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 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).

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.

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.

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.

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.

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.

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.

Recommended summer sunlight exposure amounts fail to produce sufficient vitamin D status in UK adults of South Asian origin.

BACKGROUND: The cutaneous synthesis of vitamin D is dependent on UVB from sunlight, but melanin reduces the penetration of UVB and thus contributes to vitamin D insufficiency in individuals with darker skin. The national guidance provided on amounts of sunlight exposure in the United Kingdom is for the light-skinned population, and in the absence of dedicated information, darker-skinned people may attempt to follow this guidance. OBJECTIVES: We determined the relative effect of a simulation of UK recommendations of summer sunlight exposure on the vitamin D status of individuals of South Asian ethnicity compared with that of whites. DESIGN: In a prospective cohort study, simulated summer sunlight exposures were provided under rigorous dosimetric conditions to 15 adults (aged 20-60 y) of South Asian ethnicity, and serum 25-hydroxyvitamin D [25(OH)D] was measured weekly. Dietary vitamin D intake was estimated. Outcomes were compared with those of 109 whites (aged 20-60 y) treated with the identical UV-radiation exposure protocol. RESULTS: At baseline (winter trough), all South Asians were vitamin D-insufficient [25(OH)D concentrations <20 ng/mL], and 27% of South Asians were vitamin D-deficient [25(OH)D concentrations <5 ng/mL]; although 25(OH)D concentrations increased postcourse (P < 0.0001), all South Asians remained vitamin D-insufficient. The mean increase in 25(OH)D was 4.3 compared with 10.5 ng/mL in the South Asian and white groups, respectively (P < 0.0001), and 90% of the white group reached vitamin D sufficiency postcourse. The median dietary vitamin D intake was very low in both groups. CONCLUSIONS: Sunlight-exposure recommendations are inappropriate for individuals of South Asian ethnicity who live at the UK latitude. More guidance is required to meet the vitamin D requirements of this sector of the population. This study was registered at www.isrctn.org as ISRCTN 07565297.

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.

Recommended summer sunlight exposure levels can produce sufficient (> or =20 ng ml(-1)) but not the proposed optimal (> or =32 ng ml(-1)) 25(OH)D levels at UK latitudes.

Recommendations on limitation of summer sunlight exposure to prevent skin cancer may conflict with requirements to protect bone health through adequate vitamin D levels, the principal source being UVB in summer sunlight. We determined whether sufficient (> or =20 ng ml(-1)) and proposed optimal (> or =32 ng ml(-1)) 25(OH)D levels are attained by following UK guidance advising casual short exposures to UVB in summer sunlight, and performed the study under known conditions to enhance the specificity of future recommendations. During wintertime, when ambient UVB is negligible, 120 white Caucasians, aged 20-60 years, from Greater Manchester, UK (53.5 degrees N) received a simulated summer's sunlight exposures, specifically 1.3 standard erythemal dose, three times weekly for 6 weeks, while wearing T-shirt and shorts. The baseline winter data predict that 5% (confidence interval (CI): 2.7-8.6) of Greater Manchester white Caucasians have deficient (<5 ng ml(-1)) 25(OH)D, 62.5% (CI: 55.2-69.4) have insufficient, and only 2.9% (CI: 1.4-5.6) have proposed optimal levels. After the simulated summer exposures, 90 (CI: 84.9-93.7) and 26.2% (CI: 20.1-33.2) reached 20 and 32 ng ml(-1) 25(OH)D, respectively. Assuming midday UVB levels, sufficient but suboptimal vitamin D status is attained after a summer's short (13 minutes) sunlight exposures to 35% skin surface area; these findings will assist future public health guidance on vitamin D acquisition.

A prospective study of micronutrient status in adolescent pregnancy.

BACKGROUND: Adolescents are more likely than adults to consume energy-dense, micronutrient-poor diets and to experience adverse pregnancy outcomes. OBJECTIVES: The objectives were to assess micronutrient intake and blood biomarkers prospectively in pregnant adolescents recruited to the About Teenage Eating (ATE) Study and to determine associations with pregnancy outcome. DESIGN: Pregnant adolescents (n = 500) were recruited from 2 UK inner city populations. Dietary intake was assessed with three 24-h dietary recalls, and micronutrient status was assessed by measurement of third trimester blood biomarkers. Pregnancy outcomes included small-for-gestational age (SGA) birth and preterm delivery. RESULTS: Median iron and folate intakes were lower than UK and US recommended amounts. Folate and vitamin B-12 status were lower in smokers, despite no differences in dietary intake. Serum folate was <7.0 nmol/L in 12% of subjects, and serum total homocysteine (tHcy) was elevated (>10 micromol/L) in 20% of subjects. Fifty-two percent of the subjects had iron deficiency anemia, and 30% had serum 25-hydroxyvitamin D concentrations <25 nmol/L. The incidence of SGA birth was higher in subjects with poorer folate status (red blood cell folate, P = 0.003; serum folate, P = 0.02; tHcy, P = 0.01; simple regression) and those with low folate intakes, regardless of the inclusion (P = 0.021) or exclusion (P = 0.049) of intake from supplements (simple regression). Adjustment for confounding variables confirmed the independence of these associations. The risk of SGA birth was also higher in subjects with low food iron intake (P = 0.049), but not when intake included iron from supplements (P = 0.21). The risk of SGA birth was lower in subjects with iron deficiency anemia (P = 0.002). CONCLUSION: Poor micronutrient intake and status increase the risk of SGA births in pregnant adolescents.

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.

The effect of a low-protein diet in pregnancy on offspring renal calcium handling.

Low birth weight humans and rats exposed to a low-protein diet in utero have reduced bone mineral content. Renal calcium loss during the period of rapid skeletal growth is associated with bone loss. Because young rats exposed to low protein display altered renal function, we tested the hypothesis that renal calcium excretion is perturbed in this model. Pregnant Wistar rats were fed isocalorific diets containing either 18% (control) or 9% (low) protein throughout gestation. Using standard renal clearance techniques, Western blotting for renal calcium transport proteins, and assays for Na(+)-K(+)-ATPase activity and serum calcitropic hormones, we characterized calcium handling in 4-wk-old male offspring. Histomorphometric analyses of femurs revealed a reduction in trabecular bone mass in low-protein rats. Renal calcium (control vs. low protein: 10.4 +/- 2.1 vs. 27.6 +/- 4.5 nmol x min(-1) x 100 g body wt(-1); P < 0.01) and sodium excretion were increased, but glomerular filtration rate was reduced in low-protein animals. Total plasma calcium was reduced in low-protein rats (P < 0.01), but ionized calcium, serum calcitropic hormone concentrations, and total body calcium did not differ. There was no significant change in plasma membrane Ca(2+)-ATPase pump, epithelial calcium channel, or calbindin-D(28K) expression in low-protein rat kidneys. However, Na(+)-K(+)-ATPase activity was 36% lower (P < 0.05) in low-protein rats. These data suggest that the hypercalciuria of low-protein rats arises through a reduction in passive calcium reabsorption in the proximal tubule rather than active distal tubule uptake. This may contribute to the reduction in bone mass observed in this model.

A single dose of vitamin D enhances immunity to mycobacteria.

RATIONALE: Vitamin D was used to treat tuberculosis (TB) in the preantibiotic era. Prospective studies to evaluate the effect of vitamin D supplementation on antimycobacterial immunity have not previously been performed. OBJECTIVES: To determine the effect of vitamin D supplementation on antimycobacterial immunity and vitamin D status. METHODS: A double-blind randomized controlled trial was conducted in 192 healthy adult TB contacts in London, United Kingdom. Participants were randomized to receive a single oral dose of 2.5 mg vitamin D or placebo and followed up at 6 weeks. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was assessed with a functional whole blood assay (BCG-lux assay), which measures the ability of whole blood to restrict luminescence, and thus growth, of recombinant reporter mycobacteria in vitro; the readout is expressed as a luminescence ratio (luminescence postinfection/baseline luminescence). IFN-gamma responses to the Mycobacterium tuberculosis antigens early secretory antigenic target-6 and culture filtrate protein 10 were determined with a second whole blood assay. Vitamin D supplementation significantly enhanced the ability of participants' whole blood to restrict BCG-lux luminescence in vitro compared with placebo (mean luminescence ratio at follow-up, 0.57, vs. 0.71, respectively; 95% confidence interval for difference, 0.01-0.25; p=0.03) but did not affect antigen-stimulated IFN-gamma secretion. CONCLUSIONS: A single oral dose of 2.5 mg vitamin D significantly enhanced the ability of participants' whole blood to restrict BCG-lux luminescence in vitro without affecting antigen-stimulated IFN-gamma responses. Clinical trials should be performed to determine whether vitamin D supplementation prevents reactivation of latent TB infection. Clinical trial registered with www.clinicaltrials.gov (NCT 00157066).

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).