Role of Fat-Soluble Vitamins A and D in the Pathogenesis of Influenza: A New Perspective

Abstract

Reduced exposure to solar radiation, leading to a deficiency of vitamin D and hence impaired innate immunity, has been suggested as a trigger for influenza viral replication and as an explanation of seasonal influenza. Although this hypothesis accounts for many unexplained facts about the epidemiology of influenza, gaps remain in understanding the pathogenesis and manifestations of the disease. Several observations suggest a role for vitamin A compounds (retinoids) in the disease. This paper presents a new model of the etiopathogenesis of influenza, suggesting that host resistance and susceptibility depend importantly on the ratio of vitamin D to vitamin A activity. Retinoid concentrations within normal physiological limits appear to inhibit influenza pathogenesis whereas higher background concentrations (i.e., very low vitamin D : A ratios) increase the risk of severe complications of the disease. There is also evidence that influenza-induced or preexisting liver disease, diabetes, and obesity worsen the severity of infection, possibly via liver dysfunction and alterations in retinoid metabolism. The model could be tested by determining the presence of retinoids in the secretions of patients with influenza and by studies of retinoid profiles in patients and controls. Potential strategies for prevention and treatment are discussed.