Vitamins A and D

    Vitamins are not only essential nutrients; they also play hormone-like roles. For example, vitamin D and vitamin A have hormone-like actions due to their ability to bind to specific nuclear receptors and influence gene expression on a large scale.

    Vitamin D acts as a hormone, regulating over 2,500 genes involved in critical biological processes such as energy metabolism, hormone signaling, and mineral (e.g., calcium) homeostasis. This transit highlights its role beyond bone health.

    Vitamin A is involved in the regulation of over 300 genes that affect bone metabolism, immune function, and red blood cell formation. Nearly all of vitamin A’s functions outside of its role in eye function are considered “genomic” (i.e., the impact of vitamin A on the regulation of gene expression at the DNA level) in nature. This makes it a key player in maintaining multiple aspects of health.

    Vitamin A and D receptors are expressed in multiple organs, including the intestinal epithelium, where they play a role in gene transcription and regulation. Both fat-soluble vitamins have been shown to support intestinal barrier integrity and improve immune function. Vitamin A helps regulate the growth and differentiation of intestinal epithelial cells. In animal models and in vitro studies, vitamin A deficiency is associated with altered commensal bacteria, reduced villus height, and dysregulated assembly of tight junction proteins. Vitamin D is thought to protect the intestinal barrier by inducing the expression of tight junction proteins (specifically ZO-1 and claudin). Low vitamin D levels are associated with reduced mucosal barrier integrity and increased susceptibility to mucosal damage, which may in turn increase the risk of IBD. In other experimental studies, vitamin D deficiency has been shown to alter the microbiome and dysfunction of the intestinal epithelial barrier.

    Despite their importance, vitamin deficiencies remain a global problem, with vitamin D deficiency affecting 50–90% of the population and vitamin A deficiency affecting around 25%, particularly in economically disadvantaged regions.