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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).

Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors. Hyppönen E, Power C. Am J Clin Nutr. 2007 Mar;85(3):860-8. PMID: 17344510 Conclusion: Prevalence of hypovitaminosis D in the general population was alarmingly high during the winter and spring, which warrants action at a population level rather than at a risk group level. Data from the 1958 birth cohort suggest that, at different cutoffs for hypovitaminosis D, a substantial public health problem exists in British whites. Obese participants and those living in Scotland were at the highest risk of hypovitaminosis D. However, the prevalence in the general population was very high during the winter and spring, which suggests that, to improve the situation, action is required at a population level rather than at a risk-group level. In the United States, calls have gone out for an increase in vitamin D fortification of foods (11), and the data from the current study suggest that such action is also warranted in the United Kingdom. Vitamin D is currently available without prescription as a dietary supplement only as part of cod liver oil or multivitamin products; hence, a need clearly exists to consider increased availability of over-the-counter supplements. Hypovitaminosis D has been implicated in the development of serious conditions, including diabetes, various types of cancer, and cardiovascular diseases, in addition to its essential role in maintaining bone health (1, 2). The high rates of hypovitaminosis D reported in this study suggest that immediate action is needed to improve the vitamin D status of the British population.

Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Ginde AA, Liu MC, Camargo CA Jr. Arch Intern Med. 2009 Mar 23;169(6):626-32. PMID: 19307527 Conclusions National data demonstrate a marked decrease in serum 25(OH)D levels from the 1988-1994 to the 2001-2004 NHANES data collections. Racial/ethnic differences have persisted and may have important implications for known health disparities. Current recommendations for vitamin D supplementation are inadequate to address the growing epidemic of vitamin D insufficiency.

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

Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Ginde AA, Liu MC, Camargo CA Jr. Arch Intern Med. 2009 Mar 23;169(6):626-32. PMID: 19307527 Conclusions National data demonstrate a marked decrease in serum 25(OH)D levels from the 1988-1994 to the 2001-2004 NHANES data collections. Racial/ethnic differences have persisted and may have important implications for known health disparities. Current recommendations for vitamin D supplementation are inadequate to address the growing epidemic of vitamin D insufficiency.

The following table provides factors for converting conventional units to SI units for selected clinical data. Source: JAMA Author Instructions. Contains also conversion factors for circulating form of vitamin D, 25(OH)D (calcidiol).

Annual intramuscular injection of a megadose of cholecalciferol for treatment of vitamin D deficiency: efficacy and safety data. Diamond TH, Ho KW, Rohl PG, Meerkin M. Med J Aust. 2005 Jul 4;183(1):10-2. PMID: 15992330 Conclusions: Once-yearly intramuscular cholecalciferol injection (600 000 IU) is effective therapy for vitamin D deficiency. While this therapy appears to be safe, the potential for developing hypercalciuria needs to be examined in a large randomised controlled trial.

The prevalence of hypovitaminosis D among US adults: data from the NHANES III. Zadshir A, Tareen N, Pan D, Norris K, Martins D. Ethn Dis. 2005 Autumn;15(4 Suppl 5):S5-97-101. PMID: 16315387 CONCLUSION: Serum levels of 25(OH) D3 are below the recommended levels for a large portion of the general adult population and in most minorities. Need exists for a critical review and probable revision of current recommendations for adult vitamin D intake to maintain adequate 25(OH) D3 levels.

Duration of vitamin D synthesis from weather model data for use in prospective epidemiological studies. Edvardsen K, Engelsen O, Brustad M. Int J Biometeorol. 2009 Sep;53(5):451-9. Epub 2009 May 15. PMID: 19444487

Dietary recommendations for vitamin D: a critical need for functional end points to establish an estimated average requirement. Whiting SJ, Calvo MS. J Nutr. 2005 Feb;135(2):304-9. Review. PMID: 15671232 In summary, vitamin D has emerged as a critical nutrient for which there is a compelling health need to establish adequate dietary guidelines in North America and worldwide given the increasing evidence of vitamin D deficiency and insufficient links to risk of chronic disease. We strongly argue that now there are enough data to consider setting an estimated average requirement for vitamin D and to recognize the crucial need for more research to determine the role of vitamin D in noncalciotropic functions and prevention of chronic diseases

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 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.

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.

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.

25-Hydroxylation of vitamin D3: relation to circulating vitamin D3 under various input conditions. Heaney RP, Armas LA, Shary JR, Bell NH, Binkley N, Hollis BW. Am J Clin Nutr. 2008 Jun;87(6):1738-42. PMID: 18541563 Conclusions: At physiologic inputs, there is rapid conversion of precursor to product at low vitamin D3 concentrations and a much slower rate of conversion at higher concentrations. These data suggest that, at typical vitamin D3 inputs and serum concentrations, there is very little native cholecalciferol in the body, and 25(OH)D constitutes the bulk of vitamin D reserves. However, at supraphysiologic inputs, large quantities of vitamin D3 are stored as the native compound, presumably in body fat, and are slowly released to be converted to 25(OH)D.

Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Chiu KC, Chu A, Go VL, Saad MF. Am J Clin Nutr. 2004 May;79(5):820-5. PMID: 15113720 Conclusions: The data show a positive correlation of 25(OH)D concentration with insulin sensitivity and a negative effect of hypovitaminosis D on ß cell function. Subjects with hypovitaminosis D are at higher risk of insulin resistance and the metabolic syndrome. Further studies are required to explore the underlying mechanisms.

Measurement of vitamin D levels in inflammatory bowel disease patients reveals a subset of Crohn's disease patients with elevated 1,25-dihydroxyvitamin D and low bone mineral density. Abreu MT, Kantorovich V, Vasiliauskas EA, Gruntmanis U, Matuk R, Daigle K, Chen S, Zehnder D, Lin YC, Yang H, Hewison M, Adams JS. Gut. 2004 Aug;53(8):1129-36. PMID: 15247180 doi: 10.1136/gut.2003.036657. Conclusions: These data demonstrate that elevated 1,25(OH)2D is more common in CD than previously appreciated and is independently associated with low bone mineral density. The source of the active vitamin D may be the inflamed intestine. Treatment of the underlying inflammation may improve metabolic bone disease in this subgroup of patients.

Association between plasma 25-hydroxyvitamin D and breast cancer risk. Crew KD, Gammon MD, Steck SE, Hershman DL, Cremers S, Dworakowski E, Shane E, Terry MB, Desai M, Teitelbaum SL, Neugut AI, Santella RM. Cancer Prev Res (Phila Pa). 2009 Jun;2(6):598-604. Epub 2009 May 26. PMID: 19470790 In summary, these results add to a growing body of evidence that adequate vitamin D stores may prevent breast cancer development. Whereas circulating 25-OHD levels of >32 ng/mL are associated with normal bone mineral metabolism, our data suggest that the optimal level for breast cancer prevention is ≥40 ng/mL. Well-designed clinical trials are urgently needed to determine whether vitamin D supplementation is effective for breast cancer chemoprevention.

Summary of evidence-based review on vitamin D efficacy and safety in relation to bone health. Cranney A, Weiler HA, O'Donnell S, Puil L. Am J Clin Nutr. 2008 Aug;88(2):513S-519S. Review. PMID: 18689393 We found inconsistent evidence of an association between serum 25-hydroxyvitamin D [25(OH)D] concentration and bone mineral content in infants and fair evidence of an association with bone mineral content or density in older children and older adults. The evidence of an association between serum 25(OH)D concentration and some clinical outcomes (fractures, performance measures) in postmenopausal women and older men was inconsistent, and the evidence of an association with falls was fair. We found good evidence of a positive effect of consuming vitamin D-fortified foods on 25(OH)D concentrations. The evidence for a benefit of vitamin D on falls and fractures varied. We found fair evidence that adults tolerated vitamin D at doses above current dietary reference intake levels, but we had no data on the association between long-term harms and higher doses of vitamin D.

Higher levels of 25-hydroxyvitamin D are associated with a lower incidence of multiple sclerosis only in women. Kragt J, van Amerongen B, Killestein J, Dijkstra C, Uitdehaag B, Polman Ch, Lips P. Mult Scler. 2009 Jan;15(1):9-15. Epub 2008 Aug 13. PMID: 18701572 DOI: 10.1177/1352458508095920 CONCLUSIONS: Our data suggest that higher circulating levels of 25(OH)D are associated with a lower incidence of MS and MS-related disability in women. This may imply clues to the pathogenesis of the sex difference in risk and to the nature of the environmental factors involved in MS.