Nutrigenomics studies how environmental factors, such as food intake and lifestyle, influence the expression of the genome. Vitamin D3 represents a master example of nutrigenomics, since via its metabolite 1α,25-dihydroxyvitamin D3, which binds with high-affinity to the vitamin D receptor, the secosteroid directly affects the epigenome and transcriptome at thousands of loci within the human genome. Vitamin D is important for both cellular metabolism and immunity, as it controls calcium homeostasis and modulates the response of the innate and adaptive immune system. At sufficient UV-B exposure, humans can synthesize vitamin D3 endogenously in their skin, but today’s lifestyle often makes the molecule a true vitamin and micronutrient that needs to be taken up by diet or supplementation with pills. The individual’s molecular response to vitamin D requires personalized supplementation with vitamin D3, in order to obtain optimized clinical benefits in the prevention of osteoporosis, sarcopenia, autoimmune diseases, and possibly different types of cancer. The importance of endogenous synthesis of vitamin D3 created an evolutionary pressure for reduced skin pigmentation, when, during the past 50,000 years, modern humans migrated from Africa towards Asia and Europe. This review will discuss different aspects of how vitamin D interacts with the human genome, focusing on nutritional epigenomics in context of immune responses. This should lead to a better understanding of the clinical benefits of vitamin D.
Reply: “Comment on: The Vitamin D–Folate Hypothesis as an Evolutionary Model for Skin Pigmentation: An Update and Integration of Current Ideas, Nutrients 2018, 10, 554”
