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Bioactive vitamin D or calcitriol is a steroid hormone that has long been known for its important role in regulating body levels of calcium and phosphorus, and in mineralization of bone. More recently, it has become clear that receptors for vitamin D are present in a wide variety of cells, and that this hormone has biologic effects which extend far beyond control of mineral metabolism. The active form of vitamin D binds to intracellular receptors that then function as transcription factors to modulate gene expression. Like the receptors for other steroid hormones and thyroid hormones, the vitamin D receptor has hormone-binding and DNA-binding domains. The vitamin D receptor forms a complex with another intracellular receptor, the retinoid-X receptor, and that heterodimer is what binds to DNA. In most cases studied, the effect is to activate transcription, but situations are also known in which vitamin D suppresses transcription. Each of the forms of vitamin D is hydrophobic, and is transported in blood bound to carrier proteins. The major carrier is called, appropriately, vitamin D-binding protein. The halflife of 25-hydroxycholecalciferol is several weeks, while that of 1,25-dihydroxycholecalciferol is only a few hours. The vitamin D receptor binds several forms of cholecalciferol. Its affinity for 1,25-dihydroxycholecalciferol is roughly 1000 times that for 25-hydroxycholecalciferol, which explains their relative biological potencies

Why "Vitamin D" is not a hormone, and not a synonym for 1,25-dihydroxy-vitamin D, its analogs or deltanoids. Vieth R. J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):571-3. PMID: 15225841 doi:10.1016/j.jsbmb.2004.03.037

An evaluation of the vitamin D3 content in fish: Is the vitamin D content adequate to satisfy the dietary requirement for vitamin D?\nLu Z, Chen TC, Zhang A, Persons KS, Kohn N, Berkowitz R, Martinello S, Holick MF.\nJ Steroid Biochem Mol Biol. 2007 Mar;103(3-5):642-4. Epub 2007 Jan 30.\nPMID: 17267210 \ndoi:10.1016/j.jsbmb.2006.12.010 \n

Martineau AR, Honecker FU, Wilkinson RJ, Griffiths CJ. Vitamin D in the treatment of pulmonary tuberculosis. J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):793-8. Epub 2007 Jan 12. Review. PMID: 17223549 [PubMed - indexed for MEDLINE]

Calcidiol and prostate cancer. Tuohimaa P, Golovko O, Kalueff A, Nazarova N, Qiao S, Syvälä H, Talonpoika R, Lou YR. J Steroid Biochem Mol Biol. 2005 Feb;93(2-5):183-90. Epub 2005 Jan 22. Review. PMID: 15860261

Lu Z, Chen TC, Zhang A, Persons KS, Kohn N, Berkowitz R, Martinello S, Holick MF. An evaluation of the vitamin D3 content in fish: Is the vitamin D content adequate to satisfy the dietary requirement for vitamin D? J Steroid Biochem Mol Biol. 2007 Mar;

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

The role of Vitamin D3 metabolism in prostate cancer. Lou YR, Qiao S, Talonpoika R, Syvälä H, Tuohimaa P. J Steroid Biochem Mol Biol. 2004 Nov;92(4):317-25. Epub 2004 Dec 19. Review. PMID: 15663995 doi:10.1016/j.jsbmb.2004.10.007 In summary, the local metabolism of hormonal Vitamin D seems to play an important role in the development and progression of prostate cancer.

Vitamin D and prostate cancer. Tuohimaa P, Lyakhovich A, Aksenov N, Pennanen P, Syvälä H, Lou YR, Ahonen M, Hasan T, Pasanen P, Bläuer M, Manninen T, Miettinen S, Vilja P, Ylikomi T. J Steroid Biochem Mol Biol. 2001 Jan-Mar;76(1-5):125-34. PMID: 11384870 doi:10.1016/S0960-0760(00)00141-2

25-Hydroxyvitamin D(3) is an agonistic vitamin D receptor ligand. Lou YR, Molnár F, Peräkylä M, Qiao S, Kalueff AV, St-Arnaud R, Carlberg C, Tuohimaa P. J Steroid Biochem Mol Biol. 2009 Nov 26. [Epub ahead of print] PMID: 19944755 doi:10.1016/j.jsbmb.2009.11.011 In conclusion, 25-hydroxyvitamin D3 is an agonistic vitamin D receptor ligand with gene regulatory and anti-proliferative properties.

25-Hydroxyvitamin D(3) is an agonistic vitamin D receptor ligand. Lou YR, Molnár F, Peräkylä M, Qiao S, Kalueff AV, St-Arnaud R, Carlberg C, Tuohimaa P. J Steroid Biochem Mol Biol. 2009 Nov 26. [Epub ahead of print] PMID: 19944755 doi:10.1016/j.jsbmb.2009.11.011 In conclusion, 25-hydroxyvitamin D3 is an agonistic vitamin D receptor ligand with gene regulatory and anti-proliferative properties.

Vitamin D and aging. Tuohimaa P. J Steroid Biochem Mol Biol. 2009 Mar;114(1-2):78-84. Review. PMID: 19444937

Vitamin D and prevention of breast cancer: pooled analysis. Garland CF, Gorham ED, Mohr SB, Grant WB, Giovannucci EL, Lipkin M, Newmark H, Holick MF, Garland FC. J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):708-11. PMID: 17368188 CONCLUSIONS: Intake of 2000 IU/day of Vitamin D(3), and, when possible, very moderate exposure to sunlight, could raise serum 25(OH)D to 52 ng/ml, a level associated with reduction by 50% in incidence of breast cancer, according to observational studies.

Twice single doses of 100,000 IU of vitamin D in winter is adequate and safe for prevention of vitamin D deficiency in healthy children from Ushuaia, Tierra Del Fuego, Argentina. Tau C, Ciriani V, Scaiola E, Acuña M. J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):651-4. Epub 2007 Jan 25. PMID: 17257830 doi:10.1016/j.jsbmb.2006.12.027 These results disclosed that to prevent vitamin D deficiency for children at zones of risk at the south of our country, double supplementation of 100,000 IU of vitamin D during autumn and winter, would be adequate and safe.

Vitamin D and aging. Tuohimaa P. J Steroid Biochem Mol Biol. 2009 Mar;114(1-2):78-84. Review. PMID: 19444937

Use of vitamin D in clinical practice. Cannell JJ, Hollis BW. Altern Med Rev. 2008 Mar;13(1):6-20. PMID: 18377099 The recent discovery--from a meta-analysis of 18 randomized controlled trials--that supplemental cholecalciferol (vitamin D) significantly reduces all-cause mortality emphasizes the medical, ethical, and legal implications of promptly diagnosing and adequately treating vitamin D deficiency. Not only are such deficiencies common, and probably the rule, vitamin D deficiency is implicated in most of the diseases of civilization. Vitamin D's final metabolic product is a potent, pleiotropic, repair and maintenance, seco-steroid hormone that targets more than 200 human genes in a wide variety of tissues, meaning it has as many mechanisms of action as genes it targets. One of the most important genes vitamin D up-regulates is for cathelicidin, a naturally occurring broad-spectrum antibiotic. Natural vitamin D levels, those found in humans living in a sun-rich environment, are between 40-70 ng per ml, levels obtained by few modern humans. Assessing serum 25-hydroxy-vitamin D (25(OH)D) is the only way to make the diagnosis and to assure treatment is adequate and safe. Three treatment modalities exist for vitamin D deficiency: sunlight, artificial ultraviolet B (UVB) radiation, and vitamin D3 supplementation. Treatment of vitamin D deficiency in otherwise healthy patients with 2,000-7,000 IU vitamin D per day should be sufficient to maintain year-round 25(OH)D levels between 40-70 ng per mL. In those with serious illnesses associated with vitamin D deficiency, such as cancer, heart disease, multiple sclerosis, diabetes, autism, and a host of other illnesses, doses should be sufficient to maintain year-round 25(OH)D levels between 55 -70 ng per mL. Vitamin D-deficient patients with serious illness should not only be supplemented more aggressively than the well, they should have more frequent monitoring of serum 25(OH)D and serum calcium. Vitamin D should always be

An evaluation of the vitamin D3 content in fish: Is the vitamin D content adequate to satisfy the dietary requirement for vitamin D? Lu Z, Chen TC, Zhang A, Persons KS, Kohn N, Berkowitz R, Martinello S, Holick MF. J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):642-4. Epub 2007 Jan 30. PMID: 17267210 doi: 10.1016/j.jsbmb.2006.12.010 Surprisingly, farmed salmon had approximately 25% of the vitamin D content as wild salmon had. The vitamin D content in fish varied widely even within species. These data suggest that the tables that list the vitamin D content are out-of-date and need to be re-evaluated. Little is known about the effect of cooking on the vitamin D content in fish. When farm salmon was baked, almost all of the vitamin D content, i.e. 240 IU of vitamin D3 was recovered from 3.5 oz. of salmon. The initial concentration in the uncooked salmon was 245 IU of vitamin D3. However, when the salmon was fried in vegetable oil, approximately 50% (123 IU of vitamin D3 was recovered.) We also evaluated the vitamin D content in mackerel which is traditionally considered to be an excellent source of vitamin D3 because of its oily content. However, in the one sample that we tested, we only observed 24 IU of vitamin D3 in 3.5 oz.

Conclusion We demonstrated that the VDRE in the CAMP gene originated from the exaptation of an AluSx SINE in the lineage leading to humans, apes, OWMs and NWMs and remained under purifying selection for the last 55-60 million years. We present convincing evidence of an evolutionarily fixed, Alu-mediated divergence in steroid hormone nuclear receptor gene regulation between humans/primates and other mammals. Evolutionary selection to place the primate CAMP gene under regulation of the vitamin D pathway potentiates the innate immune response and may counter the anti-inflammatory properties of vitamin D. Exaptation of an ancient Alu short interspersed element provides a highly conserved vitamin D-mediated innate immune response in humans and primates. Gombart AF, Saito T, Koeffler HP. BMC Genomics. 2009 Jul 16;10:321. PMID: 19607716 doi:10.1186/1471-2164-10-321

Circulating vitamin D3 and 25-hydroxyvitamin D in humans: An important tool to define adequate nutritional vitamin D status. Hollis BW, Wagner CL, Drezner MK, Binkley NC. J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):631-4. Epub 2007 Jan 10. PMID: 17218096 In the present study, we sought to investigate what circulating 25(OH)D levels would result in populations exhibiting no substrate limitations to the vitamin D-25-hydroxylase. To perform this, we chose two distinct populations. The first were individuals from a year-found sunny environment who spent a good deal of time outdoors. The second were a group of lactating women receiving a substantial daily oral dose of vitamin D3. Surprisingly, a study such as this previously had not been undertaken. There are several reasons for this. First, finding a group of sun-exposed individuals is not an easy task; in fact, we had to go to Hawaii to find them. Secondly, very few studies have been performed where subjects actually received adequate vitamin D3 supplementation to make them replete. Finally, it is very difficult and costly to measure circulating vitamin D3 and relate it to circulating 25(OH)D. The results of our study are far-reaching. This study also demonstrates that individuals can be vitamin D deficient with significant sun exposure if the skin area exposed is limited as was suggested several years ago (19). Finally, whether one receives their vitamin D3 orally or through UV exposure, the vitamin D-25-hydroxylase appears to handle it in an equivalent fashion with respect to maintaining circulating 25(OH)D levels. Thus, we believe that the relationship between circulating vitamin D and 25(OH)D may define adequate nutritional vitamin D status.

"Last Wednesday night I gave a lecture to my clients on hunter-gatherer diets. The turnout was great and the information was well-received. I had it professionally video-recorded and will probably offer this as a DVD for sale (with the handout included). Watch for it in the future. Part of what I discussed was vitamin D3 supplementation. Since I have been supplementing with 4,000-10,000 Units of D3 per day I have noted enhanced recovery and size response from my training. Apparently, skeletal muscle has both surface receptors and nuclear receptors for D3 that augment calcium flux during contraction (from surface receptors) and have steroid-like effects at the nuclear level WRT protein synthesis. This D3 supplementation is not really "supplementation" but is instead "augmentation" to levels that would be normal if we got normal sun exposure as we did in our evolutionary past. Check out www.vitamindcouncil.org for more information. Also, check out this abstract below for your consideration. Also, check out this article."