Effect of vitamin A on adult lung function: a triangulation of evidence approach

Background Vitamin A, an essential micronutrient obtained through the diet, plays a crucial role in lung development and contributes to lung regeneration. We aimed to investigate its effect on adult lung function using triangulation of evidence from both observational and genetic data. Methods Using data on 150 000 individuals from UK Biobank and correcting for measurement error (generalised structural equation modelling), we first investigated the association of dietary vitamin A intake (total vitamin A, carotene and retinol) with lung function (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1 )/FVC)). We then assessed the causality of these associations using Mendelian randomisation (MR), and we investigated the effects on adult lung function of 39 genes related to vitamin A, and their interaction with vitamin A intake. Findings Our observational analysis suggests a positive association between carotene intake and FVC only (13.3 mL per 100 µg/day; p=2.9×10 −9 ), with stronger associations in smokers, but no association of retinol intake with FVC or FEV 1 /FVC. The MR similarly shows a beneficial effect of serum beta-carotene on FVC only, with no effect of serum retinol on FVC nor FEV 1 /FVC. Nine of the vitamin A-related genes were associated with adult lung function, six of which have not been previously identified in genome-wide studies and three ( NCOA2, RDH10, RXRB ) in any type of genetic study of lung function. Five genes showed possible gene-vitamin A intake interactions. Interpretation Our triangulation study provides convincing evidence for a causal effect of vitamin A, carotene in particular, on adult lung function, suggesting a beneficial effect of a carotene-rich diet on adult lung health.