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Vitamin D: An Evolving Star

By: Peter T. Pugliese, MD
Posted: June 29, 2009, from the July 2009 issue of Skin Inc. magazine.
sun shining through the clouds

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The role of vitamin D in the keratinocyte remains a fascinating but controversial topic among scientists studying vitamin D. Although it is now accepted that the keratinocytes are induced to differentiate by the in vitro addition of 1,25-(OH)2D3, the absence of vitamin D does not cause a problem with keratinocyte differentiation. Possibly, the differentiation may be triggered by more than one system, which would explain why the skin functions normally with a vitamin D deficiency. However, the situation becomes more complex because, together with the differentiation of the keratinocyte, there comes an inhibition of keratinocyte proliferation. From this observation, a new treatment for psoriasis was developed.<sup>16</sup> New products called “analogues” of vitamin D have shown a significant positive effect against psoriasis with as many as 70% of patients responding to this treatment. Exactly how 1,25-(OH)2D3 induces differentiation of the keratinocyte and inhibits proliferation is the big unknown and remains to be investigated.

It has been proposed that the keratinocyte functions to serve in a paracrine<sup>d</sup> manner to stimulate the differentiation of other keratinocytes. However, it remains to be explained how vitamin D-deficient animals are able to obtain keratinocytes that are mature and function normally. Thus, the role of 1,25-(OH)2D3 in the keratinocyte under normal physiological circumstances is unknown, and certainly, the idea that the keratinocyte in vivo is able to produce 1,25-(OH)2D3 is not universally accepted. Much research remains to be done before the last word is written.

Vitamin D and skin peptides

Sunlight exposure, except for promoting vitamin formation, is generally bad. It was surprising to find that the effect of sunlight on the human innate immune system could be of great clinical significance. It has been reported that a UVB band of ultraviolet light stimulates expression of a substance known as hCAP-18, which is the precursor of the antimicrobial peptide known as LL-37 in human skin.<sup>17</sup> The skin of eight individuals was exposed to a minimal erythematous dose<sup>e</sup> of both UVA (300–400 nm) and UVB (280–315 nm) wavelengths on different body sites and was biopsied 24 hours before and after exposure. The skin samples were analyzed for the quantity of hCAP-18 messenger RNA (mRNA) and the amount of vitamin D receptor protein present. The scientists reported that each of the subjects exposed to UVB light showed an increase in both the amount of hCAP-18 mRNA and vitamin D receptor in their skin.

There was a positive correlation between the amount of skin antimicrobial peptide and the amount of vitamin D receptor present, suggesting that the level of hCAP-18 was directly influenced by the increase in vitamin D receptor levels. This is very interesting because it shows a new function of vitamin D. There was no effect shown with UVA exposure in this study, nor was there any correlation of effect with skin type.

How much do we need?

Vitamin D is produced by the human body when it is exposed to direct sunlight, but big variations exist. The season, geographical latitude, time of day, cloud cover and sunscreen use all affect UV ray exposure and thus vitamin D synthesis in the skin. I strongly recommend that you do have limited sun exposure as a good source of vitamin D. Extra vitamin D is also recommended for older adults and people with dark skin. Currently, scientists recommend 25 μg (1,000 IU) of vitamin Dbe consumed daily to maintain adequate blood concentrations of 25-hydroxy vitamin D.18