25-hydroxyvitamin-d-2 and Neoplasms

The Institute of Medicine (IOM) report on dietary reference intakes (DRI) for vitamin D is reviewed, along with its implications.. Evidence-based reviews were completed; the IOM committee conducted its own literature search, an open public workshop, and two open sessions, and maintained a public web site for stakeholder input. The consensus report of the 14 scientists on the committee was reviewed by a panel of experts.. Only bone health could be used as an indicator for DRI development. Evidence for extraskeletal outcomes was inadequate, inconsistent, or insufficient to develop DRI. The recommended dietary allowance was found to be 600 IU/d for ages 1-70 yr, corresponding on average to a serum 25-hydroxyvitamin D (25OHD) level of at least 50 nmol/liter (20 ng/ml), and 800 IU/d for those older than 70 yr. Comparison with current levels of 25OHD in the National Health and Nutrition Examination Survey population survey revealed that the vitamin D intake in the United States and Canada is adequate. An upper limit was set at 4000 IU/d for adults, corresponding to an average serum 25OHD level of 125 nmol/liter (50 ng/ml).. Previous reports of an epidemic of vitamin D deficiency in North America were based on an overestimation of adequacy. Population screening with serum 25OHD is therefore not warranted. Current laboratory reference ranges for serum 25OHD are overestimated and should be revised. Practice guidelines to treat disease should not be applied to the healthy American population where use of the DRI is appropriate.

Topics: 25-Hydroxyvitamin D 2; Accidental Falls; Aged; Bone and Bones; Calcium, Dietary; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diet; Diet Surveys; Dietary Supplements; Health Status; Humans; Metabolic Syndrome; Neoplasms; North America; Nutrition Policy; Public Health; Reference Values; Sunlight; United States; Vitamin D; Vitamin D Deficiency

Studies suggest that vitamin D supplementation may reduce cancer and fracture risks.. To examine the benefits and harms of vitamin D with or without calcium supplementation on clinical outcomes of cancer and fractures in adults.. English-language studies identified from MEDLINE and the Cochrane Central Register of Controlled Trials through July 2011.. Randomized, controlled trials (RCTs), prospective cohort studies, and nested case-control studies reporting incidence of or death from cancer and fracture outcomes.. Multiple reviewers extracted details about participant characteristics, including baseline vitamin D status and use of supplements; details of statistical analyses, including adjustments for confounding; and methodological quality. Differences were resolved by consensus.. 19 RCTs (3 for cancer and 16 for fracture outcomes) and 28 observational studies (for cancer outcomes) were analyzed. Limited data from RCTs suggested that high-dose (1000 IU/d) vitamin D supplementation can reduce the risk for total cancer, and data from observational studies suggested that higher blood 25-hydroxyvitamin D (25-[OH]D) concentrations might be associated with increased risk for cancer. Mixed-effects dose-response meta-analyses showed that each 10-nmol/L increase in blood 25-(OH)D concentration was associated with a 6% (95% CI, 3% to 9%) reduced risk for colorectal cancer but no statistically significant dose-response relationships for prostate and breast cancer. Random-effects model meta-analysis showed that combined vitamin D and calcium supplementation reduced fracture risk (pooled relative risk, 0.88 [CI, 0.78 to 0.99]) in older adults, but the effects differed according to study setting: institution (relative risk, 0.71 [CI, 0.57 to 0.89]) versus community-dwelling (relative risk, 0.89 [CI, 0.76 to 1.04]). One RCT showed adverse outcomes associated with supplementation, including increased risk for renal and urinary tract stones.. Most trial participants were older (aged≥65 years) postmenopausal women. Observational studies were heterogeneous and were limited by potential confounders.. Combined vitamin D and calcium supplementation can reduce fracture risk, but the effects may be smaller among community-dwelling older adults than among institutionalized elderly persons. Appropriate dose and dosing regimens, however, require further study. Evidence is not sufficiently robust to draw conclusions regarding the benefits or harms of vitamin D supplementation for the prevention of cancer.. Agency for Healthcare Research and Quality.

Topics: 25-Hydroxyvitamin D 2; Advisory Committees; Age Factors; Calcium; Dietary Supplements; Fractures, Bone; Humans; Neoplasms; Sex Factors; United States; Urinary Calculi; Vitamin D

The hypothesis that vitamin D is inversely associated with multiple health outcomes has been studied in the Harvard cohorts, including the Nurses' Health Study I (n=121,700 female nurses aged 37-64 at baseline in 1984), Nurses' Health Study II (n=116,671 female nurses aged 27-44 years at baseline in 1991), Health Professionals Follow-up Study (n=51,529 male health professionals aged 40-75 years at baseline in 1986), and Physicians' Health Study (n=22 071 male physicians aged 40-84 years at baseline in 1982). These studies assessed vitamin D through circulating 25-hydroxyvitamin D, dietary and supplemental intake, predicted 25-hydroxyvitamin D, and vitamin D receptor polymorphisms. This review summarizes studies of vitamin D and various endpoints considered in these cohorts, including risk of cardiovascular disease, hypertension, elevated plasma C-peptide, various cancers, bone fractures, and multiple sclerosis. Based on the multiple observed benefits of vitamin D, this article postulates recommendations for vitamin D intake in the US population for reduced incidence of multiple health outcomes.

Topics: 25-Hydroxyvitamin D 2; Adult; Calcifediol; Cardiovascular Diseases; Cohort Studies; Diet; Dietary Supplements; Female; Fractures, Bone; Health Surveys; Humans; Male; Multiple Sclerosis; Neoplasms; Nutrition Policy; Nutritional Requirements; Polymorphism, Genetic; Receptors, Calcitriol; Vitamin D; Vitamin D Deficiency

Experimental evidence has suggested that vitamin D may be protective against tobacco-related cancers through the inhibition of the formation of tumors induced by tobacco carcinogens. To our knowledge, only one previous epidemiologic study investigated the association between vitamin D status and tobacco-related cancer risk, and no study has focused on vitamin D-related gene polymorphisms.. Our objective was to prospectively study the association between plasma 25-hydroxyvitamin D [25(OH)D] concentrations, vitamin D-related gene polymorphisms, and risk of tobacco-related cancers.. A total of 209 tobacco-related cancers were diagnosed within the SU.VI.MAX (Supplémentation en vitamines et minéraux antioxydants) cohort (1994-2007) and were matched with 418 controls as part of a nested case-control study. Tobacco-related cancers (i.e., cancers for which tobacco is one of the risk factors) included several sites in the respiratory, digestive, reproductive, and urinary systems. Total plasma 25(OH)D was assessed with the use of an electrochemoluminescent assay. Polymorphisms were determined with the use of a TaqMan assay. Conditional logistic regression models were computed.. A 25(OH)D concentration ≥30 ng/mL was associated with reduced risk of tobacco-related cancers (OR for ≥30 compared with <30 ng/mL: 0.59; 95% CI 0.35, 0.99; P = 0.046). This association was observed in former and current smokers (OR for ≥30 compared with <30 ng/mL: 0.43; 95% CI: 0.23, 0.84; P = 0.01) but not in never smokers (P = 0.8). The vitamin D receptor (VDR) FokI AA genotype and retinoid X receptor (RXR) rs7861779 TT genotype were associated with increased risk of tobacco-related cancers [OR for homozygous mutant type (MT) compared with wild type (WT): 1.87; 95% CI: 1.08, 3.23; P-trend = 0.02; OR for heterozygous type (HT) plus MT compared with WT: 1.60; 95% CI: 1.07, 2.38; P = 0.02].. In this prospective study, high vitamin D status [25(OH)D concentration ≥30 ng/mL] was associated with decreased risk of tobacco-related cancers, especially in smokers. These results, which are supported by mechanistic plausibility, suggest that vitamin D may contribute to the prevention of tobacco-induced cancers in smokers and deserve additional investigation. The SU.VI.MAX trial was registered at clinicaltrials.gov as NCT00272428.

Topics: 25-Hydroxyvitamin D 2; Adult; Aged; Calcifediol; Case-Control Studies; Cohort Studies; Double-Blind Method; Female; Follow-Up Studies; France; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Neoplasms; Nutritional Status; Polymorphism, Single Nucleotide; Receptors, Calcitriol; Retinoid X Receptor alpha; Risk Factors; Tobacco Use; Vitamin D Deficiency

Children with cancer are potentially at a high risk of plasma 25-hydroxyvitamin D (25(OH)D) inadequacy, and despite UK vitamin D supplementation guidelines their implementation remains inconsistent. Thus, we aimed to investigate 25(OH)D concentration and factors contributing to 25(OH)D inadequacy in paediatric cancer patients. A prospective cohort study of Scottish children aged 75 nmol/l). In all, eighty-two patients (median age 3·9, interquartile ranges (IQR) 1·9-8·8; 56 % males) and thirty-five controls (median age 6·2, IQR 4·8-9·1; 49 % males) were recruited. 25(OH)D inadequacy was highly prevalent in the controls (63 %; 22/35) and in the patients (64 %; 42/65) at both baseline and during treatment (33-50 %). Non-supplemented children had the highest prevalence of 25(OH)D inadequacy at every stage with 25(OH)D median ranging from 32·0 (IQR 21·0-46·5) to 45·0 (28·0-64·5) nmol/l. Older age at baseline (R -0·46; P<0·001), overnutrition (BMI≥85th centile) at 3 months (P=0·005; relative risk=3·1) and not being supplemented at 6 months (P=0·04; relative risk=4·3) may have contributed to lower plasma 25(OH)D. Paediatric cancer patients are not at a higher risk of 25(OH)D inadequacy than healthy children at diagnosis; however, prevalence of 25(OH)D inadequacy is still high and non-supplemented children have a higher risk. Appropriate monitoring and therapeutic supplementation should be implemented.

Topics: 25-Hydroxyvitamin D 2; Adolescent; Age Factors; Body Mass Index; Calcifediol; Case-Control Studies; Child; Child, Preschool; Cohort Studies; Follow-Up Studies; Humans; Male; Neoplasm Staging; Neoplasms; Overnutrition; Pilot Projects; Prevalence; Prospective Studies; Risk; Scotland; Severity of Illness Index; Vitamin D Deficiency

In various populations, vitamin D deficiency is associated with chronic diseases and mortality. We examined the association between concentration of circulating 25-hydroxyvitamin D [25(OH)D], a marker of vitamin D status, and all-cause as well as cause-specific mortality.. The study included 3404 participants of the general adult Swiss population, who were recruited between November 1988 and June 1989 and followed-up until the end of 2008. Circulating 25(OH)D was measured by protein-bound assay. Cox proportional hazards regression was used to examine the association between 25(OH)D concentration and all-cause and cause-specific mortality adjusting for sex, age, season, diet, nationality, blood pressure, and smoking status. Per 10 ng/mL increase in 25(OH)D concentration, all-cause mortality decreased by 20% (HR = 0.83; 95% CI 0.74-0.92). 25(OH)D concentration was inversely associated with cardiovascular mortality in women (HR = 0.68, 95% CI 0.46-1.00 per 10 ng/mL increase), but not in men (HR = 0.97; 95% CI 0.77-1.23). In contrast, 25(OH)D concentration was inversely associated with cancer mortality in men (HR = 0.72, 95% CI 0.57-0.91 per 10 ng/mL increase), but not in women (HR = 1.14, 95% CI 0.93-1.39). Multivariate adjustment only slightly modified the 25(OH)D-mortality association.. 25(OH)D was similarly inversely related to all-cause mortality in men and women. However, we observed opposite effects in women and men with respect to cardiovascular and cancer mortality.

Topics: 25-Hydroxyvitamin D 2; Adult; Aged; Aging; Calcifediol; Cardiovascular Diseases; Cohort Studies; Female; Follow-Up Studies; Humans; Longitudinal Studies; Male; Middle Aged; Mortality; Neoplasms; Proportional Hazards Models; Risk Factors; Sex Characteristics; Switzerland; Vitamin D Deficiency

20-hydroxyvitamin D(2) [20(OH)D(2)] inhibits DNA synthesis in epidermal keratinocytes, melanocytes, and melanoma cells in a dose- and time-dependent manner. This inhibition is dependent on cell type, with keratinocytes and melanoma cells being more sensitive than normal melanocytes. The antiproliferative activity of 20(OH)D(2) is similar to that of 1,25(OH)(2)D(3) and of newly synthesized 1,20(OH)(2)D(2) but significantly higher than that of 25(OH)D(3). 20(OH)D(2) also displays tumorostatic effects. In keratinocytes 20(OH)D(2) inhibits expression of cyclins and stimulates involucrin expression. It also stimulates CYP24 expression, however, to a significantly lower degree than that by 1,25(OH)(2)D(3) or 25(OH)D(3). 20(OH)D(2) is a poor substrate for CYP27B1 with overall catalytic efficiency being 24- and 41-fold lower than for 25(OH)D(3) with the mouse and human enzymes, respectively. No conversion of 20(OH)D(2) to 1,20(OH)(2)D(2) was detected in intact HaCaT keratinocytes. 20(OH)D(2) also demonstrates anti-leukemic activity but with lower potency than 1,25(OH)(2)D(3). The phenotypic effects of 20(OH)D(2) are mediated through interaction with the vitamin D receptor (VDR) as documented by attenuation of cell proliferation after silencing of VDR, by enhancement of the inhibitory effect through stable overexpression of VDR and by the demonstration that 20(OH)D(2) induces time-dependent translocation of VDR from the cytoplasm to the nucleus at a comparable rate to that for 1,25(OH)(2)D(3). In vivo tests show that while 1,25(OH)(2)D(3) at doses as low as 0.8 μg/kg induces calcium deposits in the kidney and heart, 20(OH)D(2) is devoid of such activity even at doses as high as 4 μg/kg. Silencing of CY27B1 in human keratinocytes showed that 20(OH)D(2) does not require its transformation to 1,20(OH)(2)D(2) for its biological activity. Thus 20(OH)D(2) shows cell-type dependent antiproliferative and prodifferentiation activities through activation of VDR, while having no detectable toxic calcemic activity, and is a poor substrate for CYP27B1.

Topics: 25-Hydroxyvitamin D 2; Animals; Antineoplastic Agents; Cell Differentiation; Cell Proliferation; Cells, Cultured; Growth Inhibitors; HL-60 Cells; Humans; Keratinocytes; Melanocytes; Mice; Neoplasms

Low levels of vitamin D and excess body weight are both factors associated with increased risk of cancer. The increased risk seems to be proportional to the increase in BMI, and to decrease in serum 25-hydroxyvitamin D (25(OH)D) level. Our earlier investigations suggest that serum 25(OH)D levels decrease with increasing BMI. Although the connection between cancer risk, BMI and vitamin D status might be arbitrary, it has not been discussed in the literature so far. In this study, we analyze data published in current meta-analysis, prospective studies, and systematic reviews on cancer-specific risk attributed to high BMI and low vitamin D status. The contribution of low 25(OH)D levels associated with high BMI to increased cancer risk was calculated for 13 vitamin-D-sensitive cancers with a focus on colorectal and breast cancer as the most frequently studied vitamin-D-sensitive cancer types. Our study suggests that a low vitamin D status may explain at least 20% of the cancer risk attributable to high BMI. The contribution of low 25(OH)D to the increased cancer risk with increasing BMI may be different for different cancer types. Thus, we find 40% for breast cancer, and 26 and 75% for colorectal cancer in men and women, respectively.

Topics: 25-Hydroxyvitamin D 2; Adult; Body Mass Index; Breast Neoplasms; Calcifediol; Colorectal Neoplasms; Female; Humans; Male; Middle Aged; Neoplasms; Obesity; Prevalence; Risk Factors; Sex Factors; Vitamin D Deficiency; Young Adult