Autophagy participates in the protection role of 1,25-dihydroxyvitamin D3 in acute myocardial infarction via PI3K/AKT/mTOR pathway.

Vitamin D deficiency is associated with acute myocardial infarction (AMI); thus we aimed to explore improvement effects of 1,25-dihydroxyvitamin D3 (VD3) on the AMI and its potential mechanism. AMI models were constructed using male C57/BL6J mice and randomly treated with normal saline or VD3, using sham rats as control. Heart functions, myocardial damage, apoptosis, and inflammation were evaluated. Cardiomyocytes isolated from 3-day-old suckling mice were used for in vitro verification. After VD3 treatment, AMI-induced cardiac dysfunction was reversed with better cardiac function parameters. VD3 treatment reduced inflammatory cell infiltration and myocardial infarction area accompanied by the reduction of inflammatory factors and myocardial infarction markers compared with the AMI group. VD3 treatment obviously alleviated AMI-induced myocardial apoptosis, along with Bcl-2 upregulation and downregulation of caspase-3, caspase-9, and Bax. Both in vivo and in vitro experiments revealed that VD3 enhanced the expression of LC3II and Beclin-1 and decreased soluble p62. Furthermore, VD3 enhanced the AMI-caused inhibition of PI3K, p-AKT, and p-mTOR expression, which was conversely reversed by the addition of 3-methyladenine in vitro. The study highlights the improvement effects of VD3 on cardiac functions. We proposed a potential mechanism that VD3 protects against myocardial damage, inflammation, and apoptosis by promoting autophagy through PI3K/AKT/mTOR pathway.

The effect of vitamin D3 and thyroid hormones on the capillaroscopy-confirmed microangiopathy in pediatric patients with a suspicion of systemic connective tissue disease-a single-center experience with Raynaud phenomenon.

Raynaud phenomenon (RP) may be the first manifestation of a systemic connective tissue disease (SCTD). Early detection of dysfunction of small vessels called microangiopathy is essential for the diagnostic process. The focus of this single-center, retrospective study was to investigate the potential dependencies between microvascular image and laboratory markers measured in children with RP. The study analyzed the nail-fold video-capillaroscopy (NVC) findings and laboratory results of 81 children between the ages 6 and 17 who were referred to pediatric rheumatologist with a suspicion of SCTD. Out of 52 patients presenting with RP at the time of evaluation, abnormalities in capillary microscopic imaging were found in 34. NVC findings were then compared to levels of specific biomarkers in serum. Vitamin D3 serum levels have been significantly decreased in patients with RP (23.4 ng/mL ± 8.76 vs. 30.0 ng/mL ± 12.66, P = 0.0148). There were positive significant correlations between levels of vitamin D3 and acute-phase reactants in serum, such as C-reactive protein (P = 0.0292). Furthermore, free thyroxine levels (fT4) in patients with both RP (P = 0.0126) and micro-angiopathy (P = 0.05496) persisted in the lower range of the normal limit (< 1.0 ng/dL). Regular oral supplementation of vitamin D3 should be always considered in children with RP if deficiency is found. Additionally, low fT4 level (< 1.0 ng/dL) should be considered as an indication to perform NVC in patients suspected of SCTD even when they do not present RP.

Effect of vitamin D3 supplementation during pregnancy on high risk factors - a randomized controlled trial.

OBJECTIVES: Vitamin D plays an important role in the release of the placenta and implantation, and low levels are a risk factor for pre-eclampsia. Studies have also shown that symptomatic treatment of vitamin D3 deficiency can effectively reduce the risk of pre-eclampsia. In this study, vitamin D3 supplementation was performed on the risk of pre-eclampsia to observe its effect. METHODS: From January 2016 to December 2018, 450 women with maternal treatment and delivery in our hospital underwent an open-label randomized study. The pregnant women were divided into low-dose, medium-dose, and high-dose groups. Compare the incidence of pre-eclampsia and the dose effect of vitamin D levels. RESULTS: In the maternal and perinatal periods of the 450 maternal women, the 25[OH] index of the three groups of pregnant women was significantly increased, while the high-dose increase index was more obvious. The relative risk reduction rate was significantly lower. Compared with the low-dose and middle-dose groups, the high-dose group had a significantly lower incidence of pre-eclampsia, while the IUGR index was lower, and other obstetric indicators were comparable. CONCLUSION: Vitamin D supplementation can effectively reduce the incidence of pre-eclampsia, while reducing the IUGR index, which has important value and significance in its clinical application.

Is cholecalciferol a potential disease-modifying anti-rheumatic drug for the management of rheumatoid arthritis?

Vitamin D is a pleiotropic molecule with a well-characterised immunomodulatory activity in vitro; however, its potential clinical application in autoimmune conditions has yet to be clarified. Several authors have investigated the use of vitamin D as a disease-modifying anti-rheumatic drug (DMARD) in rheumatoid arthritis (RA), obtaining divergent conclusions. This systematic review summarises and critically analyses the findings of papers assessing the impact of vitamin D supplementation on pain relief, disease activity, functional status and flare rate. We conclude that the correction of hypovitaminosis D may have a beneficial effect on pain perception; moreover, the achievement of an adequate plasma vitamin D concentration obtained with high-dose regimens might evoke immunomodulatory activities of vitamin D and favourably impact on disease control. Nevertheless, the current evidence is still not strong enough to support the use of cholecalciferol as a DMARD in RA, and further studies are required to clarify this issue.

Free vitamin D levels in steroid-sensitive nephrotic syndrome and healthy controls.

INTRODUCTION: Body stores of vitamin D are measured as "total" serum 25-hydroxy vitamin D (25(OH)D). Its largest component is protein bound and lost in urine in nephrotic syndrome (NS). Our study investigates whether "free" 25(OH)D levels are a better guide to bone health and need for vitamin D supplementation in patients with steroid-sensitive NS (SSNS). METHODS: A cross-sectional study was performed in children with SSNS and healthy controls. Blood was tested for albumin, creatinine, calcium, phosphate, ALP, total and free (by direct ELISA) 25(OH)D, iPTH, and urine for protein-creatinine ratio. RESULTS: Seventy-nine NS patients (48 in relapse, 31 in remission) and 60 healthy controls were included. The levels of total 25(OH)D were significantly different (lowest in NS relapse and highest in controls) (p < 0.001). Corrected calcium and phosphate levels were normal, and there were no differences in free 25(OH)D, ALP, or iPTH levels between groups. Only total and not free 25(OH)D correlated significantly and negatively with urinary protein creatinine ratios (rs = - 0.42 vs. 0.04). Free 25(OH)D values of 3.75 and 2.85 pg/ml corresponded to total 25(OH)D levels of 20 and 12 ng/ml, respectively, in healthy controls. CONCLUSION: These results confirm that total 25(OH)D levels are low in NS and related to degree of proteinuria. However levels of free 25(OH)D, ALP, and iPTH did not change in relapse or remission in comparison with healthy controls. Our results suggest that in proteinuric renal diseases, free 25(OH)D rather than total 25(OH)D levels should be used to diagnose vitamin D deficiency and guide therapy.

Evaluation of vitamin D3 deficiency: A population-based study in northeastern Iran.

BACKGROUND AND AIM: In recent years, vitamin D deficiency has become a major worldwide problem that can exert harmful effects. The aim of the present study was to evaluate the sex- and age-related prevalence of vitamin D deficiency in people from Mashhad, northeastern Iran. METHODS: In this cross-sectional study conducted over a period of 1 year (2015-2016), 7504 subjects who referred to Mashhad medical centers were randomly enrolled in the study. The study population was divided into four groups based on sex and age, as following: group 1, 6 to 18 years; group 2, 19 to 35 years; group 3, 36 to 50 years; and group 4, 51 to 65 years. Since vitamin D levels <10, 10 to 20, and 20 to 30 ng/mL are considered as severe, moderate, and mild deficiency, respectively, we used these criteria for categorizing our population. RESULTS: Of the total population in our study, 65.26% (4902; 57.81% of men and 72.07% of women) showed some degree of vitamin D deficiency. In addition, we found that vitamin D deficiency was common in all age groups (6-18, 19-35, 36-50, and 51-65 years), and more common in women (58.5%, 80.12%, 63.83%, and 88.44%, respectively) than men (41.66%, 59.86%, 44.97%, and 84.75%, respectively). CONCLUSION: Vitamin D deficiency is a major health problem in all age groups and is more common in women. This information would help to provide a progressive prevention program to maintain health and manage some of the vitamin-related disorders and diseases that especially affect women.

Hypovitaminosis D exacerbates the DNA damage load in human uterine fibroids, which is ameliorated by vitamin D3 treatment.

Uterine fibroids (UFs) are the most common benign neoplastic threat to women's health and associated with DNA damage and genomic instability. Hypovitaminosis D is a known risk factor for UFs, especially among African Americans. Vitamin D3 has been shown to effectively inhibit UF phenotype, but its mechanisms remain unclear. We hypothesize that Vitamin D3 ameliorates UFs by recovering the damaged DNA repair system, thus inhibits tumor progression. We compared the DNA damage status and Vitamin D receptor (VDR) expression between normal myometrial and UF primary cells. Unrepaired DNA double-strand breaks (DSBs) accumulated but VDR expression decreased in UFs. The RNA and protein levels of key DNA repair members belonging to DNA DSB sensors (MRE11, NBS1, RAD50), mediators and effectors (CHECK2, BRCA1, RAD51) were downregulated in UFs compared with myometrial cells. VDR KD induced DSB accumulation and DNA damage response (DDR) defects in myometrial cells. Using the DNA damage PCR array, the expression of many additional DNA repair genes was downregulated in VDR KD cells. Treatment of UF cells with Vitamin D3 (100 nM) significantly decreased DNA damage and restored DDR concomitant with VDR induction. Notably, the PCR array demonstrated that among 75 downregulated genes after VDR KD, 67 (89.3%) were upregulated after vitamin D3 treatment. These studies demonstrate a novel link between DNA damage and the vitamin D3/VDR axis in UFs. Vitamin D3 suppresses the UF phenotype through orchestrated targeting at multiple molecules in DNA repair pathways, thus offering novel mechanistic insights into the clinical effectiveness of vitamin D3 on UFs.

Radiographic alveolar bone level and levels of serum 25-OH-Vitamin D3 in ethnic Norwegian and Tamil periodontitis patients and their periodontally healthy controls.

BACKGROUND: Studies suggest association between low serum 25-OH-Vitamin D3 (VitD) and chronic destructive periodontal diseases. The main sources of VitD is sun exposure and fat fish. Subjects with dark skin will therefore generate less VitD as response to sun exposure. The aim of the study was to assess the radiographic bone level and levels of serum VitD in ethnic Norwegian and Tamil periodontitis patients and their respective healthy controls. METHODS: Twenty-seven Tamil periodontitis patients living in Norway were compared to 21 Tamil controls as well as to 21 Norwegian periodontitis patients and 23 Norwegian controls. Marginal bone level was diagnosed on radiographs. VitD levels were diagnosed in blood samples by high-performance liquid chromatography-mass spectrometry. RESULTS: VitD levels were lower in Norwegian periodontitis patients than in controls, while no significant differences were observed between Tamil periodontitis patients and controls despite the significant difference between RBL between the periodontitis patients and controls in both groups. When calculating the odds ratio for having periodontal disease in both populations together, it appeared that one unit increased serum VitD (i.e. 1 nmol/L) decreased the odds of having radiographic bone loss by 4%. CONCLUSION: According to logistic regression, and after correcting for confounding factors, VitD levels showed significant association with the presence of periodontitis, as expressed by radiographic bone loss, in all patients combined.

Vitamin D deficiency and its health effects.

Vitamin D3 cholecalciferol is produced from its cholesterol precursors in the skin under the influence of ultraviolet calc. Its subsequent hydroxylation in the liver and kidneys leads to the formation of its most active metabolite calcitriol, which plays one of the key roles in the management of calcium phosphate metabolism. However, it also has the ability to regulate the function of a number of cells and tissues that express the vitamin D receptor. The most widespread method to evaluate the status of vitamin D in the body is to measure serum levels of its meta-bolite 25 hydroxyvitamin D - 25 (OH) D. Optimal values range between 75-125 nmoll / l. Its deficit is widespread in the human population worldwide and has a significant impact on the prevalence of metabolic bone diseases. Its deficiency may support the dysfunction of many other body systems. Ensuring optimal levels of vitamin D in the popula-tion is a challenge not only for health care and especially for government administration.

Effect of the dietary delivery matrix on vitamin D3 bioavailability and bone mineralisation in vitamin-D3-deficient growing male rats.

This study assessed bioavailability and utilisation of vitamin D3 in two feeding trials using young, growing Sprague-Dawley male rats. Trial one fed animals standard AIN-93G diet (casein protein) containing no vitamin D3 and goat or cow skimmed milk supplemented with vitamin D3. Trial two fed animals modified dairy-free AIN-93G diet (egg albumin) containing no vitamin D3 and goat or cow skimmed or full-fat milk supplemented with vitamin D3. Control groups received AIN-93G diets with or without vitamin D, and water. At 8 weeks of age, blood samples were collected for vitamin and mineral analysis, and femurs and spines were collected for assessment of bone mineralisation and strength. In both trials, analyses showed differences in bioavailability of vitamin D3, with ratios of serum 25-hydroxyvitamin D3 to vitamin D3 intake more than 2-fold higher in groups drinking supplemented milk compared with groups fed supplemented solid food. Bone mineralisation was higher in groups drinking supplemented milk compared with groups fed supplemented solid food, for both trials (P<0·05). There was no difference in the parameters tested between skimmed milk and full-fat milk or between cow milk and goat milk. Comparison of the two trials suggested that dietary protein source promoted bone mineralisation in a growing rat model: modified AIN-93G with egg albumin produced lower bone mineralisation compared with standard AIN-93G with casein. Overall, this study showed that effects of vitamin D3 deficiency in solid diets were reversed by offering milk supplemented with vitamin D3, and suggests that using milk as a vehicle to deliver vitamin D is advantageous.

1,25-Vitamin D3 Deficiency Induces Albuminuria.

Vitamin D plays an important role in renal (patho)physiology. Patients with glomerular diseases have an injured renal filtration barrier, leading to proteinuria and reduced renal function. An impaired renal function also leads to 1,25-vitamin D3 deficiency as a result of reduced renal 1α-hydroxylase activity. Vitamin D treatment to reduce proteinuria remains controversial, although there is an inverse correlation between vitamin D levels and proteinuria. Herein, we showed that 1,25-vitamin D3-deficient 25-hydroxy-vitamin-D3-1α-hydroxylase knockout mice and 1,25-vitamin D3-deficient rats develop podocyte injury and renal dysfunction. Glomerular injury was characterized by proteinuria and partial podocyte foot process effacement. Expression of nephrin, podocin, desmin, and transient receptor potential channel C6 in the podocyte was significantly altered in 1,25-vitamin D3-deficient animals. Supplementation with 1,25-vitamin D3 or 1,25-vitamin D2 prevented podocyte effacement or reversed glomerular and tubulointerstitial damage in 1,25-vitamin D3-deficient animals, thereby preserving and restoring renal function, respectively. The effect of 1,25-vitamin D3 deficiency and 1,25-vitamin D3 and 1,25-vitamin D2 repletion on proteinuria could not be explained by hypocalcemia, changes in parathyroid hormone, or fibroblast growth factor 23. This study demonstrates that 1,25-vitamin D3 deficiency directly leads to renal injury in rodents. Translated to human subjects, this would underline the need for early vitamin D supplementation in patients with glomerular disease and chronic renal insufficiency, which might inhibit or potentially reverse renal injury.

Vitamin D3 modulates the innate immune response through regulation of the hCAP-18/LL-37 gene expression and cytokine production.

INTRODUCTION: The steroid hormone metabolite of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25D3), promotes osteogenic activity and regulates calcium and phosphate metabolism, which are actions regarded as classical vitamin D-regulated functions. Besides its role in these processes, 1,25D3 also seems implicated in the host defense against microbial/pro-inflammatory attacks. Low serum levels of vitamin D3 (vitamin D deficiency) are associated with osteoporosis and increased risk of fractures but also inflammatory diseases and their disease progression, presumably via mechanisms associated with 1,25D3-evoked modulation of the innate immune system. 1,25D3 has been reported to modulate many inflammatory responses, suggesting that it regulates multiple transcriptional targets within the inflammatory system. RESULTS: Experimental studies in various experimental systems show that 1,25D3 differentially regulates the production of pro-inflammatory cytokines and chemokines depending on cell type. Importantly, many reports show that 1,25D3 up-regulates expression of the human antimicrobial peptide hCAP-18/LL-37 gene. The hCAP-18/LL-37 gene seems indeed to be an important transcriptional target for 1,25D3. However, only limited evidence is presented showing that 1,25D3 consistently increases the amount of biologically active LL-37 peptide. CONCLUSION: In the present review, we discuss 1,25D3-induced down-regulation of cytokine/chemokine production and stimulation of hCAP-18/LL-37 gene expression which represent two very important pathways for 1,25D3-evoked regulation of the innate immune response.

Vitamin D3-Supplemented Yogurt Drink Improves Insulin Resistance and Lipid Profiles in Women with Gestational Diabetes Mellitus: A Randomized Double Blinded Clinical Trial.

BACKGROUND: Our study aimed to examine the effects of daily consumption of vitamin D3-supplemented yogurt (VDY) drink on insulin resistance and lipid profiles in pregnant gestational diabetes mellitus (GDM) patients. METHODS: Participants aged 24-32 years in their second trimester were randomly assigned to consume either plain yogurt or VDY daily for 16 weeks. Metabolic and lipid profiles including levels of fasting plasma glucose (FPG), serum insulin, triacylglycerol (TAG), total cholesterol (TC) and low-density lipoprotein (LDL) were assessed at baseline (week 0) and end of trial (week 16). RESULTS: After 16 weeks of intervention, insulin-related variables including FPG and serum insulin levels were markedly lower in VDY group participants. Insulin resistance parameters, such as homeostasis model of assessment of insulin resistance and ß cell function, were also significantly reduced in VDY group participants. Moreover, levels of TAG, TC and LDL, as well as the TC to high-density lipoprotein ratio, had also significantly decreased in the VDY group. CONCLUSION: Daily consumption of VDY drink improves insulin resistance and lipid profiles in women with GDM.

Efficacy of high dose Vitamin D supplementation in improving serum 25(OH)D among migrant and non migrant population: a retrospective study.

BACKGROUND: Higher dose of vitamin D supplementation 50000 IU is required for those whose serum 25(OH)D levels are 50 nmol/L and below. The increment in serum 25(OH)D though not significantly affected by race, sex or age it is negatively correlated to the baseline 25(OH)D concentration. This study investigated whether the mean increase in serum 25(OH)D will be higher among participants with lower baseline 25(OH)D levels and whether the duration of supplementation has an influence on the serum 25(OH)D achieved. METHODS: A clinical audit of patients' medical records from a community health centre in Melbourne for the period 01.01.2010 to 31-12.2012 was undertaken. Paired sample t test was used to determine difference in pre and post dose serum 25(OH)D. Simple and multiple linear regressions were used to examine the association between the difference in pre and post dose serum 25(OH)D and duration of supplementation and baseline serum 25(OH)D, adjusting for socio-demographic factors. RESULTS: A total of 205 patients were included in the study. Mean difference in serum 25(OH)D was highest 52.8 nmol/L (95 % CI: 46.63-58.92) among those whose serum 25(OH)D was below 25 nmol/L at baseline. Baseline 25(OH)D alone accounted for 13.7 % of variance in the effect size (F(2, 202) = 16.0. p < 0.001), with the effect size significantly higher among participants with a baseline 25(OH)D level of 25-49 nmol/L (ß = 11.93, 95 % CI: 0.48, 23.40, p < 0.05). Mean serum 25(OH)D difference was highest, 47.53 nmol/L (95 % CI: 40.95-54.11) when measured within 3 months of supplementation. Duration of supplementation explained 2.9 % of the variance in the effect size (F (1, 203) = 6.11, p < 0.05) and there was an inverse relationship between the length of supplementation and mean pre and post supplementation serum 25(OH)D difference (ß = -1.45, 95 % CI: -2.62, -0.29, p = 0.014). CONCLUSION: Following 50000 IU vitamin D3 for 12 months mean serum 25(OH)D increase was highest among those whose baseline serum 25(OH)D was lower. Migrants especially dark-skinned are at a high risk for vitamin D deficiency in Australia. High dose vitamin D3 50000 IU (cholecalciferol) is effective in achieving sufficient serum 25(OH)D among these populations who tend to have lower baseline serum 25(OH)D.

Does Vitamin D3 Have an Impact on Clinical and Biochemical Parameters Related to Third Molar Surgery.

The purpose of this study was to evaluate the clinical effect on the biochemical inflammatory markers of a single oral high dose of cholecalciferol in vitamin D-deficient patients undergoing the surgical removal of lower third molars.A randomized, split-mouth, single-blind study was conducted on 25 vitamin D-deficient patients ranging between 18 and 40 years of age requiring lower third molars extraction and referred at the Oral Surgery Unit of the School of Dentistry of the University of Messina.All patients, with vitamin D3 blood levels ≦30 ng/mL, underwent bilateral surgical removal. The first extraction (control group) being conducted with the administration of a placebo, the second one (test group) being conducted with the preliminary administration of 300,000 IU of cholecalciferol 4 days before the procedure.At each surgery, clinical indexes, such as pain, edema and any functional limitation have been recorded. Clinical and biochemical parameters were registered 4 days before, immediately after, 3 and 7 days after the surgical procedure. The data obtained were processed using paired t-test. The clinical outcome parameters showed a slight to moderate improvement between the control and the vitamin-D treatment group, with statistical significance being obtained regarding the edema at defined time points. Interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha values were significantly lower (P < 0.01) for the test group after the surgery. The increase of vitamin D serum levels showed an impact on the outcome of the third molar surgery, eliciting a reduced inflammatory response and leading to a more favorable clinical course.

The nonskeletal effects of vitamin D3 and the threshold limit associated with the risk of health complications.

OBJECTIVE: To evaluate the threshold limit of vitamin D3 associated with the risk of nonskeletal health complications in humans. BACKGROUND: Vitamin D3 deficiency is primary caused by a reduced sun exposure, consequent limiting of vitamin D3 production in the skin, and low intake of food with this vitamin. METHODS: Ninety-two adults (25-95 years old) were admitted to III. Internal clinic or examined in outpatient department of The University hospital in Bratislava. Vitamin D3 levels were determined using electrochemical luminescence immunoassay. The least square method for the results processing was used. RESULTS: Vitamin D3 level 16 ng/ml may be threshold limit for the risk of hypertension, ischaemic heart disease, renal insufficiency and diabetes mellitus. A higher occurrence of the observed diseases was in female and male patients with vitamin D3 levels<16 ng/ml.The highest increase of occurrence of diabetes mellitus in women for vitamin D3<16 ng/ml (160%) compared to vitamin D3≥16 ng/ml (40%) was observed. Concerning the men, the highest increase refers to ischaemic heart disease (67%). CONCLUSION: The limit value of vitamin D3, 16 ng/ml, confirmed the association between vitamin D3 insufficiency and the presence of hypertension, ischaemic heart disease, renal insufficiency and diabetes mellitus. Its relation to age, sex and other variables was detected (Tab. 1, Fig. 5, Ref. 27).

Dietary vitamin D3 deficiency alters intestinal mucosal defense and increases susceptibility to Citrobacter rodentium-induced colitis.

Vitamin D deficiency affects more that 1 billion people worldwide. Although thought to increase risk of bacterial infections, the importance of vitamin D on host defense against intestinal bacterial pathogens is currently unclear since injection of the active form of vitamin D, 1,25(OH)2D3, increased susceptibility to the enteric bacterial pathogen Citrobacter rodentium by suppressing key immune/inflammatory factors. To further characterize the role of vitamin D during bacteria-induced colitis, we fed weanling mice either vitamin D3-deficient or vitamin D3-sufficient diets for 5 wk and then challenged them with C. rodentium. Vitamin D3-deficient mice lost significantly more body weight, carried higher C. rodentium burdens, and developed worsened histological damage. Vitamin D3-deficient mice also suffered greater bacterial translocation to extra-intestinal tissues, including mesenteric lymph nodes, spleen, and liver. Intestinal tissues of infected vitamin D3-deficient mice displayed increased inflammatory cell infiltrates as well as significantly higher gene transcript levels of inflammatory mediators TNF-α, IL-1ß, IL-6, TGF-ß, IL-17A, and IL-17F as well as the antimicrobial peptide REG3γ. Notably, these exaggerated inflammatory responses accelerated the loss of commensal microbes and were associated with an impaired ability to detoxify bacterial lipopolysaccharide. Overall, these studies show that dietary-induced vitamin D deficiency exacerbates intestinal inflammatory responses to infection, also impairing host defense.

Vitamin D deficiency decreases survival of bacterial meningoencephalitis in mice.

BACKGROUND: Meningoencephalitis caused by Escherichia coli is associated with high rates of mortality and risk of neurological sequelae in newborns and infants and in older or immunocompromised adults. A high prevalence of neurological disorders has been observed in geriatric populations at risk of hypovitaminosis D. METHODS: In vivo, we studied the effects of vitamin D3 on survival and the host's immune response in experimental bacterial meningoencephalitis in mice after intracerebral E. coli infection. To produce different systemic vitamin D3 concentrations, mice received a low, standard, or high dietary vitamin D3 supplementation. Bacterial titers in blood, spleen, and brain homogenates were determined. Leukocyte infiltration was assessed by histological scores, and tissue cytokine or chemokine concentrations were measured. RESULTS: Mice fed a diet with low vitamin D3 concentration died earlier than control animals after intracerebral infection. Vitamin D deficiency did not inhibit leukocyte recruitment into the subarachnoid space and did not lead to an increased density of bacteria in blood, spleen, or brain homogenates. The release of proinflammatory interleukin (IL)-6 was decreased and the release of anti-inflammatory IL-10 was increased in mice fed a diet with high vitamin D3 supplementation. CONCLUSION: Our observations suggest a detrimental role of vitamin D deficiency in bacterial central nervous system infections. Vitamin D may exert immune regulatory functions.

Maternal vitamin D supplementation during pregnancy prevents vitamin D deficiency in the newborn: an open-label randomized controlled trial.

OBJECTIVE: To determine whether maternal vitamin D supplementation, in the vitamin D deficient mother, prevents neonatal vitamin D deficiency. DESIGN: Open-label randomized controlled trial. SETTING: Metropolitan Melbourne, Australia, tertiary hospital routine antenatal outpatient clinic. PARTICIPANTS: Seventy-eight women with singleton pregnancies with vitamin D deficiency/insufficiency (serum 25-OH Vit D < 75 nmol/l) at their first antenatal appointment at 12-16-week gestation were recruited. INTERVENTION: Participants were randomized to vitamin D supplementation (2000-4000 IU cholecalciferol) orally daily until delivery or no supplementation. MAIN OUTCOME MEASURES: The primary outcome was neonatal serum 25-OH vit D concentration at delivery. The secondary outcome was maternal serum 25-OH vit D concentration at delivery. RESULTS: Baseline mean maternal serum 25-OH vit D concentrations were similar (P = 0·9) between treatment (32 nmol/l, 95% confidence interval 26-39 nmol/l) and control groups (33 nmol/l, 95% CI 26-39 nmol/l). Umbilical cord serum 25-OH vit D concentrations at delivery were higher (P < 0·0001) in neonates of treatment group mothers (81 nmol/l, 95% CI; 70-91 nmol/l) compared with neonates of control group mothers (42 nmol/l, 95% CI; 34-50 nmol/l) with a strongly positive correlation between maternal serum 25-OH Vit D and umbilical cord serum 25-OH vit D concentrations at delivery (Spearman rank correlation coefficient 0·88; P < 0·0001). Mean maternal serum 25-OH Vit D concentrations at delivery were higher (P < 0·0001) in the treatment group (71 nmol/l, 95% CI; 62-81 nmol/l) compared with the control group (36 nmol/l, 95% CI; 29-42 nmol/l). CONCLUSION: Vitamin D supplementation of vitamin D deficient pregnant women prevents neonatal vitamin D deficiency.

The effect of vitamin D supplements on the severity of restless legs syndrome.

PURPOSE: Clinical observation hinted improved symptoms of restless legs syndrome (RLS) after vitamin D supplements. Hence, the aim of this study is to evaluate the effect of vitamin D supplementation on the severity of RLS symptoms. METHODS: Twelve adult subjects diagnosed with primary RLS and vitamin D deficiency were recruited. Patients with secondary RLS were excluded from this study. The complete cell count; serum levels of ferritin, iron, glycated hemoglobin, and vitamin D3 (25 (OH) vitamin D); and renal and bone profiles of the patients were assayed. Patients with vitamin D deficiency (<50 nmol/l) were treated with vitamin D3 supplements (high oral dose or intramuscular injection). The severity scores of RLS were reassessed after the vitamin D3 level was corrected to >50 nmol/l and compared with those before the administration of the supplements. RESULTS: The median pretreatment vitamin D level was 21.7 nmol/l (13.45-57.4), which improved to 61.8 nmol/l (42.58-95.9) (P = 0.002) with the treatment. The median RLS severity score improved significantly from 26 (15-35) at baseline to 10 (0-27) after correction of the vitamin D levels (P = 0.002). CONCLUSION: This study indicates that vitamin D supplementation improves the severity of RLS symptoms and advocates that vitamin D deficiency is conceivably associated with RLS.