According to current views vitamin D should be regarded as a factor which is necessary but not sufficient for normal course of the key cellular biochemical pathways. Vitamin D is thought to be an enabler: its presence is necessary for the cellular processes to happen, but is neither their stimulant nor their cause. Therefore low level of vitamin D supplementation although not a direct cause of pathology or dysfunction – is regarded as a factor disturbing the cellular response to intra- and extracellular signals. It is now known that virtually all human body cells and tissues feature vitamin D receptors (VDR). Most cells have also capability of conversion of 25-hydroxyvitamin D [25(OH)D] to its active form 1,25-dihydroxyvitamin D [1,25(OH)₂D]. Cellular “in situ” activation of vitamin D gives the tissues an opportunity to use vitamin D in accordance to their needs. Thus with insufficient vitamin D supplementation, none of our body’s systems can work with optimum efficiency. On account of that vitamin D insufficiency being on most cases a result of low level of skin synthesis stimulation, is inevitably observed in wide range of diseases and dysfunctions (1). Modern human ancestors evolving in equatorial Africa gained the capability of constitutive production of melanin in their epidermal cells, to protect against burns and DNA damage by strong ultraviolet (UV) radiation (2, 3). Concomitantly with settling in the regions of higher latitudes a devolutional loss of this capability took place in favor to a mechanism of the UV induced melanin synthesis (4).

Another interesting adaptation to lower lighting conditions was a change of the availability of a substrate for the fotochemical reaction which is 7-dehydrocholesterol (7DHC), by tuning the activity of 7DHC dehydrogenase (DHCR7) converting 7DHC into cholesterol. In process of genetic adaptation to lower lighting conditions the variability due to single nucleotide polymorphism of the DHCR7 gene (DHCR7) played a significant role. Another interesting feature of DHCR7 is it’s inhibition by vitamin D. Therefore one of the responses the insolation is drop of the cholesterol synthesis and providing a substrate for the synthesis of vitamin D (5-9).

Another element of the system of the keratinocyte response to UV radiation is cytochrome P450 CYP11H1, converting vitamin D₃ to noncalcemic secosteroids like 20(OH)D₃ and 20,23(OH)₂D₃. Together with side-products of the previtamin D production (lumisterol, tachysterol), and 25(OH)D₃ made by CYP27A they form a UV sink supplemental to the melanin, protecting cellular DNA (8).