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"November 24, 2009 | Lisa Nainggolan Orlando, FL - Inadequate levels of vitamin D are associated with an increase in the risk of cardiovascular disease and death, a new observational study has found. Dr Tami L Bair (Intermountain Medical Center, Murray, UT) reported the findings here at the American Heart Association 2009 Scientific Sessions. Bair and colleagues followed more than 27 000 people 50 years or older with no history of cardiovascular disease for just over a year and found that those with very low levels of vitamin D (30 ng/mL). Those deficient in vitamin D were also twice as likely to develop heart failure as those with normal levels. "We concluded that even a moderate deficiency of vitamin D was associated with developing coronary artery disease, heart failure, stroke, and death," said coauthor Dr Heidi May (Intermountain Medical Center). However, "it is not known whether this is a cause and effect relationship," she told heartwire. Because this study was observational, more research is needed "to better establish the association between vitamin D deficiency and cardiovascular disease," she noted."

Effects of Atorvastatin on vitamin D levels in patients with acute ischemic heart disease. Pérez-Castrillón JL, Vega G, Abad L, Sanz A, Chaves J, Hernandez G, Dueñas A. Am J Cardiol. 2007 Apr 1;99(7):903-5. Epub 2007 Feb 8. PMID: 17398180 In conclusion, atorvastatin increases vitamin D levels. This increase could explain some of the beneficial effects of atorvastatin at the cardiovascular level that are unrelated to cholesterol levels. The mechanism by which atorvastatin increases vitamin D levels is related to inhibition of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase. Cholesterol is synthesized from 7-dehydrocholesterol, which is also a precursor of vitamin D3. For this reason, we initially observed a statistically significant relation between total cholesterol and vitamin D. HMG-CoA enzyme reductase is key to the synthesis of cholesterol, whereas ultraviolet radiation causes the formation of 25-hydroxyvitamin D. Inhibition of the enzyme may increase levels of 7-dehydrocholesterol and increase the synthesis of 25-hydroxycholecalciferol, thereby increasing vitamin D levels,10 although we observed no relation between lower cholesterol and increased vitamin D. In addition, 25-hydroxyvitamin D has been shown to inhibit HMG-CoA enzyme reductase activity in in vitro studies.11 A greater concentration of vitamin D could increase enzymatic inhibition, acting in synergy with the statin in decreasing total cholesterol.

Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration. Aloia JF, Patel M, Dimaano R, Li-Ng M, Talwar SA, Mikhail M, Pollack S, Yeh JK. Am J Clin Nutr. 2008 Jun;87(6):1952-8. PMID: 18541590 The mean daily dose was 86 microg (3440 IU). The use of computer simulations to obtain the most participants within the range of 75-220 nmol/L predicted an optimal daily dose of 115 microg/d (4600 IU). No hypercalcemia or hypercalciuria was observed. CONCLUSIONS: Determination of the intake required to attain serum 25(OH)D concentrations >75 nmol/L must consider the wide variability in the dose-response curve and basal 25(OH)D concentrations. Projection of the dose-response curves observed in this convenience sample onto the population of the third National Health and Nutrition Examination Survey suggests a dose of 95 microg/d (3800 IU) for those above a 25(OH)D threshold of 55 nmol/L and a dose of 125 microg/d (5000 IU) for those below that threshold.

Vitamin D and skin physiology: a D-lightful story. Holick MF, Chen TC, Lu Z, Sauter E. J Bone Miner Res. 2007 Dec;22 Suppl 2:V28-33. PMID: 18290718 doi: 10.1359/jbmr.07s211 Very few foods naturally contain vitamin D, and those that do have a very variable vitamin D content. Recently it was observed that wild caught salmon had between 75% and 90% more vitamin D(3) compared with farmed salmon. The associations regarding increased risk of common deadly cancers, autoimmune diseases, infectious diseases, and cardiovascular disease with living at higher latitudes and being prone to vitamin D deficiency should alert all health care professionals about the importance of vitamin D for overall health and well being. Humans have depended on sunlight for their vitamin D requirement. The impact of season, time of day, and latitude on vitamin D synthesis is well documented.(2,3) We now report that altitude also has a dramatic influence on vitamin D3 production and that living at altitudes above 3500 m permits previtamin D3 production at a time when very little is produced at latitudes below 3400 m. It was surprising that, at 27° N in Agra (169 M), little previtamin D3 production was observed. However, there was significant air pollution that caused a haze over the city. It is likely the ozone and other UVB-absorbing pollutants in the air prevented the solar UVB photons from reaching the earth's surface to produce previtamin D3.

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.

It seems not a single day passes that I don't learn something new about this unique hormone (mis)named "vitamin D." \nFrom its humble beginnings recognized only as the factor responsible for bone maturation (with deficiency leading to childhood rickets), vitamin D now commands a recognized role in almost every conceivable aspect of health and disease. \n

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.

Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. Bischoff HA, Stähelin HB, Dick W, Akos R, Knecht M, Salis C, Nebiker M, Theiler R, Pfeifer M, Begerow B, Lew RA, Conzelmann M. J Bone Miner Res. 2003 Feb;18(2):343-51. PMID: 12568412 A single intervention with vitamin D plus calcium over a 3-month period reduced the risk of falling by 49% compared with calcium alone. Over this short-term intervention, recurrent fallers seem to benefit most by the treatment. The impact of vitamin D on falls might be explained by the observed improvement in musculoskeletal function.

Serum 25-hydroxyvitamin D concentration and subsequent risk of type 2 diabetes. Mattila C, Knekt P, Männistö S, Rissanen H, Laaksonen MA, Montonen J, Reunanen A. Diabetes Care. 2007 Oct;30(10):2569-70. Epub 2007 Jul 12. PMID: 17626891 doi: 10.2337/dc07-0292 We found a significant inverse association between serum 25OHD and risk of type 2 diabetes in the simple model. However, the association was attenuated in the multivariate analysis, adjusting for potential risk factors of type 2 diabetes. To our knowledge, this is the first cohort study investigating the association between serum 25OHD and incidence of type 2 diabetes. Our results are in line with those from the Nurses' Health Study (5), where an inverse association was observed for the intake of vitamin D supplements. We could not differentiate whether the results depended on the effect of vitamin D deficiency on β-cell function or on insulin resistance. In summary, the results are in line with the hypothesis that a high serum 25OHD concentration may reduce the risk of type 2 diabetes. Further research is needed to confirm the association and to distinguish between the independent role of vitamin D and the role of healthy dietary and lifestyle patterns in reducing the risk of type 2 diabetes.

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.

Optimal vitamin D status attenuates the age-associated increase in systolic blood pressure in white Americans: results from the third National Health and Nutrition Examination Survey. Judd SE, Nanes MS, Ziegler TR, Wilson PW, Tangpricha V. Am J Clin Nutr. 2008 Jan;87(1):136-41. PMID: 18175747 Conclusions: SBP is inversely associated with serum vitamin D concentrations in nonhypertensive white persons in the United States. This observation provides a rationale for studies on the potential effects of vitamin D supplementation as a method to reduce SBP in persons at risk of hypertension.

Dietary vitamin D and cancers of the oral cavity and esophagus. Lipworth L, Rossi M, McLaughlin JK, Negri E, Talamini R, Levi F, Franceschi S, La Vecchia C. Ann Oncol. 2009 Sep;20(9):1576-81. Epub 2009 Jun 1. PMID: 19487490 Conclusion: We observed inverse associations between dietary vitamin D intake and risk of SCCE and, perhaps, oral/pharyngeal cancer, which were most pronounced among heavy current smokers and heavy consumers of alcohol.

The association of solar ultraviolet B (UVB) with reducing risk of cancer: multifactorial ecologic analysis of geographic variation in age-adjusted cancer mortality rates. Grant WB, Garland CF. Anticancer Res. 2006 Jul-Aug;26(4A):2687-99. PMID: 16886679 CONCLUSION: These results provide additional support for the hypothesis that solar UVB, through photosynthesis of vitamin D, is inversely-associated with cancer mortality rates, and that various other cancer risk-modifying factors do not detract from this link. It is thought that sun avoidance practices after 1980, along with improved cancer treatment, led to reduced associations in the latter period. The results regarding solar UVB should be studied further with additional observational and intervention studies of vitamin D indices and cancer incidence, mortality and survival rates.

The role of vitamin D in cancer prevention. Garland CF, Garland FC, Gorham ED, Lipkin M, Newmark H, Mohr SB, Holick MF. Am J Public Health. 2006 Feb;96(2):252-61. Epub 2005 Dec 27. Review. PMID: 16380576 DOI: 10.2105/AJPH.2004.045260 Vitamin D status differs by latitude and race, with residents of the northeastern United States and individuals with more skin pigmentation being at increased risk of deficiency. A PubMed database search yielded 63 observational studies of vitamin D status in relation to cancer risk, including 30 of colon, 13 of breast, 26 of prostate, and 7 of ovarian cancer, and several that assessed the association of vitamin D receptor genotype with cancer risk. The majority of studies found a protective relationship between sufficient vitamin D status and lower risk of cancer. The evidence suggests that efforts to improve vitamin D status, for example by vitamin D supplementation, could reduce cancer incidence and mortality at low cost, with few or no adverse effects

Food chain as origin of vitamin D in fish D. Sunita Rao and N. Raghuramulu. Comparative Biochemistry and Physiology Part A: Physiology Volume 114, Issue 1, May 1996, Pages 15-19 doi:10.1016/0300-9629(95)02024-1 Plankton, the chief food source of fish, was assessed as the possible dietary origin of vitamin D in fish. The presence of vitamin D compounds were examined in fresh water phytoplankton and zooplankton employing a series of chromatographic procedures. Abundant amounts of provitamins D and vitamins D (D2 and D3) were found in the fresh water plankton. The high amount of vitamin D observed may be due to exposure of plankton to sunlight because the plankton were caught during the summer month. Thus, plankton may be an important contributor to vitamin D in fish.

The role of vitamin D in cancer prevention. Garland CF, Garland FC, Gorham ED, Lipkin M, Newmark H, Mohr SB, Holick MF. Am J Public Health. 2006 Feb;96(2):252-61. Epub 2005 Dec 27. Review. PMID: 16380576 DOI: 10.2105/AJPH.2004.045260 Vitamin D status differs by latitude and race, with residents of the northeastern United States and individuals with more skin pigmentation being at increased risk of deficiency. A PubMed database search yielded 63 observational studies of vitamin D status in relation to cancer risk, including 30 of colon, 13 of breast, 26 of prostate, and 7 of ovarian cancer, and several that assessed the association of vitamin D receptor genotype with cancer risk. The majority of studies found a protective relationship between sufficient vitamin D status and lower risk of cancer. The evidence suggests that efforts to improve vitamin D status, for example by vitamin D supplementation, could reduce cancer incidence and mortality at low cost, with few or no adverse effects.

ncident invasive breast cancer, geographic location of residence, and reported average time spent outside. Millen AE, Pettinger M, Freudenheim JL, Langer RD, Rosenberg CA, Mossavar-Rahmani Y, Duffy CM, Lane DS, McTiernan A, Kuller LH, Lopez AM, Wactawski-Wende J. Cancer Epidemiol Biomarkers Prev. 2009 Feb;18(2):495-507. Epub 2009 Feb 3. PMID: 19190147 doi: 10.1158/1055-9965.EPI-08-0652 In conclusion, region of residence and geographic solar irradiance are not consistently related to risk of breast cancer and may not be sufficient proxy measures for sunlight/vitamin D exposure. The observed association between time spent outside and breast cancer risk support the hypothesis that vitamin D may protect against breast cancer.

Serum levels of vitamin D metabolites and breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial. Freedman DM, Chang SC, Falk RT, Purdue MP, Huang WY, McCarty CA, Hollis BW, Graubard BI, Berg CD, Ziegler RG. Cancer Epidemiol Biomarkers Prev. 2008 Apr;17(4):889-94. Epub 2008 Apr 1. PMID: 18381472 doi: 10.1158/1055-9965.EPI-07-2594 In this prospective study of postmenopausal women, we did not observe an inverse association between circulating 25(OH)D or 1,25(OH)2D and breast cancer risk, although we cannot exclude an association in younger women or with long-term or earlier exposure

Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of incident ovarian cancer. Tworoger SS, Lee IM, Buring JE, Rosner B, Hollis BW, Hankinson SE. Cancer Epidemiol Biomarkers Prev. 2007 Apr;16(4):783-8. PMID: 17416771 doi: 10.1158/1055-9965.EPI-06-0981 Overall, our results do not suggest that plasma vitamin D levels are associated with risk of ovarian cancer. However, we observed significant associations in some subgroups, which should be evaluated further in other studies because increasing vitamin D intake is an easy preventive measure to adopt.

To conclude, our findings suggest an association between large-dose vitamin D supplementation in infancy and an increased risk of atopy, allergic rhinitis, and asthma later in life. Further study is required to determine whether these observations could imply that vitamin D supplementation in infancy may have long-term effects on immune regulation, or if they reflect some unmeasured determinants of vitamin D supplementation Infant vitamin d supplementation and allergic conditions in adulthood: northern Finland birth cohort 1966. Hyppönen E, Sovio U, Wjst M, Patel S, Pekkanen J, Hartikainen AL, Järvelinb MR. Ann N Y Acad Sci. 2004 Dec;1037:84-95. DOI: 10.1196/annals.1337.013 PMID: 15699498