Vitamin D in Childhood Beyond Bone Health: A Review of Its Roles in Immunity, Metabolism, and Neurodevelopment

Abstract

Vitamin D has long been known as a basic modulator of calcium and phosphorus metabolism, and a critical modulator of skeletogenesis in childhood. However, in recent years, molecular studies of vitamin D have revealed that vitamin D action is far from skeletal. The vitamin D receptor (VDR) is found in many non-skeletal tissues, such as immune cells, pancreatic β-cells, adipose tissue, skeletal muscle and developing nervous system. These tissues undergo genomic and nongenomic vitamin D signaling pathways that regulate the antimicrobial response, inflammation, metabolic homeostasis, neuronal differentiation, oxidative stress and synaptic function. The biological window in childhood is of special relevance since immune maturation, metabolic programming, rapid somatic growth and neurodevelopment are all happening at the same time. The relationship between vitamin D status and respiratory infections, allergic and inflammatory disorders, obesity, insulin resistance, cardiometabolic risk, cognition, behavioral development, autism spectrum disorder, and other neurodevelopmental outcomes have thus been explored. There is good biological plausibility from mechanistic and observational evidence, but a mixture of clinical evidence. Evidence from recent randomized trials does not consistently show the reduction of acute respiratory infections with vitamin D supplementation, and the effect of vitamin D on insulin resistance and cardiometabolic outcomes in children with overweight or obesity has been variable. Likewise, some associations of vitamin D with neurodevelopment have been reported, but evidence is still limited. This review explores the mechanisms of vitamin D action in childhood, beyond bone development, including its effects on immune function, metabolic physiology, neurodevelopment, critical windows of development and clinical implications. A special focus is provided on the difference between correction of deficiency and the use of vitamin D as a disease-modifying intervention. Knowing the difference will make it easier to determine more specific and evidence-based methods for assessing and supplementing vitamin D in children.