Can you have your cake and eat it too? The sunlight D‐lema

In this issue of the BJD, Felton et al. report the results of their elegantly designed study to determine the impact on vitamin D status and skin DNA damage for healthy adults with skin types 2 and 5 of low-level simulated summer sunlight exposure as would be experienced at a latitude in the U.K. The photosynthesis of vitamin D has been occurring on this planet for more than 500 million years ever since phytoplankton were producing vitamin D during sun exposure. Although vitamin D’s function in early life forms is not well understood, recent evidence has suggested that vitamin D3 stabilizes membranes that may be important in regulating immune function. Throughout evolution, many organisms, including vertebrates, have depended on sun exposure for their vitamin D requirement. Our hairy dark-skinned ancestors in Equatorial Africa had both their hair and skin pigment as mechanisms to prevent sun-induced skin damage. As our ancestors evolved, they lost their protective hair, and in turn increased melanin production as an effective natural sunscreen. However, the increased amount of melanin in the skin still resulted in a small amount of vitamin D3-producing-ultraviolet (UV) B radiation to reach the basal layer, promoting the production of vitamin D3 throughout the epidermis, which was essential for the maintenance of skeletal health throughout life. As our ancestors migrated north and south of the equator, the increase in the zenith angle of the sun reduced the amount of vitamin D3-UVB-producing photons reaching the skin to produce an adequate amount of vitamin D3. To compensate for vitamin D deficiency, mutations occurred resulting in a reduction in skin melanin content for those who migrated to the farthest northern and southern regions including the Neanderthals who likely had a Celtic skin tone. However, the loss of skin pigment now permitted UVB-sensitive macromolecules, including DNA, to absorb the solar UVB radiation that penetrated the epidermis. This absorption caused thymidine dimerization and other alterations in the DNA structure, increasing the risk for the development of nonmelanoma skin cancer. The Surgeon General’s report from the United States and many dermatology societies have promoted abstinence from any direct sun exposure, which is thought to be a major contributor for the worldwide vitamin D deficiency epidemic. In support of this message was a recent study that reported on Danish adults exposed to high-intensity sunlight during a vacation in the Canary Islands. Peterson et al. not only observed improvement in their vitamin D status but also a significant and concerning cutaneous DNA damage as measured by increased urinary cyclobutane pyrimidine dimers (CPD), a surrogate for DNA damage. Thus, it was suggested that you could not have your cake and eat it too, i.e. take advantage of the beneficial effect of sun exposure for producing the vital vitamin D3 without significant DNA damage in the skin. However, from an evolutionary perspective, this makes little sense for survival of the species, i.e. the need to be dependent on solar UVB for bone development and health while at the same time increasing the risk for skin cancer. Female infants with infantile rickets would have had a flat pelvis with a small pelvic outlet making it difficult for normal child birthing. This is thought to be the driver for loss of skin pigmentation as people migrated north and south of the equator. Those who migrated into the far northern reaches of the European continent ultimately lost most of their skin pigment in order to permit the vitally important vitamin D-producing UVB radiation to enter the epidermis to produce vitamin D3. 8 However, the skin of the Danes with skin types 1 and 2 was not designed to be exposed to high-intensity sunlight for an average of 38 h over 6 days in an environment that was much farther south from where their ancestors evolved. Felton et al. explored the possibility that those with skin type 2, whose skin had evolved to produce adequate vitamin D3 when exposed to sunlight at latitudes in the U.K., had also developed mechanisms to repair the damage caused by the same exposure. They exposed healthy adults with little skin pigmentation (i.e. skin type 2) to low-level simulated U.K. June midday sunlight (equivalent to 13–17 min, six times weekly) and evaluated its effect on raising blood levels of 25-hydroxyvitamin D [25(OH)D; a measure of vitamin D status] and at the same time monitored various outcome measures related to cutaneous DNA damage. As expected, they observed a significant 49% increase in the circulating levels of 25(OH)D as a result of 7-dehydrocholesterol in the epidermis absorbing UVB radiation (290–315 nm) resulting in its conversion to previtamin D3. Previtamin D3 is then converted within a few hours by a membrane-enhanced isomerization to vitamin D3. Once formed, vitamin D3 travels to the liver and is converted to 25(OH)D3. 8 However, as UVB is penetrating into the epidermis to form vitamin D3, it is also absorbed by DNA resulting in the formation of CPD and other pyrimidine photoproducts that if unrepaired have been associated with increased risk for nonmelanoma skin cancer. It also resulted in CPD-positive nuclei in keratinocytes for the exposed skin compared with photoprotected skin of the same volunteer