Association of dietary folate with lung function partly mediated by phenotypic age acceleration in the general US and UK populations

Aging and inflammatory injury mediate the process of chronic respiratory diseases and the decline of lung function. With its anti-senescent and anti-inflammatory ability, the effect of dietary folate on lung function is still poorly understood, and so we aim to examine the association between folate intake and lung function in US and UK adults. This cross-sectional study used data respectively from the 2007–2012 National Health and Nutrition Examination Survey (NHANES) and the 1st cycle of UK Biobank (UKB), and investigated forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and pulse expiratory flow (PEF). Linear regression models and restricted cubic spline (RCS) analysis were used with adjustment for relevant covariates. Mediation analysis tested the effect of Phenotypic Age Acceleration (PhenoAgeAccel), one trait of relative biological aging, among these relationships. A total of 5,527 participants from NHANES and 26,349 participants from UKB had complete data for this study. Significant positive associations were shown between continuous folate intake and lung function including FEV1 (β = 0.165 with p = 0.002 in NHANES, β = 0.161 with p < 0.001 in UKB), FVC (β = 0.239 with p < 0.001 in NHANES, β = 0.282 with p < 0.001 in UKB), and PEF (β = 0.348 with p = 0.016 in NHANES, β = 0.346 with p < 0.001 in UKB), which was supported by the RCS curves. These positive correlations were also found in the regression analysis with dietary folate levels as ordinal categorical variables, where all the spirometry parameters in the group with the highest folate intake were significantly greater than those in other groups after controlling for the covariates. Sex and smoking status might have interactive effects on these relationships. Furthermore, PhenoAgeAccel demonstrated significant mediating effects between folate intake and improved lung function, which provided a partial explanation for the intrinsic mechanism. This study indicates that a diet rich in folate may be associated with better lung function within the general US and UK populations. These findings underscore the significance of folate in maintaining pulmonary health and mitigating the impact of age-related disorders.