Doses Of Vitamin D3 Research Articles

Changes in bone biomarkers in response to different dosing regimens of cholecalciferol supplementation in children with chronic kidney disease.

The effect of different dosing regimens of cholecalciferol supplementation on bone biomarkers has not been studied in children with chronic kidney disease (CKD). This is a post hoc analysis of a multi-center randomized controlled trial which included children with CKD stages 2-4 with vitamin D deficiency (25-hydroxy vitamin D (25OHD) < 30ng/ml) randomized 1:1:1 to receive an equivalent dose of oral cholecalciferol as daily, weekly or monthly treatment. Markers of bone formation (bone alkaline phosphatase (BAP), procollagen I N terminal peptide (PINP)), bone resorption (tartarate-resistant acid phosphatase 5b (TRAP), C terminal telopeptide (CTX)), and osteocyte markers (intact fibroblast growth factor 23 (iFGF23), sclerostin) and soluble klotho were measured at baseline and after 3months of intensive replacement therapy. The change in biomarkers and ratio of markers of bone formation to resorption were compared between treatment arms. BAP and TRAP were expressed as age- and sex-specific z-scores. 25OHD levels increased with cholecalciferol supplementation, with 85% achieving normal levels. There was a significant increase in the BAP/TRAP ratio (p = 0.04), iFGF23 (p = 0.004), and klotho (p = 0.002) with cholecalciferol therapy, but this was comparable across all three therapy arms. The BAPz was significantly higher in the weekly arm (p = 0.01). The change in 25OHD (Δ25OHD) inversely correlated with ΔPTH (r = - 0.4, p < 0.001). Although cholecalciferol supplementation was associated with a significant increase in bone formation, the three dosing regimens of cholecalciferol supplementation have a comparable effect on the bone biomarker profile, suggesting that they can be used interchangeably to suit the patient's needs and optimize adherence to therapy. A higher resolution version of the Graphical abstract is available as Supplementary information.

ODP096 Hypercalcemia Secondary to Vitamin D Supplementation with Normal 25-Hydroxyvitamin D Level in an Elderly Female - Case Report

Abstract Case presentation A 92-year-old female with a history of heart failure, dementia (alert and oriented to time, place and person at baseline), osteoporosis and hypothyroidism presented to the emergency department with altered mental status and constipation. She was oriented to time and person only. Labs included: WBC count 6.2 (4 - 11k/mm cu), Creatinine 1.23 (0.6 - 1.2 mg/dL), Calcium 12.8 (8.6 - 10.3 mg/dL), Albumin 3.9 (3.5 - 5.7 g/dL) and Glucose 94 (70 - 99 mg/dL). CT head showed no acute abnormality. Medication reconciliation revealed that she was taking Cholecalciferol (Vitamin D3) 2000 units daily, which was held. Intravenous fluids were started and further workup was done: PTH &amp;lt; 6 (12 - 88 pg/mL), serum 25 Hydroxyvitamin D 45.1 (30 - 100 ng/mL), serum 1, 25 Dihydroxyvitamin D 79 (19.9 - 79.3 pg/ml) and PTHrP 2.6 (0 - 3.4 pmol/L). Endocrinology was consulted for management of PTH independent hypercalcemia and recommended Zoledronic acid. Serum calcium levels normalized with bisphosphonate therapy and withholding of Vitamin D3 supplementation in addition to symptomatic improvement. Repeat 1-25-Dihydroxyvitamin D level decreased to 38.3 pg/mL while repeat PTH normalized at 20.8 pg/mL. Subsequently, serum calcium levels remained within normal limits, and she was discharged. Discussion Vitamin D, the "sunshine Vitamin", has claimed much fame and popularity for its varied benefits. With a growing user base, there is concern for potential adverse effects, primarily involving the population with an underlying propensity for hypercalcemia. According to the NIH, the safe upper limit of daily Vitamin D intake is 4000 IU; however, for adults &amp;gt; 70 years of age, 800 IU is the recommended dose. Our patient was taking 2000 IU (almost 2.5 times the recommended dose) of Vitamin D3, the most potent form which raises Vitamin D levels twice as fast as Vitamin D2. In addition, her serum 1,25 Dihydroxyvitamin D levels normalized when supplementation was withheld pointing to a cause - effect relationship and thus, effectively ruling out an endogenous source. Moreover, other factors such as prolonged duration of supplement intake, advanced age, immobility, osteoporosis and hypothyroidism contributed to her hypercalcemia. Current review of literature suggests that serum concentrations of 25-Hydroxyvitamin D at which hypercalcemia arises remains undefined. With this case, we wish to emphasize that a holistic approach should be utilized to advise patients regarding Vitamin D supplementation considering pre-existing risk factors for hypercalcemia, concurrent medical conditions, diet and functional status. Although current guidelines detail the ideal dosage and duration of Vitamin D supplementation therapy for different sectors of population, streamlining and individualizing therapy to mitigate potential harm to patients is pivotal. Presentation: No date and time listed

Effect of supplemental vitamin D3 on bone mineral density: a systematic review and meta-analysis.

There is still controversy over the effect of vitamin D3 supplementation on bone health. The effects of vitamin D3 supplementation on bone mineral density (BMD) and markers of bone turnover, as well as the dose-response relationship between vitamin D3 and bone health in adults, were evaluated. The PubMed, Scopus, Cochrane, Web of Science, and AGRIS databases were searched for articles published through April 30, 2022. Thirty-nine of the 6409 records identified met the inclusion criteria. Data were extracted from articles by 2 authors, and data extraction was cross-checked independently. A random-effects model was used to estimate the pooled effect size and the associated 95%CI for the effect of vitamin D3 for each outcome. A one-stage random-effects dose-response model was used to estimate the dose-response relationship between vitamin D3 supplementation and BMD. Results of meta-analysis showed a beneficial effect of vitamin D3 at the lumbar spine (standardized mean difference [SMD] = 0.06; 95%CI, 0.01-0.12) and femoral neck (SMD = 0.25; 95%CI, 0.09-0.41). Dose-response analysis revealed a linear relationship between vitamin D3 supplementation doses and BMD at the femoral neck, lumbar spine, and total hip sites. No significant effect of vitamin D3 supplementation on whole-body or total hip BMD was observed (P > 0.05). Vitamin D3 supplementation significantly decreased BMD at both proximal and distal forearm (SMD = -0.16; 95%CI, -0.26 to -0.06). The variables of ethnicity, age, baseline 25-hydroxyvitamin D (25[OH]D), menopause status, vitamin D3 dosing frequency, and bone health status (P interaction = 0.02) altered the effect of vitamin D3 supplementation on BMD. Additionally, a nonlinear relationship between vitamin D3 supplement doses and markers of bone turnover was found. A protective effect of vitamin D3 supplementation on BMD of the lumbar spine, femoral neck, and total hip is implicated. PROSPERO registration number CRD42017054132.

The Effect of a Single High Dose of Vitamin D on Serum Levels of Its Metabolites in the Elderly.

Vitamin D is a dietary micronutrient responsible for calcium and phosphorus metabolism and multiple extraskeletal actions. The assessment of vitamin D status is commonly based on measurement of 25(OH)D total concentration in serum. However, the usage of liquid chromatography with tandem mass spectrometry (LC-MS/MS) technique allows to reliably assess a panel of vitamin D metabolites in serum or plasma, which may help to investigate the metabolic paths of vitamin D, especially in populations at risk of deficiency. A randomized, two-arms, open study was conducted on 58 patients (28 female and 30 male; aged from 61 to 96 years old). The primary aim was to assess the effects of a single, high, oral dose of vitamin D3 (120,000 IU) on serum 25(OH)D3, 25(OH)D2, 24,25(OH)2D3, 3-epi-25(OH)D3, 1,25(OH)2D3, 24,25(OH)2D3/25(OH)D3 ratio, and 25(OH)D3/3-epi-25(OH)D3 ratio concentration (measured by LC-MS/MS) at baseline, 3 days and 7 days after administration, compared to control group. The secondary aim was assessment of influence of percentage of fat tissue on serum metabolites of vitamin D and their changes after bolus dose. 56.6% study group attained a serum 25(OH)D3 concentration >30 ng/mL. All subjects, except for one patient achieved a serum 25(OH)D3 concentration >20 ng/mL after administration. No one exceed reference value of vitamin D (30-50 ng/mL). Among participants who received vitamin D3 there were significant increase in 25(OH)D3, 3-epi-25(OH)D3, 1,25(OH)2D3, 24,25(OH)2D3 on 3rd day after administration. 24,25(OH)2D3 concentration gradually grew, achieving the highest concentration on 7th day. The percentage increase of 25(OH)D3 was negatively correlated with baseline 25(OH)D3 (r = -0.688, p = 0.001). Positive correlation between percentage increase in 25(OH)D3 and a percentage increase serum concentration of 24,25(OH)2D3 (r = 0.954, p < 0.001), 3-epi-25(OH)D3 (r = 8.03, p < 0.001) and 1,25(OH)2D3 (r = 0.789, p <0.001) were found. None of the study participants developed hypercalcemia. The baseline concentration of analyzed metabolites of vitamin D in serum and their percentage increase were neither dependent on BMI nor percentage of fat tissue. High dose of vitamin D rapidly increases 25(OH)D3 concentration in the elderly patients. The response to the bolus of vitamin D includes activation of 3-epimerase, followed by production of 24,25(OH)2D3, which protects from excessive increase of active form of vitamin D.

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.

Requirements and Metabolism for Calcium, Phosphorus and Vitamin D3 in the Growing-Furring Blue Foxes.

Simple SummaryThe nutritional needs of mink and foxes have long been clear, not specifically for blue foxes. With the development of technology, the present study aimed to study the effect of dietary calcium, phosphorus, and vitamin D3 supplementation levels on the growth performance, nutrient digestibility, and serum biochemical indicators of the growing hairy blue fox. The results showed that Ca (0.8–1.2%) and vitamin D3 (1327 IU·kg−1) doses have important effects on the growth performance and nutrient digestibility of growing blue foxes and can reduce fecal nitrogen and fecal phosphorus by improving the utilization of protein and phosphorus.A 3 × 3 factorial experiment was conducted to investigate the influence of dietary calcium, phosphorus, and vitamin D3 (VD3) supplement levels on the growth performance, nutrient digestibility, and serum biochemical indices of growing-furring blue foxes. One hundred and thirty-five 120-day-old male blue foxes were randomly allocated into nine groups. The nine treatment diets were supplemented with 0%, 0.4%, or 0.8% Ca, and 1000, 2000, or 4000 IU·kg−1 VD3. The base diet contained 0.8% Ca and 327 IU·kg−1 VD3. The dietary calcium level had a significant effect on the average daily gain (ADG) of blue foxes at 121 to 135 days of age and 136 to 150 days (p < 0.05). The ADG of blue foxes at 121 to 135 days of age was significantly decreased by VD3 level (p < 0.05). The Ca dosage decreased the nutrient digestibility (p < 0.05). The Ca dosage increased the fecal Ca and P and decreased the P digestibility (p < 0.05). Interactions were found between the Ca and VD3 levels, which affected the digestibility of Ca and P (p < 0.05). In conclusion, this research determined the suitable doses of Ca and VD3 for growing-furring blue foxes.

A Single Oral Vitamin D3 Bolus Reduces Inflammatory Markers in Healthy Saudi Males.

Vitamin D deficiency has increased in the general population and is a public health issue. Vitamin D plays an important role in regulating the immune system, e.g., by modulating the production of inflammatory cytokines. In most countries, the recommended maximal daily dose of vitamin D3 is 4000 IU (100 µg) per day. In this study, we investigated whether a single vitamin D3 bolus can reduce the levels of the inflammatory markers interleukin (IL) 6, IL8 and tumor necrosis factor (TNF) within one month. Fifty healthy Saudi males were recruited from the local community in Jeddah city and were orally supplemented with a single dose of 80,000 IU vitamin D3. Serum samples were collected at time points 0, 1 and 30 days, and serum levels of IL6, IL8 and TNF, parathyroid hormone (PTH), 25-hydroxyvitamin D3 (25(OH)D3), triglycerides, cholesterol, calcium (Ca2+) and phosphate (PO4−) were determined. On average, the vitamin D3 bolus resulted in a significant increase in vitamin D status as well as in a significant decrease in the levels of inflammatory cytokines even one month after supplementation without changing serum Ca2+, PO4− or lipid levels. In conclusion, single high-dose vitamin D3 supplementation is safe for reducing inflammation markers and may lead to an update of current recommendations for vitamin D intake, in order to prevent critical health problems.

67 Double impact: hypophosphatemic rickets and vitamin D intoxication

BackgroundVitamin D prevents deficiency rickets, but its prescription must be weighed carefully! Objective We report a rare case of iatrogenic toxic hypervitaminosis D in a child with vitamin D resistant rickets…!MethodsWe admitted a two-year-old girl, presenting signs of rickets resistant to the usual then therapeutic doses of vitamin D3. Vitamin D2 in oral suspension is then ordered in addition, for a few weeks until the onset of hearing loss motivating her hospitalization in pediatrics.ResultsBiological and radiological explorations revealed renal failure with threatening arterial hypertension, as well as diffuse and severe arteriosclerosis on Doppler signal.Eviction (stopping vitamin D in all its forms), symptomatic and conservative management by (converting-enzyme inhibitors) and hydration allowed a progressive blood pressure normalisation, arteriosclerosis disappearance (undetected by Doppler signal and by angio-scan) along with a gradual normalising of the kidney function; all this over a period of 2 yearsThe girl actually had hypophosphatemic rickets, and oral phosphorus (syrup) was also prescribedConclusionVitamin D is potentially toxic with sometimes severe renal risks (lithiasis, nephrocalcinosis), and hypercalcemia might be severe, especially if renal function is impaired.Blindly treating any rickets with vitamin D can be adventurous and might expose the child to serious morbidity.

A Single Vitamin D3 Bolus Supplementation Improves Vitamin D Status and Reduces Proinflammatory Cytokines in Healthy Females.

Vitamin D deficiency is a global health problem that not only leads to metabolic bone disease but also to many other illnesses, most of which are associated with chronic inflammation. Thus, our aim was to investigate the safety and effectiveness of a single high dose of vitamin D3 (80,000 IU) on vitamin D status and proinflammatory cytokines such as interleukin (IL)6, IL8 and tumor necrosis factor (TNF) in healthy Saudi females. Fifty healthy females were recruited and orally supplemented with a single vitamin D3 bolus (80,000 IU). All participants donated fasting blood samples at baseline, one day and thirty days after supplementation. Serum 25-hydroxyvitamin D3 (25(OH)D3), IL6, IL8, TNF, calcium, phosphate, parathyroid hormone (PTH) and blood lipid levels were determined. Serum 25(OH)D3 significantly increased one and thirty days after supplementation when compared with baseline without causing elevation in calcium or phosphate or a decrease in PTH to abnormal levels. In contrast, the concentrations of the three representative proinflammatory cytokines decreased gradually until the end of the study period. In conclusion, a single high dose (80,000 IU) is effective in improving serum vitamin D status and reducing the concentration of the proinflammatory cytokines in a rapid and safe way in healthy females.

Vitamin D Alleviates Anxiety and Depression in Elderly People with Prediabetes: A Randomized Controlled Study.

Older people are prone to frailness, present poor adherence to pharmacotherapy, and often have adverse drug effects. Therefore, it is important to develop effective and safe interventions to mitigate the burden of anxiety and depression disorders in this population. The aim of this study was to investigate the effect of vitamin D supplementation on the anxiety and depression status of elderly people with prediabetes. Participants were randomly assigned a weekly dose of vitamin D3 of 25,000 IU (n = 45, mean age 73.10 ± 7.16 years) or nothing (n = 45, mean age 74.03 ± 7.64 years), in addition to suggested lifestyle measures. The State-Trait Anxiety Inventory subscales (STAI-T and STAI-S) and the Patient Health Questionnaire-9 (PHQ-9) were used to evaluate anxiety and depression levels, respectively, at baseline, 6, and 12 months. A total of 92.68% of the participants in the vitamin D group and 97.14% of the controls exhibited vitamin D deficiency (<20 ng/mL) at baseline. Mean STAI-T scores were lower in supplemented individuals than in the control group at 6 (38.02 ± 9.03 vs. 43.91 ± 7.18, p = 0.003) and 12 months (32.35 ± 7.77 vs. 44.97 ± 7.78, p < 0.001). The same pattern was evident for STAI-S scores at 6 (37.11 ± 7.88 vs. 43.20 ± 9.33, p = 0.003) and 12 months (32.59 ± 6.45 vs. 44.60 ± 9.53, p < 0.001). Supplemented participants demonstrated lower mean PHQ-9 scores compared to controls at 6 (15.69 ± 6.15 vs. 19.77 ± 8.96, p = 0.021) and 12 months (13.52 ± 5.01 vs. 20.20 ± 8.67, p < 0.001). Participants with deficiency and insufficiency at baseline experienced equal benefits of supplementation in terms of anxiety and depression scores. In conclusion, in a high-risk population, a weekly vitamin D supplementation scheme was effective in alleviating anxiety and depression symptoms. More studies are needed to elucidate the relevant mechanisms.

Persistent or new symptoms 1 year after a single high dose of vitamin D3 in patients with moderate to severe COVID-19.

PurposeThe aim of this study was to investigate the reported persistent or new symptoms 1 year after a single dose of 200,000 IU of vitamin D3 and hospitalization in patients with moderate to severe COVID-19.MethodsThis is a post-hoc, exploratory analysis from a multicenter, double-blind, placebo-controlled, randomized clinical trial from two hospitals in São Paulo, Brazil, registered in ClinicalTrials.gov, NCT04449718. Discharged patients were followed for up to 1 year and evaluated by telephone interviews at 6 and 12 months. The primary and secondary outcomes were previously published. These post-hoc exploratory secondary outcomes are the persistent or new symptoms and quality of life (QoL) at the post-viral stage of COVID-19. Generalized estimating equations (GEE) for repeated measures with Bonferroni’s adjustment were used for testing outcomes.ResultsBetween 2 June and 27 August 2020, we randomized 240 patients of which 144 were included in this study [the vitamin D3 (n = 71) or placebo (n = 73) group]. The mean (SD) age was 54.3 (13.1) years, and body mass index (BMI) was 32.4 (6.5) kg/m2. Fever demonstrated a significant main effect of time (P < 0.001) with a reduction from baseline to 6 (52–0) and 12 months (52–0). No significant differences between groups were observed for fever, cough, fatigue, fever, myalgia, joint pain, runny nose, nasal congestion, sore throat, hypertension, diabetes, cardiovascular disease, rheumatic disease, asthma, chronic obstructive pulmonary, chronic kidney disease, QoL, and new or persistent symptoms up to 1-year of follow-up.ConclusionThe findings do not support the use of 200,000 IU of vitamin D3 compared to placebo for the management of persistence or new symptoms, and QoL reported by moderate to severe patients after hospitalization for COVID-19.

Therapeutic Potential of Chrysin in Improving Bone Health

Vitamin D deficiency is endemic worldwide. Although several strategies have been established to enhance vitamin D3 levels, studies specifically focusing on the inhibition of vitamin D metabolism, which may prolong the availability of active vitamin D in pathological conditions, have been less explored. Studies also suggest that higher doses of vitamin D3 fail to achieve optimum vitamin D levels. In this context, we focused on the enzyme CYP3A4, which promotes the inactivation of active vitamin D. The current study aimed to decipher the impact of chrysin, a proven CYP3A4 inhibitor, as an intervention and its effects in combination with low-dose vitamin D3 (40 IU) and bone health in vitamin D deficiency conditions. The in vivo activity of chrysin was evaluated in female Wistar albino rats fed a vitamin-D-deficient diet to attain vitamin D deficiency for 28 days. Chrysin was given alone and in combination with calcium carbonate (CaCO3) and/or vitamin D3. All therapeutic interventions were assessed for serum 25-hydroxyvitamin D3(25-OH-D3) by LC-MS and biochemical, urinary, and bone parameters. Animals treated with chrysin alone and in combination with low-dose vitamin D3 and/or CaCO3 showed an eminent rise in serum 25-OH-D3 levels along with increased serum biochemical parameters. In contrast, a significant decrease in the urinary parameters followed by beneficial effects on bone parameters was noticed in contrast with the vitamin-D-deficient diet group. Our findings revealed that although chrysin alone showed a notable effect on 25-OH-D3 and osseous tissue, comparatively, it showed an intensified therapeutic effect in combination with vitamin D3 and CaCO3, which can be employed as a cost-effective option to improve bone health.

25-Hydroxycholecalciferol Response to Single Oral Cholecalciferol Loading in the Normal Weight, Overweight, and Obese

Objective: The aim of the study is to evaluate the response of 25- hydroxycholecalciferol (25OHD) to a single oral administration of cholecalciferol in the normal weight, overweight, and obese individuals. Place and duration of study: The study is conducted in Pak International medical College Hayatabad and the duration of study was from March 2021 to March 2022 Material and Method: We have examined 60 healthy women from the age groups of 24-68 years(mean+ SD, 51.2+ 9.6) with a body mass index in kg/m2 ranging from19.2 to 43.2 (mean + SD 28.2+5.9). Female individuals are divided into 3 groups based on their body mass index, 1st group is having normal female individuals having BMI less than 25 kg/m2 (n=22), 2nd group having BMI of 25.1-29.9 kg/m2(n=23)and 3rd group having BMI greater than 30Kg/m2(n=15). Every participants is taken a single oral dose of cholecalciferol(300,000 IU) and their Venous blood samples are taken to measure the concentration levels of 25OHD, 1,25(OH)2D, parathyroid levels, calcium and phosphorus levels. The results are categorized in the form of mean, standard deviation, p-values, least square means with 95% confidence intervals (CI) in each group of individuals at 8th and 31st days of cholecalciferol administration. Results: The total body fat of normal weight group is significantly lesser than that overweight group of individuals, which is lesser than that of group of obese individuals. At the beseline detection of serum level of 25 OHD all the women have detectable serum levels of 25OHD. In the obese group of individuals there will be a lesser levels of 25 OHD observed than normal group of individuals and the difference is approximately equal in the case of overweight group of individuals. The obese group of individuals also have approximately lesser levels of 1,25(OH)2D than the normal group of individuals but have increasing levels of parathyroid hormones. After administration of cholecalferol the levels of parathyroid hormone is observed significantly lesser at day 8 than baseline in the normal weight of individuals not in other groups, which approximately increasing over time at day 31 in all the groups of individuals. There is a positive correlation found between the concentrations of 25OHD and 1, 25(OH)2D while there is a negative correlation found between the levels of 25 OHD and parathyroid hormone at all time points. Conclusion: Serum levels of 25 OHD become decreases in obese individuals is due to their increase body volume. The levels of decline of 25 OHD in obese is due to their larger body size and slower release of vitamin D from their body fat. Keywords: Adipose tissues, Obesity, Vitamin D, Cholecalciferol, Overweight, Calcium.

The short-chain fatty acid butyrate accelerates vascular calcification via regulation of histone deacetylases and NF-κB signaling

Recent studies have shown that short-chain fatty acids (SCFAs), primarily acetate, propionate and butyrate, play a crucial role in the pathogenesis of cardiovascular disease. Whether SCFAs regulate vascular calcification, a common pathological change in cardiovascular tissues, remains unclear. This study aimed to investigate the potential role of SCFAs in vascular calcification. Using cellular and animal models of vascular calcification, we showed that butyrate significantly enhanced high phosphate (Pi)-induced calcification and osteogenic transition of vascular smooth muscle cells (VSMC) in vitro, whereas acetate and propionate had no effects. Subsequent studies confirmed that butyrate significantly promoted high Pi-induced aortic ring calcification ex vivo and high dose vitamin D3 (vD3)-induced mouse vascular calcification in vivo. Mechanistically, butyrate significantly inhibited histone deacetylase (HDAC) expression in VSMCs, and a pan HDAC inhibitor Trichostatin A showed similar inductive effects on calcification and osteogenic transition of VSMCs to butyrate. In addition, the SCFA sensing receptors Gpr41 and Gpr109a were primarily expressed by VSMCs, and butyrate induced the rapid activation of NF-κB, Wnt and Akt signaling in VSMCs. Intriguingly, the NF-κB inhibitor SC75741 significantly attenuated butyrate-induced calcification and the osteogenic gene Msx2 expression in VSMCs. We showed that knockdown of Gpr41 but not Gpr109a attenuated butyrate-induced VSMC calcification. This study reveals that butyrate accelerates vascular calcification via its dual effects on HDAC inhibition and NF-κB activation. Our data provide novel insights into the role of microbe-host interaction in vascular calcification, and may have implications for the development of potential therapy for vascular calcification.

Effectiveness of vitamin D2 compared with vitamin D3 replacement therapy in a primary healthcare setting: a retrospective cohort study.

Introduction: Vitamin D deficiency is a worldwide public health concern, which can lead to severe diseases, such as rickets in children and osteomalacia in adults. Most studies have compared equimolar unit-to-unit doses of vitamin D2 and D3.Objectives: The current study aimed to answer the research question: “How effective is vitamin D2 (600,000 U/1.5 ml) compared to vitamin D3 (300,000 U/1 ml) parenteral supplementation for raising serum vitamin D levels in adult patients treated in a primary health care setting?”Setting: Primary Health Care Corporation (PHCC) runs 28 health centers distributed throughout the State of Qatar and its capital city, Doha. Qatar is on the east coast of the Arabic peninsula, with very hot and sunny summers and a desert climate.Study design: This was a retrospective observational cohort study.Method: A total of 15,716 participants were recruited following ethical approval. They were identified by electronic medical records (EMR) describing the clinical encounters of individuals aged 18 to 60-years-old who attended a health center operated by the PHCC during the 3.5-year study period from January 1, 2017 to June 30, 2020. The PHCC EMR system uses SNOMED codes (a systematically organized computer-processable collection of medical terms providing codes, names, synonyms, and definitions implemented for clinical documentation and reporting). Four study groups were created depending on the type of vitamin D injection and the oral form of replacement therapy. The analysis scheme used the serum vitamin D level within the preceding 4 weeks (pretreatment), followed by administration of the treatment dose. The post-treatment serum testing value should have been available within a maximum of 12 weeks. The Statistical Package for Social Sciences (IBMSPSS; IBM Corp., Armonk, NY, USA) version 23 software was used for the statistical analysis.Results: Four treatment options were compared, including a vitamin D2 injection, a vitamin D3 injection, combined use of a vitamin D2 injection + a D2 tablet, and combined use of a vitamin D3 injection + a D2 tablet. All four treatment groups were associated with a statistically significant increase in serum vitamin D within a maximum of 12 weeks of follow-up. The vitamin D2 injection alone was associated with the lowest increase in serum concentration by a mean of 3.2 ng/ml. In contrast, the vitamin D3 injection alone or with a D2 tablet increased serum vitamin D by 6.1 and 5.6 ng/ml, respectively. Using the combination of a vitamin D2 injection and a tablet only added a marginal increase of 2.3 ng/ml in serum vitamin D on top of the 3.2 ng/ml increase attained after administering the D2 injection alone.Conclusion: Utilizing vitamin D3 in an injectable form is the best choice to restore severe vitamin D deficiency. Furthermore, it was superior to the injectable form of vitamin D2, even though vitamin D2 has double the molar units.

Vitamin D Status Among Children With Juvenile Idiopathic Arthritis: A Multicenter Prospective, Non-randomized, Comparative Study.

BackgroundJuvenile idiopathic arthritis (JIA) is a chronic autoimmune disease characterized by destructive and inflammatory damage to the joints. The aim in this study was to compare vitamin D levels between children and adolescents, 1–18 years of age, with juvenile idiopathic arthritis (JIA) and a health control group of peers. We considered effects of endogenous, exogenous, and genetic factors on measured differences in vitamin D levels among children with JIA.MethodsOur findings are based on a study sample of 150 patients with various variants of JIA and 277 healthy children. The blood level of vitamin D was assessed by calcidiol level. The following factors were included in our analysis: age and sex; level of insolation in three regions of country (center, south, north); assessment of dietary intake of vitamin D; effect of prophylactic doses of cholecalciferol; a relationship between the TaqI, FokI, and BsmI polymorphisms of the VDR gene and serum 25(OH)D concentration.ResultsWe identified a high frequency of low vitamin D among children with JIA, prevalence of 66%, with the medial level of vitamin D being within the range of “insufficient” vitamin D. We also show that the dietary intake of vitamin D by children with JIA is well below expected norms, and that prophylactic doses of vitamin D supplementation (cholecalciferol) at a dose of 500–1,000 IU/day and 1,500–2,000 IU/day do not meet the vitamin D needs of children with JIA. Of importance, we show that vitamin D levels among children with JIA are not affected by clinical therapies to manage the disease nor by the present of VDR genetic variants.ConclusionProphylactic administration of cholecalciferol and season of year play a determining role in the development of vitamin D deficiency and insufficiency.

Beneficial Effect of Short-Term Supplementation of High Dose of Vitamin D3 in Hospitalized Patients With COVID-19: A Multicenter, Single-Blinded, Prospective Randomized Pilot Clinical Trial.

There is now sufficient evidence to support that vitamin D deficiency may predispose to SARS-CoV-2 infection and increase COVID-19 severity and mortality. It has been suggested that vitamin D3 supplementation may be used prophylactically as an affordable and safe strategy that could be added to the existing COVID-19 standard treatment. This multicenter, single-blinded, prospective randomized pilot clinical trial aimed to evaluate the safety, tolerability, and effectiveness of 10,000 IU/day in comparison with 2000 IU/day of cholecalciferol supplementation for 14 days to reduce the duration and severity of COVID-19 in 85 hospitalized individuals. The median age of the participants was 65 years (Interquartile range (IQR): 53–74), most of them (71%) were men and the mean baseline of 25-hydroxyvitamin D (25(OH)D) in serum was 15 ng/ml (standard deviation (SD):6). After 14 days of supplementation, serum 25(OH)D levels were significantly increased in the group who received 10,000IU/day (p < 0.0001) (n = 44) in comparison with the 2,000IU/day group (n = 41), especially in overweight and obese participants, and the higher dose was well tolerated. A fraction of the individuals in our cohort (10/85) developed acute respiratory distress syndrome (ARDS). The median length of hospital stay in these patients with ARDS was significantly different in the participants assigned to the 10,000IU/day group (n = 4; 7 days; IQR: 4–13) and the 2,000IU/day group (n = 6; 27 days; IQR: 12–45) (p = 0.04). Moreover, the inspired oxygen fraction was reduced 7.6-fold in the high dose group (p = 0.049). In terms of blood parameters, we did not identify overall significant improvements, although the platelet count showed a modest but significant difference in those patients who were supplemented with the higher dose (p = 0.0492). In conclusion, the administration of 10,000IU/day of vitamin D3 for 14 days in association with the standard clinical care during hospitalization for COVID-19 was safe, tolerable, and beneficial, thereby helping to improve the prognosis during the recovery process.

Vitamin D status in peripheral vascular diseases: A longitudinal prospective study

Background: Peripheral artery disease (PAD) is due to abnormal Narrowing of arteries other than heart and brain (primarily due to atherosclerosis). PAD is the most common form of PVD. Aims and Objectives: In the present study, we analyzed Vitamin D association with peripheral vascular diseases as well as coagulation and inflammation parameters. Materials and Methods: The study was conducted for 100 PAD patients of 18–70 years age and divided in Group I≤20ng/ml and Group II&gt;20ng/ml for serum Vitamin D level. A single, oral, and high- dose Vitamin D3 supplementation 1,20,000IU was given in GroupI. At baseline and at the end of the study after 1 month, Ankle Brachial Index, modified Rankin Scale, Vitamin D, Inflammation and coagulation parameter, HbA1c, etc., were performed in all patients. Evaluation was done using SPSS. The level P&lt;0.05 was considered as the cut off value of significance. Results: The majority of the PAD patients were Vitamin D deficient and have higher HbA1c level with statistically significant (P&lt;0.05) association. This is because low Vitamin D is the risk factor for diabetes in which HbA1c level is higher. Conclusion: Asingle, oral, and high-dose Vitamin D3 supplementation did not alter parameters of inflammation and hemostasis in patients with peripheral arterial disease, adding more data to other studies that did not confirm a causal role of Vitamin D in cardiovascular disease.

Primary prevention of lung cancer: how justified high doses of vitamin D3 are?

Primary prevention of lung cancer: how justified high doses of vitamin D3 are?

Randomized double-blind placebo-controlled proof-of-concept trial of resveratrol for outpatient treatment of mild coronavirus disease (COVID-19)

Resveratrol is a polyphenol that has been well studied and has demonstrated anti-viral and anti-inflammatory properties that might mitigate the effects of COVID-19. Outpatients (N = 105) were recruited from central Ohio in late 2020. Participants were randomly assigned to receive placebo or resveratrol. Both groups received a single dose of Vitamin D3 which was used as an adjunct. The primary outcome measure was hospitalization within 21 days of symptom onset; secondary measures were ER visits, incidence of pneumonia, and incidence of pulmonary embolism. Five patients chose not to participate after randomization. Twenty-one-day outcome was determined of all one hundred participants (mean [SD] age 55.6 [8.8] years; 61% female). There were no clinically significant adverse events attributed to resveratrol. Outpatients in this phase 2 study treated with resveratrol had a lower incidence compared to placebo of: hospitalization (2% vs. 6%, RR 0.33, 95% CI 0.04–3.10), COVID-19 related ER visits (8% vs. 14%, RR 0.57, 95% CI 0.18–1.83), and pneumonia (8% vs. 16%, RR 0.5, 95% CI 0.16–1.55). One patient (2%) in each group developed pulmonary embolism (RR 1.00, 95% CI: 0.06–15.55). This underpowered study was limited by small sample size and low incidence of primary adverse events consequently the results are statistically similar between treatment arms. A larger trial could determine efficacy.Trial Registrations: ClinicalTrials.gov NCT04400890 26/05/2020; FDA IND #150033 05/05/2020.