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Factors that influence the cutaneous synthesis and dietary sources of vitamin D. Chen TC, Chimeh F, Lu Z, Mathieu J, Person KS, Zhang A, Kohn N, Martinello S, Berkowitz R, Holick MF. Arch Biochem Biophys. 2007 Apr 15;460(2):213-7. Epub 2007 Jan 8. PMID: 17254541 doi: 10.1016/j.abb.2006.12.017 Vitamin D is rare in food. Among the vitamin D-rich food, oily fish are considered to be one of the best sources. Therefore, we analyzed the vitamin D content in several commonly consumed oily and non-oily fish. The data showed that farmed salmon had a mean content of vitamin D that was ~25% of the mean content found in wild caught salmon from Alaska, and that vitamin D2 was found in farmed salmon, but not in wild caught salmon. The results provide useful global guidelines for obtaining sufficient vitamin D3 by cutaneous synthesis and from dietary intake to prevent vitamin D deficiency and its health consequences.ensuing illness, especially, bone fractures in the elderly.

Factors that influence the cutaneous synthesis and dietary sources of vitamin D.\nChen TC, Chimeh F, Lu Z, Mathieu J, Person KS, Zhang A, Kohn N, Martinello S, Berkowitz R, Holick MF.\nArch Biochem Biophys. 2007 Apr 15;460(2):213-7. Epub 2007 Jan 8.\nPMID: 17254541\ndoi:10.1016/j.abb.2006.12.017\n

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.

In vivo threshold for cutaneous synthesis of vitamin D3. Matsuoka LY, Wortsman J, Haddad JG, Hollis BW. J Lab Clin Med. 1989 Sep;114(3):301-5. PMID: 2549141

Chen TC, Chimeh F, Lu Z, Mathieu J, Person KS, Zhang A, Kohn N, Martinello S, Berkowitz R, Holick MF. Factors that influence the cutaneous synthesis and dietary sources of vitamin D. Arch Biochem Biophys. 2007 Apr 15;460(2):213-7. Epub 2007 Jan 8. PMI

"In the September 2009 issue of the journal Advances in Therapy, German researchers report that the addition of omega-3 polyunsaturated fatty acids to the over-the-counter arthritis treatment glucosamine sulfate resulted in improved alleviation of symptoms compared to glucosamine alone. The trial is the first, to the authors' knowledge, to test the combination in patients with osteoarthritis. In their introduction to the article, Joerg Gruenwald and his coauthors explain that a chronic imbalance between the synthesis and degradation of cartilage matrix leads to the loss of joint tissue that occurs in osteoarthritis. Glucosamine and omega-3 fatty acids appear to be successful in adjusting this imbalance in the direction of new cartilage synthesis"

"5' AMP-activated protein kinase or AMPK or 5' adenosine monophosphate-activated protein kinase is an enzyme that plays a role in cellular energy homeostasis. It consists of three proteins (subunits) that together make a functional enzyme, conserved from yeast to humans. It is expressed in a number of tissues, including the liver, brain, and skeletal muscle. The net effect of AMPK activation is stimulation of hepatic fatty acid oxidation and ketogenesis, inhibition of cholesterol synthesis, lipogenesis, and triglyceride synthesis, inhibition of adipocyte lipolysis and lipogenesis, stimulation of skeletal muscle fatty acid oxidation and muscle glucose uptake, and modulation of insulin secretion by pancreatic beta-cells.[1] It should not be confused with cyclic AMP-activated protein kinase (protein kinase A), which, although being of similar nature, may have opposite effects.[2]"

Vitamin D and skin physiology: a D-lightful story. Holick MF, Chen TC, Lu Z, Sauter E. J Bone Miner Res. 2007 Dec;22 Suppl 2:V28-33. PMID: 18290718 doi: 10.1359/jbmr.07s211 Very few foods naturally contain vitamin D, and those that do have a very variable vitamin D content. Recently it was observed that wild caught salmon had between 75% and 90% more vitamin D(3) compared with farmed salmon. The associations regarding increased risk of common deadly cancers, autoimmune diseases, infectious diseases, and cardiovascular disease with living at higher latitudes and being prone to vitamin D deficiency should alert all health care professionals about the importance of vitamin D for overall health and well being. Humans have depended on sunlight for their vitamin D requirement. The impact of season, time of day, and latitude on vitamin D synthesis is well documented.(2,3) We now report that altitude also has a dramatic influence on vitamin D3 production and that living at altitudes above 3500 m permits previtamin D3 production at a time when very little is produced at latitudes below 3400 m. It was surprising that, at 27° N in Agra (169 M), little previtamin D3 production was observed. However, there was significant air pollution that caused a haze over the city. It is likely the ozone and other UVB-absorbing pollutants in the air prevented the solar UVB photons from reaching the earth's surface to produce previtamin D3.

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.

Fish oil and tocopherol-induced changes in natural killer cell-mediated cytotoxicity and PGE2 synthesis in young and old mice. Meydani SN, Yogeeswaran G, Liu S, Baskar S, Meydani M. J Nutr. 1988 Oct;118(10):1245-52. PMID: 3183771

Impact of fish oil enriched total parenteral nutrition on DNA synthesis, cytokine release and receptor expression by lymphocytes in the postoperative period. Schauder P, Röhn U, Schäfer G, Korff G, Schenk HD. Br J Nutr. 2002 Jan;87 Suppl 1:S103-10. PMID: 11895146 doi:10.1079/BJN2001463

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.

NEW YORK (Reuters Health) May 29 - Supplementation with coenzyme Q10 (CoQ10) improves endothelial dysfunction in patients with type 2 diabetes on statin therapy, according to results of a study reported in the May issue of Diabetes Care. The vascular benefits of statins might be attenuated by inhibition of CoQ10 synthesis, Dr. Gerald T. Chew and colleagues from University of Western Australia, Perth, note in their report.

SSeason of diagnosis is a prognostic factor in Hodgkin's lymphoma: a possible role of sun-induced vitamin D. Porojnicu AC, Robsahm TE, Ree AH, Moan J. Br J Cancer. 2005 Sep 5;93(5):571-4. PMID: 16136030 doi:10.1038/sj.bjc.6602722 Epidemiological data for this period indicate that season of diagnosis is a strong prognostic factor for Hodgkin's lymphoma, with approximately 20% lower case fatality for patients diagnosed during autumn vs winter diagnosis (RR = 0.783, 95% CI,-0.62 to 0.99; P = 0.041). Notably, the improved autumnal survival rate was higher than 60% (RR = 0.364, 95% CI, -0.15 to 0.87; P = 0.025) for patients younger than 30 years. This finding may be related to higher endogenous levels of vitamin D in autumn, with a favourable influence on the conventional therapy. In conclusion, we have found that the prognosis of Hodgkin's lymphoma is significantly correlated with the season of diagnosis, particularly for patients younger than 30 years. This seasonal effect is presumably due to the vitamin D3 synthesis in skin during sun exposure. The present findings should encourage further investigations of the possible adjuvant role of vitamin D derivatives in cancer therapy

Vitamin D: a D-Lightful health perspective. Holick MF. Nutr Rev. 2008 Oct;66(10 Suppl 2):S182-94. Review. PMID: 18844847 DOI: 10.1111/j.1753-4887.2008.00104.x Sunlight provides most humans with their vitamin D requirement. Adequate vitamin D(3) by synthesis in the skin or from dietary and supplemental sources is essential for bone health throughout life. Vitamin D deficiency is defined as a 25(OH)D concentration 30 ng/mL (75 nmol/L), and insufficiency as 21-29 ng/mL. Vitamin D deficiency and insufficiency has been linked to a wide variety of chronic diseases including common cancers, autoimmune, cardiovascular, and infectious diseases. Healthcare professionals need to be aware of the vitamin D deficiency pandemic. Guidelines for sensible sun exposure and supplemental vitamin D of 800-1000 IU/day are needed.

Vitamin D may suppress infections which lead to development of Multiple Sclerosis Steven R Brenner, None (16 August 2007) J Neurol Neurosurg Psychiatry 2008 I read the article with reference to the inverse relationship between multiple sclerosis clinical activity and deficiency of vitamin D by Soilu-Hannienen (1) with interest, and was considering what mechanism could be in play to cause such a relationship. 25-hydroxylated metabolites of vitamin D act as intracellular regulators of the synthesis and action of defensin (2) molecules against bacterial antigens, defensin being an endogenously synthesized antimicrobial substance (2). Human cathelicidin antimicrobial peptide gene is a target of vitamin D receptor and is strongly up-regulated by 1,25-dihydroxyvitamin D3, indicating vitamin D receptor and the 1,25-dihydroxyvitaminD3 regulate primate innate immunity (3)

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

Role of vitamin D in the pathogenesis of type 2 diabetes mellitus. Palomer X, González-Clemente JM, Blanco-Vaca F, Mauricio D. Diabetes Obes Metab. 2008 Mar;10(3):185-97. Review. PMID: 18269634 DOI: 10.1111/j.1463-1326.2007.00710.x Vitamin D deficiency has been shown to alter insulin synthesis and secretion in both humans and animal models. It has been reported that vitamin D deficiency may predispose to glucose intolerance, altered insulin secretion and type 2 diabetes mellitus. Vitamin D replenishment improves glycaemia and insulin secretion in patients with type 2 diabetes with established hypovitaminosis D, thereby suggesting a role for vitamin D in the pathogenesis of type 2 diabetes mellitus.

Thromboxane B2 is an inactive metabolite/product of thromboxane A2. It is almost completely cleared in the urine. It itself is not involved in platelet activation and aggregation in case of a wound, but its precursor, thromboxane A2, is. Thromboxane A2 synthesis is the target of the drug aspirin, which inhibits the COX-1 enzyme (the source of thromboxane A2 in platelets).

Ursolic acid, a natural pentacyclic triterpenoid carboxylic acid, is the major component of some traditional medicine herbs and is well known to possess a wide range of biological functions, such as antioxidative, anti-inflammatory, antihyperlipidemic and anticancer activities, that are able to counteract endogenous and exogenous biological stimuli. Ursolic acid has been noted for their antitumor-promotion activities. Ursolic acid is capable of inducing apoptosis in tumor cells on one side and to prevent malignant transformation of normal cells on the other side. It also interferes with numerous enzymes, including the ones serving directly to DNA synthesis