Observational studies of raised dietary antioxidants suggest a beneficial effect on respiratory health; however, findings from interventional trials have been inconsistent or null. Few studies have specifically targeted individuals exposed to high levels of environmental oxidants, where the antioxidant effects may be more pronounced.

To investigate whether genetically elevated serum levels of dietary antioxidants are causally associated with improved lung function and whether these effects differ with exposure to oxidative stress.

We conducted a two-sample Mendelian randomization (MR) study using summary-level data for genetic associations with serum levels of ascorbic acid (vitamin C), retinol (vitamin A), and β-carotene from published genome-wide association studies. 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 estimate SNP-outcome associations and applied the Wald ratio to derive causal estimates using published SNP-exposure effect sizes.

We found no consistent evidence that genetically elevated serum antioxidant levels are associated with improved lung function. There was no evidence of effect modification by exposures linked to oxidative stress, including cigarette smoke, air pollution, or dietary factors.

Our findings align with those of previous interventional studies, showing no consistent causal relationship between dietary antioxidants and respiratory health. Moreover, we found no strong support for targeted interventions to increase serum antioxidant levels in people exposed to high levels of environmental oxidants (Wellcome Grant ID: 209207/Z/17/Z and 225195/Z/22/Z).