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The aim of this study was to investigate the impact of suboptimal 25-hydroxyvitamin D (25-VitD) and cholecalciferol (VitDsub3/sub) supplementation on the pharmacokinetics of oral midazolam (MDZ) in control subjects and subjects with chronic kidney disease (CKD). Subjects with CKD (n = 14) and controls (n = 5) with suboptimal 25-VitD levels (lt;30 ng/mL) were enrolled in a 2-phase study. In phase 1 (suboptimal), subjects were administered a single oral dose of VitDsub3/sub(5000 IU) and MDZ (2 mg). In phase 2 (replete) subjects who achieved 25-VitD repletion after receiving up to 16 weeks of daily cholecalciferol were given the identical single oral doses of VitDsub3/suband MDZ as in phase 1. Concentrations of MDZ and metabolites, 1'-hydroxymidazolam (1'-OHMDZ), and 1'-OHMDZ glucuronide (1'-OHMDZ-G) were measured by liquid chromatography-tandem mass spectrometry and pharmacokinetic analysis was performed. Under suboptimal 25-VitD, reductions in MDZ clearance and renal clearance of 47% and 87%, respectively, and a 72% reduction in renal clearance of 1'-OHMDZ-G were observed in CKD vs controls. In phase 1 versus phase 2, MDZ clearance increased in all control subjects, with a median (interquartile range) increase of 10.5 (0.62-16.7) L/h. No changes in MDZ pharmacokinetics were observed in subjects with CKD between phases 1 and 2. The effects of 25-VitD repletion on MDZ disposition was largely observed in subjects without kidney disease. Impaired MDZ metabolism and/or excretion alterations due to CKD in a suboptimal 25-VitD state may not be reversed by cholecalciferol therapy. Suboptimal 25-VitD may augment the reductions in MDZ and 1'-OHMDZ-G clearance values observed in patients with CKD.

Vitamin D plays a role in innate immune system activation, and deficiency increases susceptibility to respiratory infections and disease severity including COVID-19. We determined whether vitamin D levels and medications were associated with contracting COVID-19, and disease severity defined by hospitalisation and dialysis patient mortality.We reviewed serum vitamin D levels, and prescription of cholecalciferol and alfacalcidol along with corresponding medical records of adult dialysis patients from a United Kingdom tertiary centre between March 2020 and May 2021. COVID-19 infection was determined by polymerase chain reaction (PCR) results.362 (35%) of 1035 dialysis patients tested PCR positive for COVID-19. COVID-19 positive patients had lower native median vitamin D (65 (39-95) versus 74 (40.5-101) nmol/L (p = .009) despite greater prescription of cholecalciferol (median 20 000 (20000-20 000) versus 20 000 (0-20 000) IU/week), p .001, but lower prescription of alfacalcidol 0 (0-3.0) versus 2.0 (0.-5.0) ug/week, p .001. On multivariate logistic regression COVID-19 infection was associated with haemodialysis versus peritoneal dialysis (p .001), cholecalciferol dose (p .001) and negatively with alfacalcidol (p .001). However, serum vitamin D levels and alfacalcidol dosages were not significantly different for those requiring hospitalisation compared to those managed at home, although those who died were prescribed lower alfacalcidol dosages.Dialysis patients who contracted COVID-19 had lower levels of native vitamin D prior to COVID-19 and were prescribed lower dosages of alfacalcidol. However, there was no association between vitamin D status and disease severity. This retrospective observational analysis supports a potential role for vitamin D and susceptibility to COVID-19 infection in dialysis patients.

Vitamin D is an important human hormone, known primarily to be involved in the intestinal absorption of calcium and phosphate, but it is also involved in various nonskeletal processes (molecular, cellular, immune, and neuronal). One of the main health problems nowadays is the vitamin D deficiency of the human population due to lack of sun exposure, with estimates of one billion people worldwide with vitamin D deficiency, and the consequent need for clinical intervention (i.e., prescription of pharmacological vitamin D supplements). An alternative to reduce vitamin D deficiency is to produce good dietary sources of it, a scenario in which the yeast Saccharomyces cerevisiae seems to be a promising alternative. This review focuses on the potential use of yeast as a biological platform to produce vitamin D, summarizing both the biological aspects of vitamin D (synthesis, ecology and evolution, metabolism, and bioequivalence) and the work done to produce it in yeast (both for vitamin D

Locoregional control is a significant prognostic factor for hepatocellular carcinoma (HCC). Historically, the use of radiotherapy (RT) for HCC was limited owing to the low radiotolerance of the liver and the need for high RT doses for disease control. We aimed to examine if 1α,25-dihydroxyvitamin D3 (calcitriol) has a role in the tumor inhibition and the radiation response of HCC in vitro and in vivo, and explore the underlying mechanisms. The human and murine liver cancer cell lines were selected for cellular and animal experiments to investigate the changes in tumor characteristics and the radiation response after calcitriol supplementation. The effects induced by calcitriol supplementation on interleukin-6 (IL-6) signaling and the tumor immune microenvironment following RT were also examined. Our data revealed that calcitriol supplementation attenuated tumor aggressive behavior, decrease IL-6 expression, and augmented radiation-induced tumor inhibition. The biological changes following calcitriol treatment included suppressed epithelial-mesenchymal transition, attenuated cancer stem cell-like properties and increased radiation-induced reactive oxygen species and cell death in vitro. Regarding immune microenvironment, calcitriol attenuated the recruitment of myeloid-derived suppressor cell (MDSC) recruitment and increased the infiltration of cytotoxic T cells in tumor following RT. Furthermore, When the primary liver tumor was irradiated with larger dose per fraction, calcitriol induced a smaller size of synchronous unirradiated tumor in mice, which linked with attenuated IL-6 signaling and MDSC recruitment. In conclusion, calcitriol treatment reduced tumor aggressiveness and enhanced the radiation response. The inhibited IL-6 signaling and subsequently enhanced antitumor immunity might be responsible to augment radiation-induced tumoricidal effect induced by calcitriol. Based on our results, we suggest that calcitriol could exert the antitumor and radiosensitization effects for HCC, especially for multifocal tumors.

Vitamin D plays a major role in bone health and probably also in multiple extraskeletal acute and chronic diseases. Although supplementation with calcifediol, a vitamin D metabolite, has demonstrated efficacy and safety in short-term clinical trials, its effects after long-term monthly administration have been studied less extensively. This report describes the results of a 1-year, phase III-IV, double-blind, randomized, controlled, parallel, multicenter superiority clinical trial to assess the efficacy and safety of monthly calcifediol 0.266 mg versus cholecalciferol 25,000 IU (0.625 mg) in postmenopausal women with vitamin D deficiency (25(OH)D

To overcome the limitations in the use of protein as an emulsifier, soy lecithin, a natural surfactant, was used along with whey protein isolate (WPI) to produce o/w emulsions containing cholecalciferol and α-tocopherol. The physical stability of the emulsions prepared with WPI and varying concentrations of lecithin (0, 1, 2, and 3% w/w) was measured in different heat, pH, and ionic-strength food environmental conditions.All emulsions were shown to be less than 250 nm in size and less than 0.3 in polydispersity index (PDI). The morphology of the emulsions was spherical, and the droplets of the emulsion containing lecithin were thicker and larger than those of the emulsion without lecithin (WPI_L0). After autoclaving, WPI_L0 increased in size from 197.8 ± 1.7 nm to 528.5 ± 28.4 nm, and the retention of cholecalciferol and α-tocopherol decreased to 40.83 ± 0.63% and 49.68 ± 1.84%, respectively. At pH 5.5, near the isoelectric point of WPI, WPI_L0 increased in size due to aggregation, but emulsions containing lecithin remained stable at a PDI under 0.3. Turbiscan stability index of the emulsion prepared with WPI and 3% lecithin was the lowest, indicating good storage stability. In addition, it was confirmed that the higher the lecithin content, the higher the viscosity, and the higher the amount of free fatty acids released in the in vitro digestion model.This study can provide theoretical evidence for enhancing the physical stability of protein emulsions by co-stabilization with lecithin, promoting their application in various foods. © 2022 Society of Chemical Industry.

Exclusively breastfed infants are at a high risk of vitamin D deficiency. Few studies have evaluated the effects of vitamin D supplementation. Hence, we conducted a prospective randomized controlled trial investigating the effects of oral vitamin D3 400 IU/d supplementation in exclusively breastfed newborns. Serum 25-hydroxy-vitamin D (25[OH]D) levels in pregnant women and their newborns were evaluated. Breastfed newborns were randomized to one of two regimens at age 10 days. One group received vitamin D3 supplementation at a dose of 400 IU/d (vD-400 group), whereas the placebo group received a liquid product without vitamin D3. Outcomes were assessed at 4 months of age. A total of 92 pregnant women and their infants were enrolled, and the data of 72 infants (37 in the vD-400 group and 35 in the placebo group) who completed the study at 4 months of age were assessed. The results showed severe vitamin D deficiency in 15.2% of mothers before delivery, while 54.3% had vitamin D deficiency. Moreover, 15.2% of newborns presented with severe vitamin D deficiency at birth, while 52.2% had vitamin D deficiency. Maternal vitamin D levels were significantly correlated with infant vitamin D levels at birth (r = 0.816, p 0.001). At 4 months of age, weight, head circumference, serum 25(OH)D, phosphorus, and intact parathyroid hormone levels significantly differed between the vD-400 and placebo groups. However, the body length and bone mineral density of the two groups did not differ significantly. Regardless of vitamin D supplementation, participants with severe vitamin D deficiency had significantly higher intact parathyroid hormone levels and lower bone mineral content. In conclusion, among exclusively breastfed infants, oral supplementation with vitamin D3 at a dose of 400 IU/d from age 10 days increased 25(OH)D concentrations at 4 months of age, but it did not affect bone mineralization. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Alopecia areata (AA) is a common non-scarring, inflammatory type of hair loss that affects people of all ages and genders.To evaluate the safety and efficacy of intralesional vitamin D3 injection in the treatment of alopecia areata.A randomized controlled clinical trial included a total of 60 adult patients with localized alopecia areata were randomly assigned into two groups. Group I consisted of thirty patients who received 1ml of intralesional injection of vitamin D3 every 4 weeks for a maximum of 3 sessions. Group II consisted of thirty patients who received intralesional injection of normal saline 0.9% every 4 weeks for 3 sessions as a control group. All patients had their serum levels of 25-hydroxy vitamin D, TSH, antithyroglobulin, and thyroid peroxidase antibodies estimated before starting treatment. The 5-point semiquantitative regrowth score (RGS) and dermoscopy were used to evaluate the therapeutic response.There was statistically significant difference with p-value 0.001 between two study groups regarding degree of improvement. Dermoscopic findings that explain signs of activity were decreased, and signs of improvement were appeared after the third months of treatment being better in intralesional vitamin D group. The adverse effects were negligible and transient, and there was no recurrence of lesions.Intralesional vitamin D3 is an effective treatment option for localized patchy (not more than 40% of scalp distribution) alopecia areata. There is no relation between serum vitamin D3 and efficacy of treatment, so measuring vitamin D3 before starting treatment is not advised.

Since the beginning of the COVID-19 pandemic, many Iranian people have been taking 50 000 IU of vitamin D3 on weekly or biweekly bases in order to enhance their immune system function. This cross-sectional study was conducted on the patients of endocrinology clinic to compare 25(OH)D levels of weekly or biweekly consumption with the monthly users of vitamin D3 50 000 IU. The level100 ng/mL of 25(OH)D was defined as hypervitaminosis D. In total, 211 patients (108 and 103 patients in monthly and weekly/biweekly groups, respectively) were studied. In the subgroups of weekly and biweekly users, the rates of hypervitaminosis were 18.9% and 4.5%, respectively. In contrast, only 0.9% of monthly users had hypervitaminosis D. The highest vitamin D value of 185 ng/mL was detected in a patient who had consumed 50 000 IU vitamin D3 weekly for 6 years. No hypercalcaemia was detected in patients with hypervitaminosis D.

Many studies in dairy cows are towards calcium homeostasis and there is a lack of knowledge about the effect of vitamin D in preventing insulin resistance and improving energy balance in the transition period of dairy cows.The trial was conducted in a commercial dairy farm with about 1500 lactating cows in Tehran province, Iran. Twenty-four Holstein cows had been randomly selected and divided into control and treatment groups. In the treatment group, 12 cows, received a single dose of 8,000,000 IU vitamin D3 intramuscularly and in the control group, 12 cows were injected placebo (distilled water) 2-8 days before the expected calving time. Blood samples were collected between 8 and 10 AM 2 h after feeding on 21 and 7 days before calving and 1,3,7,15 and 30 days after calving. 25(OH)vitamin D, insulin-like growth factor 1 (IGF-1), insulin, nonesterified fatty acid (NEFA), β-hydroxybutyric acid (BHBA), albumin, total protein, glucose, urea, triglyceride, cholesterol and aspartate amino transferase (AST) were measured by commercially available kits. The insulin resistance index was calculated.Vitamin D3 injection significantly affected the amounts of 25(OH) vitamin D, urea, insulin and insulin resistance index (p ≤ 0.05). On the other hand, the amounts of glucose, NEFA, BHBA concentration and AST activity were higher in control group (p ≤ 0.05). Time had a significant effect on the amounts of most measured variables except IGF-1 and insulin. There were no group and time interactions for measured variables.It seems that injection of vitamin D3 in close up period influenced lipolysis potentially modifying energy metabolism and resulted in reducing insulin resistance.

Since vitamin D's discovery, strenuous efforts to investigate its physiological exploit and deficiency on human health were done. Our body synthesizes fat‐soluble vitamin D when get exposed to sunlight. In recent years, experimental data indicate that sunlight exposure and an adequate level of circulating vitamin D can reduce the incidence of cancer. Several in vitro and in vivo studies also suggest vitamin D as a potentially valuable supplement for cancer treatment and prevention. Nevertheless, there need to be adequate clinical studies performed to substantiate the suppressive ability of vitamin D concerning cancer incidence. Thus, understanding the cellular mechanisms of vitamin D can be advantageous for preventing several chronic diseases. Consequently, this review concentrates on different studies that have been conducted to characterize the outcome of vitamin D in reducing cancer incidence and its medication by cellular progression mechanism.

Breast cancer is associated with a high rate of recurrence, resistance therapy and mortality worldwide. We aimed at investigating the inhibitory effects of Sulindac and vitamin D3 (VD) on MCF-7 human breast cancer cells. MCF-7 cells were cultured with different concentrations of Sulindac and VD over a period of 24, 48 and 72 hours for cell viability and IC50 experiments. Hochst staining was used to evaluate apoptosis, whereas quantitative PCR (qPCR) was performed to measure mRNA levels of BCL-2 and BAX genes. Immunofluorescence staining was used to monitor intracellular β-catenin expression. The protein levels of AKT, AMPK and P65 were measured by western blotting. The result showed that cell viability decreased in treated cells dose/time dependently (P .05). Hochst staining showed an increase in fragmented nuclei in treated cells. The expression of BCL-2 and BAX genes decreased and increased in treated cells, respectively (P .05). Immunofluorescence staining indicated that the expression of β-catenin significantly reduced in treated cells. The AKT-1/p-Akt-1 and AMPK/p-AMPK ratio increased in treated cells (P .05), but the P65/p-P65 ratio did not change significantly (P .05). Our results indicated that the combination of Sulindac and VD has a growth-inhibiting effect on MCF-7 cells through AMPK/Akt/β-catenin axis.

Background Tamoxifen (TAM) is a life-saving and cost-effective drug widely used in the prevention and treatment of breast cancer. However, the adverse effects of tamoxifen can lead to non-adherence and poor patient outcomes. Therefore, exploring novel strategies to improve TAM safety profile is crucial. Given the key role that vitamin D (VD) plays in modulating lipid metabolism and inflammation, in addition to its benefits in reducing risk and progression of breast cancer, we evaluated the protective potential of VD against TAM-induced hepatotoxicity focusing on lipid metabolism and microRNAs (miRNAs) regulation. Methods Female rats were pretreated with VD as cholecalciferol (500 IU/kg/day, po) for 4 weeks before receiving TAM (40 mg/kg/day, po) concurrently with VD during the fifth and sixth weeks. Liver histology, lipid profile and expression of genes, proteins, and miRNAs involved in lipid metabolism and inflammation were examined. Results TAM-induced steatohepatitis was evidenced by elevated liver triglycerides and cholesterol contents, increased serum miRNA-122 level and ALT activity, in parallel with accumulation of lipid droplets, focal necrosis and inflammatory cells infiltration in hepatocytes. Prophylactic use of VD mitigated TAM-induced steatohepatitis by modulating key transcription factors in the liver: PPAR-α, Srebf1, and NF-κB and their downstream genes/proteins Fas, CPT-1A and TNF-α resulting in reduced hepatic lipids and suppressed pro-inflammatory signaling. Notably, VD pretreatment mitigated TAM-induced alterations in the expression of serum miRNA-122, hepatic miRNA-21 and miRNA-33. Conclusions The combination therapy of VD and TAM has complementary benefits in terms of safety and not only efficacy, and should be further investigated clinically.

Klotho is an aging-suppressor gene. The purpose of this study was to investigate whether Klotho deficiency affects arterial structure. We found that Klotho-deficient (kl/kl) mice developed severe arterial calcification and elastin fragmentation. Klotho-deficient mice demonstrated higher levels of bone morphogenetic proteins (BMP2, BMP4) and runt-related transcription factor 2 (RUNX2) in aortas, indicating that Klotho deficiency upregulates expression of BMP2 and RUNX2 (a key transcription factor in osteoblasts). To exclude the potential involvement of hyperphosphatemia in arterial calcification, Klotho-deficient mice were given a low phosphate diet (0.2%). The low phosphate diet normalized blood phosphate levels and abolished calcification in the lungs and kidneys, but it did not prevent calcification in the aortas in Klotho-deficient mice. Thus, Klotho deficiency per se might play a causal role in the pathogenesis of arterial calcification, which is independent of hyperphosphatemia. In cultured mouse aortic smooth muscle cells (ASMCs), Klotho-deficient serum-induced transition of ASMCs to osteoblasts. Klotho-deficient serum promoted BMP2/vitamin D3-induced protein expression of PIT2 and RUNX2, phosphorylation of SMAD1/5/8 and SMAD2/3, and extracellular matrix calcification. Interestingly, treatments with recombinant Klotho protein abolished BMP2/vitamin D3-induced osteoblastic transition and morphogenesis and calcification. Therefore, Klotho is a critical regulator in the maintenance of normal arterial homeostasis. Klotho deficiency-induced arterial calcification is an active process that involves the osteoblastic transition of SMCs and activation of the BMP2-RUNX2 signaling.

Objective The present study was undertaken to determine whether vitamin D supplementation or maintaining sufficient vitamin D level reduces foot pain over 2 years in patients with symptomatic knee osteoarthritis (OA). Methods A post hoc study was conducted from a randomized, double-blind, placebo-controlled trial named the Vitamin D Effect on Osteoarthritis (VIDEO) study. Symptomatic knee OA patients with serum 25-hydroxyvitamin D levels between 12.5 nmoles/liter and 60 nmoles/liter were included and randomly allocated to either monthly vitamin D3 or placebo treatment (1:1) for 2 years. Manchester Foot Pain and Disability Index (MFPDI) was used to evaluate foot pain and disabling foot pain was defined as at least 1 of the 10 functional limitation items (items 1-9 and 11) being documented as on "most/every day(s)" in the last month. A repeated-measures, mixed-effects model was used to analyze the change of MFPDI scores between groups adjusting for potential confounders. Results A total of 413 patients with a mean age of 63.2 years (49.7% males) were enrolled and 340 completed the study. The mean MFPDI score was 22.8 ± 7.3, with 23.7% of participants having disabling foot pain at baseline. There were significant differences in MFPDI scores change between groups over 2 years, with more improvements in the vitamin D group than in the placebo group (-0.03 versus 1.30; P = 0.013) and more improvement in those maintaining sufficient vitamin D levels (n = 226) than those who did not (n = 114) (-0.09 versus 2.19; P = 0.001). Conclusion Vitamin D supplementation and maintenance of sufficient vitamin D levels may improve foot pain in those with knee OA.

While we generally understand the optimal ultraviolet B (UVB) environment for the growth and reproduction of female Panther Chameleons Furcifer pardalis, we do not know the relative importance of UVB irradiance and dose for optimal husbandry outcomes. Accordingly, we experimented with Panther Chameleon females to test the hypothesis that UVB dose (irradiance × exposure duration) determines the outcome, regardless of the combination of UVB irradiance and exposure duration generating the dose. We varied UVB irradiance and exposure duration across treatment groups while keeping dose similar and within a range previously documented to result in reproductive success. The growth rate, age of maturity, and measurable vitamin D status were not significantly different among the treatment groups. Individuals in all groups produced viable eggs that successfully hatched. Thus, we found some support for the hypothesis that the UVB dose determines the outcome regardless of UVB irradiance. However, mean egg vitamin D3 concentration and percent hatching were higher in the highest UVB irradiance group, despite similar doses among the three groups. Preliminary field data reveal that this species occupies UV irradiance Zone 4 in Madagascar, the highest zone for reptiles recorded. Only the irradiance of the high UVB irradiance group in our experiment approached this zone and resulted in the best reproductive success. Biosynthesis of vitamin D3 and provisioning to eggs is more efficient when exposure to UVB irradiance is similar to that in their natural environment. Establishing an optimal UVB environment, based on knowledge of the natural UVB environment, is important for the propagation of Panther Chameleons in captivity.

This study aimed to examine 25OHD3 concentration in the fluid of follicular and follicular lutein cysts of sows in comparison with preovulatory follicles as well as immunolocalize vitamin D metabolic enzymes (CYP27B1 and CYP24A1) and determine their protein abundances in the cyst wall. We have shown for the first time that 25OHD3 level in the fluid of both cyst types was significantly lower than in preovulatory follicles. Furthermore, we have demonstrated CYP27B1 and CYP24A1 protein immunolocalization and abundance in follicular and follicular lutein cysts. The abundance of protein for both metabolic enzymes was decreased in ovarian cysts when compared to preovulatory follicles. We propose that altered VD metabolism in ovarian cyst might associate with their formation in sows.

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-days-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 reduction of inflammatory factors and myocardial infarction markers compared to AMI group. VD3 treatment obviously alleviated AMI-induced myocardial apoptosis, along with Bcl-2 up-regulation and down-regulation of caspase-3, caspase-9 and Bax. Both in vivo and in vitro experiments revealed that VD3 enhanced 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 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. This article is protected by copyright. All rights reserved.

Previously, we showed that nearly 70% of children followed in our sickle cell disease (SCD) clinic were vitamin D- deficient and had low vitamin intake with poor use of supplements. We compared the change in serum 25-hydroxyvitamin D [25(OH)D], safety and clinical impact of two vitamin D supplementation regimens in children with SCD. Children (5-17 years, all genotypes) were randomized to a single bolus of vitamin D3 (300 000 IU; n = 18) or placebo (n = 20). All children received a prescription for daily 1 000 IU vitamin D3 . Serum 25(OH)D and calcium, urinary calcium/creatinine ratio, musculoskeletal pain, quality of life, haematology and bone markers were assessed at baseline and three months post intervention. Bolus administration led to a greater rise in 25(OH)D levels from baseline compared to placebo (20 ± 16 nmol/l vs. 2 ± 19 nmol/l; P = 0·003) and correction of vitamin D deficiency. No hypercalcaemia nor hypercalciuria occurred during the study, but more children in the bolus group experienced gastrointestinal symptoms within the first month (P = 0·04). There were no differences between groups for other outcomes. The use of a high-dose vitamin D bolus combined with daily 1 000 IU vitamin D3 was more efficient in raising 25(OH)D levels than daily supplementation alone in children with SCD.

Background Eosinophilic chronic rhinosinusitis (ECRS) is a chronic inflammatory disease, characterized by eosinophilic infiltration, T-helper type 2 (Th2-type) response, and olfactory dysfunction. A master regulator of Th2-type inflammation, thymic stromal lymphopoietin (TSLP), is important for basophil activation. TSLP-elicited basophils are a key factor in the pathogenesis of ECRS. Methods In order to elucidate the mechanisms of ECRS in humans, we aimed to establish a murine model of ECRS based on TSLP production in response to the topical application of MC903 (a vitamin D3 analog) and the subsequent TSLP-induced basophil activation. Histological analyses were performed to assess immune cell infiltration into the nasal mucosa and to explore the impact of eosinophilic inflammation on the olfactory epithelium. The status of Th2-type inflammation was evaluated by quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA). Results Eosinophils, basophils, and M2 macrophages increased significantly in the nasal mucosa of the mice treated with MC903 and ovalbumin (OVA), compared to those treated with OVA alone or the controls. Quantitative real-time PCR and ELISA revealed elevated expression of interleukin (IL)-4, IL-5, IL-13, TSLP, the chemokine CCL11, and CCL24 in the nasal mucosa of the ECRS mice. In parallel, thinned olfactory epithelium and decreased mature olfactory sensory neurons were observed in the ECRS mice. Conclusions Our model of ECRS displayed Th2-type inflammation in the sinonasal region, including both eosinophil infiltration and basophil infiltration. Additionally, olfactory epithelium turned out to be affected by eosinophilic inflammation. These features are consistent with the characteristics of the human ECRS.

OBJECTIVE To assess whether increment of vitamin D daily intake results in improved serum25(OH) vitamin D levels and reduced respiratory morbidity in premature infants. METHODS A randomized double-blind clinical pilot trial, including preterm infants born at 32 + 6 to 36 + 6 weeks of gestation. The control group received 400 international units (IU) of cholecalciferol daily compared to 800 IU daily in the intervention group. Levels of 25(OH) vitamin D were measured at birth and 6 and 12 months of age. Respiratory morbidity was followed until 1 year of age. RESULTS Fifty subjects were recruited during the study period; the median measured 25(OH) vitamin D levels in the control vs intervention groups were: 26.5 vs 34 nmol/L (P = .271) at birth, 99 vs 75.5 nmol/L (P = .008) at 6 months and 72.5 vs 75 nmol/L (P = .95) at 12 months of age. Infants with insufficient vitamin D (

Delivery of vitamin D3 (VD3 ) in foods should exhibit desirable physicochemical characteristics and improves absorption. In this study, gum arabic (GA) was investigated as a VD3 carrier to encapsulate VD3 . VD3 dissolved in 5 mL ethanol corresponding to 0.3 to 6.0% mass of GA, was blended in 5.0% w/v GA solution, followed by freeze drying. The encapsulation efficiency decreased while loading capacity increased with an increased amount of VD3 . At the highest VD3 level, the loading capacity (3.47%) was the highest, and the encapsulation efficiency (61.24%) was satisfactory, and the treatment was further studied. The magnitude of negative zeta-potential increased from 3.1 to 31.0 mV at pH 2.0 to 7.4. During the 100-day storage at 3 °C of capsules reconstituted at pH 2.0 to 7.4, the hydrodynamic diameter decreased at all pH conditions, most evident for reduction to 81.3 nm at pH 7.4, and no precipitation was observed, indicating the significance of steric repulsion on capsule stability. Bioaccessibility of VD3 in capsules (95.76%) was significantly higher than the nonencapsulated VD3 (68.98%). The in vivo pharmacokinetic study in Sprague-Dawley rats after a single-dose of 300 µg VD3 showed the area-under-curve of serum 25(OHD) level in 48 hr of the encapsulation treatment was 4.32-fold of the nonencapsulated VD3 and more than twice higher than the VD3 -GA physical mixture. During 2-week supplementation of 60 µg VD3 /d, rats receiving capsules or physical mixture had 25(OH)D levels of at least 81 ng/mL higher than that of the nonencapsulated VD3 group. The studied encapsulation system holds great potential as a value-added ingredient to supplement VD3 in beverages with a wide pH range. PRACTICAL APPLICATION: The findings of this study demonstrated the improved dispersion stability and absorption of vitamin D3 after encapsulation in gum arabic. The capsules exhibited good dispersion stability across a pH range between 2.0 and 7.4, showing potential application in beverages. Furthermore, the enhanced absorption of VD3 after encapsulation highlights the nutritional benefits of the studied encapsulation system.

Background Intralesional vitamin D3 has recently emerged as a new treatment for cutaneous warts. The use of the measles, mumps, and rubella (MMR) vaccine for this purpose is an established modality. However, relevant data on the efficacy of either the MMR vaccine or vitamin D3 as immunotherapy for cutaneous warts in the pediatric population are limited. Objectives To compare the efficacy and safety of intralesional injections of MMR vaccine to intralesional injections of vitamin D3 in children aged 8-16 years with multiple warts. Methods A total of 74 children were randomly allocated into two groups. Group A patients received intralesional MMR vaccine into the largest wart, and group B received intralesional vitamin D3 into the largest wart. The injections were repeated every 4 weeks until clearance or for a maximum of three treatments. After the last injection, children were followed up every 2 weeks for 3 months, and at the sixth month, a final clinical assessment was conducted. Results Of 74 children, 60 completed the study, with 30 children in each group. Complete clearance of the injected wart was observed in 26 (86.67%) patients in the MMR group (group A) and 23 (76.7%) patients in the vitamin D3 group (group B). Distant warts cleared in 23 (76.7%) patients in group A compared to 20 (66.6%) patients in group B. There was no significant difference between groups. No recurrence was seen in group A, whereas two (6.6%) children in group B exhibited recurrence in the ensuing 6-month follow-up. The most common adverse events were injection site pain and swelling. Conclusion Both intralesional MMR and vitamin D3 are safe, generally well-tolerated, and equally effective in children for the treatment of cutaneous warts.

Background Although vitamin D3 deficiency is considered as a risk factor for periodontitis, supplementation during periodontal treatment has not been shown to be beneficial to date. Human periodontal ligament cells (hPDLCs) are regulated by vitamin D3 and play a fundamental role in periodontal tissue homeostasis and inflammatory response in periodontitis. The aim of this study is to investigate possible alterations of the vitamin D3 activity in hPDLCs under inflammatory conditions. Methods Cells isolated from six different donors were treated with either 1,25(OH)2 D3 (0 to 10 nM) or 25(OH)D3 (0 to 100 nM) in the presence and absence of ultrapure or standard Porphyromonas gingivalis lipopolysaccharide (PgLPS), Pam3CSK4, or interferon-γ for 48 hours. Additionally, nuclear factor (NF)-κB inhibition was performed with BAY 11-7082. The bioactivity of vitamin D in hPDLCs was assessed based on the gene expression levels of vitamin D receptor (VDR)-regulated genes osteocalcin and osteopontin. Additionally, VDR and CYP27B1 expression levels were measured. Results The vitamin D3 -induced increase of osteocalcin and osteopontin expression was significantly decreased in the presence of standard PgLPS and Pam3CSK4, which was not observed by ultrapure PgLPS. Interferon-y had diverse effects on the response of hPDLCs to vitamin D3 metabolites. NF-kB inhibition abolished the effects of standard PgLPS and Pam3CSK4. Standard PgLPS and Pam3CSK4 increased VDR expression in the presence of vitamin D3 . CYP27B1 expression was not affected by vitamin D3 and inflammatory conditions. Conclusions This study indicates that the transcriptional activity of VDR is diminished under inflammatory conditions, which might mitigate the effectiveness of vitamin D3 supplementation during periodontal treatment.

PURPOSE The current study aimed to assess the serum levels of vitamin D and immunoglobulin E (IgE) among asthmatic Egyptian children and to find out the possible associations of vitamin D receptor (VDR) polymorphisms with bronchial asthma development. METHODS The study included 100 Egyptian children, 50 asthmatic children who were comparable with 50 age, sex, and body mass index-matched, unrelated healthy controls (HCs) clinical assessments of asthmatic children were done using global initiative of asthma. Pulmonary function tests (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], FEV1/FVC ratio) were performed. Enzyme-linked immunosorbent assays of serum vitamin D3 and total IgE were done. VDR-single nucleotide polymorphisms (SNPs) (ApaI, TaqI, and BsmI) detection has performed using polymerase chain reaction through restriction fragment length polymorphism technique. Data analysis was performed using SPSS version 20.0. The studied SNPs were followed the Hardy Weinberg equation. RESULTS The mean serum level of 25(OH) D3 was significantly lower among asthmatic children (13.46 ng/mL ± 10.50 SD) in comparison to HCs (37.53 ng/mL ± 13. 0.40 SD), P .05). TT + Tt and Bb + bb genotypes were significantly higher among cases versus the controls, P

Introduction Primary aldosteronism (PA) contributed to the cardiovascular disease and metabolic alterations independent of the blood pressure level. Evidence exists that aldosterone excess also affects calcium and mineral homeostasis. PA subjects have been shown to have greater prevalence of vitamin D deficiency. However, the impact of vitamin D treatment in this population has never been assessed. Objective This study aimed to evaluate the effect of vitamin D treatment on clinical and biochemical outcomes of PA patients. Methods Two hundred forty hypertensive subjects were screened, 31 had positive ARR, and 17 patients with newly confirmed PA following positive confirmatory test that has not been subjected for definitive treatment were enrolled. Clinical parameter (blood pressure) and biochemical parameters (renal profile, plasma aldosterone concentration, plasma renin activity, serum calcium, vitamin D, intact parathyroid hormone, 24-hour urinary calcium) were measured at baseline and 3 months of treatment with Bio-D3 capsule. Primary outcomes were the changes in the blood pressure and biochemical parameters. Results About 70% of our PA subjects have low vitamin D levels at baseline. Three months following treatment, there were significant: (a) improvement in 25(OH)D levels; (b) reduction in systolic blood pressure and plasma aldosterone concentration; and (c) improvement in the eGFR. The vitamin D deficient subgroup has the greatest magnitude of the systolic blood pressure reduction following treatment. Conclusions This study demonstrated significant proportion of PA patients has vitamin D insufficiency. Vitamin D treatment improves these interrelated parameters possibly suggesting interplay between vitamin D, aldosterone, renal function and the blood pressure.

Polycystic ovarian syndrome (PCOS) is a disorder characterized by oligomenorrhea, anovulation, and hyperandrogenism. Altered mitochondrial biogenesis can result in hyperandrogenism. The goal of this study was to examine the effect of vitamin D3 on mitochondrial biogenesis of the granulosa cells in the PCOS-induced mouse model. Vitamin D3 applies its effect via the mitogen-activated pathway kinase-extracellular signal-regulated kinases (MAPK-ERK1/2) pathway. The PCOS mouse model was induced by the injection of dehydroepiandrosterone (DHEA). Isolated granulosa cells were subsequently treated with vitamin D3, MAPK activator, and MAPK inhibitor. Gene expression levels were measured using real-time polymerase chain reaction. MAPK proteins were investigated by western blot analysis. We also determined reactive oxygen species (ROS) levels with 2', 7'-dichlorofluorescein diacetate. Mitochondrial membrane potential (mtMP) was also measured by TMJC1. Mitochondrial biogenesis (peroxisome proliferator-activated receptor gamma coactivator 1-α and nuclear respiratory factor), antioxidant (superoxide dismutase, glutathione peroxidase, and catalase), and antiapoptotic (B-cell lymphoma-2) genes were upregulated in the PCOS mice that treated with vitamin D3 compared with the PCOS mice without any treatment. Vitamin D3 and MAPK activator-treated groups also reduced ROS levels compared with the nontreated PCOS group. In summary, vitamin D3 and MAPK activator increased the levels of mitochondrial biogenesis, MAPK pathway, and mtMP markers, while concomitantly decreased ROS levels in granulosa cells of the PCOS-induced mice. This study suggests that vitamin D3 may improve mitochondrial biogenesis through stimulation of the MAPK pathway in cultured granulosa cells of DHEA-induced PCOS mice which yet to be investigated.

In bone cells vitamin D dependent regulation of gene expression principally occurs through modulation of gene transcription. Binding of the active vitamin D metabolite, 1,25-dihydroxy vitamin D3 (1,25(OH)2 D3 ) to the vitamin D receptor (VDR) induces conformational changes in its C-terminal domain enabling competency for interaction with physiologically relevant coactivators, including SRC-1. Consequently, regulatory complexes can be assembled that support intrinsic enzymatic activities with competency to posttranslationally modify chromatin histones at target genomic sequences to epigenetically alter transcription. Here we examine specific transitions in representation and/or enrichment of epigenetic histone marks during 1,25(OH)2 D3 mediated upregulation of CYP24A1 gene expression in osteoblastic cells. This gene encodes the 24-hydroxylase enzyme, essential for biological control of vitamin D levels. We demonstrate that as the CYP24A1 gene promoter remains transcriptionally silent, there is enrichment of H4R3me2s together with its "writing" enzyme PRMT5 and decreased abundance of the istone H3 and H4 acetylation, H3R17me2a, and H4R3me2a marks as well as of their corresponding "writers." Exposure of osteoblastic cells to 1,25(OH)2 D3 stimulates the recruitment of a VDR/SRC-1 containing complex to the CYP24A1 promoter to mediate increased H3/H4 acetylation. VDR/SRC-1 binding occurs concomitant with the release of PRMT5 and the recruitment of the arginine methyltransferases CARM1 and PRMT1 to catalyze the deposition of the H3R17me2a and H4R3me2a marks, respectively. Our results indicate that these dynamic transitions of histone marks at the CYP24A1 promoter, provide a "chromatin context" that is transcriptionally competent for activation of the CYP24A1 gene in osteoblastic cells in response to 1,25(OH)2 D3 .

Vitamin D3 is a prohormone that is essential for calcium homeostasis. It is naturally produced in the skin by ultraviolet‐B (UVB) irradiation of 7‐dehydrocholesterol. In the absence of skin production, vitamin D3 can also be obtained from oral sources. However, the actual biological equivalence of naturally produced (i.e., UVB‐irradiation of skin) and oral vitamin D3 has not been determined. We previously identified a unique and specific transport mechanism for skin‐generated vitamin D3 which requires vitamin D binding protein (DBP); a mechanism that differs from absorption and transport of oral vitamin D3. In the following report, we examined the impact of this difference on the biological activity of vitamin D3. We report that UVB‐generated vitamin D3 is more potent at raising serum calcium compared to oral vitamin D3, with the total biological activity being twofold higher. By examining the excretion of radiolabeled vitamin D3 injected unbound or pre‐bound by DBP, we attributed the increased activity of skin‐generated vitamin D3 to a significant reduction in biliary excretion of DBP‐bound vitamin D relative to unbound vitamin D. Thus, removal of vitamin D3 from the skin by the natural DBP system markedly improves biological activity compared to that given orally., We report that ultraviolet‐B‐generated vitamin D3 is more potent at raising serum calcium compared to oral vitamin D3, with the total biological activity being twofold higher. By examining the excretion of radiolabeled vitamin D3 injected unbound or pre‐bound by D binding protein (DBP), we attributed the increased activity of skin‐generated vitamin D3 to a significant reduction in biliary excretion of DBP‐bound vitamin D relative to unbound vitamin D. Thus, removal of vitamin D3 from the skin by the natural DBP system markedly improves biological activity compared to that given orally.

Background People of Black and Asian ethnicities have a higher infection rate and mortality as a result of COVID‐19. It has also been reported that vitamin D deficiency may play a role in this, possibly because of the multi‐gene regulatory function of the vitamin D receptor. As a result, increased dietary intake and/or supplementation to attain adequate 25‐hydroxyvitamin D (25(OH)D) levels could benefit people in these ethnicities. The present study aimed to review the literature examining the changes in 25(OH)D in different types of vitamin D supplementation from randomised controlled trials in this population. Methods This systematic review was conducted using the PRISMA guidelines. Electronic databases were systematically searched using keywords related to vitamin D supplementation in Black and Asian ethnicities. Results Eight studies were included in the review. All the included studies found that supplementation of vitamin D (D2 and D3), regardless of dosage, increased 25(OH)D levels compared to a placebo. All trials in which participants were vitamin D deficient at baseline showed increased 25(OH)D levels to a level considered adequate. Two studies that used food fortification yielded smaller 25(OH)D increases compared to similar studies that used oral supplementation (10.2 vs. 25.5 nmol L−1, respectively). Furthermore, vitamin D2 supplementation yielded significantly lower 25(OH)D increases than vitamin D3 supplementation. Conclusions Oral vitamin D supplementation may be more efficacious in increasing 25(OH)D levels than food fortification of Black and Asian ethnicities, with vitamin D3 supplementation possibly being more efficacious than vitamin D2. It is recommended that people with darker skin supplement their diet with vitamin D3 through oral tablet modes where possible, with recent literature suggesting a daily intake of 7000–10,000 IU to be potentially protective from unfavourable COVID‐19 outcomes. As a result of the paucity of studies, these findings should be treated as exploratory., Highlights Oral vitamin D supplementation could be more efficacious than food fortification in Black and Asian populations.Vitamin D3 is more efficacious than vitamin D2.It is recommended that people with darker skin supplement their diet with vitamin D3.

Background Vitamin D deficiency is often reported in people with chronic liver diseases. Therefore, improving vitamin D status could have a beneficial effect on people with chronic liver diseases. Objectives To assess the beneficial and harmful effects of vitamin D supplementation in people with chronic liver diseases. Search methods We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, and Conference Proceedings Citation Index - Science. We also searched databases of ongoing trials and the World Health Organization International Clinical Trials Registry Platform. We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials. All searches were up to January 2017. Selection criteria Randomised clinical trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention in adults with chronic liver diseases. Vitamin D could have been administered as supplemental vitamin D (vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol)), or an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol), 25-hydroxyvitamin D (calcidiol), or 1,25-dihydroxyvitamin D (calcitriol)). Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. We contacted authors of the trials to ask for missing information. We conducted random-effects and fixed-effect meta-analyses. For dichotomous outcomes, we calculated risk ratios (RRs), and for continuous outcomes, we calculated mean differences (MD), both with 95% confidence intervals (CI) and Trial Sequential Analyses-adjusted CIs. We calculated Peto odds ratio (OR) for rare events. We considered risk of bias in domains to assess the risk of systematic errors. We conducted Trial Sequential Analyses to control the risk of random errors. We assessed the quality of the evidence with GRADE. Main results We included 15 randomised clinical trials with 1034 participants randomised. All trials had a parallel group design. Nine trials were conducted in high-income countries and six trials in middle-income countries. All trials were at high risk of bias. Six trials included participants with chronic hepatitis C, four trials included participants with liver cirrhosis, four trials included participants with non-alcoholic fatty liver disease, and one trial included liver transplant recipients. All included trials reported the baseline vitamin D status of participants. Participants in six trials had baseline 25-hydroxyvitamin D levels at or above vitamin D adequacy (20 ng/mL), while participants in the remaining nine trials were vitamin D insufficient (less than 20 ng/mL). All trials administered vitamin D orally. Mean duration of vitamin D supplementation was 0.5 years and follow-up was 0.6 years. Eleven trials (831 participants; 40% women; mean age 52 years) tested vitamin D3, one trial (18 men; mean age 61 years) with three intervention groups tested vitamin D2 and 25-dihydroxyvitamin D in separate groups, and three trials (185 participants; 55% women; mean age 55 years) tested 1,25-dihydroxyvitamin D. Seven trials used placebo, and eight trials used no intervention in the control group. The effect of vitamin D on all-cause mortality at the end of follow-up is uncertain because the results were imprecise (Peto OR 0.70, 95% CI 0.09 to 5.38; I2 = 32%; 15 trials; 1034 participants; very low quality evidence). Trial Sequential Analysis on all-cause mortality was performed based on a mortality rate in the control group of 10%, a relative risk reduction of 28% in the experimental intervention group, a type I error of 2.5%, and type II error of 10% (90% power). There was no diversity. The required information size was 6396 participants. The cumulative Z-curve did not cross the trial sequential monitoring boundary for benefit or harm after the 15th trial, and the Trial Sequential Analyses-adjusted CI was 0.00 to 2534. The effect of vitamin D on liver-related mortality (RR 1.62, 95% CI 0.08 to 34.66; 1 trial; 18 participants) and on serious adverse events such as hypercalcaemia (RR 5.00, 95% CI 0.25 to 100.8; 1 trial; 76 participants), myocardial infarction (RR 0.75, 95% CI 0.08 to 6.81; 2 trials; 86 participants), and thyroiditis (RR 0.33 95% CI 0.01 to 7.91; 1 trial; 68 participants) is uncertain because the results were imprecise. The evidence on all these outcomes is of very low quality. The effect of vitamin D3 on non-serious adverse events such as glossitis (RR 3.70, 95% CI 0.16 to 87.6; 1 trial; 65 participants; very low quality of evidence) is uncertain because the result was imprecise. Due to few data, we did not conduct Trial Sequential Analysis on liver-related mortality, and serious and non-serious adverse events. We found no data on liver-related morbidity and health-related quality of life in the randomised trials included in this review. Authors' conclusions We are uncertain as to whether vitamin D supplements in the form of vitamin D3, vitamin D2, 1,25-dihydroxyvitamin D, or 25-dihydroxyvitamin D have important effect on all-cause mortality, liver-related mortality, or on serious or non-serious adverse events because the results were imprecise. There is no evidence on the effect of vitamin D supplementation on liver-related morbidity and health-related quality of life. Our conclusions are based on few trials with an insufficient number of participants and on lack of data on clinically important outcomes. In addition, the analysed trials are at high risk of bias with significant intertrial heterogeneity. The overall quality of evidence is very low.

Medial artery calcification results from deposition of calcium hydroxyapatite crystals on elastin layers, and osteogenic changes in vascular smooth muscle cells. It is highly prevalent in patients with chronic kidney disease, diabetes, and peripheral artery disease (PAD), and when identified in lower extremity vessels, it is associated with increased amputation rates. This study aims to evaluate the effects of medial calcification on perfusion and functional recovery after hindlimb ischemia in rats. Medial artery calcification and acute limb ischemia were induced by vitamin D3 (VitD3) injection and femoral artery ligation in rats. VitD3 injection robustly induced calcification in the medial layer of femoral arteries in vivo. Laser Doppler perfusion imaging revealed that perfusion decreased and then partially recovered after hindlimb ischemia in vehicle‐injected rats. In contrast, VitD3‐injected rats showed markedly impaired recovery of perfusion following limb ischemia. Accordingly, rats with medial calcification showed worse ischemia scores and delayed functional recovery compared with controls. Immunohistochemical and histological staining did not show differences in capillary density or muscle morphology between VitD3‐ and vehicle‐injected rats at 28 days after femoral artery ligation. The evaluation of cardiac and hemodynamic parameters showed that arterial stiffness was increased while cardiac function was preserved in VitD3‐injected rats. These findings suggest that medial calcification may contribute to impaired perfusion in PAD by altering vascular compliance, however, the specific mechanisms remain poorly understood. Reducing or slowing the progression of arterial calcification in patients with PAD may improve clinical outcomes., Medial calcification is associated with poor outcomes in patients with peripheral artery disease. Rats with medial calcification showed delayed recovery of perfusion and function after femoral artery ligation. These findings were associated with increased arterial stiffness, but no changes in cardiac function or muscle histology.

Vitamin D deficiency during critical illness has been associated with worsened outcomes. Because most critically ill patients with severe traumatic injuries are vitamin D deficient, we investigated the efficacy and safety of cholecalciferol therapy for these patients.Fifty-three patients (17 years of age) admitted to the trauma intensive care unit who had a serum 25-hydroxy vitamin D (25-OH vit D) concentration20 ng/mL were given 10,000 IU of cholecalciferol daily. Efficacy was defined as achievement of a 25-OH vit D of 30-79.9 ng/mL. Safety was evaluated by the presence of hypercalcemia (serum ionized calcium [iCa]1.32 mmol/L) or hypervitaminosis D (25-OH vit D79.9 nmol/L). Patients were monitored for 2 weeks during cholecalciferol therapy.Twenty-four patients (45%) achieved target 25-OH vit D. No patients experienced hypervitaminosis D. Hypercalcemia occurred in 40% (n = 21) of patients; 2 patients experienced an iCa1.49 nmol/L. 25-OH vit D was significantly greater for those who developed hypercalcemia (37.2 + 11.2 vs 28.4 + 5.6 ng/mL, respectively, P0.001) by the second week of cholecalciferol. Of 24 patients who achieved target 25-OH vit D, 14 (58%) experienced hypercalcemia in contrast to 24% of patients (7 out of 29) who did not achieve target 25-OH vit D (P = 0.024).Cholecalciferol normalized serum 25-OH vit D concentrations in less than half of patients yet was associated with a substantial proportion of patients with hypercalcemia without hypervitaminosis D.

Nowadays, fortified vegetable oils with vitamin D3 are widely available in different countries and are consumed daily. The reduction rate of added vitamin D3 in fortified canola oil during heating process, the changes in oxidative status, and the thermal kinetic degradation of vitamin D3 in the fortified oil were investigated. For this purpose, canola oil was fortified at two levels of vitamin D3 with 5.625 µg/mL (low concentration or LC) and 13.585 µg/mL (a high concentration or HC). Samples were heated isothermally at 100, 150, and 180 °C for 30 min. The vitamin D3 concentration was determined by the high-performance liquid chromatographic method. The retention of vitamin D3 in samples treated at 100 °C for 30 min showed no significant reduction. Samples treated at 150 and 180 °C depending on the initial concentration showed the retention of 67.5% to 72.97% and 33.16% to 40.35% of vitamin D3 , respectively. An inverse relationship was found between the increment of lipid oxidation products (peroxide and anisidine values) and the retention of vitamin D3 . Kinetic parameters such as rate constant, activation energy, decimal reduction time, and quotient indicator were also calculated. An Arrhenius relationship was used for the assessment of temperature dependence of vitamin D3 degradation. Activation energies for vitamin D3 in LC and HC between 100 and 180 °C were found to be 44.01 and 38.77 kJ/mol, respectively. PRACTICAL APPLICATION: The oil can be fortified with vitamin D3 at low cost and offers a good bioavailability. A high-temperature cooking method may not be appropriate for the fortified products containing high lipid content.