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Holick, M. F., MacLaughlin, J. A. & Doppelt, S. H. (1981) Factors that influence the cutaneous photosynthesis of previtamin D3. Science 211:590-593 When human skin was exposed to simulated solar ultraviolet radiation, epidermal 7-dehydrocholesterol was converted to previtamin D3. During prolonged exposure to simulated solar ultraviolet radiation, the synthesis of previtamin D3 reached a plateau at about 10 to 15 percent of the original 7-dehydrocholesterol content, and previtamin D3 was photoisomerized to two biologically inert isomers, lumisterol3 and tachysterol3. Increases either in skin melanin concentration or in latitude necessitated increases in the exposure time to simulated solar ultraviolet radiation required to maximize the formation, but not the total content, of previtamin D3. In order of importance, the significant determinants limiting the cutaneous production of previtamin D3 are (i) photochemical regulation, (ii) pigmentation, and (iii) latitude.

Current impediments to acceptance of the ultraviolet-B-vitamin D-cancer hypothesis. Grant WB, Boucher BJ. Anticancer Res. 2009 Sep;29(9):3597-604. PMID: 19667154 The ultraviolet-B (UVB)-vitamin D-cancer hypothesis was proposed in 1980. There have been numerous ecological, observational and other studies of the hypothesis. There are about 14 types of cancer for which it seems to apply: bladder, breast, colon, endometrial, esophageal, gallbladder, gastric, ovarian, pancreatic, rectal, renal and vulvar cancer and both Hodgkin's and non-Hodgkin's lymphoma. Nonetheless, the hypothesis has not yet been accepted by public health agencies. Some of the reasons for this include a distrust of ecological studies, some mistrust of observational studies, and the existence of just one positive randomized controlled trial, an analysis of a vitamin D and calcium supplementation study involving post-menopausal women in Nebraska. Paradigm shifts such as this generally take time, in part due to opposition from those content with the status quo. In this paper, results of ecological studies in the United States using summertime solar UVB as the index of vitamin D production, which is highly asymmetrical with respect to latitude, and indices for other cancer risk-modifying factors (air pollution, alcohol consumption, dietary iron and zinc, ethnic background, socioeconomic status, smoking and urban/rural residence) are discussed in terms of supporting the hypothesis. These studies were not considered while other ecological studies were examined in recent critiques of the hypothesis. While additional randomized controlled trials would, of course, be helpful, the current evidence seems to satisfy the criteria for causality as outlined by A. Bradford Hill.

Explaining multiple sclerosis prevalence by ultraviolet exposure: a geospatial analysis. Beretich B, Beretich T. Mult Scler. 2009 Aug;15(8):891-8. PMID: 19667017 DOI: 10.1177/1352458509105579 Conclusion This analysis suggests a strong association between UV radiation and MS distribution, and an increase in risk for MS in those areas with a low UVI.

Vitamin D is a fat-soluble vitamin that is essential for maintaining normal calcium metabolism (1). Vitamin D3 (cholecalciferol) can be synthesized by humans in the skin upon exposure to ultraviolet-B (UVB) radiation from sunlight, or it can be obtained from the diet. Plants synthesize ergosterol, which is converted to vitamin D2 (ergocalciferol) by ultraviolet light. Vitamin D2 is less active in birds than vitamin D3 and may also be less active in humans (2). When exposure to UVB radiation is insufficient for the synthesis of adequate amounts of vitamin D3 in the skin, adequate intake of vitamin D from the diet is essential for health.

An acknowledged benefit of exposure to ultraviolet radiation is synthesis of vitamin D in human skin. Here we have defined a standard vitamin D dose based upon recommended requirements for vitamin D, and present a simplified web-based tool that enables the user to calculate associated exposure times for any time and place ( http://nadir.nilu.no/~olaeng/fastrt/VitD-ez_quartMED.html). This www page is a simplified version of the more complex web tool ( http://nadir.nilu.no/~olaeng/fastrt/VitD_quartMED.html). The simplified www page is convenient for users unfamiliar to radiative transfer modelling, because the model input is limited and more intuitive.

An acknowledged benefit of exposure to ultraviolet radiation is synthesis of vitamin D in human skin. Here we have defined a standard vitamin D dose based upon recommended requirements for vitamin D, and present a web-based tool that enables the user to calculate associated exposure times for any time and place ( http://nadir.nilu.no/~olaeng/fastrt/VitD_quartMED.html). The recommended UV exposure times depends on latitude, time, total ozone, clouds, aerosols, surface reflectivity and altitude all of which can be specified by the user. A simpler version for non-experts is available at http://nadir.nilu.no/~olaeng/fastrt/VitD-ez_quartMED.html

An ecologic study of dietary and solar ultraviolet-B links to breast carcinoma mortality rates. Grant WB. Cancer. 2002 Jan 1;94(1):272-81. PMID: 11815987 CONCLUSIONS It is hypothesized that animal products are associated with risk for breast carcinoma because they are associated with greater amounts of insulin-like growth factor-1and lifetime doses of estrogen. Vegetable products contain several risk reduction components including antioxidants and phytoestrogens. The association with latitude is very likely because of solar UV-B radiation and vitamin D. Alcohol modulates estrogen's effects on breasts. Fish intake is associated with risk reduction through vitamin D and n-3 oils. These results are consistent with those of many case-control and cohort studies but should be assessed in well designed cohort studies.

The association of solar ultraviolet B (UVB) with reducing risk of cancer: multifactorial ecologic analysis of geographic variation in age-adjusted cancer mortality rates. Grant WB, Garland CF. Anticancer Res. 2006 Jul-Aug;26(4A):2687-99. PMID: 16886679 CONCLUSION: These results provide additional support for the hypothesis that solar UVB, through photosynthesis of vitamin D, is inversely-associated with cancer mortality rates, and that various other cancer risk-modifying factors do not detract from this link. It is thought that sun avoidance practices after 1980, along with improved cancer treatment, led to reduced associations in the latter period. The results regarding solar UVB should be studied further with additional observational and intervention studies of vitamin D indices and cancer incidence, mortality and survival rates.

Ecological studies of ultraviolet B, vitamin D and cancer since 2000. Grant WB, Mohr SB. Ann Epidemiol. 2009 Jul;19(7):446-54. Epub 2009 Mar 9. PMID: 19269856 CONCLUSION: These findings provide strong evidence that vitamin D status plays an important role in controlling the outcome of cancer. Support for the UVB-vitamin D-cancer theory is now scientifically strong enough to warrant use of vitamin D in cancer prevention, and as a component of treatment. More research studies would help to explore whether there are benefits beyond the substantial effects that have been observed.

Ecological Studies Of Ultraviolet B, Vitamin D And Cancer Since 2000. Grant WB, Mohr SB. Ann Epidemiol. 2009 Mar 6. [Epub ahead of print] PMID: 19269856 doi:10.1016/j.annepidem.2008.12.014

Ecological Studies Of Ultraviolet B, Vitamin D And Cancer Since 2000. Grant WB, Mohr SB. Ann Epidemiol. 2009 Mar 6. [Epub ahead of print] PMID: 19269856

Vitamin D effective ultraviolet wavelengths due to scattering in shade. Turnbull DJ, Parisi AV, Kimlin MG. J Steroid Biochem Mol Biol. 2005 Sep;96(5):431-6. Epub 2005 Jul 6. PMID: 16005208

Ecological studies of ultraviolet B, vitamin D and cancer since 2000. Grant WB, Mohr SB. Ann Epidemiol. 2009 Jul;19(7):446-54. Epub 2009 Mar 9. Review. PMID: 19269856 CONCLUSION: These findings provide strong evidence that vitamin D status plays an important role in controlling the outcome of cancer. Support for the UVB-vitamin D-cancer theory is now scientifically strong enough to warrant use of vitamin D in cancer prevention, and as a component of treatment. More research studies would help to explore whether there are benefits beyond the substantial effects that have been observed.

Ultraviolet exposure scenarios: risks of erythema from recommendations on cutaneous vitamin D synthesis. Webb AR, Engelsen O. Adv Exp Med Biol. 2008;624:72-85. PMID: 18348448 DOI: 10.1007/978-0-387-77574-6_6

Relationship between low ultraviolet B irradiance and higher breast cancer risk in 107 countries. Mohr SB, Garland CF, Gorham ED, Grant WB, Garland FC. Breast J. 2008 May-Jun;14(3):255-60. Epub 2008 Apr 17. PMID: 18422861 DOI: 10.1111/j.1524-4741.2008.00571.x There was a protective effect of UVB irradiance on risk of breast cancer that was independent of fertility rate, proportion of the population overweight, alcohol intake, animal energy intake, and other covariates.

Effects of Atorvastatin on vitamin D levels in patients with acute ischemic heart disease. Pérez-Castrillón JL, Vega G, Abad L, Sanz A, Chaves J, Hernandez G, Dueñas A. Am J Cardiol. 2007 Apr 1;99(7):903-5. Epub 2007 Feb 8. PMID: 17398180 In conclusion, atorvastatin increases vitamin D levels. This increase could explain some of the beneficial effects of atorvastatin at the cardiovascular level that are unrelated to cholesterol levels. The mechanism by which atorvastatin increases vitamin D levels is related to inhibition of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase. Cholesterol is synthesized from 7-dehydrocholesterol, which is also a precursor of vitamin D3. For this reason, we initially observed a statistically significant relation between total cholesterol and vitamin D. HMG-CoA enzyme reductase is key to the synthesis of cholesterol, whereas ultraviolet radiation causes the formation of 25-hydroxyvitamin D. Inhibition of the enzyme may increase levels of 7-dehydrocholesterol and increase the synthesis of 25-hydroxycholecalciferol, thereby increasing vitamin D levels,10 although we observed no relation between lower cholesterol and increased vitamin D. In addition, 25-hydroxyvitamin D has been shown to inhibit HMG-CoA enzyme reductase activity in in vitro studies.11 A greater concentration of vitamin D could increase enzymatic inhibition, acting in synergy with the statin in decreasing total cholesterol.

Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation. Garland FC, Garland CF, Gorham ED, Young JF. Prev Med. 1990 Nov;19(6):614-22. PMID: 2263572 doi:10.1016/0091-7435(90)90058-R Vitamin D from sunlight exposure may be associated with low risk for fatal breast cancer, and differences in ultraviolet light reaching the United States population may account for the striking regional differences in breast cancer mortality. The ecological nature of this study is emphasized, and the possibility that an indirect association with dietary and socioeconomic factors could explain these findings is discussed.

Aging decreases the capacity of human skin to produce vitamin D3. MacLaughlin J, Holick MF. J Clin Invest. 1985 Oct;76(4):1536-8. PMID: 2997282 doi:10.1172/JCI112134 An evaluation of surgically obtained skin (age range, 8-92 yr) revealed that there is an age-dependent decrease in the epidermal concentrations of provitamin D3 (7-dehydrocholesterol). To ascertain that aging indeed decreased the capacity of human skin to produce vitamin D3, some of the skin samples were exposed to ultraviolet radiation and the content of previtamin D3 was determined in the epidermis and dermis. The epidermis in the young and older subjects was the major site for the formation of previtamin D3, accounting for greater than 80% of the total previtamin D3 that was produced in the skin. A comparison of the amount of previtamin D3 produced in the skin from the 8- and 18-yr-old subjects with the amount produced in the skin from the 77- and 82-yr-old subjects revealed that aging can decrease by greater than twofold the capacity of the skin to produce previtamin D3. Recognition of this difference may be extremely important for the elderly, who infrequently expose a small area of skin to sunlight and who depend on this exposure for their vitamin D nutritional needs.

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Robert P. Heaney is John A. Creighton University Professor, Creighton University, Omaha, Nebraska, United States. Hominid evolution took place in an environment (equatorial East Africa) that provided a superabundance of both calcium and vitamin D, the first in available foods and the second through conversion of 7-dehydrocholesterol to pre-vitamin D in the skin, a reaction catalysed by the intense solar ultraviolet (UV) radiation. Seemingly as a consequence, the evolving human physiology incorporated provisions to prevent the potential of toxic excesses of both nutrients. For vitamin D the protection was of two sorts: skin pigmentation absorbed the critical UV wavelengths and thereby limited dermal synthesis of cholecalciferol; and slow delivery of vitamin D from the skin into the bloodstream left surplus vitamin in the skin, where continuing sun exposure led to its photolytic degradation to inert compounds. For calcium, the adaptation consisted of very inefficient calcium absorption, together with poor to absent systemic conservation. The latter is reflected in unregulated dermal calcium losses, a high sensitivity of renal obligatory calcium loss to other nutrients in the diet and relatively high quantities of calcium in the digestive secretions. Today, chimpanzees in the original hominid habitat have diets with calcium nutrient densities in the range of 2 to 2.5 mmol per 100 kcal, and hunter-gatherer humans in Africa, South America and New Guinea still have diets very nearly as high in calcium (1.75 to 2 mmol per 100 kcal) (Eaton and Nelson, 1991). With energy expenditure of 3 000 kcal per day (a fairly conservative estimate for a contemporary human doing physical work), such diets would provide substantially in excess of 50 mmol of calcium per day. By contrast, median intake in women in North America and in many European countries today is under 15 mmol per day. Two factors altered the primitive situation: the migration of humans from Africa to higher latitude