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Meta-analysis of vitamin D, calcium and the prevention of breast cancer. Chen P, Hu P, Xie D, Qin Y, Wang F, Wang H. Breast Cancer Res Treat. 2009 Oct 23. [Epub ahead of print] PMID: 19851861 These results provide strong evidence that vitamin D and calcium have a chemopreventive effect against breast cancer.

A Review - Vitamin D and Calcium in Sarcoidosis\nTrevor G Marshall, PhD, 5 July 2003

A phase 2 trial exploring the effects of high-dose (10,000 IU/day) vitamin D(3) in breast cancer patients with bone metastases. Amir E, Simmons CE, Freedman OC, Dranitsaris G, Cole DE, Vieth R, Ooi WS, Clemons M. Cancer. 2009 Nov 13. [Epub ahead of print] PMID: 19918922 DOI: 10.1002/cncr.24749 METHODS: Patients with bone metastases treated with bisphosphonates were enrolled into this single-arm phase 2 study. Patients received 10,000 IU of vitamin D3 and 1000 mg of calcium supplementation each day for 4 months. The effect of this treatment on palliation, bone resorption markers, calcium metabolism, and toxicity were evaluated at baseline and monthly thereafter. CONCLUSIONS: Daily doses of 10,000 IU vitamin D3 for 4 months appear safe in patients without comorbid conditions causing hypersensitivity to vitamin D. Treatment reduced inappropriately elevated parathyroid hormone levels, presumably caused by long-term bisphosphonate use. There did not appear to be a significant palliative benefit nor any significant change in bone resorption. Cancer 2010. © 2009 American Cancer Society.

"Dr. Jodie Burton is the acting principal investigator (PI) of the dose-escalation trial of oral vitamin D3 with calcium supplementation in patients with multiple sclerosis with Dr. O'Connor. She started the trial as his fellow, while doing an additional 2 years of training in MS specifically after she received her neurology certification. She completed her fellowship training in 2007. Now she is staff doing clinical research and continuing with the vitamin D trial. As of August 2009, she will be Assistant Professor in Neurology in the Department of Clinical Neuroscience in Calgary and at the University of Calgary. She will be part of the MS team there with Dr. Luanne Metz and the MS group. Please scroll down for an abstract of the trial: A Phase I/II dose-escalation trial of oral vitamin D3 with calcium supplementation in patients with multiple sclerosis." Conclusions: High-dose VD3 (~10 000 IU/day, possibly higher) in MS is safe and tolerable, with evidence of clinical improvement."

Long-latency deficiency disease: insights from calcium and vitamin D. Heaney RP. Am J Clin Nutr. 2003 Nov;78(5):912-9. Review. PMID: 14594776

The Toronto group gave a fixed low dose (2,000 units) of the prehormone, cholecalciferol, a very safe compound that never causes high calcium in the doses used. In fact, the lowest dose of cholecalciferol known to cause high blood calcium is more than 20,000 units. Therefore, the Toronto group got better results with one-tenth the comparable dose of deltanoids! Vieth wanted to use more cholecalciferol but widespread ignorance about the physiology and pharmacology of vitamin D remains and he could not get adequate dosing past the various review committees.

Calcium, dairy foods, vitamin D, and colorectal cancer risk: the Fukuoka Colorectal Cancer Study. Mizoue T, Kimura Y, Toyomura K, Nagano J, Kono S, Mibu R, Tanaka M, Kakeji Y, Maehara Y, Okamura T, Ikejiri K, Futami K, Yasunami Y, Maekawa T, Takenaka K, Ichimiya H, Imaizumi N. Cancer Epidemiol Biomarkers Prev. 2008 Oct;17(10):2800-7. PMID: 18843026

Calcium plus vitamin D supplementation and the risk of breast cancer. Chlebowski RT, Johnson KC, Kooperberg C, Pettinger M, Wactawski-Wende J, Rohan T, Rossouw J, Lane D, O'Sullivan MJ, Yasmeen S, Hiatt RA, Shikany JM, Vitolins M, Khandekar J, Hubbell FA; Women's Health Initiative Investigators. J Natl Cancer Inst. 2008 Nov 19;100(22):1581-91. Epub 2008 Nov 11. PMID: 19001601

Calcium, vitamin D and cancer. Peterlik M, Grant WB, Cross HS. Anticancer Res. 2009 Sep;29(9):3687-98. Review. PMID: 19667166

Effectiveness and safety of vitamin D in relation to bone health. Cranney A, Horsley T, O'Donnell S, Weiler H, Puil L, Ooi D, Atkinson S, Ward L, Moher D, Hanley D, Fang M, Yazdi F, Garritty C, Sampson M, Barrowman N, Tsertsvadze A, Mamaladze V. Evid Rep Technol Assess (Full Rep). 2007 Aug;(158):1-235. Review. PMID: 18088161 CONCLUSIONS: The results highlight the need for additional high quality studies in infants, children, premenopausal women, and diverse racial or ethnic groups. There was fair evidence from studies of an association between circulating 25(OH)D concentrations with some bone health outcomes (established rickets, PTH, falls, BMD). However, the evidence for an association was inconsistent for other outcomes (e.g., BMC in infants and fractures in adults). It was difficult to define specific thresholds of circulating 25(OH)D for optimal bone health due to the imprecision of different 25(OH)D assays. Standard reference preparations are needed so that serum 25(OH)D can be accurately and reliably measured, and validated. In most trials, the effects of vitamin D and calcium could not be separated. Vitamin D(3) (>700 IU/day) with calcium supplementation compared to placebo has a small beneficial effect on BMD, and reduces the risk of fractures and falls although benefit may be confined to specific subgroups. Vitamin D intake above current dietary reference intakes was not reported to be associated with an increased risk of adverse events. However, most trials of higher doses of vitamin D were not adequately designed to assess long-term harms.

Effectiveness and safety of vitamin D in relation to bone health. Cranney A, Horsley T, O'Donnell S, Weiler H, Puil L, Ooi D, Atkinson S, Ward L, Moher D, Hanley D, Fang M, Yazdi F, Garritty C, Sampson M, Barrowman N, Tsertsvadze A, Mamaladze V. Evid Rep Technol Assess (Full Rep). 2007 Aug;(158):1-235. Review. PMID: 18088161 CONCLUSIONS: The results highlight the need for additional high quality studies in infants, children, premenopausal women, and diverse racial or ethnic groups. There was fair evidence from studies of an association between circulating 25(OH)D concentrations with some bone health outcomes (established rickets, PTH, falls, BMD). However, the evidence for an association was inconsistent for other outcomes (e.g., BMC in infants and fractures in adults). It was difficult to define specific thresholds of circulating 25(OH)D for optimal bone health due to the imprecision of different 25(OH)D assays. Standard reference preparations are needed so that serum 25(OH)D can be accurately and reliably measured, and validated. In most trials, the effects of vitamin D and calcium could not be separated. Vitamin D(3) (>700 IU/day) with calcium supplementation compared to placebo has a small beneficial effect on BMD, and reduces the risk of fractures and falls although benefit may be confined to specific subgroups. Vitamin D intake above current dietary reference intakes was not reported to be associated with an increased risk of adverse events. However, most trials of higher doses of vitamin D were not adequately designed to assess long-term harms.

Effects of calcium, dairy product, and vitamin D supplementation on bone mass accrual and body composition in 10-12-y-old girls: a 2-y randomized trial. Cheng S, Lyytikäinen A, Kröger H, Lamberg-Allardt C, Alén M, Koistinen A, Wang QJ, Suuriniemi M, Suominen H, Mahonen A, Nicholson PH, Ivaska KK, Korpela R, Ohlsson C, Väänänen KH, Tylavsky F. Am J Clin Nutr. 2005 Nov;82(5):1115-26; quiz 1147-8. PMID: 16280447

Reducing fracture risk with calcium and vitamin D. Lips P, Bouillon R, van Schoor NM, Vanderschueren D, Verschueren S, Kuchuk N, Milisen K, Boonen S. Clin Endocrinol (Oxf). 2009 Sep 10. [Epub ahead of print] PMID: 19744099 DOI: 10.1111/j.0300-0664.2009.03701.x

Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. Heaney RP, Dowell MS, Hale CA, Bendich A. J Am Coll Nutr. 2003 Apr;22(2):142-6. PMID: 12672710

Schematic diagram of cutaneous production of vitamin D and its metabolism and regulation for calcium homeostasis and cellular growth - Figure 3 from the study Holick MF. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, can

Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab. 2007 Jun;92(6):2017-29. Epub 2007 Mar 27. Review. PMID: 17389701 [PubMed - indexed for MEDL

Pittas AG, Harris SS, Stark PC, Dawson-Hughes B. The Effects of Calcium and Vitamin D Supplementation on Blood Glucose and Markers of Inflammation in Non-diabetic Adults. Diabetes Care. 2007 Feb 2; [Epub ahead of print] PMID: 17277040 [PubMed - as sup

Harinarayan CV, Ramalakshmi T, Prasad UV, Sudhakar D, Srinivasarao PV, Sarma KV, Kumar EG. High prevalence of low dietary calcium, high phytate consumption, and vitamin D deficiency in healthy south Indians. Am J Clin Nutr. 2007 Apr;85(4):1062-7. PMID

Park SY, Murphy SP, Wilkens LR, Nomura AM, Henderson BE, Kolonel LN. Calcium and vitamin D intake and risk of colorectal cancer: the Multiethnic Cohort Study. Am J Epidemiol. 2007 Apr 1;165(7):784-93. Epub 2007 Jan 10. PMID: 17215380 [PubMed - indexed

Heaney RP. Long-latency deficiency disease: insights from calcium and vitamin D. Am J Clin Nutr. 2003 Nov;78(5):912-9. Review. PMID: 14594776 [PubMed - indexed for MEDLINE]