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The concentration or threshold of 25-hydroxyvitamin D [25(OH)D] needed to maximally suppress intact serum parathyroid hormone (iPTH) has been suggested as a measure of optimal vitamin D status. Depending upon the definition of maximal suppression of iPTH and the 2-phase regression approach used, 2 distinct clusters for a single 25(OH)D threshold have been reported: 16-20 ng/mL (40-50 nmol/L) and 30-32 ng/mL (75-80 nmol/L). To rationalize the apparently disparate published results, we compared thresholds from several regression models including a 3-phase one to estimate simultaneously 2 thresholds before and after adjusting for possible confounding for age, BMI, glomerular filtration rate, dietary calcium, and season (April-September vs. October-March) within a single data set, i.e. data from the Tufts University Sites Testing Osteoporosis Prevention/Intervention Treatment study, consisting of 181 men and 206 women (total n = 387) ages 65-87 y. Plasma 25(OH)D and serum iPTH concentrations were (mean [+ or -] SD) 22.1 [+ or -] 7.44 ng/mL (55.25 [+ or -] 18.6 nmol/L) and 36.6 [+ or -] 16.03 pg/mL (3.88 [+ or -] 1.7 pmol/L), respectively. The 3-phase model identified 2 thresholds of 12 ng/mL (30 nmol/L) and 28 ng/mL (70 nmol/L); similar results were found from the 2-phase models evaluated, i.e. 13-20 and 27-30 ng/mL (32.5-50 and 67.5-75 nmol/L) and with previous results. Adjusting for confounding did not change the results substantially. Accordingly, the 3-phase model appears to be superior to the 2-phase approach, because it simultaneously estimates the 2 threshold clusters found from the 2-phase approaches along with estimating confidence limits. If replicated, it may be of both clinical and public health importance. doi: 10.3945/jn.109.116681.

Population level data on how older individuals living at high latitudes achieve optimal vitamin D status are not fully explored. Our objective was to examine the intake of vitamin D among healthy older individuals with 25-hydroxyvitamin D [25(OH)D] concentrations [greater than or equal to] 75 nmol/L and to describe current sources of dietary vitamin D. We conducted a population-based, cross-sectional study of 404 healthy men and women aged 69 to 83 y randomly selected from the NuAge longitudinal study in Quebec, Canada. Dietary intakes were assessed by 6 24-h recalls. We examined the contribution of foods and vitamin/ mineral supplements to vitamin D intake. Serum 25(OH)D was assessed by RIA. We assessed smoking status, season of 25(OH)D measurement, physical activity, and anthropometric and sociodemographic variables. Vitamin D status was distributed as follows: 7% (75 nmol/L had mean intakes of 14.1 [micro]g/d from food and supplements. Supplement use is an important contributor to achieve a minimal target of 25(OH)D concentration [greate than or equal to] 75 nmol/L. doi: 10.3945/jn.109.115626.

Cutaneous cholecalciferol synthesis has not been considered in making recommendations for vitamin D intake. Our objective was to model the effects of sun exposure, vitamin D intake, and skin reflectance (pigmentation) on serum 25-hydroxyvitamin D (25[OH]D) in young adults with a wide range of skin reflectance and sun exposure. Four cohorts of participants (n = 72 total) were studied for 7-8 wk in the fall, winter, spring, and summer in Davis, CA [38.5[degrees]N, 121.7[degrees]W, Elev. 49 ft (15 m)]. Skin reflectance was measured using a spectrophotometer, vitamin D intake using food records, and sun exposure using polysulfone dosimeter badges. A multiple regression model ([R.sup.2] = 0.55; P < 0.0001) was developed and used to predict the serum 25(OH)D concentration for participants with low ]median for African ancestry (AA)] and high [median for European ancestry (EA)] skin reflectance and with low [20th percentile, ~20 min/d, ~18% body surface area (BSA) exposed] and high (80th percentile, ~90 min/d, ~35% BSA exposed) sun exposure, assuming an intake of 200 IU/d (5 ug/d). Predicted serum 25(OH)D concentrations for AA individuals with low and high sun exposure in the winter were 24 and 42 nmol/L and in the summer were 40 and 60 nmol/L. Corresponding values for EA individuals were 35 and 60 nmol/L in the winter and in the summer were 58 and 85 nmol/L. To achieve 25(OH)D [greater than or equal to] 75 nmol/L, we estimate that EA individuals with high sun exposure need 1300 IU/d vitamin D intake in the winter and AA individuals with low sun exposure need 2100-3100 IU/d year-round. doi: 10.3945/jn.109.115253.

The article discusses the consequences and etiology of falls among the elderly, especially those living in community-based settings, and predisposing factors responsible for falls and preventive strategies for the same. The most effective strategies include intervening on multiple-risk factors and the intake of vitamin D.

Valdivielso JM, Cannata-Andia J, Coll B, Fernandez E. A new role for vitamin D receptor activation in chronic kidney disease. Am J Physiol Renal Physiol 297: F1502-F1509, 2009. First published July 22, 2009; doi: 10.1152/ajprenal.00130.2009.--Vitamin D has proven to be much more than a simple 'calcium hormone.' The fact that the vitamin D receptor has been found in cells not related to mineral metabolism supports that statement. The interest of nephrologists in vitamin D and its effects beyond mineral metabolism has increased over the last few years, evidencing the importance of this so-called 'sunshine hormone.' In the present review, we highlight the most recent developments in the traditional use of vitamin D in chronic kidney disease (CKD) patients, namely, the control of secondary hyper- parathyroidism (sHPT). Furthermore, we also explore the data available regarding the new possible therapeutic uses of vitamin D for the treatment of other complications present in CKD patients, such as vascular calcification, left ventricular hypertrophy, or proteinuria. Finally, some still scarce but very promising data regarding a possible role of vitamin D in kidney transplant patients also are reviewed. The available data point to a potential beneficial effect of vitamin D in CKD patients beyond the control of mineral metabolism. doi: 10.1152/ajprenal.00130.2009

1,25[(OH).sub.2][D.sub.3] decreases parathyroid hormone (PTH) gene transcription through the vitamin D receptor (VDR). Total body [VDR.sup.-/-] mice have high PTH levels, hypocalcemia, hypophosphatemia, and bone malformations. To investigate PTH regulation by the VDR specifically in the parathyroid, we generated parathyroid-specific VDR knockout mice (PT-[VDR.sup.-/-]). In both strains, there was a decrease in parathyroid calcium receptor (CAR) levels. The number of proliferating parathyroid cells was increased in the [VDR.sup.-/-] mice but not in the PT-[VDR.sup.-/-] mice. Serum PTH levels were moderately but significantly increased in the PT-[VDR.sup.-/-] mice with normal serum calcium levels. The sensitivity of the parathyroid glands of the PT-[VDR.sup.-/-] mice to calcium was intact as measured by serum PTH levels after changes in serum calcium. This indicates that the reduced CaR in the PT-[VDR.sup.-/-] mice enables a physiologic response to serum calcium. Serum C-terminal collagen crosslinks, a marker of bone resorption, were increased in the PT-[VDR.sup.-/-] mice with no change in the bone formation marker, serum osteocalcin, consistent with a resorptive effect due to the increased serum PTH levels in the PT-[VDR.sup.-/-] mice. Therefore, deletion of the VDR specifically in the parathyroid decreases parathyroid CaR expression and only moderately increases basal PTH levels, suggesting that the VDR has a limited role in parathyroid physiology. serum calcium; calcium homeostasis; secondary hyperparathyroidism; calcium receptor; parathyroid hormone doi: 10.1152/ajprenal.00360.2009.

Potential long-term negative effects of increased vitamin D consumption are not thoroughly examined. The aim of this study was to investigate possible negative effects of vitamin D supplementation on serum lipids and lipoproteins. A 1-year long randomised double-blinded placebo-controlled intervention study with two doses of vitamin D3 (10 and 20 [micro]g/day) was carried out among 89 women (18-53 years of age) and 84 men (18-64 years of age) of Pakistani origin living in Denmark with low vitamin D status. This study did not find changes in total cholesterol, LDL-cholesterol, HDL-cholesterol, LDL-cholesterol/ HDL-cholesterol ratio, VLDL-cholesterol and triacylglycerol after daily supplementation with 10 or 20 [micro]g vitamin D for 1 year. In conclusion, increasing the vitamin D intake by 10-20 [micro]g per day for 1 year is safe for Pakistani immigrants with regards to serum lipids and lipoproteins. doi:10.1038/ejcn.2009.18; published online 8 April 2009 Keywords: vitamin D supplementation; HDL-cholesterol; LDL-cholesterol; total cholesterol; triacylglycerol; Pakistani immigrants, Introduction Increasing vitamin D intake through fortification and/or supplementation to groups in risk of deficiency is topical in most European countries. Presently, the tolerable upper intake level is set to [...]

While recent laboratory-based studies have substantially advanced our understanding of the action of vitamin D in the brain, much is still unknown concerning how vitamin D relates to mood. The few epidemiological studies of vitamin D and depression have produced inconsistent results and generally have had substantial methodological limitations. Recent findings from a randomized trial suggest that high doses of supplemental vitamin D may improve mild depressive symptoms, but important questions persist concerning how vitamin D may affect monoamine function and hypothalamic-pituitary-adrenal axis response to stress, whether vitamin D supplementation can improve mood in individuals with moderate-to-severe depression, and whether vitamin D sufficiency is protective against incident depression and recurrence. At this time, it is premature to conclude that vitamin D status is related to the occurrence of depression. Additional prospective studies of this relationship are essential.

ABSTRACT Psoriasis affects more than 5 million adults in the United States (U.S.), causing significant impairments in quality of life and incurring substantial costs in treatment. The disease is characterized [...]

Background. The objective of this study was to examine the association between 25-hydroxyvitamin D, 25(OH)D, and cognitive function. Methods. A cross-sectional investigation of 25(OH)D and cognition was completed in 377 black and 703 non-black (mainly Caucasian) elders (65-99 years) participating in the nutrition and memory in elders study. Participants underwent a comprehensive neuropsychological battery, and 25(OH)D concentrations were obtained. Results. More than 65% of elders had suboptimal 25(OH)D concentrations ([less than or equal to]20 ng/mL or [less than or equal to]50 nmol/L). Approximately 18% were deficient in 25(OH)D (< 10 ng/mL or 20 ng/mL were associated with better performance on tests of executive function, including trails A (80.5 vs 95, p < .05), trails B (205s vs 226s, p < .05), matrix reasoning (7.8 vs 7.0, p = .03), and digit symbol (31.5 vs 37, p < .01). There were no associations between 25(OH)D and memory tests. Factor analysis yielded factors for memory, executive function, and attention/ processing speed. Alter adjustment, 25(OH)D was associated with the executive function ([beta] = 0.01, p < 0.01) and attention/ processing speed factors ([beta] = 0.01, p = .03), but not the memory factor ([beta] = -0.001, p = 0.65). Conclusions. 25(OH)D was positively associated with cognitive performance, particularly with measures of executive function in this elderly population. Key Words: Cognitive function--Vitamin D--Elderly people--Dementia.

The active vitamin D metabolite 1[alpha],25-dihydroxyvitamin [D.sub.3] [1[alpha],25[(OH).sub.2][D.sub.3] has wide but not fully understood antitumor activity. A previous transcriptomic analysis of 1[alpha],25[(OH).sub.2][D.sub.3] action on human colon cancer cells revealed cystatin D (CST5), which encodes an inhibitor of several cysteine proteases of the cathepsin family, as a candidate target gene. Here we report that 1[alpha],25[(OH).sub.2][D.sub.3] induced vitamin D receptor (VDR) binding to, and activation of, the CST5 promoter and increased CST5 RNA and protein levels in human colon cancer cells. In cells lacking endogenous cystatin D, ectopic cystatin D expression inhibited both proliferation in vitro and xenograft tumor growth in vivo. Furthermore, cystatin D inhibited migration and anchorage-independent growth, antagonized the Wnt/[beta]-catenin signaling pathway, and repressed c-MYC expression. Cystatin D repressed expression of the epithelial-mesenchymal transition inducers SNAI1, SNAI2, ZEB1, and ZEB2 and, conversely, induced E-cadherin and other adhesion proteins. CST5 knockdown using shRNA abrogated the antiproliferative effect of 1[alpha],25[(OH).sub.2][D.sub.3], attenuated E-cadherin expression, and increased c-MYC expression. In human colorectal tumors, expression of cystatin D correlated with expression of VDR and E-cadherin, and loss of cystatin D correlated with poor tumor differentiation. Based on these data, we propose that CST5 has tumor suppressor activity that may contribute to the antitumoral action of 1[alpha],25[(OH).sub.2][D.sub.3] in colon cancer., Introduction There is an increasing interest in the active vitamin D metabolite 1[alpha],25-dihydroxyvitamin [D.sub.3] [1[alpha],25[(OH).sub.2][D.sub.3] and its analogs as preventive and therapeutic anticancer agents, and a number of clinical trials [...]

Background. Calcium and vitamin D (CaD) supplementation trials including the Women's Health Initiative (WHI) trial of CaD have shown nonsignificant reductions in total mortality. This report examines intervention effects on total and cause-specific mortality by age and adherence. Methods. The WHI CaD trial was a randomized, double-blind, placebo-controlled trial that enrolled 36,282 postmenopausal women aged 51-82 years from 40 U.S. clinical centers. Women were assigned to 1,000 mg of elemental calcium carbonate and 400 IU of vitamin [D.sub.3] daily or placebo with average follow-up of 7.0 years. Results. The hazard ratio (HR) for total mortality was 0.91 (95% confidence interval [CI], 0.83-1.01) with 744 deaths in women randomized to CaD versus 807 deaths in the placebo group. HRs were in the direction of reduced risk but nonsignificant for stroke and cancer mortality, but near unity for coronary heart disease and other causes of death. HRs for total mortality were 0.89 in the 29,942 women younger than 70 years (95% CI, 0.79-1.01) and 0.95 in the 6,340 women aged 70 and older (95% CI, 0.80 1.12; p value for age interaction =. 10). No statistically significant interactions were observed for any baseline characteristics. Treatment effects did not vary significantly by season. Conclusions. In the WHI CaD trial, supplementation did not have a statistically significant effect on mortality rates bur the findings support the possibility that these supplements may reduce mortality rates in postmenopausal women. These data can neither support nor refute recommendations for higher dose vitamin D supplementation to reduce cancer or total mortality. Key Words: Calcium--Vitamin D--Mortality--Cause-specific mortality Women's Health Initiative.

Tuberculosis is highly prevalent worldwide, accounting for nearly two million deaths annually. Vitamin D influences the immune response to tuberculosis, and vitamin D deficiency has been associated with increased tuberculosis risk in different populations. Genetic variability may influence host susceptibility to developing active tuberculosis and treatment response. Studies examining the association between genetic polymorphisms, particularly the gene coding for the vitamin D receptor (VDR), and TB susceptibility and treatment response are inconclusive. However, sufficient evidence is available to warrant larger epidemiologic studies that should aim to identify possible interactions between VDR polymorphisms and vitamin D status.

Our goal in this cross-sectional study was to investigate the influence of low-vitamin D status on bone mass, bone turnover, and muscle strength in 301 healthy Chinese adolescent girls. Blood plasma 25-hydroxyvitamin D [25(OH)D] was measured by RIA and plasma and urine biomarkers of bone turnover were measured. Bone mineral content (BMC) and density and bone area for the whole body and the distal and proximal forearm were measured by dual energy X-ray absorptiometry. When vitamin D deficiency was defined as a serum 25(OH)D concentration of [less than or equal to] 50 nmol/L and severe deficiency as

Background/Objectives: Vitamin D is required for bone growth and normal insulin secretion. Maternal hypovitaminosis D may impair fetal growth and increase the risk of gestational diabetes. We have related maternal vitamin D status in pregnancy to maternal and newborn glucose and insulin concentrations, and newborn size, in a South Indian population. Subjects/Methods: Serum 25 hydroxy vitamin D (25(OH)D) concentrations, glucose tolerance, and plasma insulin, proinsulin and 32-33 split proinsulin concentrations were measured at 30 weeks gestation in 559 women who delivered at the Holdsworth Memorial Hospital, Mysore. The babies&apos; anthropometry and cord plasma glucose, insulin and insulin precursor concentrations were measured. Results: In total 66% of women had hypovitaminosis D (25(OH)D concentrations Conclusions: Hypovitaminosis D at 30 weeks gestation is common in Mysore mothers. It is not associated with an increased risk of gestational diabetes, impaired fetal growth or altered neonatal cord plasma insulin secretory profile. doi:10.1038/ejcn.2008.14; published online 20 February 2008 Keywords: vitamin D; prenatal nutrition; pregnancy outcome; birth weight; India; gestational diabetes, Introduction The best-known function of vitamin D is the maintenance of calcium homeostasis through its actions on phosphate and calcium handling in the intestine, kidney and bone. Vitamin D is [...]

Background/Objective: To study whether a free supply of vitamin [D.sub.2] drops to 6-week-old infants together with tailor-made information handouts improves the vitamin D status after 7 weeks in the intervention group compared to a control group. Subjects/Methods: In this cluster randomized controlled trial in eight child health clinics in Oslo, Norway, 66 healthy infants with Pakistani, Turkish or Somali background were included. The intervention group received daily supplementation of vitamin D drops containing 10 [micro]g (400 IU) of ergocalciferol (vitamin [D.sub.2]) with a tailor-made information brochure about vitamin D and its sources, and instruction on how to administer the drops. They were compared to a control group receiving usual care. The principal outcome measure was increase in serum 25-hydroxyvitamin D (S-25OHD) 7 weeks later. S-25OHD was analyzed by high-performance liquid chromatography-ultraviolet-mass spectrometry. Results: Total 78% (n=51) of the included infants completed the stud. At follow-up, S-25OHD was significantly higher in the intervention group than in the control group (93.5 versus 72.7 [nmoll.sup.-1], P=0.03). The mean increase in S-25OHD adjusted for baseline was 28 [nmoll.sup.-1] (95% confidence interval 10.9-45.2, P=0.002) higher in the intervention group than in the control group. Among exclusively breastfed infants at baseline, S-25OHD increased by 32.3 [nmoll.sup.-1] (P=0.035) in the intervention group compared to control group. Conclusion: Free supply of vitamin D drops to 6-week-old infants together with tailor-made information handouts significantly improved the vitamin D status of infants with immigrant background compared to usual care. Keywords: vitamin D deficiency; breastfeeding; immigrants; infants; 25-hydroxyvitamin D; randomized controlled trial doi: 10.1038/sj.ejcn.1602982; published online 30 January 2008, Introduction Small children grow fast and have a high demand of calcium to build their skeleton. An association has recently been reported between maternal vitamin D status during pregnancy and [...]

The active form of vitamin D, 1[alpha], 25-dihydroxyvitamin [D.sub.3] [1,25[(OH).sub.2][D.sub.3]], suppresses disease development in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). However, complete disease prevention only occurs with doses that dramatically elevate serum calcium levels, thus limiting the usefulness of 1,25[(OH).sub.2][D.sub.3] as a potential MS therapeutic agent. Because calcitonin (CT) is believed to be released by hypercalcemia and has been shown to be anti-inflammatory, we examined whether suppression of EAE by 1,25[(OH).sub.2][D.sub.3] could be mediated either in part or entirely by CT. Continuous administration of pharmacological doses of CT did not prevent EAE. However, a combination of CT and a subtherapeutic dose of 1,25[(OH).sub.2][D.sub.3] additively suppressed EAE without causing hypercalcemia. Moreover, CT decreased the dose of 1,25[(OH).sub.2][D.sub.3] required for disease suppression. Our results suggest that CT may be a significant factor but cannot account entirely for 1,25[(OH).sub.2][D.sub.3]-mediated suppression of EAE. calcium | calcium homeostasis | immune system | multiple sclerosis | vitamin D

The consumption of calcium, vitamin D, and dairy products may be associated with a reduced risk of type 2 diabetes mellitus. However, whether this reduction is due to calcium, vitamin D, or other components of dairy products is not clear. We examined intakes of total calcium and vitamin D, and plasma concentrations of 25 hydroxyvitamin D [25(OH)D] in relation to fasting plasma concentrations of C-peptide in 2 cross-sectional studies among healthy men from the Health Professionals Follow-up Study and among healthy women from the Nurses' Health Study f. Intake of total calcium was modestly inversely associated with C-peptide concentration in women (P-trend = 0.05); however, the inverse association was not significant in men (P = 0.7). Concentrations of C-peptide were 20% lower among men who had plasma concentrations of 25(OH)D in the highest quartile compared with those in the lowest quartile (P-trend = 0.08); there was no association in women (P = 0.3). The inverse association between calcium intake and the plasma C-peptide concentration was stronger in hypertensive individuals of both sexes. The difference in the C-peptide concentrations between extreme quartiles of calcium intake was 17% in men and 20% in women. Plasma concentrations of C-peptide for the combination of the highest tertiles of calcium intake and plasma 25(OH)D compared with the opposite extreme were 35% lower (P = 0.03) in men and 12% lower (P = 0.01) in women. The results suggest that calcium intake or systemic vitamin D status, after adjustment for intake of dairy products, is associated with decreased insulin secretion.

We examined the cross-sectional association between plasma 25-hydroxyvitamin D [25(OH)D] and markers of the insulin resistant phenotype. Plasma 25(OH)D concentrations were measured in 808 nondiabetic participants of the Framingham Offspring Study. Outcome measures included fasting and 2-h post 75-g oral glucose tolerance test (OGTT) glucose and insulin; these were used to calculate the homeostatic model assessment-insulin resistance (HOMA IR) and insulin sensitivity index ([ISI.sub.0,120]). We also measured plasma adiponectin, triacylglycerol, and HDL cholesterol concentrations as markers of the insulin-resistant phenotype. After adjusting for age, sex, BMI, waist circumference, and current smoking status, plasma 25(OH)D concentration was inversely associated with fasting plasma glucose and insulin concentrations, and HOMA-IR. Compared with the participants in the lowest tertile category of plasma 25(OH)D, those in the highest tertile category had a 1.6% lower concentration of fasting plasma glucose (P-trend = 0.007), 98% lower concentration of fasting plasma insulin (P-trend = 0.001), and 12.7% lower HOMA-I R score (P-trend < 0.001). After adjusting for age and sex, plasma 25(OH)D was positively associated with [ISI.sub.0,120], plasma adiponectin, and HDL cholesterol and inversely associated with plasma triacylglycerol, but these associations were no longer significant after further adjustment for BMI, waist circumference, and current smoking status. 25(OH)D and 2-h post-OGTT glucose were not associated. Among adults without diabetes, vitamin D status was inversely associated with surrogate fasting measures of insulin resistance. These results suggest that vitamin D status may be an important determinant for type 2 diabetes mellitus.

Background. Although both vitamin D (25-hydroxyvitamin D [25(OH)D]) insufficiency and the frailty syndrome are more prevalent in women than men, sex-specific associations have not been explored. We estimated sex-specific associations of low 25(OH)D with frailty. Vitamin D insufficiency can result in hyperparathyroidism, and thus, parathyroid hormone (PTH) was explored as a potential mediator in the relationship between 25(OH)D levels and frailty. Methods. The sample included 444 male and 561 female participants aged 65 years and older from the InCHIANTI study for whom 25(OH)D levels and frailty information were available. Frailty was defined as the presence of at least three of the five following criteria: slowness, weakness, low energy expenditure, exhaustion, and weight loss. Logistic regression models estimated the association between serum levels of 25(OH)D and PTH with frailty, controlling for potential confounders. Results. Independent of covariates, men with 25(OH)D Conclusions. Vitamin D insufficiency was associated with frailty in men, but not in women. Results suggest that PTH mediates the relationship between 25(OH)D and nonenergy expenditure aspects of frailty. Key Words: Vitamin D--Frailty syndrome--Parathyroid hormone--InCHIANTI.

The authors analyzed data from the Women's Health Initiative (WHI) Calcium and Vitamin D Supplementation Trial (CAD) to learn more about factors affecting adherence to clinical trial study pills (both active and placebo). Most participants (36,282 postmenopausal women aged 50-79 years) enrolled in CaD 1 year after joining either a hormone trial or the dietary modification trial of WHI. The WHI researchers measured adherence to study pills by weighing the amount of remaining pills at an annual study visit; adherence was primarily defined as taking [greater than or equal to] 80% of the pills. The authors in this study examined a number of behavioral, demographic, procedural, and treatment variables for association with study pill adherence. They found that relatively simple procedures (ie, phone contact early in the study [4 weeks post randomization] and direct social contact) later in the trial may improve adherence. Also, at baseline, past pill-use experiences, personal supplement use, and relevant symptoms may be predictive of adherence in a supplement trial. Index Terms: adherence, calcium supplementation, clinical trial, women, In the Women's Health Initiative (WHI) Calcium and Vitamin D Supplementation Trial (CAD), an intention-to-treat analysis showed that active treatment did not significantly reduce hip fracture, which was the primary [...]

Specific pathogen-free IL-10 KO mice failed to develop inflammatory bowel disease (IBD), whereas IL-10/vitamin D receptor (VDR) double KO mice developed fulminating IBD. WT CD4 T cells inhibited experimental IBD, while VDR KO CD4 T cells failed to suppress IBD. VDR KO mice had normal numbers and functions of regulatory T cells. The percentages of IL-17- and IFN-[gamma]-secreting T cells in the gut of mice reconstituted with WT and VDR KO CD4 T cells were also not different. Instead, there were twice as many CD8[alpha][alpha] intraepithelial lymphocytes (IEL) in mice that were reconstituted with WT CD4 T cells than in mice reconstituted with VDR KO CD4 T cells. Furthermore, VDR KO mice had reduced numbers of CD8[alpha][alpha] IEL, absent CD4/CD8[alpha][alpha] populations, and as a result low IL-10 production in the IEL. The lack of CD8[alpha][alpha] IEL was due in part to decreased CCR9 expression on T cells that resulted in the failure of the VDR KO T cells to home to the small intestine. We conclude that the VDR mediates T cell homing to the gut and as a result the VDR KO mouse has reduced numbers of CD8[alpha][alpha] IEL with low levels of IL-10 leading to increased inflammatory response to the normally harmless commensal flora. inflammatory bowel disease | mucosal immunity | regulatory T cell

The classic role of vitamin D has involved its function in calcium metabolism. However, a much broader perspective of the importance of vitamin D is now emerging. Therefore, a new approach is needed based on a combination of molecular biological, physiological, and clinical/epidemiological studies. The remarkable range of the effects of vitamin D relates to our new understanding of both the role of the vitamin D receptor and analyses of what might be considered an optimum vitamin D status in populations exposed to very different diets and levels of sun exposure. Assessing the breadth of the current approaches was the basis of the 22nd Marabou Symposium that took place in Stockholm in June 2007.

Sunlight provides most humans with their vitamin D requirement. Adequate vitamin [D.sub.3] by synthesis in the skin or from dietary and supplemental sources is essential for bone health throughout life. Vitamin D deficiency is defined as a 25(OH)D concentration < 20 ng/mL (50 nmol/L); vitamin D sufficiency as a 25(OH)D > 30 ng/mL (75 nmol/L), and insufficiency as 21-29 ng/mL. Vitamin D deficiency and insufficiency has been linked to a wide variety of chronic diseases including common cancers, autoimmune, cardiovascular, and infectious diseases. Healthcare professionals need to be aware of the vitamin D deficiency pandemic. Guidelines for sensible sun exposure and supplemental vitamin D of 800-1000 IU/day are needed.

The functional status indicator for vitamin D, for both safety and efficacy, is serum 25-hydroxyvitamin D concentration. Efficacy for several health endpoints requires levels of 80 nmol/L or higher. Toxicity occurs at levels of 500 nmol/L or higher. The input needed for efficacy, in addition to typical food and cutaneous inputs, will usually be 1000-2000 IU/day of supplemental cholecalciferol. Toxicity is associated only with excessive supplemental intake (usually well above 20,000 IU/day).

Target intakes of vitamin D to prevent rickets and osteomalacia are difficult to estimate because of the dual sources of vitamin D with dermal production and absorption from the intestine. However, vitamin D deficiency is associated with other diseases, e.g., myopathy, falls, fractures, autoimmune disorders, cardiovascular diseases, and malignancies, which underlines the necessity of redefining recommendations. A plasma level of 25-hydroxyvitamin D (250HD)

The development of our understanding of the function of vitamin D from its discovery in the second and third decades of the 20th century to its hormonal activation of its nuclear receptor and to its present position of an important factor in public health has been traced. The key discoveries of the conversion of vitamin D to its hormonal form, its regulation, and the evolving picture of its molecular mechanism of action are presented. The recognition of its role beyond mineralization of the skeleton to its role in skin, the immune system, and its protective role in some forms of malignancy represent more recent developments. The evolution of derivatives of 1[alpha], 25-dihydroxyvitamin [D.sub.3] as therapeutic agents suggests a richness of therapeutic potential. All of this nevertheless illustrates that much more remains to be discovered and applied to our armaments for preventing and treating disease.

Vitamin D has pleiotropic effects that go beyond its traditional role in calcium homeostasis. Hundreds of genes with vitamin D receptor response elements directly or indirectly influence cell cycling and proliferation, differentiation, and apoptosis. Vitamin D compounds also have effects on cell function that are nongenomic. The noncalcemic actions of vitamin D influence normal and pathological cell growth, carcinogenesis, immune function, and cardiovascular physiology. This review examines many of the various mechanisms by which vitamin D alters cellular growth and differentiation and explores cell-specific factors that influence responsiveness to vitamin D.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jada.2008.06.432 Byline: Robert L. Brunner, Barbara Cochrane, Rebecca D. Jackson, Joseph Larson, Cora Lewis, Marian Limacher, Milagros Rosal, Sally Shumaker, Robert Wallace Abstract: The Women's Health Initiative (WHI) randomized trial of calcium/vitamin D supplementation found reduced bone loss with active treatment compared to placebo. Now we examine whether the treatment affected self-reported physical functioning and objective measures of physical functioning. Article History: Accepted 25 March 2008

Objective: To describe the vitamin D status of women living in two Asian cities,--Jakarta (6[degrees]S) and Kuala-Lumpur (2[degrees]N), to examine the association between plasma 25-hydroxyvitamin D and parathyroid hormone (PTH) [...]

Rickets, the state of vitamin D deficiency, has reemerged as a potential problem in the United States. At the dawn of the 20th century, rickets was pervasive among infants residing in the polluted cities of Europe and the northeastern United States. Important milestones in the history of rickets were the understanding that photosynthesized vitamin D and dietary vitamin D were similar, the discernment of the antirachitic potency of artificial and natural ultraviolet rays, and the discovery that ultraviolet irradiation could render various foods antirachitic. Clinical guidelines were instituted to promote sensible exposure to sunlight and artificial ultraviolet radiation. In addition, irradiated ergosterol from yeast became the major vitamin D source for food fortification and the treatment of rickets, leading to a public health campaign to eradicate rickets by the 1930s. We review the sequence and turn of events pertaining to the discovery of vitamin D and the strategies for the eradication of the reemerging rickets problem. (Am J Public Health. 2007; 97: 1740-1748. doi:10.2105/AJPH.2006.091736)

BACKGROUND: Inadequate sun exposure and dietary vitamin D intake can result in vitamin D insufficiency. However, limited data are available on actual vitamin D status and predictors in healthy individuals in different regions and by season. METHODS: We compared vitamin D status [25-hydroxyvitamin D; 25(OH)D] in people < 60 years of age using data from cross-sectional studies of three regions across Australia: southeast Queensland (27[degrees]S; 167 females and 211 males), Geelong region (38[degrees]S; 561 females), and Tasmania (43[degrees]S; 432 females and 298 males). RESULTS: The prevalence of vitamin D insufficiency ([less than or equal to] 50 nmol/L) in women in winter/spring was 40.5% in southeast Queensland, 37.4% in the Geelong region, and 67.3% in Tasmania. Season, simulated maximum daily duration of vitamin D synthesis, and vitamin D effective daily dose each explained around 14% of the variation in 25(OH)D. Although latitude explained only 3.9% of the variation, a decrease in average 25(OH)D of 1.0 (95% confidence interval, 0.7-1.3) nmol/L for every degree increase in latitude may be clinically relevant. In some months, we found a high insufficiency or even deficiency when sun exposure protection would be recommended on the basis of the simulated ultraviolet index. CONCLUSION: Vitamin D insufficiency is common over a wide latitude range in Australia. Season appears to be more important than latitude, but both accounted for less than one-fifth of the variation in serum 25(OH)D levels, highlighting the importance of behavioral factors. Current sun exposure guidelines do not seem to fully prevent vitamin D insufficiency, and consideration should be given to their modification or to pursuing other means to achieve vitamin D adequacy. KEY WORDS: 25(OH)D, behavior, latitude, UV index, UVR, vitamin D, vitamin D index. Environ Health Perspect 115:1132-1139 (2007). doi:10.1289/ehp.9937 available via http://dx.doi.org/ [Online 17 April 2007], Most (90-100%) vitamin D is produced endogenously following solar ultraviolet radiation (UVR) of precursors within sun-exposed skin (Holick 1994). Only a few foods, such as oily fish, contain significant amounts [...]

ABSTRACT Background Vitamin D insufficiency is a common public health problem nationwide. Circulating 25-hydroxyvitamin [D.sub.3] (25[OH]D), the most commonly used index of vitamin D status, is converted to the active [...]

An essential element of the innate immune response to injury is the capacity to recognize microbial invasion and stimulate production of antimicrobial peptides. We investigated how this process is controlled [...]

In utero or early-life vitamin D deficiency is associated with skeletal problems, type 1 diabetes, and schizophrenia, but the prevalence of vitamin D deficiency in U.S. pregnant women is unexplored. We sought to assess vitamin D status of pregnant women and their neonates residing in Pittsburgh by race and season. Serum 25-hydroxyvitamin D (25(OH)D) was measured at 4-21 wk gestation and predelivery in 200 white and 200 black pregnant women and in cord blood of their neonates. Over 90% of women used prenatal vitamins. Women and neonates were classified as vitamin D deficient [25(OH)D 80 nmol/L]. At delivery, vitamin D deficiency and insufficiency occurred in 29.2% and 54.1% of black women and 45.6% and 46.8% black neonates, respectively. Five percent and 42.1% of white women and 9.7% and 56.4% of white neonates were vitamin D deficient and insufficient, respectively. Results were similar at

A prospective study investigates whether levels of 25-hydroxyvitamin D, a good marker of vitamin D availability to tissues, are associated with risk of multiple sclerosis (MS). Results suggest that high serum levels of 25-hydroxyvitamin D are associated with a lower risk of multiple sclerosis.

Genomic actions induced by 1[alpha]25-dihydroxyvitamin [D.sub.3] [1,25[(OH).sub.2] [D.sub.3]] are crucial for normal bone metabolism, mainly because they regulate active intestinal calcium transport. To evaluate whether the vitamin D receptor (VDR) [...]

The major circulating form of vitamin D is 25-hydroxycholecalciferol [25(OH)D3], which is delivered to target tissues in complex with the serum vitamin D binding protein (DBP). We recently observed that mammary cells can metabolize 25(OH)D3 to 1,25-dihydroxycholecalciferol [1,25[(OH).sub.2]D3], the vitamin D receptor (VDR) ligand, and the objective of our study was to elucidate the mechanisms by which the 25(OH)D3-DBP complex is internalized by mammary cells prior to metabolism. Using fluorescent microscopy and temperature-shift techniques, we found that T-47D breast cancer cells rapidly internalize DBP via endocytosis, which is blunted by receptor-associated protein, a specific inhibitor of megalinmediated endocytosis. Endocytosis of DBP was associated with activation of VDR by 25(OH)D3 but not 1,25[(OH).sub.2]D3 (as measured by induction of the VDR target gene, CYP24). We also found that megalin and its endocytic partner, cubilin, are coexpressed in normal murine mammary tissue, in nontransformed human mammary epithelial cell lines, and in some established human breast cancer cell lines. To our knowledge, our studies are the first to demonstrate that mammaryderived cells express megalin and cubilin, which contribute to the endocytic uptake of 25(OH)D3-DBP and activation of the VDR pathway.

OBJECTIVES. Previous studies of vitamin D status in pediatric patients with inflammatory bowel disease have revealed conflicting results. We sought to report (1) the prevalence of vitamin D deficiency (serum 25-hydroxy-vitamin D concentration [less than or equal to] 15 ng/mL) in a large population with inflammatory bowel disease, (2) factors predisposing to this problem, and (3) its relationship to bone health and serum parathyroid hormone concentration. PATIENTS AND METHODS. A total of 130 patients (8-22 years of age) with inflammatory bowel disease, 94 with Crohn disease and 36 with ulcerative colitis, had serum 25-hydroxy-vitamin D, intact parathyroid hormone, and lumbar spine bone mineral density (using dual-energy x-ray absorptiometry) measured at Children&apos;s Hospital Boston. RESULTS. The prevalence of vitamin D deficiency was 34.6%. Mean serum 25-hydroxy-vitamin D concentration was similar in patients with Crohn disease and ulcerative colitis, 52.6% lower among patients with dark skin complexion, 33.4% lower during the winter months (December 22 to March 21), and 31.5% higher among patients who were taking vitamin D supplements. Serum 25-hydroxy-vitamin D concentration was positively correlated with weight and BMI z score, disease duration, and serum albumin concentration and negatively correlated with erythrocyte sedimentation rate. Patients with Crohn disease and upper gastrointestinal tract involvement were more likely to be vitamin D deficient than those without it. Serum 25-hydroxy-vitamin concentration was not associated with lumbar spine bone mineral density z score or serum parathyroid hormone concentration. CONCLUSIONS. Vitamin D deficiency is highly prevalent among pediatric patients with inflammatory bowel disease. Factors predisposing to the problem include having a dark-skin complexion, winter season, lack of vitamin D supplementation, early stage of disease, more severe disease, and upper gastrointestinal tract involvement in patients with Crohn disease. The long-term significance of hypovitaminosis D for this population is unknown at present and merits additional study. Key Words vitamin D deficiency, 25-hydroxy vitamin D, inflammatory bowel disease, pediatric, bone mineral density, parathyroid hormone Abbreviations 250HD--25-hydroxy-vitamin D BMD--bone mineral density IBD--inflammatory bowel disease CD--Crohn disease UC--ulcerative colitis UGI--upper gastrointestinal tract LSBMD--lumbar spine bone mineral density PTH--parathyroid hormone ESR--erythrocyte sedimentation rate DXA--dual-energy x-ray absorptiometry GCRC--General Clinical Research Center zLSBMD--z score of lumbar spine bone mineral density zWt--z score of weight zHt--score of height zBMI--z score of BMI OR--odds ratio CI--confidence interval DBP--vitamin D-binding protein, VITAMIN D IS essential for bone mineralization throughout life. Severe deficits cause rickets in children (1) and osteomalacia in adults. (2) 25-Hydroxy-vitamin D (25OHD) is the most abundant metabolite of [...]

The 2005 Dietary Guidelines for Americans recommend that older adults, people with dark skin, and those exposed to insufficient ultraviolet radiation (i.e., sunlight) consume extra vitamin D from vitamin D-fortified foods and/or supplements. Individuals in these high-risk groups should consume 25 [micro]g (1000 IU) of vitamin D daily to maintain adequate blood concentrations of 25-hydroxyvitamin D, the biomarker, for vitamin D status. This review considers recommendations for vitamin D-rich foods and dietary supplements, as well as specific problems with self-prescribing sun exposure or artificial sources of ultraviolet radiation to meet the vitamin D recommendations for older people. Key words: aging, Dietary Guidelines for Americans, older adults, sunlight, supplements, vitamin D doi: 10.1301/nr.2006.sept.410- 421