Vitamin A Linked to Better Lung Function in Kids, Adults

Higher vitamin A levels were linked to better lung function in adults and children, with the benefit seen with vitamin D among adults as well, a study showed.

Higher vitamin A levels correlated with significantly higher forced expiratory volume in 1 second (FEV1; β=2.5 in children and 4.7 in adults) and forced vital capacity (FVC; β=7.6 in children and 3.4 in adults), Michael McGeachie, PhD, of Brigham and Women’s Hospital in Boston, and colleagues reported in Thorax.

Children showed a lower ratio of FEV1/FVC with higher vitamin A (β=-3.9), whereas the relationship was positive for adults (β=2.5).

The two age groups also differed on impact of vitamin D, which didn’t correlate with lung function measures in kids but had significantly positive associations with FEV1 (β=0.16) and FVC (β=0.18) among adults. “This discrepancy in children may stem from insufficient statistical power to detect trends in vitamin D levels in our childhood cohort,” the researchers noted, as only about half of the child cohort had these levels measured.

Both vitamins “are versatile micronutrients involved in lung development, primarily through regulation of gene expression,” the group noted.

They looked at the biological mechanisms behind the associations via gene expression, or what an accompanying editorial called “nutritional epigenetics.”

“Specifically, they examined how vitamin A and D levels influence regulators (miRNA) and markers of epigenetics (DNA methylation) and used mediation analyses to demonstrate that miRNAs and DNA methylation partially mediate the relationship between vitamin levels and lung function,” wrote editorialists Sze Man Tse, MDCM, MPH, and Genevieve Mailhot, PhD, both of the University of Montreal.

Reduced methylation of the IRF5 gene with higher vitamin levels was linked to improved lung function in children and adults. “IRF5 is a transcription factor that plays a critical role in regulating airway macrophage differentiation, inducing proinflammatory responses to microbial and viral infections through the production of interferon (IFN)-α and IFN-β, and controlling allergic and eosinophilic airway inflammation,” the editorialists noted. Otherwise limited overlap in the global DNA methylation patterns associated with vitamin levels between the two age groups “likely reflects the age-specific effects of DNA methylation,” they added. “This would also be concordant with the hypothesis that vitamin A and D have different roles across the lifespan (i.e., lung development and growth in childhood vs lung repair and regeneration in adulthood).”

While there were unique miRNAs associated with vitamin A and D not shared between the adult and child cohorts, others were. For example, there was enrichment in interleukin-4/13 signalling, estrogen receptor-mediated signalling, alpha-linoleic metabolism, and cell cycle pathways. “Interestingly, these common miRNAs regulate 248 genes along pathways that are known to modulate lung inflammation and function and thus could be potential therapeutic targets,” Tse and Mailhot wrote.

The epigenetic findings also point to potential targets for personalized nutrition in asthma care, the researchers wrote, although the editorialists pointed to failure of interventional studies to show a benefit of vitamin D supplementation on lung function in children and adults with asthma.

The associations with vitamin D might, in part, reflect residual confounding, as higher levels are often associated with healthier behaviors and overall better health that may independently influence lung function, Tse and Mailhot wrote.

The study utilized two asthma cohorts: 1,165 children ages 6-14 years (average 9.2 years) in the Genetic Epidemiology of Asthma in Costa Rica Study and 1,041 adults (average age 58.8 years) in the Omic Determinants of Longitudinal Lung Function in Asthma study of the Mass General Brigham Biobank. Serum miRNA profiles, blood DNA methylation, and plasma or serum vitamin A and D levels were assessed in both cohorts.

Limitations of the study were inability to determine causality, relative quantification of plasma vitamin A, lack of mRNA expression data, and absence of longitudinal data limiting conclusions about temporal effects.

“Future work should address these gaps using absolute, repeated measures to clarify vitamin–lung function dynamics over time,” McGeachie and colleagues wrote.