Vitamin D status: effects on parathyroid hormone and 1, 25-dihydroxyvitamin D in postmenopausal women

BACKGROUND: Low serum 25-hydroxyvitamin D ?25(OH)D concentrations are commonly found in the elderly and are associated with hip fracture. Treatment with vitamin D and calcium can reduce the risk of fracture. The relation between the rise in parathyroid hormone (PTH) with age and the decrease in 25(OH)D is not clear. Neither is there any consensus on the serum concentration of 25(OH)D required for bone health. OBJECTIVE: Our objective was to study the relations between serum PTH, serum vitamin D metabolites, and other calcium-related variables in postmenopausal women. DESIGN: This was a cross-sectional study of 496 postmenopausal women without vertebral fractures attending our menopausal osteoporosis clinics. RESULTS: PTH was significantly positively related to age and serum 1, 25-dihydroxyvitamin D ?1,25(OH)(2)D and inversely related to 25(OH)D and plasma ionized calcium. There was a step-like increase in PTH as serum 25(OH)D fell below 40 nmol/L. In women with 25(OH)D concentrations >40 nmol/L, 1,25(OH)(2)D was positively related to 25(OH)D; in women with 25(OH)D concentrations 40 nmol/L, 1,25(OH)(2)D was most closely (inversely) related to plasma creatinine. Therefore, with serum 25(OH)D concentrations increasingly <40 nmol/L, serum 1,25(OH)(2)D becomes critically dependent on rising concentrations of PTH. CONCLUSION: The data suggest that aging women should maintain 25(OH)D concentrations >40 nmol/L (which is the lower limit of our normal range for healthy young subjects) for optimal bone health.     

Vitamin D status in kidney transplant patients: need for intensified routine supplementation

BACKGROUND: A high prevalence of vitamin D insufficiency has been found in the general population and in patients with chronic kidney disease. OBJECTIVE: The aim was to examine vitamin D status and determinants and metabolic correlates of serum 25-hydroxyvitamin D in a population of adult Danish kidney transplant patients. DESIGN: This was a cross-sectional study of 173 adult kidney transplant patients with a mean (+/-SD) age of 53.4 +/- 11.7 y and a median graft age of 7.4 y (interquartile range: 3.3-12.7 y). Serum concentrations of intact parathyroid hormone (S-PTH), 25-hydroxyvitamin D [S-25(OH)D], and 1,25-dihydroxyvitamin D [S-1,25(OH)(2)D] were measured. Dietary and supplementary intake of vitamin D, avoidance of solar ultraviolet B exposure, and selected lifestyle factors were assessed in a subgroup (n = 97). RESULTS: Fifty-one percent of the patients had vitamin D insufficiency [S-25(OH)D 40-75 nmol/L], and an additional 29% had moderate-to-severe vitamin D deficiency [S-25(OH)D < or = 39 nmol/L]. In multiple regression analysis, sun avoidance (negative association) and vitamin D supplementation (positive association) were independent determinants of S-25(OH)D concentrations. Low S-25(OH)D concentrations were associated with 1) increased S-PTH concentrations (P = 0.0002), independently of S-1,25(OH)(2)D concentrations, and 2) decreased S-1,25(OH)(2)D concentrations (P = 0.002), independently of graft function. CONCLUSIONS: Hypovitaminosis D is common among Danish kidney transplant patients and is associated with reduced concentrations of S-1,25(OH)(2)D and increased S-PTH concentrations. Sun avoidance and vitamin D supplementation are important determinants of vitamin D status. The observed hypovitaminosis D might be corrected by intensified routine vitamin D supplementation as opposed to the current supplementation practice.     

Relationship of calcium absorption with 25(OH)D and calcium intake in children with rickets

Nutritional rickets has long been considered a disease caused by vitamin D deficiency, but recent data indicate that inadequate dietary calcium intake is an important cause of rickets, particularly in tropical countries. Children with rickets due to calcium deficiency do not have very low 25(OH)D concentrations, and serum 1,25(OH)(2) D values are markedly elevated. Studies of Nigerian children with rickets demonstrated they have high fractional calcium absorption. A high-phytate diet was demonstrated to increase calcium absorption compared with the fasting state, and enzymatic dephytinization did not significantly improve calcium absorption. When given vitamin D, children with rickets have a marked increase in 1,25(OH)(2) D concentrations without any change in fractional calcium absorption. No positive relationship was found between fractional calcium absorption and serum 25(OH)D concentrations in children on low-calcium diets. More research is needed to understand the interaction between calcium and vitamin D and the role of vitamin D in calcium absorption.     

Vitamin D insufficiency in obese patients with severe mental illness taking olanzapine

The purpose of the study was to assess the vitamin D status of obese patients with severe mental illness (SMI) treated with olanzapine. Fifteen obese SMI patients treated with olanzapine were pair-matched with healthy obese subjects. Another 52 overweight and obese SMI patients volunteered to participate in the study (total n?=?67) and were divided into three subgroups (group A?=?overweight, group B?=?obese, group C?=?severely obese). Anthropometric, body composition, blood glucose, lipids, 25(OH)D, intact parathyroid hormone, and calcium measurements were performed. No differences were found between healthy and SMI subjects in any of the dependent variables (p?>?0.05). The obese and severely obese patients demonstrated significantly lower levels of serum 25(OH)D concentration (p?<?0.01) compared with overweight. A significant inverse correlation was found between serum 25(OH)D concentration and all anthropometric parameters (p?<?0.05). The results indicate that obese SMI patients appear to be vitamin D deficient, similar to healthy obese subjects. The level of obesity seems to play a significant role in their vitamin D status: the greater the body fat of the patients the lower the serum 25(OH)D concentration. Thus, as in healthy individuals, an inverse association exists between the degree of adiposity and the serum 25(OH)D concentration in SMI patients     

Serial ultraviolet B exposure and serum 25 hydroxyvitamin D response in young adult American blacks and whites: no racial differences

We tested the hypothesis that repeated whole body suberythemal ultraviolet B (UVB) exposure would result in less increase of serum 25-hydroxyvitamin D (25OHD) concentrations in black compared with white young adults with no significant change or racial differences in serum calciotropic hormones concentrations. Thirteen white and 7 black adults ranging from 22 to 35 years of age were submitted to sequential total body suberythemal doses of UVB (280-315 nm) biweekly for 6 weeks. Initial UVB dose was 5% below the minimal erythemal dose for the most sensitive skin, followed by 10% increase per exposure for 4 weeks. Blood samples were drawn weekly. Baseline 25OHD concentrations were significantly lower in blacks compared to whites, but the increases in serum 25OHD concentrations were similar in both groups; there were no significant differences by sex or age. Serum 24,25-dihydroxyvitamin D [24,25-(OH)2D] concentrations paralleled the serum 250HD response. Mean serum calcium (total and ionized), magnesium, phosphate, alkaline phosphatase, vitamin D binding protein, C-terminal parathyroid hormone, calcitonin, 1,25-dihydroxyvitamin D [1,25-(OH)2D], and osteocalcin concentrations did not differ between blacks and whites at any time. The ratio of the concentration of 1,25-(OH)2D to 25OHD in their serum was initially higher in blacks compared to whites (p less than 0.0001); the ratios decreased to levels similar to whites by the third UVB exposure. We conclude that, in blacks and whites, sequential suberythemal UVB exposure produces similar elevations of serum 25OHD concentrations and unchanged calciotropic hormones concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vitamin D deficiency among older women with and without disability

BACKGROUND: Vitamin D deficiency is associated with bone loss and bone fractures, and the identification of vulnerable populations is important to clinical practice and public health. OBJECTIVE: The objectives of this study were to determine the prevalence of vitamin D deficiency and to examine associated risk factors for vitamin D deficiency in older women. DESIGN: We measured serum concentrations of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1, 25(OH)(2)D], intact parathyroid hormone (PTH), osteocalcin, and ionized calcium in women aged >/=65 y who were participating in the Women's Health and Aging Study I, an observational study of women representing the approximately one-third most disabled women living in the community, and women aged 70-80 y who were participating in the Women's Health and Aging Study II, an observational study of women among the two-thirds least disabled women living in the community in Baltimore. RESULTS: The women were classified into 4 domains of physical disability. Among 371 women with 0 or 1 domain of disability and 682 women with >/=2 domains of disability, 6.2% and 12.6%, respectively, had vitamin D deficiency [serum concentrations of 25(OH)D < 25 nmol/L]. In univariate analyses, risk factors for vitamin D deficiency included increasing age, black race, low educational level, high body mass index, high triceps skinfold thickness, increasing level of disability, winter season, and elevated creatinine concentration. In multivariate models, black race had a strong association with vitamin D deficiency when other risk factors were adjusted for. CONCLUSIONS: Vitamin D deficiency, a preventable disorder, is a common and important public health problem for older disabled women living in the community; black women are at higher risk than are white women.     

Serum 25-hydroxyvitamin D, dietary calcium intake, and distal colorectal adenoma risk

Vitamin D has recently emerged as a potentially protective agent against colorectal neoplasia. We assessed the associations between dietary vitamin D, plasma 25-hydroxyvitamin D [25(OH)D], dietary calcium, and colorectal adenomas in a large screening sigmoidoscopy-based case-control study in Southern California. Because conversion of serum 25(OH)D to serum 1,25-vitamin D is highly regulated by serum calcium, we also assessed modification of the 25(OH)D-adenoma association by calcium intake. Cases were 473 subjects with a primary adenoma, and controls were 507 subjects who had no adenomas at sigmoidoscopy and no history of adenomas. Compared with those in the lowest quartile of intake, those in the highest quartile of dietary vitamin D had an adjusted odds ratio (OR) of 0.83 [95% confidence interval (CI) = 0.49-1.41] and those in the highest quartile of dietary calcium had an OR of 0.82 (95% CI = 0.49-1.25). There was a suggestion that plasma 25(OH)D may be protective in this population (OR for highest vs. lowest quartile = 0.74, 95% CI = 0.51-1.09). A significant protective effect of 25(OH)D was clearly evident only in those with calcium intakes below (OR = 0.40 for highest vs. lowest quartile, 95% CI = 0.22-0.71, p for trend = 0.005) and above (OR = 1.17, 95% CI = 0.69-1.99, p for trend = 0.94) the median calcium intake.     

Blood biomarkers of vitamin D status

In the past quarter century, more than 50 metabolites of vitamin D have been described. To date, only a few of these have been quantified in blood, but this has widened our understanding of the pathologic role that altered vitamin D metabolism plays in the development of diseases of calcium homeostasis. Currently, awareness is growing of the prevalence of vitamin D insufficiency in the general population in association with an increased risk of several diseases. However, for many researchers, it is not clear which vitamin D metabolites should be quantified and what the information gained from such an analysis tells us. Only 2 metabolites, namely, 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D], have received the greatest attention. Of these, the need for measuring serum 1,25(OH)2D is limited, and this metabolite should therefore not be considered as part of the standard vitamin D testing regimen. On the other hand, serum 25(OH)D provides the single best assessment of vitamin D status and thus should be the only vitamin D assay typically performed. Currently, numerous formats exist for measuring serum 25(OH)D concentrations, each with its own advantages and disadvantages. This article reviews the currently available methods for serum 25(OH)D quantitation and considers important issues such as whether both the D2 and the D3 forms of the vitamin should be assayed, whether total or free concentrations are most important, and what measures should be taken to ensure the fidelity of the measurements.     

Moderate cholecalciferol supplementation depresses intestinal calcium absorption in growing dogs

Hormonal regulation of calcium (Ca) absorption was investigated in a cholecalciferol (vitamin D(3))-supplemented group (hVitD) vs. a control group (cVitD) of growing Great Danes (100 vs. 12.5 micro g vitamin D(3)/kg diet). Although Ca intakes did not differ, fractional Ca absorption was significantly lower in the hVitD group than in the cVitD group. There were no differences in plasma concentrations of Ca, inorganic phosphate, parathyroid hormone, growth hormone or insulin-like growth factor I between groups. Plasma 25-hydroxycholecalciferol [25(OH)D(3)] concentrations were maintained in the hVitD dogs at the same levels as in the cVitD dogs due to increased turnover of 25(OH)D(3) into 24,25-dihydroxycholecalciferol [24,25(OH)(2)D(3)] and 1,25-dihydroxycholecalciferol [1,25(OH)(2)D(3)]. In hVitD dogs, the greater plasma 24,25(OH)(2)D(3) concentration and the enhanced metabolic clearance rate (MCR) of 1,25(OH)(2)D(3) indicated upregulated 24-hydroxylase activity. The increased MCR of 1,25(OH)(2)D(3) decreased plasma 1,25(OH)(2)D(3) concentrations. In hVitD dogs, the greater production rate of 1,25(OH)(2)D(3) was consistent with the 12.9-fold greater renal 1alpha-hydroxylase gene expression compared with cVitD dogs and compensated to a certain extent for the accelerated MCR of 1,25(OH)(2)D(3). The moderately decreased plasma 1,25(OH)(2)D(3) concentration can only partially explain the decreased Ca absorption in the hVitD dogs. Intestinal vitamin D receptor concentrations did not differ between groups and did not account for the decreased Ca absorption. We suggest that 24,25(OH)(2)D(3) may downregulate Ca absorption.     

肥胖儿童血清维生素D、甲状旁腺素及胰岛素抵抗水平分析

目的:分析肥胖儿童血清VD、PTH及胰岛素抵抗水平,探讨肥胖与上述指标的关系。方法:在健康体检时,利用体重指数(BMI),以中国肥胖工作组制定的标准进行筛查,将研究对象分为肥胖组与对照组,采集空腹静脉血分别测定25(OH)D、1,25(OH)2D、PTH、血钙、磷和碱性磷酸酶(AP),测定FINS和FPG计算HOMA-IR,测定身高、体重计算BMI。结果:肥胖组VD缺乏率明显高于对照组。与对照组相比,肥胖儿童的BMI、PTH和HOMA-IR明显升高,VD水平明显降低(P0.05)。BMI与血清VD呈明显负相关,与PTH和HOMA-IR呈明显正相关。PTH与25(OH)D呈明显负相关,与HOMA-IR呈明显正相关;25(OH)D与HOMA-IR呈明显负相关。结论:肥胖儿童血清VD水平降低,PTH增高,胰岛素抵抗增强。肥胖与VD、PTH和HOMA-IR相关,PTH、25(OH)D与HOMA-IR分别相关。     

Vitamin D insufficiency in children, adolescents, and young adults with cystic fibrosis despite routine oral supplementation

BACKGROUND: Cystic fibrosis (CF) with pancreatic insufficiency is associated with poor absorption of fat and fat-soluble vitamins, including vitamin D. Pancreatic enzyme supplementation does not completely correct fat malabsorption in CF patients. OBJECTIVE: The objective of the study was to compare the vitamin D status of children, adolescents, and young adults with CF who were treated with routine vitamin D and pancreatic enzyme supplements with the vitamin D status of a healthy reference group from a similar geographic area. DESIGN: Growth, dietary intake, and serum concentrations of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], and parathyroid hormone (PTH) were measured in 101 white subjects with CF and a reference group of 177 white subjects. RESULTS: The median daily vitamin D supplementation in the CF group was 800 IU. The mean +/- SD serum concentrations of 25(OH)D were 20.7 +/- 6.5 ng/mL in the CF group and 26.2 +/- 8.6 ng/mL in the reference group (P < 0.001). Vitamin D deficiency and insufficiency were defined as 25(OH)D concentrations < 11 ng/mL and < 30 ng/mL, respectively. Seven percent of the CF group and 2% of the healthy reference group were vitamin D deficient (P < 0.03). Ninety percent of the CF group and 74% of the healthy reference group were vitamin D insufficient (P < 0.01). Twenty-five percent of the CF group and 9% of the healthy reference group had elevated PTH (P < 0.006). The odds of vitamin D insufficiency in the CF group, compared with the healthy reference group, were 1.2 (95% CI: 1.1, 1.3) after adjustment for season and age. CONCLUSION: Despite daily vitamin D supplementation, serum 25(OH)D concentrations remain low in children, adolescents, and young adults with CF.     

Prevalence and significance of low 25-hydroxyvitamin D concentrations in healthy subjects in Delhi

BACKGROUND: Despite abundant sunlight, rickets and osteomalacia are prevalent in South Asian countries. The cause of this paradox is not clear. OBJECTIVE: The objective was to assess 25-hydroxyvitamin D [25(OH)D] status and its functional significance in apparently healthy subjects residing in Delhi, a city in the northern part of India. DESIGN: Serum 25(OH)D, total calcium, inorganic phosphate, alkaline phosphatase, intact parathyroid hormone, and 1, 25-dihydroxyvitamin D [1,25(OH)(2)D] were measured in groups of healthy subjects who differed with respect to variables relevant to vitamin D and bone mineral metabolic status, such as direct sunlight exposure, season of measurement, skin pigmentation, dietary calcium and phytate contents, and altered physiologic states such as pregnancy and neonatal age. RESULTS: All groups except one with maximum direct sunlight exposure had subnormal concentrations of 25(OH)D. The 25(OH)D-deficient groups tended to have an imbalance in bone mineral metabolic homeostasis when exposed to winter weather and low dietary calcium and high dietary phytate, with significantly low calcium and elevated intact parathyroid hormone concentrations, chemical osteomalacia, or both. Increased values of 1,25(OH)(2)D during pregnancy did not help correct the imbalance in bone mineral metabolic homeostasis. CONCLUSION: Healthy subjects with low 25(OH)D concentrations are at risk of bone mineral metabolic imbalance when exposed to factors that strain bone mineral homeostasis.     

Diabetes prevalence is associated with serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in US middle-aged Caucasian men and women: a cross-sectional analysis within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

Hypovitaminosis D may be associated with diabetes, hypertension and CHD. However, because studies examining the associations of all three chronic conditions with circulating 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) are limited, we examined these associations in the US Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial (n 2465). Caucasian PLCO participants selected as controls in previous nested case-control studies of 25(OH)D and 1,25(OH)(2)D were included in this analysis. Diabetes, CHD and hypertension prevalence, risk factors for these conditions and intake of vitamin D and Ca were collected from a baseline questionnaire. Results indicated that serum levels of 25(OH)D were low (< 50 nmol/l) in 29 % and very low (< 37 nmol/l) in 11 % of subjects. The prevalence of diabetes, hypertension and CHD was 7, 30 and 10 %, respectively. After adjustment for confounding by sex, geographical location, educational level, smoking history, BMI, physical activity, total dietary energy and vitamin D and Ca intake, only diabetes was significantly associated with lower 25(OH)D and 1,25(OH)(2)D levels. Caucasians who had 25(OH)D ≥ 80 nmol/l were half as likely to have diabetes (OR 0·5 (95 % CI 0·3, 0·9)) compared with those who had 25(OH)D < 37 nmol/l. Those in the highest quartile of 1,25(OH)(2)D (≥ 103 pmol/l) were less than half as likely to have diabetes (OR 0·3 (95 % CI 0·1, 0·7)) than those in the lowest quartile (< 72 pmol/l). In conclusion, the independent associations of 25(OH)D and 1,25(OH)(2)D with diabetes prevalence in a large population are new findings, and thus warrant confirmation in larger, prospective studies.     

郑州中原区小学儿童1000例血清25羟维生素D水平调查及影响因素分析

目的调查郑州中原区小学儿童血清25羟维生素D水平并探讨分析影响儿童维生素D水平的因素。方法采用多阶段分层整群随机抽样的方法选取郑州中原区小学的1000例儿童作为本次研究对象,所有儿童均行血清25(OH)D水平检测。比较不同年龄段、不同性别、不同体质量的儿童维生素D水平情况,并采用多因素Logistic回归分析维生素D水平的影响因素。结果1000例儿童中,血清25(OH)D水平的平均值为(70.15±8.96)nmol/L,其中维生素D不足占比最高,为56.20%,其次是维生素D充足,占比为30.30%,维生素D缺乏占比最低,为13.50%;6~9岁儿童的血清25(OH)D水平显著高于10~12岁儿童,且6~9岁儿童的维生素D缺乏或不足人数占比(66.98%)显著少于10~12岁儿童(74.52%),差异均有统计学意义(P<0.05);男童的血清25(OH)D水平显著高于女童,且男童的维生素D缺乏或不足人数占比(66.82%)显著少于女童(75.22%),差异均有统计学意义(P<0.05);正常儿童的血清25(OH)D水平显著高于超重儿童和肥胖儿童,超重儿童的血清25(OH)D水平显著高于肥胖儿童,正常儿童的维生素D缺乏或不足人数占比显著少于超重儿童和肥胖儿童,超重儿童的维生素D缺乏或不足人数占比显著少于肥胖儿童,差异均有统计学意义(P<0.05);多因素Logistic回归分析结果显示,BMI、年龄、日照辐射、饮食均是维生素D水平的重要影响因素。结论郑州中原区小学部分儿童存在维生素D不足或缺乏,相关工作者应予以重视,加强儿童的维生素D补充。     

Elevated serum parathyroid hormone, calcitonin, and 1,25-dihydroxyvitamin D in lactating women nursing twins

The roles of vitamin D, calcitonin, and parathyroid hormone in calcium metabolism during lactation may be more evident in women secreting very large amounts of milk for a number of months, as in mothers nursing twins. We report significant increases in serum concentrations of parathyroid hormone, calcitonin, and 1,25(OH)2 vitamin D in mothers nursing twins compared to mothers nursing single infants. Serum concentrations of calcium actually increased in both groups during lactation. Maternal intakes of calories, calcium, and phosphorus were significantly higher in mothers nursing twins. Thus, mothers nursing twins were able to compensate for higher calcium losses in breast milk by increased dietary intakes of calcium as well as increased serum concentrations of parathyroid hormone, calcitonin, and 1,25(OH)2 vitamin D.     

Food and health for the aged.

We tested the hypothesis that repeated whole body suberythemal ultraviolet B (UVB) exposure would result in less increase of serum 25-hydroxyvitamin D (25OHD) concentrations in black compared with white young adults with no significant change or racial differences in serum calciotropic hormones concentrations. Thirteen white and 7 black adults ranging from 22 to 35 years of age were submitted to sequential total body suberythemal doses of UVB (280-315 nm) biweekly for 6 weeks. Initial UVB dose was 5% below the minimal erythemal dose for the most sensitive skin, followed by 10% increase per exposure for 4 weeks. Blood samples were drawn weekly. Baseline 25OHD concentrations were significantly lower in blacks compared to whites, but the increases in serum 25OHD concentrations were similar in both groups; there were no significant differences by sex or age. Serum 24,25-dihydroxyvitamin D [24,25-(OH)2D] concentrations paralleled the serum 250HD response. Mean serum calcium (total and ionized), magnesium, phosphate, alkaline phosphatase, vitamin D binding protein, C-terminal parathyroid hormone, calcitonin, 1,25-dihydroxyvitamin D [1,25-(OH)2D], and osteocalcin concentrations did not differ between blacks and whites at any time. The ratio of the concentration of 1,25-(OH)2D to 25OHD in their serum was initially higher in blacks compared to whites (p less than 0.0001); the ratios decreased to levels similar to whites by the third UVB exposure. We conclude that, in blacks and whites, sequential suberythemal UVB exposure produces similar elevations of serum 25OHD concentrations and unchanged calciotropic hormones concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Optimal Vitamin D Supplementation Doses that Minimize the Risk for Both Low and High Serum 25-Hydroxyvitamin D Concentrations in the General Population

The Recommended Dietary Allowance (RDA) is the nutrient intake considered to be sufficient to meet the requirements of 97.5% of the population. Recent reports revealed a statistical error in the calculation of the RDA for vitamin D opening the question of what the recommendation should be. We took a dual approach to answer this question: (1) we aggregated 108 published estimates on vitamin D supplementation and vitamin D status; and (2) we analyzed 13,987 observations of program participants. The aggregation of published data revealed that 2909 IU of vitamin D per day is needed to achieve serum 25-hydroxyvitamin D (25(OH)D) concentrations of 50 nmol/L or more in 97.5% of healthy individuals. For normal weight, overweight and obese program participants this was 3094, 4450 and 7248 IU respectively. These supplementation doses would also result in 2.5% of normal weight, overweight and obese participants having 25(OH)D concentrations above 210, 200 and 214 nmol/L respectively. As these concentrations are high, an approach that minimizes the risk for both low and high concentrations seems desirable. With this approach we estimated, for example, that doses of 1885, 2802 and 6235 IU per day are required for normal weight, overweight and obese individuals respectively to achieve natural 25(OH)D concentrations (defined as 58 to 171 nmol/L). In conclusion, the large extent of variability in 25(OH)D concentrations makes a RDA for vitamin D neither desirable nor feasible. We therefore propose recommendations be articulated in the form of an optimal intake that minimizes the risk for both low and high serum 25(OH)D concentrations. This contribution includes body weight specific recommendations for optimal intakes for various combinations of lower and upper 25(OH)D concentration targets.     

Association between Subcutaneous White Adipose Tissue and Serum 25-Hydroxyvitamin D in Overweight and Obese Adults

Cholecalciferol is known to be deposited in human adipose tissue, but it is not known whether 25-hydroxyvitamin D (25(OH)D) is found in detectable concentrations. Therefore, our objective was to determine whether 25(OH)D is detectable in subcutaneous white adipose tissue (SWAT) in overweight and obese persons enrolled in a twelve week energy restricted diet. Baseline and post-intervention gluteal SWAT biopsies were collected from 20 subjects participating in a larger clinical weight loss intervention. LC-MS/MS was utilized to determine SWAT 25(OH)D concentrations. Serum 25(OH)D and 1,25(OH)₂D were measured by RIA. Body composition was assessed by dual energy x-ray absorptiometry. SWAT 25(OH)D concentrations were 5.8 ± 2.6 nmol/kg tissue and 6.2 ± 2.7 nmol/kg tissue pre- and post-intervention SWAT, respectively. There was a significant positive association between SWAT 25(OH)D concentration and serum 25(OH)D concentration (r = 0.52, P < 0.01). Both SWAT and serum 25(OH)D concentrations did not significantly change after a twelve-week period of energy restriction with approximately 5 kg of fat loss. In conclusion, we have demonstrated our LC-MS/MS method can detect 25(OH)D₃ in human subcutaneous fat tissue from overweight and obese individuals and is consistent with previously reported concentrations in swine. Additionally, our findings of no significant changes in SWAT 25(OH)D₃ or serum 25(OH)D after a 6% loss of total body weight and 13% reduction in total fat provides the first human evidence that adipose 25(OH)D does not likely contribute to serum 25(OH)D with moderate weight loss; whether this is also the case with larger amounts of weight loss is unknown. Weight loss alone is not sufficient to increase serum 25(OH)D and increases in dietary or dermal biosynthesis of vitamin D appear to be the most critical contributors to in vitamin D status.     

Megalin-mediated endocytosis of vitamin D binding protein correlates with 25-hydroxycholecalciferol actions in human mammary cells

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)(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 megalin-mediated endocytosis. Endocytosis of DBP was associated with activation of VDR by 25(OH)D3 but not 1,25(OH)(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 mammary-derived cells express megalin and cubilin, which contribute to the endocytic uptake of 25(OH)D3-DBP and activation of the VDR pathway.