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Vitamin D

Vitamin D, Hormones, and Breast Cancer

New research suggests that Vitamin D could oppose estrogen’s breast cancer-promoting effects. Published in the American Journal of Clinical Nutrition, a study of over 57,000 postmenopausal women found that, among women who had ever used hormone therapy, those that were supplementing with vitamin D had a 26 percent reduced risk of breast cancer.1

Vitamin D is known to have cellular effects thatoppose the development of cancer, such as promoting cell adhesion, inhibiting cancer cell proliferation, and anti-inflammatory effects.2 ACochrane meta-analysis published in 2014 concluded that supplementation with vitamin D3 was associated with a 12 percent lower risk of death from cancer.3

There has been extensive research on vitamin D in relation to breast cancer risk. Some meta-analyses have shown significantly reduced breast cancer risk with higher blood vitamin D, whereas others have shown only a weak association.4-6 The protective effects of vitamin D appear to be quite strong in studies of breast cancer patients. In a 2014 meta-analysis of six studies, higher vitamin D blood levels (above 29.1 ng/ml) were associated with a 42 percent reduction in the risk of death from breast cancer compared to lower levels (lower than 21 ng/ml).4 Another meta-analysis reported that breast cancer patients with low vitamin D levels (less than 20 ng/ml or less than 30 ng/ml, depending on the particular study) had more than double the risk of recurrence of their cancer.7 Furthermore, studies that have shown that an inherited variation in the vitamin D receptor gene increases breast cancer risk.8,9

We know Vitamin D has overall anti-cancer effects, but interestingly the new research suggests that vitamin D may oppose some effects of female hormones, making vitamin D especially helpful for breast cancer prevention. Experiments carried out in vitro suggest that the active form of vitamin D suppresses aromatase expression in breast cancer cells, resulting in lower production of estrogen. Vitamin D also downregulated the estrogen receptor in breast cancer cells, making the cells less responsive to estrogen’s cancer-promoting signals.2

This research makes it even more important for women to get their blood vitamin D levels (25(OH)D) tested and supplement to reach the sweet spot of 30-45 ng/ml. This favorable range has been suggested by much research on cancer, bone fractures, and all-cause mortality.10-15 I recommend taking vitamin D3, the more potent form of the vitamin, the form the skin produces when it is exposed to sunlight. In my experience 2000 IU is an appropriate dose to bring most people into the 30-45 ng/ml range.

However, there are always exceptions and for those whose blood results fall outside of this range taking more or less can be indicated.


References: 

1. Cadeau C, Fournier A, Mesrine S, et al. Interaction between current vitamin D supplementation and menopausal hormone therapy use on breast cancer risk: evidence from the E3N cohort. Am J Clin Nutr 2015, 102:966-973. 
2. Krishnan AV, Swami S, Feldman D. The potential therapeutic benefits of vitamin D in the treatment of estrogen receptor positive breast cancer. Steroids 2012, 77:1107-1112. 
3. Bjelakovic G, Gluud LL, Nikolova D, et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev 2014, 1:CD007470. 
4. Kim Y, Je Y. Vitamin D intake, blood 25(OH)D levels, and breast cancer risk or mortality: a meta-analysis. Br J Cancer2014, 110:2772-2784. 
5. Chen P, Hu P, Xie D, et al. Meta-analysis of vitamin D, calcium and the prevention of breast cancer. Breast Cancer Res Treat 2010, 121:469-477. 
6. Bauer SR, Hankinson SE, Bertone-Johnson ER, Ding EL. Plasma vitamin D levels, menopause, and risk of breast cancer: dose-response meta-analysis of prospective studies. Medicine (Baltimore) 2013, 92:123-131. 
7. Rose AA, Elser C, Ennis M, Goodwin PJ. Blood levels of vitamin D and early stage breast cancer prognosis: a systematic review and meta-analysis. Breast Cancer Res Treat 2013, 141:331-339. 
8. Zhang K, Song L. Association between vitamin D receptor gene polymorphisms and breast cancer risk: a meta-analysis of 39 studies. PLoS One 2014, 9:e96125. 
9. Alimirah F, Peng X, Murillo G, Mehta RG. Functional significance of vitamin D receptor FokI polymorphism in human breast cancer cells. PLoS One 2011, 6:e16024. 
10. Zittermann A, Iodice S, Pilz S, et al. Vitamin D deficiency and mortality risk in the general population: a meta-analysis of prospective cohort studies. Am J Clin Nutr 2012, 95:91-100. 
11. Schottker B, Ball D, Gellert C, Brenner H. Serum 25-hydroxyvitamin D levels and overall mortality. A systematic review and meta-analysis of prospective cohort studies. Ageing Res Rev 2013, 12:708-718. 
12. Bischoff-Ferrari HA. Vitamin D and fracture prevention. Rheum Dis Clin North Am 2012, 38:107-113. 
13. Melamed ML, Michos ED, Post W, Astor B. 25-Hydroxyvitamin D Levels and the Risk of Mortality in the General Population. Arch Intern Med 2008, 168:1629-1637. 
14. Durup D, Jorgensen HL, Christensen J, et al. A reverse J-shaped association of all-cause mortality with serum 25-hydroxyvitamin D in general practice: the CopD study. J Clin Endocrinol Metab 2012, 97:2644-2652. 
15. Sempos CT, Durazo-Arvizu RA, Dawson-Hughes B, et al. Is there a reverse J-shaped association between 25-hydroxyvitamin D and all-cause mortality? Results from the U.S. nationally representative NHANES. J Clin Endocrinol Metab 2013, 98:3001-3009.

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