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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 is associated with improved survival in early-stage non-small cell lung cancer patients. Zhou W, Suk R, Liu G, Park S, Neuberg DS, Wain JC, Lynch TJ, Giovannucci E, Christiani DC. Cancer Epidemiol Biomarkers Prev. 2005 Oct;14(10):2303-9. PMID: 16214909 In conclusion, the joint effects of surgery season and recent vitamin D intake seem to be associated with the survival of early-stage non-small cell lung cancer patients. In summary, for early-stage NSCLC patients, patients who had surgery in summer with "high" recent vitamin D intake have a statistically significantly improved RFS and OS than patients who had surgery in winter with "low" vitamin D intake. These results should be confirmed in a prospective study to assess the serum vitamin D levels at time of surgery. If the results are confirmed, our results, combined with findings in other studies, suggest that dietary vitamin D supplementation may be advisable for early stages of lung cancer patients, particularly during the winter season and in groups that tend to be deficient in vitamin D.

Vitamin D is associated with improved survival in early-stage non-small cell lung cancer patients. Zhou W, Suk R, Liu G, Park S, Neuberg DS, Wain JC, Lynch TJ, Giovannucci E, Christiani DC. Cancer Epidemiol Biomarkers Prev. 2005 Oct;14(10):2303-9. PMID: 16214909 In conclusion, the joint effects of surgery season and recent vitamin D intake seem to be associated with the survival of early-stage non-small cell lung cancer patients.

Myalgias or non-specific muscle pain in Arab or Indo-Pakistani patients may indicate vitamin D deficiency. Badsha H, Daher M, Ooi Kong K. Clin Rheumatol. 2009 Mar 10. [Epub ahead of print] PMID: 19277814 DOI: 10.1007/s10067-009-1146-7

Inverse association between serum 25(OH) vitamin D levels and non-melanoma skin cancer in elderly men. Tang JY, Parimi N, Wu A, John Boscardin W, Shikany JM, Chren MM, Cummings SR, Epstein EH Jr, Bauer DC; for the Osteoporotic Fractures in Men (MrOS) Study Group. Cancer Causes Control. 2009 Nov 18. [Epub ahead of print] PMID: 19921445 Our results suggest that a diagnosis of NMSC is not a surrogate for adequate 25(OH)D levels or increased UV exposure, and high 25(OH)D levels may be associated with a reduced risk of NMSC.

Genetic and non-genetic correlates of vitamins K and D.\nShea MK, Benjamin EJ, Dupuis J, Massaro JM, Jacques PF, D'Agostino RB Sr, Ordovas JM, O'Donnell CJ, Dawson-Hughes B, Vasan RS, Booth SL.\nEur J Clin Nutr. 2007 Nov 21. [Epub ahead of print]\nPMID: 18030310 \ndoi: 10.1038/sj.ejcn\n\n

Tuohimaa P, Pukkala E, Scelo G, Olsen JH, Brewster DH, Hemminki K, Tracey E, Weiderpass E, Kliewer EV, Pompe-Kirn V, McBride ML, Martos C, Chia KS, Tonita JM, Jonasson JG, Boffetta P, Brennan P. Does solar exposure, as indicated by the non-melanoma skin

Pittas AG, Harris SS, Stark PC, Dawson-Hughes B. The Effects of Calcium and Vitamin D Supplementation on Blood Glucose and Markers of Inflammation in Non-diabetic Adults. Diabetes Care. 2007 Feb 2; [Epub ahead of print] PMID: 17277040 [PubMed - as sup

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.

Fatigue fractures in military conscripts : A study on risk factors, diagnostics and long-term consequences Ruohola, Juha-Petri University of Helsinki, Faculty of Medicine, Institute of Clinical Medicine, Orthopaedics and Traumatology, Helsinki University Central Hospital Centre of Military Medicine, Helsinki 2007-03-09 Doctoral dissertation (article-based) It seems likely that low vitamin D levels are related to fatigue fractures, and that an increasing trend exists between TRACP-5b bone resorption marker elevation and fatigue fracture incidence. Though seldom detected by plain radiography, fatigue fractures often underlie unclear lower leg stress-related pain occurring in the distal parts of the tibia. Femoral neck fatigue fractures, when displaced, lead to long-term morbidity in a high percentage of patients, whereas, when non-displaced, they do not predispose patients to subsequent adverse complications. Importantly, an educational intervention can diminish the incidence of fracture displacement by enhancing awareness and providing instructions for earlier diagnosis of fatigue fractures

Why would vitamin D be prescribed when vitamin D3 is available over-the-counter? Let's review the known differences between vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol): --D3 is the human form; D2 is the non-human form found in plants. --Dose for dose, D3 is more effective at raising blood levels of 25-hydroxy vitamin D than D2. It requires roughly twice to 250% of the dose of D2 to match that of D3 (Trang H et al 1998). --D2 blood levels don't yield long-term sustained levels of 25-hydroxy vitamin D as does D3. When examined as a 28-day area under the curve (AUC--a superior measure of biologic exposure), D3 yields better than a 300% increased potency compared to D2. This means that it requires around 50,000 units D2 to match the effects of 15,000 units D3 (Armas LA et al 2004). --D2 has lower binding affinity for vitamin D-binding protein, compared to D3 --Mitochondrial vitamin D 25-hydroxylase converts D3 to the 25-hydroxylated form five times more rapidly than D2. --As we age, the ability to metabolize D2 is dramatically reduced, while D3 is not subject to this phenomenon

Dietary Reference Intakes for Vitamin D and Calcium An IOM committee has been named to undertake a study to assess current relevant data and update as appropriate the DRIs for vitamin D and calcium. The review will include consideration of chronic and non-chronic disease indicators. The study will also incorporate, as appropriate, systematic evidence-based reviews of the literature and an assessment of potential indicators of adequacy and of excess intake. Indicators for adequacy and excess will be selected based on the strength and quality of the evidence and the demonstrated public health significance, taking into consideration sources of uncertainty in the evidence.

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.

This is a very long newsletter. I will answer questions about oil versus water-soluble Vitamin D, depression, mental clarity, malignant melanoma, Crohn's disease, an imagist poet, multiple sclerosis, sun-exposure, high-intensity red light and collagen repair in the skin, non-alcoholic fatty liver disease, influenza, the 1918 influenza pandemic, statins, the new Food and Nutrition Board, thyroid disease, chronic fatigue syndrome, athletes, the upcoming 14th Vitamin D Workshop, prostate cancer, the wrong blood test, pregnancy, autism, Alzheimer's disease, soap and sebum, asthma, sleep, the co-factors vitamin D needs to work (all contained in spinach), and-my favorite-UVC light and Vitamin D

A few researchers are turning their attention to the sunshine vitamin as a culprit, prompted by the experience of immigrants that have moved from their equatorial country to two northern latitude locations As evidence of widespread vitamin D deficiency grows, some scientists are wondering whether the sunshine vitamin-once only considered important in bone health-may actually play a role in one of neurology's most vexing conditions: autism. The idea, although not yet tested or widely held, comes out of preliminary studies in Sweden and Minnesota. Last summer, Swedish researchers published a study in Developmental Medicine and Child Neurology that found the prevalence of autism and related disorders was three to four times higher among Somali immigrants than non-Somalis in Stockholm. The study reviewed the records of 2,437 children, born between 1988 and 1998 in Stockholm, in response to parents and teachers who had raised concerns about whether children with a Somali background were overrepresented in the total group of children with autism

True to form, Dr. John Cannell has published yet another wonderfully insightful Vitamin D Newsletter. One item caught my eye, a response to a question about the Marshall Protocol. I, like Dr. Cannell, was inundated with questions about this so-called protocol, which amounts to little more than the unfounded speculations of a non-physician, actually someone not even involved in health care. In all honesty, I blew the whole issue off after I read Dr. Marshall's rants. They smack of pure quackery, though from somebody who clearly has a command of scientific lingo. To Dr. Cannell's credit, he took the time and effort to construct a rational response in the latest issue of the newsletter. I reproduce his response here:

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

Vitamin D and calcium insufficiency-related chronic diseases: molecular and cellular pathophysiology. Peterlik M, Cross HS. Eur J Clin Nutr. 2009 Dec;63(12):1377-86. Epub 2009 Sep 2. PMID: 19724293 doi:10.1038/ejcn.2009.105 A compromised vitamin D status, characterized by low 25-hydroxyvitamin D (25-(OH)D) serum levels, and a nutritional calcium deficit are widely encountered in European and North American countries, independent of age or gender. Both conditions are linked to the pathogenesis of many degenerative, malignant, inflammatory and metabolic diseases. Studies on tissue-specific expression and activity of vitamin D metabolizing enzymes, 25-(OH)D-1alpha-hydroxylase and 25-(OH)D-24-hydroxylase, and of the extracellular calcium-sensing receptor (CaR) have led to the understanding of how, in non-renal tissues and cellular systems, locally produced 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and extracellular Ca2+ act jointly as key regulators of cellular proliferation, differentiation and function. Impairment of cooperative signalling from the 1,25-(OH)2D3-activated vitamin D receptor (VDR) and from the CaR in vitamin D and calcium insufficiency causes cellular dysfunction in many organs and biological systems, and, therefore, increases the risk of diseases, particularly of osteoporosis, colorectal and breast cancer, inflammatory bowel disease, insulin-dependent diabetes mellitus type I, metabolic syndrome, diabetes mellitus type II, hypertension and cardiovascular disease. Understanding the underlying molecular and cellular processes provides a rationale for advocating adequate intake of vitamin D and calcium in all populations, thereby preventing many chronic diseases worldwide.

Vitamin D and mood disorders among women: an integrative review. Murphy PK, Wagner CL. J Midwifery Womens Health. 2008 Sep-Oct;53(5):440-6. Review. PMID: 18761297 Four of six studies reviewed imparted significant results, with all four showing an association between low 25(OH)D levels and higher incidences of four mood disorders: premenstrual syndrome, seasonal affective disorder, non-specified mood disorder, and major depressive disorder. This review indicates a possible biochemical mechanism occurring between vitamin D and mood disorders affecting women, warranting further studies of these variables using rigorous methodologies.