Vitamin D3 improves lipophagy-associated renal lipid metabolism and tissue damage in diabetic mice.

Oxidative stress and abnormal lipid metabolism in diabetes can trigger renal lipotoxicity, extending to diabetic nephropathy. Vitamin D3 has been known to be involved in lipid metabolism as well as insulin secretion or inflammation. Therefore, we hypothesized that vitamin D3 supplementation attenuated hyperglycemia-induced renal damage in diabetic mice. Diabetes was induced by a 40% kJ high-fat diet with 30 mg/kg body weight of streptozotocin by intraperitoneal injection twice in male C57BL/6J mice. Among diabetic mice (fasting blood glucose > 140 mg/dL), mice were supplemented with 300 ng/kg body weight of vitamin D3 dissolved in olive oil for 12 weeks. Normal control and diabetic control mice were orally administrated with olive oil as a vehicle. Normal control mice were fed with an AIN-93G diet during the experiment. Vitamin D3 supplementation in diabetic mice improved glucose intolerance and kidney function, demonstrated by diminishing glomerular areas. Vitamin D3 supplementation in diabetic mice significantly reduced triglycerides and low-density lipoprotein cholesterol in plasma as well as triglycerides and total cholesterol in the kidney. Furthermore, vitamin D3 supplementation attenuated lipid synthesis, oxidative stress, and apoptosis, accompanied by activation of ß-oxidation, antioxidant defense enzymes, and autophagy in diabetic mice. In conclusion, vitamin D3 supplementation ameliorates hyperglycemia-induced renal damage through the regulation of lipid metabolisms, oxidative stress, apoptosis, and autophagy in diabetes. Vitamin D3 could be a promising nutrient to weaken diabetic nephropathy.

Circulating Vitamin D Levels and Alzheimer's Disease: A Mendelian Randomization Study in the IGAP and UK Biobank.

Observational studies strongly supported the association of low levels of circulating 25-hydroxyvitamin D (25OHD) and cognitive impairment or dementia in aging populations. However, randomized controlled trials have not shown clear evidence that vitamin D supplementation could improve cognitive outcomes. In fact, some studies reported the association between vitamin D and cognitive impairment based on individuals aged 60 years and over. However, it is still unclear that whether vitamin D levels are causally associated with Alzheimer's disease (AD) risk in individuals aged 60 years and over. Here, we performed a Mendelian randomization (MR) study to investigate the causal association between vitamin D levels and AD using a large-scale vitamin D genome-wide association study (GWAS) dataset and two large-scale AD GWAS datasets from the IGAP and UK Biobank with individuals aged 60 years and over. Our results showed that genetically increased 25OHD levels were significantly associated with reduced AD risk in individuals aged 60 years and over. Hence, our findings in combination with previous literature indicate that maintaining adequate vitamin D status in older people especially aged 60 years and over, may contribute to slow down cognitive decline and forestall AD. Long-term randomized controlled trials are required to test whether vitamin D supplementation may prevent AD in older people especially those aged 60 years and may be recommended as preventive agents.

Relationships between circulating 25(OH) vitamin D, leptin levels and visceral adipose tissue volume: results from a 1-year lifestyle intervention program in men with visceral obesity.

BACKGROUND/OBJECTIVES: Obesity has been associated with elevated leptinemia and vitamin D deficiency. To date, whether there is an association between vitamin D and leptin levels independent from adiposity remains uncertain. Our objective was to investigate the associations between changes in 25(OH) vitamin D levels, changes in adiposity variables, and changes in leptin levels produced by a 1-year lifestyle intervention program. SUBJECTS/METHODS: Sedentary men (n = 113) with abdominal obesity, dyslipidemic, and non-vitamin D supplemented were involved in a 1-year lifestyle modification program. Subjects were individually counseled by a kinesiologist and a nutritionist once every 2 weeks during the first 4 months with subsequent monthly visits in order to elicit a 500 kcal daily energy deficit and to increase physical activity/exercise habits. Adiposity mapping by computed tomography and cardiometabolic biomarkers, as well as vitamin D measurements were performed at baseline and at the 1-year visit. RESULTS: The 1-year intervention resulted in a 26% decrease in visceral adipose tissue volume (from 1951 ± 481 to 1463 ± 566 cm3), a 27% decrease in leptin levels (from 12.0 ± 8.1 to 8.5 ± 7.8 ng/mL) and a 27% increase in plasma 25(OH) vitamin D concentrations (from 50 ± 18 to 60 ± 18 nmol/L, p < 0.0001). One-year increases in 25(OH) vitamin D levels were inversely correlated with 1-year changes in leptin levels (r = -0.41, p < 0.001). The association remained significant after adjustment for 1-year changes in various adiposity indices: visceral adipose tissue (r = -0.30, p = 0.0019), subcutaneous adipose tissue (r = -0.35, p = 0.0004), total abdominal adipose tissue (r = -0.31, p = 0.0015), and fat mass (r = -0.31, p = 0.001). CONCLUSIONS: In response to a 1-year lifestyle intervention, changes in 25(OH) vitamin D levels were independently associated with changes in leptinemia after adjustment for adiposity changes. This finding supports a possible physiological link between leptinemia and 25(OH) vitamin D levels independent from adiposity and underscores the role of lifestyle modifications leading to lowered leptinemia in the clinical management of vitamin D deficiency.

Effect of Vitamin D Supplementation in the Prevention of Recurrent Pneumonia in Under-Five Children.

OBJECTIVE: To assess the effect of vitamin D supplementation in the prevention of recurrent pneumonia in under-five children. METHODS: The present one year 8 months longitudinal, community-based randomized controlled study included a total of 100 under-five children with pneumonia. Children were divided into two groups: intervention group (Group I: standard treatment with vitamin D 300,000 IU; n = 50) and control group (Group C: standard treatment only; n = 50). As nine samples were hemolyzed, groups I and C comprised of 46 and 45 children, respectively. The children were followed up for 1 y and signs of upper respiratory tract infections (URTI), lower respiratory tract infections (LRTI), vitamin D deficiency, and vitamin D toxicity were recorded. RESULTS: The male to female ratio in group C and I was 1.27:1 and 1.5:1, respectively (P = 0.420). Age, gender, birth, anthropometric and clinical characteristics, and feeding habits were not statistically significant (P > 0.05) between both the cohorts (Group C and I). Children with reduced vitamin D levels were high in group C (25) when compared to the group I (15). During all the follow-ups, the URTI and LRTI episodes, severity of pneumonia, number of hospital admissions, complications, mean episodes of LRTI, and mean duration of LRTI were comparable between group I and group C (P > 0.05). CONCLUSIONS: Overall, the present study highlights that oral vitamin D (300,000 IU bolus dose quarterly) has some beneficial effect in the prevention of recurrent pneumonia in under-five children, although, not to a significant degree. Hence, it is recommended that further studies are required to demonstrate a significant effect of vitamin D in the prevention of pneumonia.

Effects of vitamin D supplementation on cognitive function and blood Aß-related biomarkers in older adults with Alzheimer's disease: a randomised, double-blind, placebo-controlled trial.

OBJECTIVE: Our study aimed to assess the effect of a 12-month vitamin D supplementation on cognitive function and amyloid beta (Aß)-related biomarkers in subjects with Alzheimer's disease (AD). METHODS : This was a randomised, double-blind, placebo-controlled trial. 210 AD patients were randomly divided into intervention and control groups. Participants received 12-month 800 IU/day of vitamin D or starch granules as placebo. Tests of cognitive performance and Aß-related biomarkers were measured at baseline, 6 months and 12 months. RESULTS : Repeated-measures analysis of variance showed significant improvements in plasma Aß42, APP, BACE1, APPmRNA, BACE1mRNA (p<0.001) levels and information, arithmetic, digit span, vocabulary, block design and picture arrange scores (p<0.05) in the intervention group over the control group. According to mixed-model analysis, vitamin D group had significant increase in full scale IQ during follow-up period (p<0.001). CONCLUSIONS: Daily oral vitamin D supplementation (800 IU/day) for 12 months may improve cognitive function and decrease Aß-related biomarkers in elderly patients with AD. Larger scale longer term randomised trials of vitamin D are needed. TRIAL REGISTRATION NUMBER: ChiCTR-IIR-16009549.

Vitamin D supplementation and bone markers in ambulatory children on long-term valproic acid therapy. A prospective interventional study.

PURPOSE: Our aim was to investigate any adverse effects of long-term valproic acid (VPA) therapy on bone biochemical markers in ambulatory children and adolescents with epilepsy, and the possible benefits of vitamin D supplementation on the same markers. METHODS: In this single center, the prospective interventional study levels of 25-hydroxyvitamin D (25OHD) and the bone turnover indices of Crosslaps (CTX), total alkaline phosphatase (tALP), osteoprotegerin (OPG), and the receptor activator for nuclear factor kB (RANK) ligand (sRANKL) were assessed before and after one year of vitamin D intake (400 IU/d) and were compared with those of clinically healthy controls. Fifty-four ambulatory children with mean (±standard deviation [SD]) age 9.0 ±â€¯4.5 yrs on VPA (200-1200 mg/d) long-term monotherapy (mean: 3.2 ±â€¯2.6 yrs) were studied, before and after a year's vitamin D intake (400 IU/d). RESULTS: Nearly half of the cases were vitamin D insufficient/deficient with mean levels 23.1 ±â€¯12.8 vs 31.8 ±â€¯16.2 ng/mL of controls (p = 0.004) and after the year of vitamin D intake increased to 43.2 ±â€¯21.7 ng/mL (p < 0.0001). In parallel, serum CTX and tALP had a decreasing trend approaching control levels but OPG and sRANKL did not change and were not different from controls. However, after vitamin D intake, a positive correlation was seen between 25OHD and OPG but not before. CONCLUSIONS: The findings imply a higher bone turnover in the young patients on long-term VPA therapy that decreased after vitamin D intake.

The synergistic effects of vitamin D and estradiol deficiency on metabolic syndrome in Chinese postmenopausal women.

OBJECTIVE: Recent studies show that vitamin D (VitD) deficiency is associated with metabolic syndrome (MetS). Current evidence suggests that estrogen and VitD have similar physiological functions and potentially interact with bone health. We investigated the association between estradiol (E2) and 25-hydroxyvitamin-D [25(OH)D] with MetS and its components in Chinese postmenopausal women. METHODS: In this cross-sectional study, we examined 616 postmenopausal women (aged 49-86 y) from southern China who were not taking estrogen and VitD/calcium supplements. At the end of data collection, serum E2 and 25(OH)D were measured for each participant. MetS was defined according to the 2006 International Diabetes Federation standard. RESULTS: There was a positive correlation between 25(OH)D and E2. Higher 25(OH)D was associated with a favorable lipid profile, blood pressure, and glucose level. E2 was negatively associated with cholesterol, triglycerides, and blood pressure. The odds ratio for MetS was 2.19 (95% CI, 1.19-4.01, P value for trend=0.009) for deficient compared with sufficient women after multivariable adjustment. This association remained unchanged after further adjusting for E2 levels. After stratified analysis by VitD status, low E2 increased MetS risk in women with VitD deficiency (odds ratio = 3.49, 95% CI, 1.45-8.05 for the lowest vs the highest tertile). CONCLUSIONS: These results suggest a synergistic role of VitD and E2 deficiency in MetS in Chinese postmenopausal women.

Vitamin D-Binding Protein Deficiency and Homozygous Deletion of the GC Gene.

A 58-year-old woman with debilitating ankylosing spondylitis who was born to consanguineous parents was found to have an apparent severe vitamin D deficiency that did not respond to supplementation. Liquid chromatography-tandem mass spectrometry showed the absence of circulating vitamin D-binding protein, and chromosomal microarray confirmed a homozygous deletion of the group-specific component (GC) gene that encodes the protein. Congenital absence of vitamin D-binding protein resulted in normocalcemia and a relatively mild disruption of bone metabolism, in this case complicated by severe autoimmune disease. (Funded by the National Institutes of Health and the University of Washington.).

Vitamin D status in cervical spondylotic myelopathy: comparison of fusion rates and patient outcome measures.

BACKGROUND: Patients undergoing elective spinal fusion have an alarming rate of vitamin D deficiency, but its impact on bone fusion and patient outcomes is unclear. We investigated the association of perioperative vitamin D levels, fusion rates, and patient-reported outcome in patients undergoing spinal fusion for cervical spondylotic myelopathy. METHODS: In this one-year, prospective, single-center observational study, serum 25-OH vitamin D levels were measured perioperatively in adult patients. Serum vitamin D levels <30 ng/mL were considered abnormal. The primary outcome measures were postoperative patient-reported outcomes (Neck Disability Index, Visual Analog Scale, EuroQol EQ-5D-3L, EQ-VAS). Secondary outcome measures were the presence of and time to solid bony fusion, controlling for Body Mass Index (BMI), age, and number of motion segments. RESULTS: Forty-one of 58 patients (71%) had laboratory-confirmed abnormal vitamin D levels. Patients with low vitamin D were younger (P<0.05) and had a higher BMI (P<0.05) than patients with adequate vitamin D, but the groups were otherwise similar. There were no differences in mean time to fusion between the two groups, but patients with low vitamin D reported more postoperative disability (P<0.05). Multivariate model analysis demonstrated an independent, significant association between normal vitamin D and lower postoperative neck disability index (P=0.05) and EQ-5D-3L (P=0.03). CONCLUSIONS: Vitamin D deficiency (<30 ng/mL) is highly prevalent in patients undergoing elective spinal fusion for cervical myelopathy. Low vitamin D levels were associated with worse patient-reported outcomes and were an independent predictor of greater disability, which suggests vitamin D supplementation may offer some benefit in these patients.

The prevalence and risk factors of vitamin D inadequacy among male athletes in Kuwait: A cross-sectional study.

The aim of this study was to determine the prevalence of vitamin D inadequacy in male athletes living in Kuwait, and to assess its relationship with possible risk factors including body composition, lifestyle and fasting Ramadan. A Cross- sectional study was conducted on a total of 250 male athletes registered in official sports clubs in Kuwait were included. Blood tests, anthropometric measurements and a lifestyle questionnaire were performed. Serum 25(OH)D level was used as a measure of vitamin D status. Vitamin D inadequacy was defined as serum 25(OH)D < 75 nmol/L, inadequate levels were further classified as vitamin D insufficiency (50-75 nmol/L), vitamin D deficiency (<50 nmol/L) and severe deficiency (<25 nmol/L). Thirty-six percent of the sample were football players, 13% were futsal players and the rest were players of 15 different outdoor and indoor sports. A prevalence of 83% of vitamin D inadequacy (< 75 nmol/L) was observed in male athletes in Kuwait, of which 23% had severe deficiency (< 25 nmol/L). The prevalence increased from 80% (n = 130) before Ramadan to 90% (n = 79) after Ramadan. There was a significant positive association between serum 25(OH)D concentrations and vitamin D intake (p < 0.001). Serum 25(OH)D concentrations were significantly inversely associated with risk of injuries (p = 0.008) and with the concentrations of parathyroid hormone (PTH) (p = 0.029). No statistically significant associations between 25(OH)D concentrations and sun exposure, physical activity or anthropometric levels were found. Similar to other studies in the Middle East, we found that healthy male athletes in Kuwait have a high prevalence of vitamin D inadequacy. The results of this study suggest the need for regular supplement intake and vitamin D awareness campaigns for athletes in Kuwait. More research is needed to assess the effect of Ramadan.

Normal physiological functions in two animal species with highly different vitamin d status compared to that of humans / Funciones fisiológicas normales en dos especies animales con estatus de vitamina d muy diferentes del actual en seres humanos

Mole rats live in permanent darkness, in networks of underground tunnels (which extend up to 1 km in the subsoil), excavated with their incisors, in warm and semi-arid areas of South Africa. Mole rats have an unusually impoverished vitamin D3 status with undetectable and low plasma concentrations of 25- hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3, respectively. They express 25-hydroxylase in the liver and 1-hydroxylase and 24-hydroxylase in their kidneys. The presence of specific receptors (VDR) was confirmed in the intestine, kidney, Harderʼs glands and skin. In spite of their poor vitamin D3 status, the apparent fractional intestinal absorption of calcium, magnesium and phosphate was high, always greater than 90%. Oral supplementation with cholecalciferol to mole rats did not improve the efficiency of gastrointestinal absorption of these minerals. Mole ratsdo not display the typical lesion of rickets: hypertrophic and radiolucent growth cartilages. Histological studies reported normal parameters of trabecular and cortical bone quality. Marmosets (monkeys of the New World) are not hypercalcaemic, eventhough they exhibit much higher levels of 25-hydroxyvitamin D3, 1α,25-dihydroxyvitamin D3 and parathyroid hormonethan that of rhesus monkeys and humans. Fed a high vitamin D3 intake (110 IU/day/100 g of body weight), a fraction of the experimental group was found to display osteomalacic changes in their bones: distinct increases in osteoid surface, relative osteoid volume, and active osteoclastic bone resorption. These findings suggest that some marmosets appears to suffer vitamin D-dependent rickets, type II. The maximum binding capacity of the VDR or the dissociation constant of VDR1α,25(OH)2D3 complex of mole rats and New World monkeys are distinctly different of VDR isolated from human cells. Health status of those species appears to be adaptations to the mutations of their VDR. Though rare, as mutations may occur at any time in any patient, the overall message of this review to clinicians may be: recent clinical studies strongly suggests that the normality of physiological functions might be a better indicator of the health status than the serum levels of vitamin D metabolites. (AU)

Las ratas topo viven en la oscuridad permanente, en redes de túneles subterráneos excavadas con sus incisivos (que se extienden hasta 1 km en el subsuelo), en áreas cálidas y semiáridas de Sudáfrica. Las ratas topo tienen un estatus de vitamina D3 inusualmente empobrecido con concentraciones plasmáticas indetectables de 25-hidroxivitamina D3 y bajas de 1α, 25-dihidroxivitamina D3. Poseen 25-hidroxilasa en el hígado y 1-hidroxilasa y 24-hidroxilasa en sus riñones. La presencia de receptores específicos (VDR) ha sido confirmada en el intestino, el riñón, las glándulas de Harder y la piel. A pesar de su pobre estatus de vitamina D3,la absorción fraccional intestinal aparente de calcio, magnesio y fosfato fue alta, siempre superior al 90%. La suplementación oral con colecalciferol a las ratas topo no mejoró la eficacia de la absorción gastrointestinal de estos minerales. No muestran la lesión típica del raquitismo: cartílagos de crecimiento hipertróficos y radiolúcidos. Varios estudios histológicos confirman los hallazgos radiológicos y se informan parámetros normales de la calidad ósea trabecular y cortical. Los titíes (monos del Nuevo Mundo) exhiben calcemias normales con niveles más elevados de 25-hidroxivitamina D3, 1α,25-dihidroxivitamina D3 y hormona paratiroidea que los monos rhesus y los seres humanos. Un tercio de un grupo de titíes alimentados con una alta ingesta de vitamina D3 (110 I/día/100 g de peso corporal) exhibió cambios osteomalácicos en sus huesos: aumento en la superficie osteoide, volumen osteoide y activa reabsorción osteoclástica. Estos hallazgos sugieren que una fracción de la población de titíes padece raquitismo dependiente de vitamina D, tipo II. Debido a mutaciones ocurridas hace millones de años, las máximas capacidades de ligamiento del VDR o los valores de la constante de disociación del complejo VDR-1α,25(OH)2D3 de las ratas topo o monos del Nuevo Mundo son muy diferentes de los verificables en receptores aislados de células humanas actuales. El mensaje de esta revisión a los médicos clínicos podría ser: varios estudios clínicos recientes indican que la normalidad de las funciones fisiológicas de un paciente es un mejor indicador de su salud que los niveles séricos de los metabolitos de la vitamina D. (AU)

S-25-hydroxyvitamin D and C3-epimers in pregnancy and infancy: An Odense Child Cohort study.

BACKGROUND: Analysis of serum 25-hydroxyvitamin D (s-25(OH)D) may be complicated by the less active or in-active vitamin D metabolite C3-epi-25(OH)D3 (C3-epimer). We aimed to explore the relationship between s-C3-epimer and s-25(OH)D and other determinants and describe the longitudinal course of the C3-epimer fraction in paired mother-child samples. METHOD: S-25(OH)D and s-C3-epimer were estimated by liquid chromatography mass spectrometry in 290 mother-infant pairs from the population-based Odense Child Cohort. Longitudinal analyses were feasible in two subcohorts; B) early and late pregnancy, cord, three and 18months (n=132); and C) early and late pregnancy, delivery and cord (n=105). RESULTS: Mean s-25(OH)D was 50.6-110.4nmol/L at the six time points. The mean C3-epimer fraction was 10.1% at three months, 1.1%-3.0% at the other time points. In multivariate analyses, the s-C3-epimer correlated with s-25(OH)D (all time points, p<0.001), and season, maternal and infant age and maternal vitamin D supplementation at some time points. The C3-epimer fraction fluctuated between adjacent time points. By cosinor analyses, a season-dependent sinusoidal pattern for s-25(OH)D and C3-epimer fraction was found and changes between adjacent time points depended on season (p<0.007 or trend). In early infancy, subtraction of the C3-epi-25(OH)D3 from total s-25(OH)D resulted in reclassification of 8% of the children by use of the 75nmol/L cut off for s-25(OH)D. CONLCUSION: The s-C3-epimer was independently correlated to s-25(OH)D, season, maternal vitamin D supplementation, maternal and infant age. The C3-epimer fraction was only of clinical importance in early infancy, where it could lead to misclassification of the vitamin D status.

Vitamin D, bone metabolism and fracture risk.

Insufficient serum levels of 25OH vitamin D (25OHD) is a risk factor for osteoporosis. A new paradigm has emerged with the locally synthesized 1,25(OH)2D within osteoblasts and osteoclasts as the essential pathway for the effects of 25OHD in regulating bone remodeling via direct or indirect activation of the specific receptor VDR. Vitamin D has positive effects on fracture risk but these results have been consistently observed whenever daily doses were above 800 UI/d administered to compliant patients together with adequate calcium supplementation and with an achieved biological target of serum 25OHD levels above 30 ng/mL.

Vitamin D status, body composition and glycemic control in Polish adolescents with type 1 diabetes.

BACKGROUND: High prevalence of vitamin D deficiency in adolescents with type 1 diabetes (T1DM) has been recorded but data focused on the relationship between vitamin D, glycemic control and body composition is limited in T1DM patients. The study was aimed to investigate vitamin D status in T1DM patients and its association with body composition (fat and lean body mass) and clinical data. METHODS: The study group comprised of 100 adolescents (15.3±1.9 yrs; 54 girls), including 60 T1DM patients (15.1±1.9 yrs; 32 girls) and 40 controls (15.6±1.8 yrs; 20 girls) from Warsaw, Poland. Serum total 25-hydroxyvitamin D (25(OH)D) levels and iPTH were measured by an ECLIA (Roche Diagnostics). Glycosylated hemoglobin (% HbA1c), serum calcium and inorganic phosphorous, and the use of dietary supplements were also assessed. DXA (GE Prodigy) was used to assess lean body mass (LBM; g), fat mass (FM; g), FM/LBM ratio, and respective Z-scores. RESULTS: Mean 25(OH)D level of 15.3±7.0 ng/mL (range 4.2-37.7 ng/mL) in T1DM was not different from that observed in controls (17.9±9.3 ng/mL; range 6.3-40.4 ng/mL). Eighty-two percent of T1DM patients and 67% controls had 25(OH)D levels <20 ng/mL, among them 25% T1DM and 12.5% controls revealed values <10 ng/mL. 5% T1DM and 15% controls had 25(OH)D>30 ng/mL. 25% from T1DM and 22% from control groups declared to use vitamin D supplementation and had significantly higher 25(OH)D levels compared to non-users (22.6±7.6 vs. 12.8±4.8 ng/mL in the T1DM; 26.9±11.5 vs. 15.3±6.8 ng/mL in controls, respectively). In the T1DM, low 25(OH)D levels negatively correlated with HbA1c (r=-0.320, P=0.013) and with iPTH (r=-0.434, P=0.001). 25(OH)D levels correlated negatively with Z-scores for FM/LBM ratio (r=-0.324; P=0.012) and Z-scores for FM (r=-0.229; P=0.079) and positively with LBM Z-scores (r=0.300; P=0.020). Serum Ca, serum iPTH did not differ T1DM and control groups but serum P level was significantly higher in T1DM patients compared to controls (1.39±0.19 mmol/L vs. 1.18±0.18 mmol/L; P=0.001, respectively). CONCLUSIONS: In T1DM adolescents vitamin D deficiency coincided with poor glycemic control and disturbed body composition. 25(OH)D levels were positively related to muscle stores and negatively with fat stores. Therefore, to limit a risk of disease related clinical complications both disturbed body composition and vitamin D deficiency should be corrected by implementation of regular vitamin D supplementation and increased intake of vitamin D-rich foods, as well as increased outdoors activities.

The effect of body composition and BMI on 25(OH)D response in vitamin D-supplemented athletes.

Fat mass is inversely associated with vitamin D status, and athletes with the most adipose tissue may have the greatest risk for insufficient (25(OH)D 20-32 ng mL(-1)) or deficient (25(OH)D < 20 ng ml(-1)) status. The effects of fat and lean mass on 25(OH)D change in response to vitamin D supplementation have yet to be elucidated in athletes. In addition, vitamin D has a known role in bone health yet a link between short-term changes in 25(OH)D and bone turnover in indoor athletes have not yet been described. Thirty-two collegiate swimmers and divers (19 male, 13 female; 19 (1) years) participated in a 6-month randomized controlled trial and consumed either 4000 IU d(-1) of vitamin D3 (n = 19) or placebo (PLA; n = 13). Anthropometry and blood collection of 25(OH)D, bone-specific alkaline phosphatase (B-ALP) and N-terminal telopeptide (NTx) occurred at three time points. Dual-energy X-ray absorptiometry measured body composition analysis at baseline and endpoint. In the vitamin D group, BMI was negatively correlated with 6-month 25(OH)D change (R = -0.496; P = .03) and a stronger predictor of 25(OH)D change (P = .04) than ultraviolet B exposure and fat mass change. Athletes in the high bone turnover group showed significantly greater losses of 25(OH)D over 6-months compared to athletes in the low bone turnover group (P = .03). These results suggest athletes within the normal BMI category experience a diminished response to 4000 IU d(-1) of vitamin D3 supplementation, and periods of high bone turnover may be an additional risk factor for developing compromised vitamin D status in athletes.

High Prevalence of Hypovitaminosis D in Indian Chronic Low Back Patients.

BACKGROUND: Vitamin D has a significant role to play in bone metabolism and neuromuscular function. Several researchers have indicated that Vitamin D deficiency may be possibly related to chronic musculoskeletal pain including chronic low back pain (CLBP). OBJECTIVES: The present study was conducted to determine the prevalence of hypovitaminosis D and its contribution to chronic lower back pain. STUDY DESIGN: Controlled study. SETTING: Outpatient pain clinic of tertiary care hospital. METHODS: Data presented in this manuscript are from patients who were screened for inclusion in an open label, single arm clinical trial aimed to assess the effectiveness of vitamin D supplementation in patients with CLBP. Consecutive patients visiting the outpatient pain clinic of a tertiary care hospital with a diagnosis of CLBP with or without leg pain were recruited. A visual analogue scale (VAS) was used to measure low back pain intensity, and the Modified Oswestry disability questionnaire (MODQ) was used to measure functional ability. Plasma 25-OHD levels of all patients were measured and the prevalence of hypovitaminosis D was calculated. The multivariate logistic regression model was used to investigate the association between vitamin D deficiency and patient characteristics. RESULTS: A total of 328 patients were included in the study. Mean age of the study population was 43.8 years. Two hundred eighty-two (86%) (men 153/172 [89%], women 129/156 [83%]) of patients had below normal plasma vitamin D levels. Among these, 217 (66%) (men 126 [73%], women 91 [58%]) were found to be deficient and 65 (20%) (men 27 [16%], women 38 [24%]) were had insufficient levels. Multivariate regression analysis found that men were significantly more prone to have deficiency as compared to women (OR = 1.78 (1.10-2.88), P = 0.02). We also found a significantly positive relationship between vitamin D deficiency and increased functional disability (OR = 1.53 (1.24-1.87), P = 0.01). However, we did not find any relationship with pain severity, presence of other co-morbidities and educational level. LIMITATIONS: Not possible to access a good quality data on sun exposure and vitamin D dietary inake dieat in study population. No bone scans were performed. CONCLUSION: The result of this study provides a message about the high prevalence of hypovitaminosis D in the Indian CLBP population. Clinical guidelines for managing CLBP should include assessment of vitamin D status, together with advice on appropriate vitamin D supplementation in those found to be deficient. CLINICAL TRIAL REGISTRATION: CTRI/2014/03/004459.

Vitamin D Deficiency in Children and Adolescents in Bagcilar, Istanbul.

OBJECTIVE: This study aimed to evaluate the frequency of seasonal 25-hydroxyvitamin D [25(OH)D] deficiency and insufficiency in children and adolescents living in Bagcilar, district of Istanbul city. METHODS: Serum vitamin D levels of 280 children aged 3-17 years old were measured at the end of winter and at the end of summer. Of the total group, vitamin D levels were re-measured in 198 subjects. Vitamin D deficiency was defined as a serum 25(OH)D level less than 15 ng/mL and insufficiency-as levels between 15 and 20 ng/mL. Patients whose vitamin D levels were less than 15 ng/mL at the end of winter were treated with 2000 units/day of vitamin D for 3 months. RESULTS: In the "end of winter" samples, 25(OH)D deficiency was present in 80.36% of the subjects and insufficiency in 11.79%. In the "end of summer" samples, vitamin D deficiency was detected in 3.44% and insufficiency in 27.75%. Vitamin D levels in the "end of winter" samples were not significantly different between boys and girls, while "end of summer" levels were significantly lower in girls (p=0.015). Sunlight exposure was significantly higher in boys (p=0.011). The group with sufficient dairy product consumption had significantly higher vitamin D levels in both "end of summer" and "end of winter" samples. Limb pain was frequently reported in children with low vitamin D levels in the "end of winter" samples (p=0.001). Negative correlations were observed between vitamin D levels and season and also between vitamin D levels and age. CONCLUSION: It is essential to provide supplemental vitamin D to children and adolescents to overcome the deficiency seen especially at the end of winter.

Combination of oral vitamin D3 with photodynamic therapy enhances tumor cell death in a murine model of cutaneous squamous cell carcinoma.

Photodynamic therapy (PDT), in which 5-ALA (a precursor for protoporphyrin IX, PpIX) is administered prior to exposure to light, is a nonscarring treatment for skin cancers. However, for deep tumors, ALA-PDT is not always effective due to inadequate production of PpIX. We previously developed and reported a combination approach in which the active form of vitamin D3 (calcitriol) is given systemically prior to PDT to improve PpIX accumulation and to enhance PDT-induced tumor cell death; calcitriol, however, poses a risk of hypercalcemia. Here, we tested a possible strategy to circumvent the problem of hypercalcemia by substituting natural dietary vitamin D3 (cholecalciferol; D3 ) for calcitriol. Oral D3 supplementation (10 days of a 10-fold elevated D3 diet) enhanced PpIX levels 3- to 4-fold, and PDT-mediated cell death 20-fold, in subcutaneous A431 tumors. PpIX levels and cell viability in normal tissues were not affected. Hydroxylated metabolic forms of D3 were only modestly elevated in serum, indicating minimal hypercalcemic risk. These results show that brief oral administration of cholecalciferol can serve as a safe neoadjuvant to ALA-PDT. We suggest a clinical study, using oral vitamin D3 prior to PDT, should be considered to evaluate this promising new approach to treating human skin cancer.

Changes in serum hydroxyvitamin D levels of breast cancer patients during tamoxifen treatment or chemotherapy in premenopausal breast cancer patients.

BACKGROUND: We investigated the effect of breast cancer adjuvant treatment on vitamin D status, as measured by serum hydroxyvitamin D (25OHD). METHODS: Premenopausal patients (n=483) diagnosed with non-metastatic breast cancer in 2009 at Asan Medical Center had serum 25OHD levels prospectively analysed at diagnosis and 6 and 12months after surgery. We excluded patients who took vitamin D supplements or received neoadjuvant chemotherapy. Vitamin D sufficiency was defined as a serum level of ⩾30ng/ml, insufficiency as 20-29ng/ml and deficiency as <20ng/ml. RESULTS: Compared with baseline serum 25OHD, patients who received chemotherapy had decreased serum 25OHD levels at 6months (-5.52ng/ml, p=0.003) and 12months (-1.24ng/ml, p=0.517) and patients who received anti-hormone therapy had significantly increased serum 25OHD levels at 6months (+3.00ng/ml, p=0.681) and 12months (+6.47ng/ml, p=0.002, respectively). Among patients who received chemotherapy, 49.5% were vitamin D sufficient at diagnosis but only 26.9% were sufficient 6months after finishing chemotherapy and this percentage increased to 45.2% at 12months. CONCLUSIONS: Vitamin D levels decrease during chemotherapy but recover after treatment ends. Anti-hormone therapy with tamoxifen causes serum vitamin D levels to increase. Whether the increased serum vitamin D affects the antitumour effect of the tamoxifen has yet to be determined.

Review: higher vitamin D status and supplementation may be associated with risks.

The prevalence of low vitamin D levels and associated risks has led to an increase in supplementation. However, a "U-shaped" relationship has been suggested between vitamin D status and adverse effects, with risks observed both in low and high levels. While risks associated with low levels of vitamin D have been extensively studied, the risks of higher levels of vitamin D have not been as widely circulated. We sought to describe key observed adverse risks with vitamin D supplementation and higher serum 25(OH)-D levels in healthy adult populations.