Vitamin D and Prevention of Cancer - Ready for Prime Time?

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
New England Journal of Medicine (Impact Factor: 55.87). 03/2011; 364(15):1385-7. DOI: 10.1056/NEJMp1102022
Source: PubMed


Given that the potential role of vitamin D in cancer prevention has been widely touted, many people were surprised that cancer-related considerations didn't figure prominently in the new Dietary Reference Intakes for vitamin D established by the Institute of Medicine (IOM).(1) An IOM committee on which we served, charged with determining the population needs for vitamin D in North America, reviewed the evidence linking vitamin D with both skeletal and nonskeletal health outcomes. The committee concluded that vitamin D plays an important role in bone health and that the evidence provides a sound basis for determining the population's needs. For . . .

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Available from: Steven Clinton, Jun 01, 2014
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    • "However, most of the clinical data stem from observational studies. These studies consistently show a likely benefit for vitamin D supplementation in colon and breast cancer, but randomized clinical trial data of sufficient size and duration with sufficient doses of vitamin D to be definitive are lacking (Chung et al., 2011; Manson et al., 2011). Development of an analog with tissue specificity relative to effects on calcium absorption/bone resorption would enhance the chances of success in treating malignancies. "
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    ABSTRACT: Vitamin D3 is made in the skin from 7-dehydrocholesterol under the influence of UV light. Vitamin D2 (ergocalciferol) is derived from the plant sterol ergosterol. Vitamin D is metabolized first to 25 hydroxyvitamin D (25OHD), then to the hormonal form 1,25-dihydroxyvitamin D (1,25(OH)2D). CYP2R1 is the most important 25-hydroxylase; CYP27B1 is the key 1-hydroxylase. Both 25OHD and 1,25(OH)2D are catabolized by CYP24A1. 1,25(OH)2D is the ligand for the vitamin D receptor (VDR), a transcription factor, binding to sites in the DNA called vitamin D response elements (VDREs). There are thousands of these binding sites regulating hundreds of genes in a cell-specific fashion. VDR-regulated transcription is dependent on comodulators, the profile of which is also cell specific. Analogs of 1,25(OH)2D are being developed to target specific diseases with minimal side effects. This review will examine these different aspects of vitamin D metabolism, mechanism of action, and clinical application.
    Chemistry & biology 02/2014; 21(3). DOI:10.1016/j.chembiol.2013.12.016 · 6.65 Impact Factor
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    • "Results from this study add to the growing debate regarding the potential beneficial effects of vitamin D against breast cancer and other malignancies [29,30]. Higher circulating vitamin D3 and vitamin D levels were associated with a lower risk of postmenopausal breast cancer among white women whose circulating 25(OH)D3 and 25(OH)D levels exceeded those of women in other race/ethnic groups. "
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    ABSTRACT: Higher sunlight exposure is correlated with lower incidence of breast cancer in ecological studies, but findings from prospective studies regarding the association of circulating levels of vitamin D with the risk of breast cancer have been null. The objective of this study was to examine the relation between plasma levels of vitamin D and the risk of postmenopausal breast cancer. We conducted a nested case-control study within the Multiethnic Cohort Study of five race/ethnic groups (white, African-American, Native Hawaiian, Japanese, and Latino) from Hawaii and Los Angeles between 2001 and 2006. Pre-diagnostic plasma levels of 25-hydroxyvitamin D2 [25(OH)D2], 25-hydroxyvitamin D3 [25(OH)D3] and 25(OH)D (sum of 25(OH)D2 and 25(OH)D3) were examined among 707 postmenopausal breast cancer cases and matched controls. Using conditional logistic regression models, 20 ng/mL increases of plasma 25(OH)D3 (odds ratio (OR) 0.28; 95% confidence interval (CI) 0.14-0.56) and 25(OH)D (OR 0.43; 95% CI 0.23-0.80) were inversely associated with breast cancer risk among white women, but not among women in other race/ethnic groups. Using two-segmented, piecewise-linear logistic regression models, the change-points of the ORs, either for 25(OH)D3 or for 25(OH)D, were detected as 20 ng/mL among whites. Circulating 25(OH)D3 and 25(OH)D were associated with a reduced risk of postmenopausal breast cancer among whites, but not in other ethnic groups, who reside in low latitude regions.
    BMC Cancer 01/2014; 14(1):29. DOI:10.1186/1471-2407-14-29 · 3.36 Impact Factor
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    • "Many epidemiologic studies suggest that low vitamin D status may also be associated with risk of non-skeletal chronic diseases, such as, all-cause mortality [2-4], type 2 diabetes [5-7], cardiovascular diseases (CVD) [8,9], and colorectal cancer [10-12]. However, findings have not been entirely consistent [13-16]. Large-scale clinical trials of vitamin D supplementation are ongoing [13,14,17]. "
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    ABSTRACT: Magnesium plays an essential role in the synthesis and metab ABSTRACT: BACKGROUND: Magnesium plays an essential role in the synthesis and metabolism of vitamin D and magnesium supplementation substantially reversed the resistance to vitamin D treatment in patients with magnesium-dependent vitamin-D-resistant rickets. We hypothesized that dietary magnesium alone, particularly its interaction with vitamin D intake, contributes to serum 25-hydroxyvitamin D (25(OH)D) levels, and the associations between serum 25(OH)D and risk of mortality may be modified by magnesium intake level. We tested these novel hypotheses utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2001 to 2006, a population-based cross-sectional study, and the NHANES III cohort, a population-based cohort study. Serum 25(OH)D was used to define vitamin D status. Mortality outcomes in the NHANES III cohort were determined by using probabilistic linkage with the National Death Index (NDI). High intake of total, dietary or supplemental magnesium was independently associated with significantly reduced risks of vitamin D deficiency and insufficiency respectively. Intake of magnesium significantly interacted with intake of vitamin D in relation to risk of both vitamin D deficiency and insufficiency. Additionally, the inverse association between total magnesium intake and vitamin D insufficiency primarily appeared among populations at high risk of vitamin insufficiency. Furthermore, the associations of serum 25(OH)D with mortality, particularly due to cardiovascular disease (CVD) and colorectal cancer, were modified by magnesium intake, and the inverse associations were primarily present among those with magnesium intake above the median. Our preliminary findings indicate it is possible that magnesium intake alone or its interaction with vitamin D intake may contribute to vitamin D status. The associations between serum 25(OH)D and risk of mortality may be modified by the intake level of magnesium. Future studies, including cohort studies and clinical trials, are necessary to confirm the findings.
    BMC Medicine 08/2013; 11(1):187. DOI:10.1186/1741-7015-11-187 · 7.25 Impact Factor
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