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Your cells use vitamin D to directly regulate your genes, making it one of the most powerful compounds in human health.

"THURSDAY, Dec. 3 (HealthDay News) -- New research points to the possibility of a genetic link between vitamin D and heart disease. People with high blood pressure who had a gene variant that reduces vitamin D activation in the body were found to be twice as likely as those without the variant to have congestive heart failure, the study found. The finding may lead to a way to identify people at increased risk for heart disease, according to Robert U. Simpson, an assistant professor of pharmacology at the University of Michigan Medical School and his research colleagues. They analyzed the genetic profiles of 617 people. One-third had hypertension, one-third had hypertension and congestive heart failure, and the remaining third served as healthy controls. The researchers found that a variant in the CYP27B1 gene was associated with congestive heart failure in people with hypertension. The study is in the November issue of Pharmacogenomics."

Association study on two vitamin D receptor gene polymorphisms and vitamin D metabolites in multiple sclerosis. Smolders J, Damoiseaux J, Menheere P, Tervaert JW, Hupperts R. Ann N Y Acad Sci. 2009 Sep;1173:515-20. PMID: 19758194 DOI: 10.1111/j.1749-6632.2009.04656.x Discussion: We found no association of the Apal and Taql VDR gene SNPs with MS or with vitamin D metabolism in our population. Further research should assess the complex interaction between vitamin D, the VDR, and susceptibility to MS.

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

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

The vitamin D-antimicrobial peptide pathway and its role in protection against infection. Gombart AF. Future Microbiol. 2009 Nov;4:1151-65. PMID: 19895218 Vitamin D deficiency has been correlated with increased rates of infection. Since the early 19th century, both environmental (i.e., sunlight) and dietary sources (cod liver) of vitamin D have been identified as treatments for TB. The recent discovery that vitamin D induces antimicrobial peptide gene expression explains, in part, the 'antibiotic' effect of vitamin D and has greatly renewed interest in the ability of vitamin D to improve immune function. Subsequent work indicates that this regulation is biologically important for the response of the innate immune system to wounds and infection and that deficiency may lead to suboptimal responses toward bacterial and viral infections. The regulation of the cathelicidin antimicrobial peptide gene is a human/primate-specific adaptation and is not conserved in other mammals. The capacity of the vitamin D receptor to act as a high-affinity receptor for vitamin D and a low-affinity receptor for secondary bile acids and potentially other novel nutritional compounds suggests that the evolutionary selection to place the cathelicidin gene under control of the vitamin D receptor allows for its regulation under both endocrine and xenobiotic response systems. Future studies in both humans and humanized mouse models will elucidate the importance of this regulation and lead to the development of potential therapeutic applications

Vitamin D receptor gene polymorphisms influence susceptibility to type 1 diabetes mellitus in the Taiwanese population. Chang TJ, Lei HH, Yeh JI, Chiu KC, Lee KC, Chen MC, Tai TY, Chuang LM. Clin Endocrinol (Oxf). 2000 May;52(5):575-80. PMID: 10792336 DOI: 10.1046/j.1365-2265.2000.00985.x CONCLUSIONS Vitamin D receptor gene polymorphisms were associated with type 1 diabetes in a Taiwanese population. However, functional studies are needed to establish the role of the vitamin D receptor in the pathogenesis of type 1 diabetes mellitus.

The relevance of vitamin D receptor (VDR) gene polymorphisms for cancer: a review of the literature. Köstner K, Denzer N, Müller CS, Klein R, Tilgen W, Reichrath J. Anticancer Res. 2009 Sep;29(9):3511-36. Review. PMID: 19667145 CONCLUSION: Significant associations with VDR polymorphisms have been reported in cancer of the breast (Fok1, Bsm1, Taq1, Apa1, poly (A)), prostate (Fok1, Bsm1, Taq1, poly (A)), skin (Fok1, Bsm1, A-1210), colorectum (Fok1, Bsm1), ovary (Fok1, Apa1) and bladder (Fok1), and in renal cell carcinoma (Taq1, Apa1). However, conflicting data have been reported for most malignancies. After careful evaluation of the actual literature, it can be summarized that data indicating an association of VDR polymorphisms and cancer risk are strongest for breast cancer (Bsm1, Fok1), prostate cancer (Fok1) and malignant melanoma (MM) (Fok1). Data indicating an association of VDR polymorphisms and cancer prognosis are strongest for prostate cancer (Fok1), breast cancer (Bsm1, Taq1), MM (Bsm1) and renal cell carcinoma (Taq1).

Vitamin D receptor gene polymorphism: association with Crohn's disease susceptibility.\nSimmons JD, Mullighan C, Welsh KI, Jewell DP.\nGut. 2000 Aug;47(2):211-4.\nPMID: 10896912 \ndoi:10.1136/gut.47.2.211

NaturalNews) Researchers from Oxford University and the University of British Columbia have discovered that Vitamin D deficiency affects a section of the human genome already linked with multiple sclerosis (MS) risk, adding further weight to theories that this vitamin deficiency might play a role in development of the disease. "Here we show that the main environmental risk candidate -- vitamin D -- and the main gene region are directly linked and interact," said co-author George Ebers.

Diagnosis and treatment of vitamin D deficiency. Cannell JJ, Hollis BW, Zasloff M, Heaney RP. Expert Opin Pharmacother. 2008 Jan;9(1):107-18. PMID: 18076342 The recent discovery - in a randomised, controlled trial - that daily ingestion of 1100 IU of colecalciferol (vitamin D) over a 4-year period dramatically reduced the incidence of non-skin cancers makes it difficult to overstate the potential medical, social and economic implications of treating vitamin D deficiency. Not only are such deficiencies common, probably the rule, vitamin D deficiency stands implicated in a host of diseases other than cancer. The metabolic product of vitamin D is a potent, pleiotropic, repair and maintenance, secosteroid hormone that targets > 200 human genes in a wide variety of tissues, meaning it has as many mechanisms of action as genes it targets. A common misconception is that government agencies designed present intake recommendations to prevent or treat vitamin D deficiency. They did not. Instead, they are guidelines to prevent particular metabolic bone diseases. Official recommendations were never designed and are not effective in preventing or treating vitamin D deficiency and in no way limit the freedom of the physician - or responsibility - to do so. At this time, assessing serum 25-hydroxy-vitamin D is the only way to make the diagnosis and to assure that treatment is adequate and safe. The authors believe that treatment should be sufficient to maintain levels found in humans living naturally in a sun-rich environment, that is, > 40 ng/ml, year around. Three treatment modalities exist: sunlight, artificial ultraviolet B radiation or supplementation. All treatment modalities have their potential risks and benefits. Benefits of all treatment modalities outweigh potential risks and greatly outweigh the risk of no treatment. As a prolonged 'vitamin D winter', centred on the winter solstice, occurs at many temperate latitudes, ≤ 5000 IU (125 μg) of vitamin D/d

"Hi! This is Amy Proal. I wrote the article referenced at the start of the thread about vitamin D. Dr. Marshall is not concerned with vitamin D toxicity. Rather his molecular modeling research has clarified the actions of the two vitamin D metabolites 25-D and 1,25-D. The Vitamin D Receptor (VDR) is a fundamental receptor of the body - it controls the expression thousands of genes, as well as the activity of the innate immune system and the antimicrobial peptides. If you think of the VDR as a switch, 25-D (which is a corticosteroid) turns it off (inactivates it) and 1,25-D turn it on (activates it). What is commonly believed among vitamin D researchers is that if people supplement with extra vitamin D it will be converted into 1,25-D and activate the VDR. Unfortunately, Marshall's work revealed that the type of vitamin D derived from supplements and sun remains, for the most part, in it's precursor form 25-D. This means that the extra vitamin D we get from fortified food products and supplements is turning the VDR off, not on. That causes a decrease in immune function and gene transcription."

"Vitamin D is not just a sun-derived vitamin, but is a crucial steroid precursor that is transformed into one of the most potent hormones in the human body for strength, power, lung function and regulating gene expression in every organ system. Athletes need Vitamin D. Dr. Cannell has written quite extensively about the role of vitamin D in athletes"

Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3.\nGombart AF, Borregaard N, Koeffler HP.\nFASEB J. 2005 Jul;19(9):1067-77.\nPMID: 15985530

Vitamin D receptor (VDR) gene polymorphisms and haplotypes, interactions with plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and prostate cancer risk. Mikhak B, Hunter DJ, Spiegelman D, Platz EA, Hollis BW, Giovannucci E. Prostate. 2007 Jun 15;67(9):911-23. PMID: 17440943 DOI: 10.1002/pros.20570 RESULTS No association was found between these SNPs or their associated haplotypes and all PC subtypes except that haplotype 2 (A-f-b) with Cdx2 A, Fok1 f, and Bsm1 b alleles and haplotype 3 (A-F-B) with Cdx2 A, Fok1 F and Bsm1 B alleles compared to the most common haplotype (A-F-b), were associated with reduced risk of aggressive PC (high stage or Gleason sum 7; P = 0.02), both with two alleles suspected of being low risk. Carriers of the variant Cdx2 A allele who were deficient in plasma 25-hydroxyvitamin D (15 ng/ml) compared to non-carriers with normal 25-hydroxyvitamin D, had a lower risk of total and poorly differentiated PCs (Gleason sum 7) (P for interaction = 0.02 and 0.04, respectively). Plasma 1,25-dihydroxyvitamin D deficiency (26 pg/ml) was associated with a threefold risk of poorly differentiated PC (P for interaction = 0.01) when comparing carriers of the Cdx2 A allele to non-carriers with normal 1,25-dihydroxyvitamin D. CONCLUSION In this population of men, none of the VDR polymorphisms studied was associated with susceptibility to PC. Carriers of the variant Cdx2 A allele with low plasma 25-hydroxyvitamin D may experience a reduction in risk of total and poorly differentiated prostate cancers compared to non-carriers with adequate 25-hydroxyvitamin D.

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)

The calcitriol receptor, also known as the vitamin D receptor (VDR) and also known as NR1I1 (nuclear receptor subfamily 1, group I, member 1), is a member of the nuclear receptor family of transcription factors.[1] Upon activation by vitamin D, the VDR forms a heterodimer with the retinoid-X receptor and binds to hormone response elements on DNA resulting in expression or transrepression of specific geneproducts. In humans, the vitamin D receptor is encoded by the VDR gene.[2]

Research finds people with gene variant who lack vitamin D, produced from sun exposure, can develop condition

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

Vitamin D-induced up-regulation of tumour necrosis factor alpha (TNF-alpha) in prostate cancer cells. Golovko O, Nazarova N, Tuohimaa P. Life Sci. 2005 Jun 17;77(5):562-77. Epub 2005 Feb 25. PMID: 15904673 doi:10.1016/j.lfs.2004.10.072 Combined addition of human recombinant TNF-alpha with calcitriol or CB1093 cause enhanced effect in induction of apoptosis. We conclude that under physiological conditions vitamin D activates only the transcription of TNF-alpha gene, for TNF-alpha protein synthesis additional cofactors are required. Therefore a cooperation of vitamin D and TNF-alpha may play an important role in the control of cell growth in prostate cancer.