Vitamin D

Abstract

The fat‐soluble secosteroid vitamin D 3 is synthesised in UV (ultraviolet)‐B exposed human skin. It regulates calcium and phosphorus homeostasis and thus plays an important role in bone mineralisation. Moreover, vitamin D 3 contributes to the control of cellular growth and differentiation as well as to the responsiveness of the innate and adaptive immune system. At insufficient sun exposure, the molecule is a true vitamin and needs to be taken up via diet or by direct supplementation with pills. During the past 50 000 years, the need of sufficient vitamin D 3 synthesis acted an evolutionary driver for skin lightening of anatomically modern humans migrating out of Africa. The vitamin D 3 metabolite 1α,25‐dihydroxyvitamin D 3 is the exclusive high‐affinity ligand of the transcription factor vitamin D receptor and has a direct effect on the expression of >1000 genes. Thus, vitamin D 3 is a modulator of the human epigenome and transcriptome in more than half of all human tissues and cell types. Key Concepts In UV‐B exposed human skin, the cholesterol precursor 7‐dehydrocholesterol converts to pre‐vitamin D 3 and then isomerises in a nonenzymatic reaction into vitamin D 3 . Lifestyle changes significantly reduced the average endogenous vitamin D 3 production in human and caused vitamin D deficiency in most human populations. Vitamin D 3 is a biologically inert molecule and is enzymatically converted in a two‐step reaction to the nuclear hormone 1,25(OH) 2 D 3 . 25(OH)D 3 serum levels are used as biomarker for the vitamin D status. Only vertebrates have a full vitamin D endocrine system, formed by plasma transport proteins, metabolising enzymes and a high‐affinity receptor. The migration of modern humans to less sunny regions in Asia and Europe caused an evolutionary pressure for genetic adaptation in form of gradual skin lightening for more efficient vitamin D 3 production. The genome‐wide VDR binding pattern is rather cell‐specific, which has an impact on the panel of vitamin D target genes in VDR expressing tissues and cell types. Vitamin D 3 has a direct effect on the accessibility of chromatin, that is it serves as a modulator of the epigenome. Humans have an individual response to vitamin D 3 , referred to a vitamin D response index, which allows segregation into high, mid and low responders. The vitamin D response index suggests for each individual a vitamin D 3 supplementation protocol that will direct to a personal optimal vitamin D status.