Vitamin D status of White pregnant women and infants at birth and 4 months in North West England: A cohort study.

The prevalence of vitamin D deficiency in pregnant white-skinned women (WSW) and their infants has not been investigated at northern latitudes in a developed county. A 2-year observational cohort study was undertaken in the North West of England to determine 25-hydroxyvitamin D (25OHD) levels in WSW and their infants during pregnancy and 4 months postdelivery and to explore factors associated with these levels. Nutritional and lifestyle questionnaires were completed and 25OHD levels measured at 28 weeks and 4 months postdelivery. Twenty-seven percent and 7% of WSW had insufficient and deficient levels of 25OHD during pregnancy and 48% and 11% four months postdelivery. WSW with Fitzpatrick skin-type I (FST I) have significantly lower 25OHD than other skin types after controlling for time spent outside and vitamin D intake. Twenty-four percent and 13% of infants had insufficient and deficient 25OHD levels at 4 months. Unsupplemented breast-fed infants have the highest level of insufficiency (67%) compared with formula-fed infants (2%). Factors associated with infant serum 25OHD levels at 4 months included breast feeding, supplementation, and time outside. WSW have a high prevalence of insufficiency and deficiency during pregnancy which doubles 4 months after birth. Breast-fed infants of WSW are rarely considered at risk of vitamin D insufficiency but have high rates compared with formula-fed infants. This is the first study to show the finding that FST I WSW have significantly lower levels of 25OHD than those with FST II-IV (difference adjusted for diet and time outside 14 (95%CI 7-21) nmol/L).

A modeling approach to determine how much UV radiation is available across the UK and Ireland for health risk and benefit studies.

A detailed map of the available UV across the UK from 2003 to 2012 is provided. A suite of data derived from climatologies and satellite observations are used to calculate spectral UV irradiance and related weighted doses (erythema, DNA damage, vitamin D). The result is a well-validated tool that has two advantages: (i) the output is simulated spectral UV irradiance that can be weighted with any action spectrum for use in any research studies that require ambient UV data, (ii) reliance on instruments with planned operational lives of at least several years that ensures data and method homogeneity for extension to future studies. The model-derived doses are satisfactory validated against spectral ground-based measurements at two sites. According to the calculated climatology, the southern part of the UK receives 1.5-2 times more UV than the north during spring, summer and autumn. During wintertime, the UV doses in the far north are an order of magnitude lower than southern values. Even for the same latitude, regional variations of cloudiness result in doses at coastal sites being up to 25% higher than inland areas.

25-Hydroxyvitamin D deficiency is associated with increased aortic stiffness in patients with systemic lupus erythematosus.

OBJECTIVE: To determine the relationship between serum vitamin D and markers of subclinical cardiovascular disease (CVD) in patients with SLE. METHODS: We recruited SLE patients (≥ 4 ACR 1997 criteria) from outpatient clinics between January 2007 and January 2009. Vitamin D deficiency was defined as serum 25(OH)D <20 ng/ml measured by ELISA. Disease activity was measured using the SLEDAI-2K score. Aortic pulse wave velocity (aPWV) was measured using PulseTrace 3600 (Micromedical) and carotid plaque (CP) and intima-media thickness (IMT) assessed using B-mode Doppler US. RESULTS: Seventy-five women with SLE were recruited with a median (interquartile range) disease duration of 16 (8-27) years. Patients with vitamin D deficiency had higher BMI (P = 0.014) and insulin resistance (P = 0.023) than those with 25(OH)D >20 ng/ml. Subjects with SLEDAI-2K ≥ 4 had lower 25(OH)D than those with SLEDAI-2K <4 (median 12.9 vs 20.3 ng/ml, P = 0.031). Aortic stiffness was significantly associated with serum 25(OH)D [log(aPWV) ß (95% CI) -0.0217 (-0.038, -0.005), P = 0.010] independently of BMI, CVD risk factors and serum insulin. Adjustment for disease activity reduced the strength of the association. There was no association between 25(OH)D and CP or IMT. CONCLUSIONS: Vitamin D deficiency is associated with increased aortic stiffness in SLE, independent of CVD risk factors and insulin. Increased inflammatory disease activity may be the mechanism by which vitamin D deficiency mediates vascular stiffness in this patient group.

Vitamin D status and muscle function in post-menarchal adolescent girls.

CONTEXT: There has been a resurgence of vitamin D deficiency among infants, toddlers, and adolescents in the United Kingdom. Myopathy is an important clinical symptom of vitamin D deficiency, yet it has not been widely studied. OBJECTIVE: Our objective was to investigate the relationship of baseline serum 25 hydroxyvitamin D [25(OH)D] concentration and PTH with muscle power and force. DESIGN: This was a cross-sectional study. SETTING: The study was community based in a secondary school. PARTICIPANTS: A total of 99 post-menarchal 12- to 14-yr-old females was included in the study. MAIN OUTCOME MEASURES: Jumping mechanography to measure muscle power, velocity, jump height, and Esslinger Fitness Index from a two-legged counter movement jump and force from multiple one-legged hops was performed. Body height, weight, and serum concentrations of 25(OH)D, PTH, and calcium were measured. RESULTS: Median serum 25(OH)D concentration was 21.3 nmol/liter (range 2.5-88.5) and PTH 3.7 pmol/liter (range 0.47-26.2). After correction for weight using a quadratic function, there was a positive relationship between 25(OH)D and jump velocity (P = 0.002), jump height (P = 0.005), power (P = 0.003), Esslinger Fitness Index (P = 0.003), and force (P = 0.05). There was a negative effect of PTH upon jump velocity (P = 0.04). CONCLUSION: From these data we conclude that vitamin D was significantly associated with muscle power and force in adolescent girls.

Fractional Sunburn Threshold UVR Doses Generate Equivalent Vitamin D and DNA Damage in Skin Types I-VI but with Epidermal DNA Damage Gradient Correlated to Skin Darkness.

Public health guidance recommends limiting sun exposure to sub-sunburn levels, but it is unknown whether these can gain vitamin D (for musculoskeletal health) while avoiding epidermal DNA damage (initiates skin cancer). Well-characterized healthy humans of all skin types (I-VI, lightest to darkest skin) were exposed to a low-dose series of solar simulated UVR of 20%-80% their individual sunburn threshold dose (minimal erythema dose). Significant UVR dose responses were seen for serum 25-hydroxyvitamin D and whole epidermal cyclobutane pyrimidine dimers (CPDs), with as little as 0.2 minimal erythema dose concurrently producing 25-hydroxyvitamin D and CPD. Fractional MEDs generated equivalent levels of whole epidermal CPD and 25-hydroxyvitamin D across all skin types. Crucially, we showed an epidermal gradient of CPD formation strongly correlated with skin darkness (r = 0.74, P < 0.0001), which reflected melanin content and showed increasing protection across the skin types, ranging from darkest skin, where high CPD levels occurred superficially, with none in the germinative basal layer, to lightest skin, where CPD levels were induced evenly across the epidermal depth. People with darker skin can be encouraged to use sub-sunburn UVR-exposure to enhance their vitamin D. In people with lighter skin, basal cell damage occurs concurrent with vitamin D synthesis at exquisitely low UVR levels, providing an explanation for their high skin cancer incidence; greater caution is required.

Vitamin D status and bone mass in UK South Asian women.

INTRODUCTION: Low vitamin D status is prevalent among South Asians living in the UK. The relationship, however, between serum 25-hydroxyvitamin D level (25OHD), serum parathyroid level (PTH) and bone mass in this group of women is unknown. The aim of this study was to determine the association between serum PTH, 25OHD and bone mass in a population based sample of young UK South Asian women. MATERIALS AND METHODS: Names of South Asian women aged 18 to 36 years of Pakistani origin living in the Greater Manchester area were identified from primary care registers using validated computer software. Subjects were invited to attend for (i) a blood test for assessment of serum calcium (Ca), albumin, PTH and 25OHD and (ii) for bone mineral density (BMD) scanning using the following: areal BMD at the hip (femoral neck, total hip) and lumbar spine using dual X-ray absorptiometry (Hologic QDR 4500), and volumetric BMD at the distal radius using peripheral quantitative computed tomography (Norland Stratec XCT 2000). Linear regression was used to determine the association between serum 25OHD, PTH and BMD at the different sites with adjustments made for age. RESULTS: In all, 78 women (mean age 29.2 years) were included in the analysis. Mean serum Ca level was 2.42 mmol/l, 25OHD, 7.9 ng/ml and PTH, 52.8 pg/ml. The majority of women (94%) had serum 25OHD levels 15 ng/ml, though rose progressively in subjects with levels below 10 ng/ml. Serum 25OHD was positively associated with BMD at the hip and spine while PTH was negatively associated with BMD at the hip and spine. When categorized by serum 25OHD level there was an increase in BMD at the total hip and distal radial site at least up to levels of 15 ng/ml. CONCLUSIONS: Despite widespread recognition, hypovitaminosis D is still prevalent among young UK South Asian women. In these women a decrease in serum 25OHD level

Observations from the UK Supra-Regional Assay Service laboratory for the measurement of Vitamin D metabolites.

As a Supra-Regional Assay Service (SAS) laboratory, we receive samples from all over the UK. Of these some are sent frozen and others by post or courier. We have examined transport and storage conditions to see whether they affect the measurement of Vitamin D metabolites and potentially contribute to the variation in measurement of 25-hydroxyvitamin D (25OHD) seen in the DEQAS scheme. We have also examined the samples received during 2005. We found that different transport and storage conditions did not contribute significantly to the normal variation seen in measuring Vitamin D metabolites (CV% (+/-S.E.) for stored versus assay controls: 5.1+/-0.06% versus 4.5+/-0.04% for 25OHD and 10.8+/-1.0% versus 12.3+/-1.0% for 1,25D). A review of the service showed a 240% increase in samples received over the last 5 years. Despite an increased awareness of the need to measure Vitamin D status, in this cross-section of patient samples 92% of Asian and 86% of white patients were found to be Vitamin D-insufficient (<30 ng/ml) and 27% of Asian and 14% of white patients were profoundly deficient (<5 ng/ml) and at risk of bone disease.

The effects of Vitamin D metabolites on expression of genes for calcium transporters in human duodenum.

The role of Vitamin D in the regulation of calcium absorption in the intestine is well recognized but the mechanisms of the effects on human genes are surprisingly poorly understood. We have determined the expression of transcripts of the apical membrane calcium transporter TRPV6, the cytoplasmic calcium binding protein calbindin-D9k, the basolateral plasma membrane Ca(2+)-ATPase (PMCA1) and the Vitamin D receptor (VDR) in normal endoscopic duodenal mucosal biopsies using quantitative real-time RT-PCR and related baseline expression to Vitamin D metabolites. TRPV6 transcript levels have been shown to be significantly correlated with serum 1,25(OH)(2)D levels in men, but not overall in women, where negative effects of age predominate. TRPV6 and VDR expression were significantly related in both men and women, but were significantly lower in older women. Associations with bone mineral density and fractional calcium absorption were also studied. In a second series of subjects, duodenal biopsies were incubated in organ culture for 6h with Vitamin D metabolites. TRPV6 expression was significantly increased by 1,25(OH)(2)D(3) (10(-9)mol/l) as was PMCA1 to a much smaller extent. TRPV6 expression also increased with 25(OH)D(3). CYP27B1 expression was found in all samples, and CYP24 transcripts were detected after incubation with 1,25(OH)(2)D(3) or 25(OH)D(3).

Daily supplementation with 15 µg vitamin D2 compared with vitamin D3 to increase wintertime 25-hydroxyvitamin D status in healthy South Asian and white European women: a 12-wk randomized, placebo-controlled food-fortification trial.

Background: There are conflicting views in the literature as to whether vitamin D2 and vitamin D3 are equally effective in increasing and maintaining serum concentrations of 25-hydroxyvitamin D [25(OH)D], particularly at lower doses of vitamin D.Objective: We aimed to investigate whether vitamin D2 or vitamin D3 fortified in juice or food, at a relatively low dose of 15 µg/d, was effective in increasing serum total 25(OH)D and to compare their respective efficacy in South Asian and white European women over the winter months within the setting of a large randomized controlled trial.Design: A randomized, double-blind, placebo-controlled food-fortification trial was conducted in healthy South Asian and white European women aged 20-64 y (n = 335; Surrey, United Kingdom) who consumed placebo, juice supplemented with 15 µg vitamin D2, biscuit supplemented with 15 µg vitamin D2, juice supplemented with 15 µg vitamin D3, or biscuit supplemented with 15 µg vitamin D3 daily for 12 wk. Serum 25(OH)D was measured by liquid chromatography-tandem mass spectrometry at baseline and at weeks 6 and 12 of the study.Results: Postintervention in the 2 ethnic groups combined, both the vitamin D3 biscuit and the vitamin D3 juice groups showed a significantly greater absolute incremental change (Δ) in total 25(OH)D when compared with the vitamin D2 biscuit group [Δ (95% CI): 15.3 nmol/L (7.4, 23.3 nmol/L) (P < 0.0003) and 16.0 nmol/L (8.0, 23.9 nmol/L) ( P < 0.0001)], the vitamin D2 juice group [Δ (95% CI): 16.3 nmol/L (8.4, 24.2 nmol/L) (P < 0.0001) and 16.9 nmol/L (9.0, 24.8 nmol/L) (P < 0.0001)], and the placebo group [Δ (95% CI): 42.3 nmol/L (34.4, 50.2 nmol/L) (P < 0.0001) and 42.9 nmol/L (35.0, 50.8 nmol/L) (P < 0.0002)].Conclusions: With the use of a daily dose of vitamin D relevant to public health recommendations (15 µg) and in vehicles relevant to food-fortification strategies, vitamin D3 was more effective than vitamin D2 in increasing serum 25(OH)D in the wintertime. Vitamin D3 may therefore be a preferential form to optimize vitamin D status within the general population. This trial was registered at www.controlled-trials.com as ISRCTN23421591.

Relationship between vitamin D status and leukocytes in hospitalised cats.

Objectives Vitamin D deficiency, as assessed by serum 25-hydroxyvitamin D (25[OH]D) concentrations, has been linked to markers of systemic inflammation in human and canine medicine. However, the relationship between vitamin D status and inflammation has not been previously investigated in cats. The aim of this study was to examine the relationship between serum 25(OH)D concentrations and leukocyte counts in hospitalised sick cats. Methods Serum 25(OH)D concentrations and haematology profiles were measured in 170 consecutive hospitalised sick cats. A binary logistical regression model examined the relationship between serum 25(OH)D concentration, age, sex, breed and neutrophil, monocyte, eosinophil and lymphocyte counts. Results Cats with neutrophilia had lower serum 25(OH)D concentrations than cats with neutrophil concentrations below the upper limit of the reference interval (RI). There were no differences in serum 25(OH)D concentrations in cats with monocyte, lymphocyte or eosinophil counts above their respective RI compared with cats with counts below the upper limit of the RI. Conclusions and relevance Hospitalised cats with a neutrophil count above the RI had lower vitamin D status. There is a need to establish whether lower vitamin D status is a cause or consequence of increased neutrophil counts.

Calcium channel TRPV6 expression in human duodenum: different relationships to the vitamin D system and aging in men and women.

UNLABELLED: Intestinal absorption of calcium affects bone mineralization and varies greatly. In human duodenum, expression of the calcium channel TRPV6 was directly related to blood 1,25-dihydroxyvitamin D in men, but effects of age with lower median vitamin D receptor levels were more significant in women. INTRODUCTION: The TRPV6 calcium channel/transporter is implicated in animal studies of intestinal calcium absorption, but in humans, its role and relationship to differences in mineral metabolism is unclear. We aimed to characterize TRPV6 expression in human intestine including defining relationships to the vitamin D endocrine system. MATERIALS AND METHODS: TRPV6 transcript expression was determined in endoscopic mucosal biopsies obtained from normal duodenum. Expression was compared with that in ileum and with in situ hybridization in archival tissues and related to sequence variants in genomic DNA. TRPV6 expression was related in 33 subjects to other transcripts involved in calcium absorption including the vitamin D receptor (VDR) and to blood vitamin D metabolites including 1,25-dihydroxyvitamin D [1,25(OH)(2)D]. RESULTS: TRPV6 transcripts were readily detected in duodenum but not in ileum. Expression was highest in villous epithelial cells. Sequence variants in the coding and upstream regions of the gene did not affect TRPV6 expression. The relationship between duodenal TRPV6 expression and 1,25(OH)(2)D differed in men and women. In men, linear regression showed a strong association with 1,25(OH)(2)D (r = 0.87, p < 0.01), which was unaffected by age. In women, there was no significant overall relationship with 1,25(OH)(2)D, but there was a significant decrease with age (r = -0.69, p < 0.001). Individual expression of TRPV6 and VDR was significantly correlated. The group of older women (>50) had lower median levels of both TRPV6 and VDR transcripts than younger women (p < 0.001 and 0.02, respectively). CONCLUSIONS: Duodenal TRPV6 expression is vitamin D dependent in men, but not in older women, where expression of TRPV6 and VDR are both reduced. These findings can explain, at least in part, the lower fractional calcium absorption seen in older postmenopausal women.

Vitamin D status predicts reproductive fitness in a wild sheep population.

Vitamin D deficiency has been associated with the development of many human diseases, and with poor reproductive performance in laboratory rodents. We currently have no idea how natural selection directly acts on variation in vitamin D metabolism due to a total lack of studies in wild animals. Here, we measured serum 25 hydroxyvitamin D (25(OH)D) concentrations in female Soay sheep that were part of a long-term field study on St Kilda. We found that total 25(OH)D was strongly influenced by age, and that light coloured sheep had higher 25(OH)D3 (but not 25(OH)D2) concentrations than dark sheep. The coat colour polymorphism in Soay sheep is controlled by a single locus, suggesting vitamin D status is heritable in this population. We also observed a very strong relationship between total 25(OH)D concentrations in summer and a ewe's fecundity the following spring. This resulted in a positive association between total 25(OH)D and the number of lambs produced that survived their first year of life, an important component of female reproductive fitness. Our study provides the first insight into naturally-occurring variation in vitamin D metabolites, and offers the first evidence that vitamin D status is both heritable and under natural selection in the wild.

Sun Exposure Behavior, Seasonal Vitamin D Deficiency, and Relationship to Bone Health in Adolescents.

CONTEXT: Vitamin D is essential for bone health in adolescence, when there is rapid bone mineral content accrual. Because cutaneous sun exposure provides vitamin D, there is no recommended oral intake for UK adolescents. OBJECTIVE: Our objective was to assess seasonal vitamin D status and its contributors in white Caucasian adolescents and examine bone health in those found deficient. DESIGN: Prospective cohort study was undertaken. SETTING: Six schools in Greater Manchester, UK, were included. PARTICIPANTS: Participants were 131 adolescents between 12 and 15 years of age. INTERVENTION(S): Seasonal assessment of circulating 25-hydroxyvitamin D (25OHD), personal sun exposure, and dietary vitamin D. Adolescents deficient (25OHD <10 ng/ml/25 nmol/liter) in at least one season underwent dual-energy X-ray absorptiometry (lumbar spine, femoral neck), with bone mineral apparent density correction for size, and peripheral quantitative computed tomography (distal radius) for volumetric bone mineral density (BMD). MAIN OUTCOME MEASURE: Serum 25OHD and BMD measurements. RESULTS: Mean 25OHD was highest in September: 24.1 (SD, 6.9) ng/ml and lowest in January: 15.5 (5.9) ng/ml. Over the year, 16% were deficient in ≥ one season and 79% insufficient (25OHD <20 ng/ml/50 nmol/liter) including 28% in September. Dietary vitamin D was low year-round, whereas personal sun exposure was seasonal and predominantly across the school week. Holidays accounted for 17% variation in peak 25OHD (P < .001). Nineteen adolescents underwent bone assessment, which showed low femoral neck bone mineral apparent density vs matched reference data (P = .0002), three with Z less than or equal to -2.0 distal radius trabecular volumetric BMD. CONCLUSIONS: Sun exposure levels failed to provide adequate vitamin D, with approximately one-quarter of adolescents insufficient even at summer peak. Seasonal vitamin D deficiency was prevalent and those affected had low BMD. Recommendations on vitamin D acquisition are indicated in this age-group.

Biphasic hypercalcemia in severe rhabdomyolysis: serial analysis of PTH and vitamin D metabolites. A case report and literature review.

Calcemic fluxes with hypocalcemia leading to hypercalcemia in acute rhabdomyolisis are poorly understood. Analyses in the literature of the factors modulating the blood calcium level include 2, possibly 3 systems. Conflicting results implicate the parathyroid hormone and vitamin D metabolites, but additional contribution from skeletal and muscle calcium ion deposition and dissolution have been cited in some cases, potentially even dominating control of blood calcium during recovery. We have had the opportunity to study in detail a patient presenting with the most severe rhabdomyolisis, serum creatine phosphokinase levels exceeding 10(6) U/L, thus providing an analysis that delineates major changes in regulatory factors controlling calcium status. We found an exaggerated and clearly defined, phasic sequence of changes in these factors that led to ostensibly atypical, biphasic hypercalcemia juxtaposing the transient and well-described hypocalcemia in such patients. Our conclusions help to clarify the controversy, adding substance to the argument that there is no disruption in the parathyroid hormone-vitamin D axis regulating blood calcium levels in this rare disease.

A comparison of in situ hybridisation, reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ-RT-PCR for the detection of canine distemper virus RNA in Paget's disease.

Previous evidence implicating Paramyxoviruses in the aetiopathology of Paget's disease of bone has proved controversial. Whilst several groups have demonstrated Paramyxoviruses using techniques such as in situ hybridisation (ISH), reverse transcriptase-polymerase chain reaction (RT-PCR), and in situ-RT-PCR (IS-RT-PCR), others have found no evidence of viruses using only RT-PCR. To investigate this latter finding, we have now compared detection of canine distemper virus by ISH, RT-PCR (three different methods) and IS-RT-PCR, in 10 patients with Paget's disease, and samples of non-diseased bone from four patients. Canine distemper virus was detectable in six of the samples by ISH, but only in five of the samples by RT-PCR, using one of the methods. Neither of the other RT-PCR methods detected canine distemper virus. IS-RT-PCR demonstrated canine distemper virus in all 10 samples. There was no evidence of virus in the control samples. We have shown that the ability to detect canine distemper virus in bone is dependent on the technique used. IS-RT-PCR clearly showed that canine distemper virus was present in 100% of Pagetic samples, whereas canine distemper virus was only found in 60% by ISH and in 50% using one particular RT-PCR method. These results provide conclusive evidence that canine distemper virus is present within Pagetic bone, and provide a possible explanation for the failure of some groups to detect Paramyxovirus sequences. These findings also have wider implications for other studies investigating viral expression.

The direction of shift-work rotation impacts metabolic risk independent of chronotype and social jetlag--an exploratory pilot study.

The aim of this pilot study was to explore the risk of metabolic abnormalities in steel workers employed in different shift-work rotations. Male workers in a steel factory [16 employed in a fast clockwise rotation (CW), 18 in slow counterclockwise rotation (CC), 9 day workers (DW); mean age 43.3 ± SD 6.8 years] with at least 5 years experience in their current work schedule participated. All workers provided fasting blood samples between 06:00 and 08:00 h for plasma glucose, insulin, apo-lipoproteins A and B (ApoA, ApoB), high- and low-density lipoproteins (HDL and LDL), total cholesterol (tCH), triglycerides (TG), minimally oxidized (mox) LDL, C-reactive protein (CRP), interleukin-8 (IL-8) and serum 25-hydroxyvitamin D (25(OH)D). HOMA index (homeostatic model assessment) was calculated to evaluate insulin resistance, beta cell function and risk of diabetes. Information on demographics, health, stimulants, sleep, social and work life, chronotype (phase of entrainment) and social jetlag (difference between mid-sleep on workdays and free days) as a surrogate for circadian disruption was collected by questionnaire. Neither chronotype nor social jetlag was associated with any of the metabolic risk blood markers. There were no significant differences in 25(OH)D, ApoA, ApoB, CRP, HDL, IL-8, insulin, LDL, mox-LDL, mox-LDL/ApoB ratio, tCH and TG levels between the three work groups. Although we did observe absolute differences in some of these markers, the small sample size of our study population might prevent these differences being statistically significant. Fasting glucose and HOMA index were significantly lower in CW compared to DW and CC, indicating lower metabolic risk. Reasons for the lower fasting glucose and HOMA index in CW workers remains to be clarified. Future studies of workers in different shift rotations are warranted to understand better the differential effects of shift-work on individual workers and their health indices.

Differential effects of different vitamin D replacement strategies in patients with diabetes.

BACKGROUND: The optimal treatment regimen for correcting vitamin D insufficiency in diabetic patients has not been established. METHODS: Two hundred and forty four adult diabetic patients with vitamin D insufficiency were enrolled to receive: Ergocalciferol (D2) 50,000 IU daily over 10 days (500,000 IU) followed by Calcichew D3 (calcium carbonate/Cholecalciferol) BID (~24,000 IU cholecalciferol/month) (ECC) (n=53); Cholecalciferol (D3) 40,000 IU daily over 10 days (400,000 IU) followed by Calcichew D3 BID (~24,000 IU cholecalciferol/month) (CCC) (n=94) or Cholecalciferol 40,000 IU daily over 10 days (400,000 IU) followed by Cholecalciferol 40,000 IU monthly (CC) (n=97). The 25(OH)D, HbA1c, lipids, blood pressure and eGFR were assessed at baseline and after a mean follow up of 8.0±4.0 months. RESULTS: Treatment increased 25(OH)D concentrations significantly in ECC (17.4±13.8 vs 29.9±9.6 ng/ml, P<0.0001), CCC (14.2±6.6 vs 30.9±13.1 ng/ml, p<0.0001) and CC (13.5±8.4 vs 33.9±14.4 ng/ml, P<0.0001). The relative increase in 25(OH)D was significantly lower with ECC compared to CC (+14.6±12.2 vs +20.6±15.0, P=0.01) and the majority of subjects in the ECC group (63%) remained vitamin D deficient (25(OH)D <30 ng/ml) compared to CCC (46%) and CC (36%) (P=0.0005). CONCLUSION: This study demonstrates that relatively aggressive treatment regimens of both vitamin D2 and D3 increase 25(OH)D concentrations in diabetic patients, but the ability to raise 25(OH)D status to 'sufficient' levels is inadequate in a large proportion of individuals.

Efficacy of a dose range of simulated sunlight exposures in raising vitamin D status in South Asian adults: implications for targeted guidance on sun exposure.

BACKGROUND: Vitamin D is essential for bone health, and cutaneous synthesis is an important source. South Asians cannot attain adequate amounts of vitamin D by following general recommendations on summer sunlight exposure at northerly latitudes, and increased exposure may be appropriate for improving their vitamin D status. OBJECTIVE: We examined the efficacy of a dose range of simulated summer sunlight exposures in raising vitamin D status in UK adults of South Asian ethnicity. DESIGN: In a dose-response study, healthy adults of South Asian ethnicity (n = 60; 20-60 y old) received 1 of 6 ultraviolet exposures ranging from 0.65 to 3.9 standard erythema doses (SEDs), which were equivalent to 15-90 min unshaded noontime summer sunlight at 53.5°N (Manchester, United Kingdom), 3 times/wk for 6 wk, while wearing casual clothes that revealed a 35% skin area. Serum 25-hydroxyvitamin D [25(OH)D] was measured weekly, and dietary vitamin D was estimated. RESULTS: At baseline, all completing participants (n = 51) were vitamin D insufficient [25(OH)D concentrations <20 ng/mL], and a high proportion of participants were deficient [35% of subjects had 25(OH)D concentrations <5 ng/mL, and 90% of subjects had 25(OH)D concentrations <10 ng/mL, which are concentrations at which osteomalacia and rickets occur). The 25(OH)D concentration rose significantly in all dose groups. Postcourse, all participants achieved 25(OH)D concentrations ≥5 ng/mL, whereas only 6 subjects attained 25(OH)D concentrations ≥20 ng/mL. Participants who received exposures ≥1.95 SEDs (equivalent to 45 min unshaded sunlight; n = 33) attained a mean (±SD) 25(OH)D concentration of 15.7 ± 5 ng/mL (mean rise: 8.7 ± 5.7 ng/mL; 95% CI: 6.8, 10.6 ng/mL; P < 0.001), and 94% of subjects achieved concentrations >10 ng/mL. CONCLUSIONS: Targeted guidance on sunlight exposure could usefully enhance vitamin D status to avoid deficiency [25(OH)D concentration >10 ng/mL] in South Asians living at latitudes distant from the equator. This trial was registered at the ISRCTN Register (www.isrctn.org) as 07565297.

Adaptations in tibial cortical thickness and total volumetric bone density in postmenopausal South Asian women with small bone size.

There is some evidence that South Asian women may have an increased risk of osteoporosis compared with Caucasian women, although whether South Asians are at increased risk of fracture is not clear. It is unknown whether older South Asian women differ from Caucasian women in bone geometry. This is the first study, to the authors' knowledge, to use peripheral Quantitative Computed Tomography (pQCT) to measure radial and tibial bone geometry in postmenopausal South Asian women. In comparison to Caucasian women, Asian women had smaller bone size at the 4% (-18% p<0.001) and 66% radius (-15% p=0.04) as well as increased total density at the 4% (+13% p=0.01) radius. For the tibia, they had a smaller bone size at the 4% (-16% p=0.005) and 14% (-38% p=0.002) sites. Also, Asians had increased cortical thickness (-17% p=0.04) at the 38% tibia, (in proportion to bone size (-30% p=0.003)). Furthermore, at the 4% and 14% tibia there were increased total densities (+12% to +29% p<0.01) and at the 14% tibia there was increased cortical density (+5% p=0.005) in Asians. These differences at the 14% and 38% (but not 4%) remained statistically significant after adjustment for Body Mass Index (BMI). These adaptations are similar to those seen previously in Chinese women. Asian women had reduced strength at the radius and tibia, evidenced by the 20-40% reduction in both polar Strength Strain Index (SSIp) and fracture load (under bending). Overall, the smaller bone size in South Asians is likely to be detrimental to bone strength, despite some adaptations in tibial cortical thickness and tibial and radial density which may partially compensate for this.

The vitamin D debate: translating controlled experiments into reality for human sun exposure times.

Exposure to sunlight, specifically the ultraviolet radiation, has both positive and negative health effects. Maximizing the benefits (vitamin D synthesis) while minimizing the damage is a multifaceted problem in which many of the elements are poorly quantified. Here we show how rigorously conducted large sample size laboratory studies of the effect of ultraviolet radiation dose on vitamin D status can be applied to real-life situations. This was achieved by modeling the radiation incident on different surfaces for different solar locations, and equating with the controlled exposures in the laboratory studies. Results from both model and experimental data show that relatively short exposures of a modest amount of unprotected skin to summer sunlight in northern climes, on a regular basis during lunchtime hours, increases vitamin D to sufficiency status (≥20 ng mL(-1) ) in the white Caucasian population. While both sun exposure conditions and human skin responses are variable in real life, these quantitative findings provide a guide for authorities devising sunlight exposure recommendations.