Different Doses Of Vitamin D3 Research Articles

In vivo electrophysiological study of vitamin D3 protective effects on PTZ-induced seizures in rats.

The purpose of the current study was to investigate the protective effects of acute and chronic administration of different doses of vitamin D3 on pentylenetetrazol (PTZ)-induced epileptiform activities in rats. Sixty Wistar rats in chronic and acute groups were used in this study. In the chronic groups, animals received vitamin D3 at 50, 100, and 150 μg/kg; vitamin D3 (50 μg/kg, i.p.) + diazepam (0.1 mg/kg, i.p.), and almond oil (i.p.) daily for two weeks whereas, in the acute groups the animal received a single dose of chemicals just 30 min before PTZ administration. The electrophysiological recording was performed by implanting a unilateral bipolar electrode in the pyramidal cell layer of the CA1 region of the hippocampus. Epileptic activities were induced by intraperitoneal injection of PTZ (80 mg/kg, i.p.). The spike count and amplitude were analyzed using the eTrace software. Chronic administration of all doses of vitamin D3 and its combination with diazepam significantly reduced both spike counts and amplitudes following PTZ administration. While the acute doses were ineffective. The results of the study indicated that chronic but not acute administration of vitamin D3 has a protective effect on PTZ-induced epileptiform activity in rats.

A Comparison between Vitamin D3 and 25-Hydroxyvitamin D3 on Laying Performance, Eggshell Quality and Ultrastructure, and Plasma Calcium Levels in Late Period Laying Hens.

Simple SummaryThe sharp decline of laying performance and eggshell quality is a common problem in late period laying hens. Vitamin D3 (VD3) is a necessary micronutrient which plays an important role in mineral and skeletal homeostasis. With the rapid development of genetic selection, commercial laying hens have increased requirements for performance and nutrients. The commercial supplementary dose of VD3 (62.5 µg/kg) for late period laying hens may be not enough to satisfy the production. In addition, 25-hydroxyvitamin D3 (25-OHD3) as an active metabolite of VD3, is a viable alternative to replace VD3. Therefore, the objective of this study was to compare the effects of different supplementary doses and sources between VD3 and 25-OHD3 on the laying performance and eggshell quality in late period laying hens. The results showed that supplementary 125 µg/kg doses of VD3 or 25-OHD3 had better effects in late period laying hens compared with 62.5 µg/kg doses of VD3. Additionally, there were no different effects on laying performance or eggshell quality in the hens fed dietary 125 µg/kg doses of VD3 or 25-OHD3.The objective of this study was to compare high supplementary doses (125 µg/kg) of vitamin D3 (VD3) or 25-hydroxyvitamin D3 (25-OHD3) with commercial supplementary doses (62.5 µg/kg) of VD3 on laying performance, eggshell quality and ultrastructure, and plasma calcium levels in late period laying hens. A total of 1512 Roman Gray (60-week-old) laying hens were allotted into three treatments with 12 replicates and 42 birds in each replicate. During the 12-week trial period, the layers were fed a basal diet supplemented with different doses of VD3 or 25-OHD3 (62.5 µg/kg VD3 in control group, CON; 125 µg/kg VD3 in high level VD3 group, VD3; 125 µg/kg 25-OHD3 in high level 25-OHD3 group, 25-OHD3). The results showed that high supplementary doses of VD3 or 25-OHD3 increased laying rate (p < 0.05). Moreover, the layers fed high doses of VD3 or 25-OHD3 diets had decreased unqualified egg rate and mortality (p < 0.05). High supplementary doses of VD3 or 25-OHD3 increased eggshell strength and eggshell thickness (p < 0.05). From observation in eggshell ultrastructure, high doses of VD3 or 25-OHD3 diets increased the palisade layer thickness and mammillary knob density (p < 0.05). Furthermore, high doses of VD3 or 25-OHD3 diets increased the calcium levels in plasma (p < 0.05). In summary, compared with 62.5 µg/kg doses of VD3, supplementary 125 µg/kg doses of VD3 or 25-OHD3 improved the laying performance, eggshell quality, and plasma calcium levels in late period laying hens. Additionally, there was an equal effect on laying performance and eggshell quality in the hens fed dietary 125 µg/kg doses of VD3 or 25-OHD3.

Influence of vitamin D on the histostructure of the testis and morphometric indications of spermatogenesis of intact rats

One of the current problems is the study of the effects of vitamin D on the body, and in men its action is closely related to the pathogenesis of androgen deficiency and hypofertility. Particular attention needs to be paid to determining whether cholecalciferol (D3) has a negative effect on the gonads and spermatogenesis of intact individuals, as vitamin D therapy is used in reproductive disorders with or without vitamin D deficiency. The aim of the study was to determine the effect of vitamin D on the histological structure of gonads and morphometric parameters of spermatogenesis of adult intact male rats. The studies were performed on adult sexually active male Wistar rats. Vitamin D3 was administered orally in doses of 1000 IU, 4000 IU and 10000 IU. The solutions were made on seed oil. The control was intact rats. Vitamin D and its solvent were administered throughout the period of spermatogenesis and the time of maturation of sperm in the epididymis, after which the structural organization of the testes was determined. Gonadal samples were fixed in 10 % formalin solution, leave in alcohols of increasing strength, and embedded in paraffin. In addition to survey microscopy, morphometric evaluation of the process of spermatogenesis was performed on sections of gonads stained with hematoxylin and eosin. Micropreparations were examined using a Granum L 30 (03) light microscope, and microscopic images were taken with a Granum DSM 310 digital video camera. Photographs were processed on a Pentium 2.4 GHz computer using Toup View. Statistical processing of data results was performed in the standard software package "Statistica 6.0" using Student's t-test and using a non-parametric analogue of one-way analysis of variance – Kruskal-Wallis criterion. In rat testicular sections, seminiferous tubules were located transversely or obliquely and were oval or round in shape. The diameter of the tubules is normal, the tubular membrane, as well as the protein and vascular membranes were normal. The basal department contains the youngest cells of the germinal epithelium – spermatogonia. Cells have a pronounced functional activity. Morphometric characteristics of spermatogenesis of intact rats corresponded to the physiological norm. The introduction of the solvent throughout the period of spermatogenesis and maturation of mature sperm in the epididymis did not affect the histoarchitectonics of the testicles. The testicular lobes are filled with concentric or flattened profiles of sections of the seminal tubules, which are close enough to each other. The diameter of the tubules is normal, the intrinsic membrane of the tubules, as well as the protein and vascular membranes corresponded to those in intact animals. 3-4 generations of spermatogenic cells, which were at different stages of development, can be seen in the tubules. However, few tubules with focal destruction of the germinal epithelium and exfoliation of germ cells in the lumen of the tubules have been observed. No significant changes in the microstructure of the seminal tubules were observed after administration of vitamin D at all doses studied. Not only spermatogenesis but also spermiogenesis is clearly traced in different tubules of rats – stages of cellular transformations from spermatid to sperm. Morphometric parameters of the process of spermatogenesis of rats receiving different doses of vitamin D3 do not differ from those of intact rats. Thus, the use of vitamin D in these doses revealed the safety of its effect on the number of spermatogonia and tubules with stage 12 meiosis. When cholecaciferol was used in male rats for 68 days, the spermatogenesis index remained at the level of animals that did not receive the test substance. The use of vitamin D3 in intact adult male rats does not adversely affect the histological structure of the testes.

An emerging role of vitamin D3 in amino acid absorption in different intestinal segments of on-growing grass carp (Ctenopharyngodon idella).

Vitamin D3 (VD3), an essential nutrient for animals, has been demonstrated to stimulate the uptake of certain amino acids. However, the role of VD3 in the intestine, the primary site for digestion and absorption of nutrients, remains poorly characterized. Here, the grass carp (Ctenopharyngodon idella) was studied to assess the influence of different doses of VD3 (15.2, 364.3, 782.5, 1,167.9, 1,573.8, and 1,980.1 IU/kg) on growth performance, intestinal morphology, digestive absorption, amino acid transport, and potential signaling molecule levels in a feeding experiment. As a result, dietary VD3 improved growth performance, intestinal structure, and digestive and brush border enzyme activities. Additionally, most intestinal free amino acids and their transporters were upregulated after VD3 intake, except for Ala, Lys, Asp, Leu, solute carrier (SLC) 7A7, SLC1A5, and SLC1A3 mRNA in different segments, Leu and SLC6A14 mRNA in the proximal intestine, and SLC7A5 mRNA in the mid and distal intestine. In the crucial target of rapamycin (TOR) signal pathway of amino acid transport, the gene and protein expression of TOR, S6 kinase 1, and activating transcription factor 4 were elevated, whereas 4E-binding protein 1 was decreased, further suggesting an advanced amino acid absorption capacity in the fish due to VD3 supplementation. Based on percentage weight gain, feed efficiency, and trypsin activity, the VD3 requirements of on-growing grass carp were estimated to be 968.33, 1,005.00, and 1,166.67 IU/kg, respectively. Our findings provide novel recommendations for VD3 supplementation to promote digestion and absorption capacities of fish, contributing to the overall productivity of aquaculture.

Therapeutic effect of acute and chronic use of different doses of vitamin D3 on seizure responses and cognitive impairments induced by pentylenetetrazole in immature male rats

Objective(s):This study aimed to evaluate the effects of acute and chronic intake of different doses of vitamin D3 on seizure responses and cognitive impairment induced by pentylenetetrazole (PTZ) in immature male rats.Materials and Methods:Sixty-six immature male NMRI rats were divided into control (10), epileptic (10), and treatment groups (46). The stage 5 latency (S5L) and stage 5 duration (S5D) were assessed along with the shuttle box test. Levels of antioxidant enzymes and inflammatory factors along with genes involved in inflammation, oxidative damage, apoptosis, and mTORc1 were measured in the hippocampus tissue of the brain of controlled and treated rats. Serum levels of parathyroid hormone (PTH), vitamin D, calcium, and phosphorus were also assessed.Results:The results showed that the ability to learn, memory consolidation, and memory retention in epileptic rats were reduced. In addition, S5D increased and S5L decreased in epileptic rats, while being effectively ameliorated by chronic and acute vitamin D intake. The results showed that vitamin D in different doses acutely and chronically decreased the levels of oxidative and inflammatory biomarkers in hippocampus tissue and inhibited the expression of genes involved in inflammation, oxidative damage, apoptosis, and mTORc1 in the hippocampus tissue of epileptic rats. Conclusion:The results showed that vitamin D in different doses acutely and chronically could improve cognitive impairments and convulsive responses in epileptic rats by improving neurotransmission, inflammation, apoptosis, and oxidative damage.

Vitamin D3 Supplement Attenuates Blood-Brain Barrier Disruption and Cognitive Impairments in a Rat Model of Traumatic Brain Injury.

This study was designed to study the effects of vitamin D3 supplementation on the cognitive dysfunction and neurological function of traumatic brain injury (TBI) and the possible underlying mechanisms. To this purpose, different doses of vitamin D3 were intraperitoneally injection to TBI rats for one week before TBI surgery and three consecutive weeks after TBI. Brain edema evaluation was conducted on the third day and Evans blue staining for blood-brain barrier (BBB) permeability on the seventh day after TBI. Rat behavior was assessed by evaluation of neurological scores and morris water maze. It was revealed that vitamin D levels increased in serum after the administration of vitamin D3 for one week. TBI led to neurological deficit, together with brain edema, BBB disruption and inflammation. Vitamin D3 supplement ameliorated neurological deficit and cognitive impairments induced by TBI. Vitamin D3 administration reduced brain edema and impairments of blood-brain barrier induced by TBI, as well as decreased inflammatory response in TBI rat brain. Our results showed that vitamin D3 administration alleviated neurobehavioral deficits and improved brain edema after TBI. Vitamin D3 inhibited inflammatory cytokines and decreased BBB disruption in TBI rats. Vitamin D3 may be used for the treatment of TBI as a protective intervention.

Effects of Parenteral Vitamin D3 Supplementation on Hematological Parameters of Healthy Holstein Bulls.

Vitamin D has been shown to play physiological functions beyond calcium and phosphorus homeostasis and control bone metabolism in the body since its cellular receptors are present in numerous tissues. A total of 20 healthy bulls were divided into four groups to evaluate the effect of different doses of vitamin D3 on the number of bovine blood cells. Groups A, B, C, and D received 11,000, 22,000, 33,000, and 44,000 units/kg of vitamin D3, respectively. The control group was injected with 10 ml of physiological saline intramuscularly. Blood samples were taken before the injection, as well as 2, 4, and 6 days after the injection; furthermore, the white blood cell counts (including granulocytes and lymphocytes), hematocrit, haemoglobin, and platelets were examined by a cell counter. The results showed that vitamin D could cause leukopenia (e.g., neutropenia and lymphopenia), thrombocytopenia, as well as an increase in hematocrit and hemoglobin levels in the blood. Although the mentioned increase or decrease is largely dose- and time-dependent, the first and best group to indicate this is group B. To find the second group, the investigation of the long-term effects of injections, especially in high doses, and evaluation of different tests are required with larger groups over a longer period.

Supplementation with high-dose cholecalciferol throughout pregnancy induces fetal growth restriction through inhibiting placental proliferation and trophoblast epithelial-mesenchymal transition

Vitamin D deficiency has been associated with adverse pregnant outcomes. Several studies investigated the effects of maternal vitamin D3 supplementation on fetal development with inconsistent results. The aim of this study was to investigate the effects of maternal supplementation with different doses of vitamin D3 on fetal development. Pregnant mice were administered with different doses of cholecalciferol (0, 2,000, 10,000, 40,000 IU/kg/day) by gavage throughout pregnancy. Fetal weight and crown-rump length were measured. Placental proliferation and mesenchymal characteristics were detected. HTR-8/SVneo cells were incubated in the absence or presence of calcitriol (500 nmol/L) to evaluate the effects of active vitamin D3 on migration and invasion of human trophoblast cells. Although a low dose of cholecalciferol was safe, fetal weight and crown-rump length were decreased in dams treated with high-dose cholecalciferol throughout pregnancy. Placental weight and labyrinth thickness were reduced in mice administered with high-dose cholecalciferol. An obvious calcification was observed in placentae of mice administered with high-dose cholecalciferol. Ki67-positive cells, a marker of placental proliferation, were reduced in mice administered with high-dose cholecalciferol. N-cadherin and vimentin, two mesenchymal markers, were decreased in cholecalciferol-treated mouse placentae and calcitriol-treated human trophoblast cells. MMP-2 and MMP-9, two matrix metalloproteinases, were downregulated in cholecalciferol-treated mouse placentae and calcitriol-treated human trophoblast cells. In addition, trophoblast migration and invasion were suppressed by calcitriol. Supplementation with high-dose cholecalciferol induces fetal growth restriction partially through inhibiting placental proliferation and trophoblast epithelial-mesenchymal transition.

Daily vitamin D3 in overweight and obese children and adolescents: a randomized controlled trial.

To assess the efficacy of different doses of vitamin D3 on serum 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone(iPTH), calcium, phosphorus, and alkaline phosphatase concentrations in overweight and obese school-children. A total of 378 children and adolescents, 6-13years of age, with age- and sex-specific body mass index(BMI) Z-score ≥ 1(according to the World Health Organization criteria) were allocated to receive 600, 1000, and 2000IU vitamin D3/days. 25(OH)D, iPTH, calcium, phosphorus, and alkaline phosphatase concentrations were measured at baseline, 6, and 12months. In this intention-to-treat analysis, we fitted a linear mixed effect model involving a random effect of participants within treatment groups and fixed effects of dose, time, and their interactions. Mean(SD) of age and BMI Z-score were 9.3 (1.7)years and 2.55 (0.73), respectively. The median (IQR) for 25(OH)D was 11.5 (8.9), 11.7 (10.5), 12.2 (10.2) ng/mL (28.75, 29.25, and 30.50nmol/L) at baseline and 23.1 (8.0), 25.6 (8.3), 28.6 (10.4) ng/mL (57.75, 64.00, and 71.50nmol/L) at the end of 12months in 600, 1000, and 2000IU, respectively (p values for dose, time, and the interaction being < 0.0001, < 0.0001,and 0.082, respectively). Prevalence of vitamin D deficiency (< 20ng/mL) was 80.2, 77.5, and 75.5% in 600, 1000, and 2000IU groups at baseline, respectively, which decreased to 34, 18.4, and 7.5%, respectively, at 12months. Patterns of iPTH, calcium, phosphorus, and alkaline phosphatase response over time did not differ significantly among groups (p values = 0.452, 0.670, 0.377, 0.895, respectively). Increases in 25(OH)D concentration were found with supplementation of 1000 and 2000IU, compared with 600IU/days, whereas there was no evidence of iPTH suppression or change in serum calcium, phosphorus, and alkaline phosphatase among children with excess weight.

Vitamin D3 Activates Phosphatidylinositol-3-Kinase/Protein Kinase B via Insulin-Like Growth Factor-1 to Improve Testicular Function in Diabetic Rats.

Objective In diabetes mellitus, vitamin D3 deficiency affects sex hormone levels and male fertility; however, the mechanism leading to the disorder is unclear. This research was designed to investigate the mechanism of vitamin D3 deficiency and hypogonadism in diabetic rats. Our aim was to assess serum vitamin D3 levels and the relationship among vitamin D3, insulin-like growth factor-1 (IGF-1), and testicular function. Materials and Methods Rats with streptozotocin-induced diabetes were randomly divided into four groups and treated with different doses of vitamin D3: no vitamin D3, low (0.025 μg/kg/day), high (0.1 μg/kg/day), and high (0.1 μg/kg/day) with JB-1 (the insulin-like growth factor-1 receptor inhibitor group, 100 μg/kg/day). The groups were compared with wild-type rats, which function as the control group. Various parameters such as vitamin D3 and IGF-1 were compared between the experimental and wild-type groups, and their correlations were determined. Results Twelve weeks of vitamin D3 supplementation improved the testosterone levels, as shown by the increase in the level of serum IGF-1 in diabetic rats. Phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT), which was a downstream of the signaling pathway of IGF-1, was significantly increased after vitamin D3 treatment. Conclusions The study shows that vitamin D3 may promote the expression of testosterone and improve testicular function in diabetic rats by activating PI3K/AKT via IGF-1.

Neuroprotective Effect of Different Doses of Vitamine D3 in Diabetic-Induced Alzheimer Rat Model

Background: Many studies revealed that diabetes is an independent risk factor for developing cognitive dysfunction, and Alzheimer. During diabetes, overexpression of nitric oxide, tumor necrosis factor, interleukin-6 and interleukin-1 beta could lead to Aβ accumulation and neuronal death. &#x0D; Aim: To examine the neuroprotective effect of different doses of vitamin D3 against diabetic-induced cognitive dysfunction in rats. Moreover, possible underlying mechanisms were also investigated.&#x0D; Methods: High-fat diet plus streptozotocin were used to induce diabetes in Westar rats. We sub-grouped the diabetic rats into six subgroups, positive control, vitamin D3 groups (100, 500 and 1000 IU/kg/day), vitamin D3 plus rivastigmine, and rivastigmine monotherapy. After the induction of diabetes, we started treatment for sixteen months. Morris water maze test was used to evaluate cognitive function, followed by estimation of beta-amyloid-42, inducible nitric oxide synthase, nitric oxide, tumor necrosis factor, interleukin-6, and interleukin-1β levels in the hippocampus by ELIZA kits.&#x0D; Results: Vitamin D3 treatment significantly (p&lt;0.05) and dose-dependently mitigated cognitive deficits observed in Morris water maze test, with significant, suppresses in beta-amyloid-42 and nitric oxide synthase pathway via attenuated hippocampal inducible nitric oxide synthase and nitric oxide overproduction (p&lt;0.05). Moreover, vitamin D3 decreased inflammation state of diabetic rats brains by significantly lowered (p&lt;0.05) pro-inflammatory cytokines levels including, tumor necrosis factor, interleukin-6 and interleukin-1β as an underlying mechanism for the resulted improvement.&#x0D; Conclusion: The results of this research suggest that upregulation of nitric oxide synthase pathway along with the increase in pro-inflammatory cytokines is critically involved in cognitive dysfunction associated with diabetes. Vitamin D3 can ameliorate these effects and has a promising neuroprotective effect in diabetic-induced cognitive dysfunction.

Impact of three different daily doses of vitamin D3 supplementation in healthy schoolchildren and adolescents from North India: a single-blind prospective randomised clinical trial.

In India, there is a lack of information about the adequate daily dose of vitamin D3 supplementation in school children. Hence, we undertook this study to evaluate the adequacy and efficacy of different doses of vitamin D3 in schoolchildren. A total of 1008 vitamin D-deficient (VDD) children, aged 6-16 years with serum 25-hydroxyvitamin D (25(OH)D) levels &lt;50nmol/l, were cluster randomised into three groups (A-344, B-341 and C-232) for supplementation (600, 1000 and 2000 IU daily) of vitamin D3 under supervision for 6 months. Of the 1008 subjects who completed the study, 938 (93 %) were compliant. Baseline and post-supplementation fasting blood and urine samples were evaluated for Ca, phosphates, alkaline phosphatase, 25(OH)D and parathormone and urine Ca:creatinine ratio. The mean age of the subjects was 11·7 (sd 2·4) years, and the overall mean baseline serum 25(OH)D level was 24·3 (SD 9·5)nmol/l. Post-supplementation rise in serum 25(OH)D in compliant group was maximum with 2000 IU (70·0 (SD 30·0)nmol/l), followed by 1000 IU (46·8 (SD 22·5)nmol/l) and 600 IU (36·5 (SD 18·5)nmol/l), and serum 25(OH)D levels of ≥50nmol/l were achieved in 71·5, 81·8 and 92·9 % by groups A, B and C, respectively. Secondary hyperparathyroidism decreased from 31·7 to 8·4 % post-supplementation. Two participants developed hypercalciuria, but none developed hypercalcaemia. Children with VDD benefit maximum with the daily supplementation of 2000 IU of vitamin D3. Whether recommendations of 400 IU/d by Indian Council of Medical Research or 600 IU by Indian Academy of Pediatrics or Institute of Medicine would suffice to achieve vitamin D sufficiency in children with VDD remains debatable.

Therapeutic and maintenance regimens of vitamin D3 supplementation in healthy adults: A systematic review

Studies carried out assessing the effect of different doses of cholecalciferol (vitamin D3) on correcting serum 25-hydroxyvitamin D deficiency in healthy adults are limited and review studies are lacking. Moreover, the maintenance dose and its duration offered by these few studies are inconsistent. We performed a systematic review of randomized clinical controlled trials (RCTs) that assessed the effect of different doses of vitamin D3 on serum 25(OH)D in healthy adults. PubMed database was searched from 2010 to 2018 using the following search terms: "vitamin D deficiency", "Cholecalciferol", "vitamin D3 dose", "vitamin D supplement", "vitamin D therapy". RCTs and original articles that evaluated different doses of vitamin D3 were identified. A total of sixteen (out of 3016) acceptable studies fulfilling our inclusion criteria were included in the current systematic review. Our results revealed that supplementation with vitamin D3 had a significant positive effect in raising serum 25(OH) D concentrations. Our findings indicated that the best regimen of vitamin D3 supplement consisted of an initial large bolus dose either IM injection of 600.000 IU monthly or oral dose of 200.000 IU monthly or 50.000 IU weekly for 8 weeks, followed by a maintenance dose of 50.000 IU monthly or bimonthly. A large bolus therapeutic dose of vitamin D3, frequently or infrequently for 8 weeks, followed by long-term oral maintenance dose of 50.000 IU monthly or bimonthly optimiz and manitain vitamin D serum levels year round.

Supplementation with Three Different Daily Doses of Vitamin D3 in Healthy Pre-pubertal School Girls: A Cluster Randomized Trial

To compare the adequacy and efficacy of different doses of vitamin D3 in pre-pubertal girls. Cluster Randomized controlled trial. Public school in Delhi, India, between August 2015 and February 2016. 216 healthy pre-pubertal girls, aged 6.1-11.8 years. Daily supplementation with 600 IU (n=74), 1000 IU (n=67) or 2000 IU (n=75) of vitamin D3 under supervision for 6 months. Primary: Rise in serum 25 hydroxy Vitamin D (25(OH)D); Secondary: Change in bone formation and resorption markers. Following 6 months of supplementation, the mean (SD) rise in serum 25(OH)D was maximum with 2000 IU (24.09 (8.28) ng/mL), followed by with 1000 IU (17.96 (6.55) ng/mL) and 600 IU (15.48 (7.00) ng/mL). Serum 25(OH)D levels of ≥20 ng/mL were seen in 91% in 600 IU group , 97% in 1000 IU group and 100% in 2000 IU group. The overall mean (SD) rise in urinary calcium creatinine ratio (0.05 (0.28) to 0.13 (0.12) mg/mg), and serum procollagen type I N-terminal propeptide (538.9 (199.78) to 655.5 (218.24) ng/mL), and reduction in serum carboxy-terminal telopeptide (0.745 (0.23) to 0.382 (0.23) ng/mL) was significant (P<0.01). The change in the above parameters was comparable among the three groups after adjustment for age. Daily vitamin D supplementation with 600 IU to 2000 IU for 6 months results in Vitamin D sufficiency in >90% of pre-pubertal girls.

Effect of increasing doses of vitamin D on bone mineral density and serum N-terminal telopeptide in elderly women: a randomized controlled trial.

There are few controlled studies of the effect of different doses of vitamin D3 on bone mineral density (BMD). We conducted a randomized placebo-controlled trial of increasing doses of vitamin D3 in 163 Caucasian and 31 African American women with serum 25-hydroxyvitamin D (25OHD) ≤50 nmol/L. This is an analysis of secondary outcome BMD to see if there is an association between percent change in BMD and dose of vitamin D3. Participants were randomly assigned to placebo, vitamin D3 400, 800, 1600, 2400, 3200, 4000, or 4800 IU/day; calcium supplements, average 600mg, were given to provide a total calcium intake of 1200 mg/d. The primary outcome was 12-month serum 25OHD level. Analysis methods include ANOVA and Pearson correlations. The mean percent increase (±SD) in BMD at 12 months for all women was small; total body, 0.62% (± 2.72), femoral neck 0.59% (±3.58) and spine 0.43% (±2.80). There was no difference in BMD or serum N-telopeptide in response to vitamin D by dose or race. The increase in total body, spine and hip BMD in elderly women given vitamin D doses between 400 and 4800 IU daily and calcium supplementation is small, unrelated to dose or 12-month serum 25OHD, free 25OHD or 1,25(OH)2D. There was no evidence of a threshold change in BMD with increasing serum 25OHD or free 25OHD in this population. We found no significant effect of daily vitamin D dose ranging from 400 to 4800 IU/day on BMD or serum N-terminal telopeptides in elderly women with initially low serum 25OHD.

Vitamin D3 supplementation improves testicular function in diabetic rats through peroxisome proliferator-activated receptor-γ/transforming growth factor-beta 1/nuclear factor-kappa B.

Aims/IntroductionVitamin D3 deficiency can lead to male hypogonadism in diabetes mellitus, but the target organs and the mechanism driving the disorder are unclear. This experiment was designed to study the relationship between vitamin D3 deficiency and hypogonadism in diabetes mellitus.Materials and MethodsRats with streptozotocin‐induced diabetes were randomly divided into four groups and treated with different doses of vitamin D3: blank (no vitamin D3), low (0.025 μg/kg/day), high (0.1 μg/kg/day), high (0.1 μg/kg/day) and with bisphenol A diglycidyl ether (peroxisome proliferator‐activated receptor gamma inhibitor 30 mg/kg/day). They were compared with wild‐type rats.ResultsAfter 12 weeks, the vitamin D3 supplements had partially restored testicular pathological changes, as shown by reduced testicular fibrosis related to downregulation transforming growth factor beta 1 and apoptosis related to downregulation of nuclear factor kappa B, but not the pituitary gland. The expression of peroxisome proliferator‐activated receptor gamma, which can inhibit transforming growth factor beta 1 and nuclear factor kappa B, was significantly increased after treatment with vitamin D3.ConclusionsThese results suggest that treatment with vitamin D3 can improve testicular function in diabetic rats through the peroxisome proliferator‐activated receptor gamma/transforming growth factor beta 1/nuclear factor kappa B signaling pathway.

CYP2R1 polymorphisms are important modulators of circulating 25-hydroxyvitamin D levels in elderly females with vitamin insufficiency, but not of the response to vitamin D supplementation.

This study evaluated the association between polymorphisms in four single nucleotide polymorphisms (SNPs) of the CYP2R1 gene and 25(OH)D levels before and 1year after supplementation with two different doses of vitamin D3 (600IU daily or a dose equivalent to 3750IU daily), in a cohort of 218 (96 men and 122 women) Lebanese elderly overweight subjects. Genotyping was performed for rs12794714, rs10741657, rs1562902, and rs10766197 SNPs using real-time PCR. The 25(OH)D levels were measured by liquid chromatography tandem mass spectrometry. At baseline, the mean±SD age was 71.0±4.7years, BMI 30.3±4.6kg/m2, and 25(OH)D level was 20.5±7.6ng/ml. There were significant differences in mean 25(OH)D levels between genotypes in women, but not in men. After adjustment for age, season, and BMI, the homozygous for the low frequency gene variant (HLV) of rs1562902 and rs10741657 SNPs had the highest mean 25(OH)D levels with difference of 7.6ng/ml for rs1562902 SNP (p<0.01) and of 5.9ng/ml for rs10741657 (p=0.05) compared to the homozygous for the major polymorphisms (HMPs). Conversely, for rs10766197 and rs12794714 SNPs, HMP had the highest mean 25(OH)D levels with difference of 6ng/ml for rs10766197 (p=0.003) and of 4.8ng/ml (p=0.02) for rs12794714, compared to the HLV. CYP2R1 genetic polymorphisms explained 4.8 to 9.8% of variability in 25(OH)D in women. After 1year, there was no difference in the response to vitamin D3 supplementation between genotypes in either gender. This study showed a difference in 25(OH)D levels between CYP2R1 genotypes that equates a daily supplementation of 400-800IU vitamin D, depending on genotype. It underscores possible important genetic contributions for the high prevalence of hypovitaminosis D in the Middle East.

In vitro Modulation of the LPS-Induced Proinflammatory Profile of Hepatocytes and Macrophages- Approaches for Intervention in Obesity?

Low grade endotoxemia is a feature of obesity which is linked to development of steatohepatitis in non-alcoholic fatty liver disease. In this study, macrophages (J774) and hepatocytes (HepG2) were stimulated with lipopolysaccharide (LPS) from E. coli 0111: B4 and analyzed for modulation of this response when preconditioned or stimulated subsequent to LPS, with different doses of Vitamin D3 or docosahexaenoic acid (DHA) over a time period of 1 and 5 days. Pro-inflammatory TNFα and pro-fibrotic TGFβ released into the supernatants were measured by ELISA; qPCR was performed for Srebp-1c and PPARα mRNA (genes for products involved in fatty acid synthesis and catabolism, respectively). Vitamin D3 and DHA exerted a consistent, dose dependent anti-inflammatory effect, and increased PPARα relative to Srebp-1c in both cell types. By contrast, addition of free fatty acids (FFA, oleic acid/palmitic acid 2:1) caused aggravation of LPS-induced inflammatory reaction and an increase of Srebp-1c relative to PPARα. Our results argue in favor of dietary supplementation of Vitamin D3 or DHA (and avoidance of monounsaturated/saturated fatty acids) to alleviate development of fatty liver disease.

The effect of vitamin D supplementation on arterial stiffness in an elderly community–based population

Vitamin D deficiency may lead to impaired vascular function and abnormalities in central arterial stiffness. We compared the effects of two different doses of vitamin D3 on arterial stiffness in an elderly population with deficient serum 25–hydroxy–vitamin D levels. A total of 119 known vitamin D deficient (<50 nmol/L) subjects were randomized to receive either 50,000 international units (IU) or 100,000 IU single intramuscular vitamin D3. In the group that received 100,000 IU vitamin D, median pulse wave velocity decreased from 12.2 m/s (range, 5.1–40.3 m/s) to 11.59 m/s (range, 4.3–14.9 m/s) after 8 weeks (P = .22). A mean decrease of 3.803 ± 1.7 (P = .032) in augmentation index (a measure of systemic stiffness) was noted. Only 3/51 (5.8%) who received 100,000 IU vitamin D reached levels of sufficiency (>75 nmol/L). A significant decrease in augmentation index was seen in the group that received 100,000 IU vitamin D. Serum levels of 25–hydroxy–vitamin D were still deficient at 8 weeks in the majority of patients, which may be attributable to impaired bioavailability.

25-Hydroxyvitamin D Response to Graded Vitamin D3Supplementation Among Obese Adults

Guidelines have suggested that obese adults need 2 to 3 times more vitamin D than lean adults to treat vitamin D deficiency, but few studies have evaluated the vitamin D dose response in obese subjects. The purpose of this study was to characterize the pharmacokinetics of 25-hydroxyvitamin D [25(OH)D] response to 3 different doses of vitamin D₃ (cholecalciferol) in a group of obese subjects and to quantify the 25(OH)D dose-response relationship. DESIGN, SETTING, INTERVENTION, PATIENTS: This was a randomized, single-blind study of 3 doses of oral vitamin D₃ (1000, 5000, or 10,000 IU) given daily to 67 obese subjects for 21 weeks during the winter months. Serum 25(OH)D levels were measured at baseline and after vitamin D replacement, and 25(OH)D pharmacokinetic parameters were determined, fitting the 25(OH)D concentrations to an exponential model. Mean measured increments in 25(OH)D at week 21 were 12.4 ± 9.7 ng/mL in the 1000 IU/d group, 27.8 ± 10.2 ng/mL in the 5000 IU/d group, and 48.1 ± 19.6 ng/mL in the 10,000 IU/d group. Steady-state increments computed from the model were 20.6 ± 17.1, 35.2 ± 14.6, and 51.3 ± 22.0 ng/mL, respectively. There were no hypercalcuria or hypercalcemia events during the study. Our data show that in obese people, the 25(OH)D response to vitamin D₃ is directly related to dose and body size with ∼2.5 IU/kg required for every unit increment in 25(OH)D (nanograms per milliliter).