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Serum 25(OH)-vitamin D concentration and risk of esophageal squamous dysplasia. Abnet CC, Chen W, Dawsey SM, Wei WQ, Roth MJ, Liu B, Lu N, Taylor PR, Qiao YL. Cancer Epidemiol Biomarkers Prev. 2007 Sep;16(9):1889-93. PMID: 17855710 doi: 10.1158/1055-9965.EPI-07-0461 Background: Squamous dysplasia is the precursor lesion for esophageal squamous cell carcinoma, and nutritional factors play an important role in the etiology of this cancer. Previous studies using a variety of measures for vitamin D exposure have reached different conclusions about the association between vitamin D and the risk of developing esophageal cancer. Conclusions: Higher serum 25(OH)D concentrations were associated with significantly increased risk of squamous dysplasia. No obvious source of measured or unmeasured confounding explains this finding. In conclusion, we found that a higher serum 25(OH)D concentration was associated with an increased risk of esophageal squamous dysplasia, the precursor lesion for ESCC. This finding concurs with our previous prospective study which found that higher vitamin D status was associated with increased risk of incident ESCC in this same population. These unexpected findings suggest that further studies of the association of vitamin D and digestive tract cancers are needed before the effect of vitamin D in different populations can be elucidated.

A multicountry ecologic study of risk and risk reduction factors for prostate cancer mortality. Grant WB. Eur Urol. 2004 Mar;45(3):271-9. PMID: 15036670 CONCLUSIONS: These results are consistent with insulin-like growth factor-I (IGF-I), being an important risk factor for prostate cancer, with alcohol and calcium being less important risk factors, and with allium family vegetables, and, to a lesser extent, vitamin D being important risk reduction factors. These results should provide guidance for additional studies on dietary and environmental links to prostate cancer.

Prospective study of serum 25(OH)-vitamin D concentration and risk of oesophageal and gastric cancers. Chen W, Dawsey SM, Qiao YL, Mark SD, Dong ZW, Taylor PR, Zhao P, Abnet CC. Br J Cancer. 2007 Jul 2;97(1):123-8. Epub 2007 Jun 5. PMID: 17551495 We prospectively examined the relation between pretrial serum vitamin D status and risk of oesophageal and gastric cancers among subjects who developed cancer over 5.25 years of follow-up, including 545 oesophageal squamous cell carcinomas (ESCC), 353 gastric cardia adenocarcinomas, 81 gastric noncardia adenocarcinomas, and an age- and sex-stratified random sample of 1105 subjects. We found no associations for gastric cardia or noncardia adenocarcinoma. Among subjects with low vitamin D status, higher serum 25(OH)D concentrations were associated with significantly increased risk of ESCC in men, but not in women. Further refinements of the analysis did not suggest any factors, which could explain this unexpected result. In conclusion, we found a direct association between higher serum 25(OH)D concentration and increased risk of ESCC in men but not women in a large population-based prospective cohort study from rural China. We found no association with risk of gastric cardia or noncardia adenocarcinoma in either sex. Greater than 50% of our cohort had an inadequate serum 25(OH)D concentration, yet higher concentrations were associated with increased risk of ESCC compared to lower concentrations.

Serum vitamin D concentration and prostate cancer risk: a nested case-control study. Ahn J, Peters U, Albanes D, Purdue MP, Abnet CC, Chatterjee N, Horst RL, Hollis BW, Huang WY, Shikany JM, Hayes RB; Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Project Team. J Natl Cancer Inst. 2008 Jun 4;100(11):796-804. Epub 2008 May 27. PMID: 18505967 doi:10.1093/jnci/djn152 CONCLUSION: The findings of this large prospective study do not support the hypothesis that vitamin D is associated with decreased risk of prostate cancer; indeed, higher circulating 25(OH)D concentrations may be associated with increased risk of aggressive disease. In summary, results from this large prospective study of men who underwent standardized prostate cancer screening in the context of a screening trial do not support the hypothesis that higher serum vitamin D status is associated with decreased risk of prostate cancer. The study showed no association of vitamin D level with nonaggressive disease; however, it raises the possibility that higher vitamin D level may be associated with increased risks for aggressive disease, although a clear monotonic dose-response relationship was lacking. Along with recent reports of adverse associations for higher vitamin D status and risk of pancreatic (32) and esophageal (33,34) cancer, caution should be taken in recommending high doses of vitamin D or sunlight exposure to the general public for prostate cancer prevention. Future analyses are warranted to confirm these results and to further clarify the effects of vitamin D on aggressive prostate cancer.

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.

"In a prospective study involving 6,937 men and women, higher levels of vitamin D were associated with a significantly lower risk of lung cancer in women and younger participants. During a maximum follow-up of 24 years, 122 cases of lung cancer were identified. After adjusting for potential confounders, higher serum 25-hydroxyvitamin D levels were associated with reduced risk of lung cancer risk in women (84% reduced risk) and younger participants (66% reduced risk). No association was observed between vitamin D status and lung cancer risk in men and older participants. "

Amsterdam, The Netherlands, May 26, 2009 - There are several risk factors for the development of Alzheimer's disease and vascular dementia. Based on an increasing number of studies linking these risk factors with Vitamin D deficiency, an article in the current issue of the Journal of Alzheimer's Disease (May 2009) by William B. Grant, PhD of the Sunlight, Nutrition, and Health Research Center (SUNARC) suggests that further investigation of possible direct or indirect linkages between Vitamin D and these dementias is needed. Low serum levels of 25-hydroxyvitamin D [25(OH)D] have been associated with increased risk for cardiovascular diseases, diabetes mellitus, depression, dental caries, osteoporosis, and periodontal disease, all of which are either considered risk factors for dementia or have preceded incidence of dementia. In 2008, a number of studies reported that those with higher serum 25(OH)D levels had greatly reduced risk of incidence or death from cardiovascular diseases

Geographic variation of prostate cancer mortality rates in the United States: Implications for prostate cancer risk related to vitamin D. Grant WB. Int J Cancer. 2004 Sep 1;111(3):470-1; author reply 472. No abstract available. PMID: 15221981 10.1002/ijc.20220 The implications of our results and those of Tuohimaa et al.[1] include the following. Vitamin D supplementation should be undertaken in wintertime, a period when it is impossible to produce vitamin D by solar UVB exposure in northeastern states.[13] Given these new results, the optimal vitamin D intake and production and serum 25(OH)-vitamin D3 levels for prostate cancer appear to be lower than for other cancers. However, when developing guidelines for vitamin D fortification, many factors should be included in the analysis, including all of the potential health benefits and possible risks of vitamin D, as well as age, sex, residence, child-bearing status, etc.[14] Also, the suggestion that daily vitamin D3 supplement doses of 100 g (4,000 IU)/day are safe[15] should be reexamined. Finally, in terms of preventing prostate cancer, more attention should be given to diet, which has the greatest environmental impact on risk of prostate cancer, with animal products being important risk factors and vegetable products, especially onions and other allium family members, being important risk-reduction factors.[16]

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.

Breastfeeding does not protect against urinary tract infection in the first 3 months of life, but vitamin D supplementation increases the risk by 76%. Katikaneni R, Ponnapakkam T, Ponnapakkam A, Gensure R. Clin Pediatr (Phila). 2009 Sep;48(7):750-5. Epub 2009 Mar 4. PMID: 19264720 DOI: 10.1177/0009922809332588 The relative risk of UTI with breastfeeding versus formula feeding was 1.03 (0.58-1.82), and any breastfeeding versus no breastfeeding was 0.92 (0.58-1.45). Vitamin D supplementation increased the UTI risk, with a relative risk of 1.76 (1.07-2.91, P < .05). However, only formula-fed infants showed an increased risk of UTI after vitamin D supplementation.

The Diet-Heart Hypothesis: Subdividing Lipoproteins Two posts ago, we made the rounds of the commonly measured blood lipids (total cholesterol, LDL, HDL, triglycerides) and how they associate with cardiac risk. It's important to keep in mind that many things associate with cardiac risk, not just blood lipids. For example, men with low serum vitamin D are at a 2.4-fold greater risk of heart attack than men with higher D levels. That alone is roughly equivalent to the predictive power of the blood lipids you get measured at the doctor's office. Coronary calcium scans (a measure of blood vessel calcification) also associate with cardiac risk better than the most commonly measured blood lipids. Lipoproteins Can be Subdivided into Several Subcategories In the continual search for better measures of cardiac risk, researchers in the 1980s decided to break down lipoprotein particles into sub-categories. One of these researchers is Dr. Ronald M. Krauss. Krauss published extensively on the association between lipoprotein size and cardiac risk, eventually concluding (source): The plasma lipoprotein profile accompanying a preponderance of small, dense LDL particles (specifically LDL-III) is associated with up to a threefold increase in the susceptibility of developing [coronary artery disease]. This has been demonstrated in case-control studies of myocardial infarction and angiographically documented coronary disease. Krauss found that small, dense LDL (sdLDL) doesn't travel alone: it typically comes along with low HDL and high triglycerides*. He called this combination of factors "lipoprotein pattern B"; its opposite is "lipoprotein pattern A": large, buoyant LDL, high HDL and low triglycerides. Incidentally, low HDL and high triglycerides are hallmarks of the metabolic syndrome, the quintessential modern metabolic disorder. Krauss and his colleagues went on to hypothesize that sdLDL promotes atherosclerosis because of its ability to penetrate the artery wall more easily

Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Am J Clin Nutr. 2007 Jun;85(6):1586-91. Erratum in: Am J Clin Nutr. 2008 Mar;87(3):794. PMID: 17556697 Conclusions: Improving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women.

Serum vitamin D and risk of prostate cancer in a case-control analysis nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). Travis RC, Crowe FL, Allen NE, Appleby PN, Roddam AW, Tjønneland A, Olsen A, Linseisen J, Kaaks R, Boeing H, Kröger J, Trichopoulou A, Dilis V, Trichopoulos D, Vineis P, Palli D, Tumino R, Sieri S, Bueno-de-Mesquita HB, van Duijnhoven FJ, Chirlaque MD, Barricarte A, Larrañaga N, González CA, Argüelles MV, Sánchez MJ, Stattin P, Hallmans G, Khaw KT, Bingham S, Rinaldi S, Slimani N, Jenab M, Riboli E, Key TJ. Am J Epidemiol. 2009 May 15;169(10):1223-32. Epub 2009 Apr 9. PMID: 19359375 In summary, the results of this large nested case-control study provide no evidence in support of a protective effect of circulating concentrations of vitamin D on the risk of prostate cancer.

A prospective nested case-control study of vitamin D status and pancreatic cancer risk in male smokers. Stolzenberg-Solomon RZ, Vieth R, Azad A, Pietinen P, Taylor PR, Virtamo J, Albanes D. Cancer Res. 2006 Oct 15;66(20):10213-9. PMID: 17047087 Higher vitamin D concentrations were associated with a 3-fold increased risk for pancreatic cancer (highest versus lowest quintile, >65.5 versus <32.0 nmol/L: OR, 2.92; 95% CI, 1.56-5.48, Ptrend = 0.001) that remained after excluding cases diagnosed early during follow-up. Contrary to expectations, subjects with higher prediagnostic vitamin D status had an increased pancreatic cancer risk compared with those with lower status. Our findings need to be replicated in other populations and caution is warranted in their interpretation and implication. Our results are intriguing and may provide clues that further the understanding of the etiology of this highly fatal cancer. In conclusion, contrary to expectation, subjects with higher 25(OH)D concentrations were at greater risk for pancreatic cancer compared with those with lower concentrations in our prospective study with long-term follow-up. Caution is warranted in the interpretation and implication of our findings, however, as vitamin D inadequacy is an important public health problem and adequate status is desirable to prevent bone and other diseases (5). Our results, however, are intriguing and may provide clues that further the understanding of the etiology of this highly fatal cancer.

"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."

"Had enough about reading/hearing about Vitamin D? Well, it keeps on coming. And for my lack of surprise, the medical community in general is not catching on like wild fire. I really don't understand it. A recent study from the Heart Institute at Intermountain Medical Center in Salt Lake City (click) followed 27,686 patients greater than 50 years of age with no prior history of cardiovascular disease. The Vitamin D levels were checked and classified as such: * normal - greater than 30 ng/ml * low - 15 to 30 * very low - less than 15 The results of the study showed that patients with very low Vitamin D levels in comparison to normal had: * 77% greater risk of death * 45% increased risk of coronary artery disease * 78% increased risk of stroke * twice the risk of developing heart failure"

Serum Vitamin D and Risk of Prostate Cancer in a Case-Control Analysis Nested Within the European Prospective Investigation into Cancer and Nutrition (EPIC). Travis RC, Crowe FL, Allen NE, Appleby PN, Roddam AW, Tjønneland A, Olsen A, Linseisen J, Kaaks R, Boeing H, Kröger J, Trichopoulou A, Dilis V, Trichopoulos D, Vineis P, Palli D, Tumino R, Sieri S, Bueno-de-Mesquita HB, van Duijnhoven FJ, Chirlaque MD, Barricarte A, Larrañaga N, González CA, Argüelles MV, Sánchez MJ, Stattin P, Hallmans G, Khaw KT, Bingham S, Rinaldi S, Slimani N, Jenab M, Riboli E, Key TJ. Am J Epidemiol. 2009 Apr 9. [Epub ahead of print] PMID: 19359375 doi:10.1093/aje/kwp022

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

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.

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.