Group items tagged

"I discussed in my last post how Dr Vieth has a model of tissue 1,25(OH)2D synthesis and degradation in which the level of active substance is pretty well independent of blood vitamin D level, provided the level is either rising or stable. I think it is also worth pointing out that he is talking, hypothetically, about tissue 1,25(OH)2D, not plasma level... As we know, almost nothing is known about tissue 1,25(OH)2D control. By Vieth's hypothesis tissue 1,25(OH)2D is OK so long as there is at least SOME vitamin D present in plasma and the level dose not vary too much. Obviously there is a level below which you can have as much of the enzyme for converting vitamin D to the active form as you like, if there is no vitamin D in your blood you can't make any 1,25(OH)2D in your tissues, or in your kidneys for export to your blood to control calcium levels. At the lower extremes we have rickets and osteomalacia. These are clear cut, unarguable markers of vitamin D deficiency, in the absence of confounding factors (there are a few)."

Serum levels of free 1,25-dihydroxyvitamin D in vitamin D toxicity. Pettifor JM, Bikle DD, Cavaleros M, Zachen D, Kamdar MC, Ross FP. Ann Intern Med. 1995 Apr 1;122(7):511-3. PMID: 7872586 CONCLUSIONS: Although the patients had normal or near-normal total 1,25-(OH)2D values, most patients had elevated free 1,25-(OH)2D levels. These findings suggest that elevated free 1,25-(OH)2D levels might play a role in the pathogenesis of hypercalcemia in vitamin D toxicity.

"Under year round UV exposure conditions (low latitudes, broken line, "High UV") there is no association between 25(OH)D and either prostate or pancreatic cancer. At high latitudes (Solid line, "Low UV") there is a positive association between blood levels of 25(OH)D and these cancers. The average year round levels of 25(OH)D actually tend to be higher in northern latitudes, higher than those where there is year-round solar UVB. Vieth explains that we know almost nothing about the enzymes controlling tissue 1,25(OH)2D levels and much of his discussion is extrapolated from renal enzyme activity."

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

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

Association of vitamin D deficiency with heart failure and sudden cardiac death in a large cross-sectional study of patients referred for coronary angiography. Pilz S, März W, Wellnitz B, Seelhorst U, Fahrleitner-Pammer A, Dimai HP, Boehm BO, Dobnig H. J Clin Endocrinol Metab. 2008 Oct;93(10):3927-35. Epub 2008 Aug 5. PMID: 18682515 doi:10.1210/jc.2008-0784 Conclusions: Low levels of 25(OH)D and 1,25(OH)2D are associated with prevalent myocardial dysfunction, deaths due to heart failure and SCD. Interventional trials are warranted to elucidate whether vitamin D supplementation is useful for treatment and/or prevention of myocardial diseases.

1,25(OH)2 vitamin d inhibits foam cell formation and suppresses macrophage cholesterol uptake in patients with type 2 diabetes mellitus. Oh J, Weng S, Felton SK, Bhandare S, Riek A, Butler B, Proctor BM, Petty M, Chen Z, Schechtman KB, Bernal-Mizrachi L, Bernal-Mizrachi C. Circulation. 2009 Aug 25;120(8):687-98. Epub 2009 Aug 10. PMID: 19667238 doi: 10.1161/CIRCULATIONAHA.109.856070 Conclusion- These results identify reduced vitamin D receptor signaling as a potential mechanism underlying increased foam cell formation and accelerated cardiovascular disease in diabetic subjects.

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.

Low vitamin d levels predict stroke in patients referred to coronary angiography.\nPilz S, Dobnig H, Fischer JE, Wellnitz B, Seelhorst U, Boehm BO, März W.\nStroke. 2008 Sep;39(9):2611-3. Epub 2008 Jul 17.\nPMID: 18635847 \ndoi: 10.1161/STROKEAHA.107.513655

Why "Vitamin D" is not a hormone, and not a synonym for 1,25-dihydroxy-vitamin D, its analogs or deltanoids. Vieth R. J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):571-3. PMID: 15225841 doi:10.1016/j.jsbmb.2004.03.037

Vitamin D's days of obscurity seem pretty much over. Once just an afterthought to most people-relegated to the sides of milk cartons and the pages of medical texts-it's now on the cusp of becoming a full-fledged disease prevention star. Although vitamin D has long been known as an important factor in bone health, a quickly growing body of evidence now shows that it may also help lower the risk of cancer, heart disease, and even premature death.[1], [2] Not surprisingly, scientists and the public have started to take note, particularly of vitamin D's potential to protect against cancer

P.T. Liu, S. Stenger, H. Li, L. Wenzel, B.H. Tan, S.R. Krutzik, M.T. Ochoa, J. Schauber, K. Wu, C. Meinken, et al.\nVitamin D3-Triggered Antimicrobial Response--Another Pleiotropic Effect beyond Mineral and Bone Metabolism: Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response. Science 311: 1770-1773, 2006\nJ. Am. Soc. Nephrol., November 1, 2006; 17(11): 2949 - 2953.

'Vitamin D Induces Innate Antibacterial Responses in Human Trophoblasts via an Intracrine Pathway.\nLiu N, Kaplan AT, Low J, Nguyen L, Liu GY, Equils O, Hewison M.\nBiol Reprod. 2009 Mar;80(3):398-406. Epub 2008 Nov 12.\nPMID: 19005165DOI: 10.1095/biolreprod.108.073577

Back to the future: a new look at 'old' vitamin D. Chun RF, Adams JS, Hewison M. J Endocrinol. 2008 Aug;198(2):261-9. Epub 2008 May 21. PMID: 18495944 DOI: 10.1677/JOE-08-0170

Cutting edge: vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin.\nLiu PT, Stenger S, Tang DH, Modlin RL.\nJ Immunol. 2007 Aug 15;179(4):2060-3.\nPMID: 1767546

Vitamin D and Cancer Mini-Symposium: The Risk of Additional Vitamin D. Vieth R. Ann Epidemiol. 2009 Apr 11. [Epub ahead of print] PMID: 19364661 doi:10.1016/j.annepidem.2009.01.009   

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.

Vitamin D and multiple sclerosis. Hayes CE, Cantorna MT, DeLuca HF. Proc Soc Exp Biol Med. 1997 Oct;216(1):21-7. Review. PMID: 9316607

Vitamin D: a natural inhibitor of multiple sclerosis. Hayes CE. Proc Nutr Soc. 2000 Nov;59(4):531-5. Review. PMID: 11115787

Vitamin D metabolites as clinical markers in autoimmune and chronic disease. Blaney GP, Albert PJ, Proal AD. Ann N Y Acad Sci. 2009 Sep;1173:384-90. PMID: 19758177 DOI: 10.1111/j.1749-6632.2009.04875.x