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Induction of ovarian cancer cell apoptosis by 1,25-dihydroxyvitamin D3 through the down-regulation of telomerase. Jiang F, Bao J, Li P, Nicosia SV, Bai W. J Biol Chem. 2004 Dec 17;279(51):53213-21. Epub 2004 Oct 12. PMID: 15485861 doi: 10.1074/jbc.M410395200 Overall, the study suggests that the down-regulation of telomerase activity by 1,25(OH)2VD3 and the resulting cell death are important components of the response of OCa cells to 1,25(OH)2VD3-induced growth suppression. Progressive shortening of telomere associated with cell divisions limits the life span of normal cells and eventually leads to senescence. To become immortal, human cancers including OCa are invariably associated with activation of mechanism that maintains telomere length. Approximately 85-90% of cancers show reactivation of telomerase. The present study shows that telomerase in OCa cells is down-regulated by 1,25(OH)2VD3. Down-regulation of telomerase is due to decreased stability of hTERT mRNA rather than VDRE-mediated transcriptional repression through the putative VDRE present in the regulatory region of the hTERT gene. It is known that the inhibition of telomerase may lead to a phenotypic lag during which cells would continue to divide until the point at which the telomeres became critically short. This phenomenon may explain why the apoptotic induction by 1,25(OH)2VD3 needs the treatment for more than 6 days. As mentioned in the results, no detectable shortening of telomeric repeats was observed in parental OVCAR3 cells after 9 days of treatment with 1,25(OH)2VD3 (Fig. 4D). This is likely due to the fact that the short telomere (about 3 kb) in OVCAR3 cells is very close to the minimal length required for survival and that cells with detectably shorter telomere may have been selected against apoptosis. It has been shown that transformed human cells enter crisis once the terminal restriction fragment of the telomere reaches a length of about 4 kb. This is insufficient to protect chro

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

"Study Shows Vitamin D Supplements May Be Useful in Preventing Heart Disease Nov. 16, 2009 (Orlando, Fla.) -- Some men with low levels of vitamin D in their blood are at particularly high risk of developing heart disease and weakened bones that can lead to osteoporosis, researchers report. In a study of more than 1,000 men, those with low levels of both vitamin D and the sex hormone estrogen were at significantly increased risk of having cardiovascular disease, says study head Erin Michos, MD, a cardiologist at Johns Hopkins. "They were also at dramatically increased risk of osteopenia," or bone loss that can lead to osteoporosis, she says. "Our results suggest that vitamin D supplements, which are already prescribed to treat osteoporosis, may also be useful in preventing heart disease," Michos tells WebMD. Men with low levels of vitamin D and testosterone, on the other hand, were not at heightened risk for heart disease or osteopenia."

"(NaturalNews) Treatment with vitamin D supplements may slow the progress of , according to a study published in the journal BJU International. In the United States, prostate cancer is the second leading cause of cancer death among men, after lung cancer. Approximately 240,000 new cases are diagnosed every year, leading to 30,000 deaths. Researchers have suspected for nearly two decades that the so-called "sunshine vitamin" may play a role in the risk and progression of prostate cancer, but no studies have previously been conducted on its usefulness as a treatment."

"If you're running low on vitamin D - as an estimated 70 percent of the U.S. population is - your immune system may not be functioning as well as it should. As a result, you may be more vulnerable to infectious diseases than you would if your vitamin D levels were optimal. Worse, you could be at higher than normal risk of a long list of diseases including heart disease and several kinds of cancer. A report recently published journal, Future Microbiology, highlighted research at the Linus Pauling Institute at Oregon State University, which has shown that vitamin D induces expression of an antimicrobial peptide gene called cathelicidin that is the "first line of defense" in the immune system's response to minor wounds, cuts and bacterial and viral infections. The regulation of cathelicidin by vitamin D could help explain its vital role in immune function. The report noted that vitamin D is a key cofactor in reducing inflammation, in blood pressure control and helping to protect against heart disease. Author Adrian Gombart explains that there is still much to explore about D's mechanisms of action, the potential use of synthetic analogs of it in new treatments, and its duty in fighting infection."

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Continuous changes in the healthcare reimbursement criteria require executives across the industry to focus on enterprise-wide changes that have a positive effect on supply chain savings. It's a complex problem and it's easy to get distracted on one issue when having the ability to see a clear BIG picture of your entire supply chain is what can lead to the most dramatic results and return on investments. Register for MHS' webinar on November 01 (2:00pm EST) to learn about how their customers experience an average 4:1 ROI with continual savings into the millions and a positive financial impact to their bottom line through inventory reduction, avoidance of obsolete and expired inventory, improved charge capture for each patient, and physician preference card optimization. Click on http://bit.ly/UvD3nq Presenters *Michael Ferris: Co-Founder, MHS with over 30 years of supply chain management experience *Steve Basiliere: Former Director of Supply Chain Services at Saints Medical Center, Lowell, MA *Art Kozyrovicius: Finance and Procurement Systems Support at New York-Presbyterian Hospital, New York, NY WHY ATTEND? Join a unique discussion with healthcare supply chain thought leaders and understand how to drive significant and sustainable supply chain operational improvements. Get a jump on making an immediate and positive impact on your bottom line as you head into 2013. Register by clicking on http://bit.ly/UvD3nq Note: Event will be online, through WebEx Please Register at http://bit.ly/UvD3nq

Vitamin D in preventive medicine: are we ignoring the evidence? Zittermann A. Br J Nutr. 2003 May;89(5):552-72. Review. PMID: 12720576 Vitamin D is metabolised by a hepatic 25-hydroxylase into 25-hydroxyvitamin D (25(OH)D) and by a renal 1alpha-hydroxylase into the vitamin D hormone calcitriol. Calcitriol receptors are present in more than thirty different tissues. Apart from the kidney, several tissues also possess the enzyme 1alpha-hydroxylase, which is able to use circulating 25(OH)D as a substrate. Serum levels of 25(OH)D are the best indicator to assess vitamin D deficiency, insufficiency, hypovitaminosis, adequacy, and toxicity. European children and young adults often have circulating 25(OH)D levels in the insufficiency range during wintertime. Elderly subjects have mean 25(OH)D levels in the insufficiency range throughout the year. In institutionalized subjects 25(OH)D levels are often in the deficiency range. There is now general agreement that a low vitamin D status is involved in the pathogenesis of osteoporosis. Moreover, vitamin D insufficiency can lead to a disturbed muscle function. Epidemiological data also indicate a low vitamin D status in tuberculosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel diseases, hypertension, and specific types of cancer. Some intervention trials have demonstrated that supplementation with vitamin D or its metabolites is able: (i) to reduce blood pressure in hypertensive patients; (ii) to improve blood glucose levels in diabetics; (iii) to improve symptoms of rheumatoid arthritis and multiple sclerosis. The oral dose necessary to achieve adequate serum 25(OH)D levels is probably much higher than the current recommendations of 5-15 microg/d.

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

Strong correlations have been noted between cardiovascular diseases and low bone density / osteoporosis-connections so strong that the presence of one type of pathology is considered a likely predictor of the other. This potentially causal relationship has led to the hypothesis that these conditions share core mechanisms. Recent advances in our understanding of the complimentary roles played by vitamin D3 and vitamin K2 in vascular and bone health provide support for this hypothesis, along with insight into key metabolic dysfunctions underlying cardiovascular disease and osteoporosis. Part I of this review summarizes current research linking vitamin D deficiency to cardiovascular disease, the physiological mechanisms underlying vitamin D's cardiovascular effects, and leading vitamin D researchers' recommendations for significantly higher supplemental doses of the pro-hormone. Part II reviews the vitamin K connection to cardiovascular disease; the ways in which vitamin D and vitamin K pair up to prevent inflammation, vascular calcification and osteoporosis; and the necessity of providing vitamin K along with vitamin D to preclude adverse effects associated with hypervitaminosis D, which include vascular and other soft tissue calcification.

ScienceDaily (Aug. 25, 2009) - Low levels of vitamin D are known to nearly double the risk of cardiovascular disease in patients with diabetes, and researchers at Washington University School of Medicine in St. Louis now think they know why. They have found that diabetics deficient in vitamin D can't process cholesterol normally, so it builds up in their blood vessels, increasing the risk of heart attack and stroke. The new research has identified a mechanism linking low vitamin D levels to heart disease risk and may lead to ways to fix the problem, simply by increasing levels of vitamin 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 panel selected to analyze the health claims is being criticized for not including the medical researchers whose work prompted intense scientific interest in the nutrient in the first place. "If you were publicly in favour of vitamin D, you were not included, and I find that outrageous," said Reinhold Vieth, a professor in the department of nutritional sciences at the University of Toronto, and one of Canada's leading experts on the nutrient.

Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Kong J, Zhang Z, Musch MW, Ning G, Sun J, Hart J, Bissonnette M, Li YC. Am J Physiol Gastrointest Liver Physiol. 2008 Jan;294(1):G208-16. Epub 2007 Oct 25. PMID: 17962355 These observations suggest that VDR plays a critical role in mucosal barrier homeostasis by preserving the integrity of junction complexes and the healing capacity of the colonic epithelium. Therefore, vitamin D deficiency may compromise the mucosal barrier, leading to increased susceptibility to mucosal damage and increased risk of IBD.

Vitamin D plays a critical role in the human body's response to tuberculosis, according to new research that explains why people of African descent are more susceptible to TB. The research also suggests a new way to fight one of the world's deadliest diseases: with a simple dietary supplement. Tuberculosis, usually caused when a person inhales tuberculosis bacteria, killed an estimated 1.7 million people in 2003 and is the leading cause of death for people afflicted with AIDS, according to the World Health Organization (WHO).

Together, the earlier data and the data of Heaney et al indicate that an oral dose of vitamin D2 or vitamin D3 would lead to a comparable increase in circulating 25(OH)D concentrations in children and adults when the initial 25(OH)D3 concentrations in the groups are similar and when equivalent oral vitamin D doses expressed per kilogram body weight/d are given. Serum 25-hydroxyvitamin D response to oral vitamin D intake in children. Zittermann A. Am J Clin Nutr. 2003 Sep;78(3):496-7. PMID: 12936937

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

Can vitamin D supplementation prevent winter-time blues? A randomised trial among older women. Dumville JC, Miles JN, Porthouse J, Cockayne S, Saxon L, King C. J Nutr Health Aging. 2006 Mar-Apr;10(2):151-3. PMID: 16554952 CONCLUSIONS: Supplementing elderly women with 800 IU of vitamin D daily did not lead to an improvement in mental health scores.

Are sunlight deprivation and influenza epidemics associated with the onset of acute leukemia? Timonen T, Näyhä S, Koskela T, Pukkala E. Haematologica. 2007 Nov;92(11):1553-6. PMID: 18024404 doi:10.3324/haematol.10799 Month of diagnosis of 7,423 cases of acute leukemia (AL) in Finland during 1964-2003 were linked with data on influenza and solar radiation. Acute myeloblastic leukemia (AML) showed the highest risk in the dark season. During the light season, the incidence decreased by 58% (95% confidence interval, 16-79%) per 1,000 kJ/m2/d increase of solar radiation. Independent of solar radiation, AML increased by 9% (95% confidence interval, 0-19%) during influenza epidemics. Reoccurring at the same time annually, darkness-related vitamin D deficiency and influenza could cause successive and co-operative mutations leading to AL with a short latency.

Vitamin D and cancer mini-symposium: the risk of additional vitamin D. Vieth R. Ann Epidemiol. 2009 Jul;19(7):441-5. Epub 2009 Apr 11. Review. PMID: 19364661 Conclusion The results of well-conducted trials of vitamin D lead to the conclusion that the current U.S. National Academy of Sciences-Institute of Medicine upper limit for vitamin D intake of 2000IU per day 1, 37 is excessively conservative. That intake would raise serum 25(OH)D by an average of about 50 nmol/L (20 ng/mL), well within the safe range of serum 25(OH)D concentrations that extends to 500 nmol/L (200 ng/mL). Intake of 4,000IU per day would raise serum 25(OH)D by an average of about 100 nmol/L (40 ng/mL). Even prolonged physiologic-replacement intake of 10,000IU per day of vitamin D3 would pose no known risk of adverse effects in virtually all adults.