Oral Vitamin D3 Research Articles

Effects of different routes and forms of vitamin D administration on CD4+ T cell homeostasis and renin-angiotensin system-associated lung injury in obese mice complicated with polymicrobial sepsis

This study investigated the impacts of enteral cholecalciferol and/or intravenous calcitriol administration on the balance of cluster of differentiation 4-positive T cell subsets, the renin-angiotensin system (RAS), and the severity of acute lung injury (ALI) in obese mice with sepsis. Mice were fed a high-fat diet and then cecal ligation and puncture (CLP) was performed. Obese mice were divided into four sepsis groups: without vitamin D (VD) (S), with oral cholecalciferol 1 d before CLP (G), with intravenous calcitriol 1 h after CLP (V), and with both cholecalciferol before and intravenous calcitriol after CLP (GV). Mice were euthanized after CLP. The V and GV groups showed higher blood T helper (Th)1/Th2 and lower Th17/T regulatory (Treg) ratios than did the S and G groups. In the lungs, The V group had the lowest nuclear factor-κB and interleukin-1β gene expressions among all groups 24 h post-CLP. In parallel, gene expressions of angiotensin type 2 receptor (AT2R), angiotensin-converting enzyme 2 (ACE2), and Mas receptor (MasR) were highest in the V group compared to other groups. The protein levels of MasR in the GV group and the AT2R/AT1R ratio in the V group were higher than those in the G and/or S groups. All of the VD-treated groups had lower injury scores than the S group. These findings suggest that calcitriol administration had more-pronounced impacts on regulating the homeostasis of Th/Treg cells and is prone to RAS-associated anti-inflammatory pathway in the lungs. However, both forms of VD attenuated sepsis-induced ALI in obese animals.

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.

PSAT173 Evaluation of efficacy and safety of different doses of cholecalciferol supplementation in healthy adults- a single blind randomized control trial.

Abstract Background Vitamin-D (VD) has been shown to be associated various skeletal and non-skeletal benefits. Despite synthesis in the body, 70-80% of population has been found to be VD deficient, due to poor sunlight exposure, increasing environmental pollution, indoor habits etc. Institute of medicine recommended daily allowance (RDA) of 600 IU/day, while Endocrine society recommends a daily intake of 1500-2000 IU/day for age group 19-70 years. In the absence of mandatory food fortification with VD, supplementation is an effective alternate strategy to mitigate the issue of VD deficiency. Optimal supplementation dose for achieving and maintaining sufficient VD levels in Indian adults is still not known. Aim To evaluate optimal dose of oral cholecalciferol supplementation to achieve and maintain serum hydroxy vitamin D [25(OH)D] sufficiency in Indian adults. Methodology In this single center blinded randomized control study, a total of 168 healthy subjects age (18-60 years) were randomized in four groups (A, B, C and D). Subjects were supplemented with 600, 1000, 2000 IU/day and 60,000 IU/month of cholecalciferol to group A, B, C and D in two phases, winter phase and summer phase of three months each with a washout period of three months in between. Serum 25(OH)D, iPTH, calcium, phosphorus, alkaline phosphatase levels and urine calcium/creatinine ratio was assessed at baseline, 12 weeks, 24 weeks and 36 weeks. Results The mean increase in serum 25(OH)D following supplementation was 21.67±6.54, 32.50±7.33 and 27.72±5.64 ng/ml after three months, 25.96±7.95, 31.52±8.95, 48.05±9.88 and 40.73±12.96 ng/ml after six months of supplementation in group A, B, C and D respectively, with 9.1%, 16.2%, 50% and 39.5% of subjects achieved levels of &amp;gt;30ng/ml after three months and 27.3%, 59.5%, 93.8% and 76.3% after six month of VD supplementation in group A, B, C and D respectively. Supplementation with VD at various doses raised serum 25(OH)D levels in a dose dependent manner, with an average rate constant of 1.79±0.79 ng/ml/100IU/day. Higher BMI and baseline serum 25(OH)D levels negatively associated with gain in serum VD levels. Overall, secondary hyperparathyroidism decreased from 29.3 to 8·6% post-supplementation. No significant difference in urinary Ca/Cr ratio between baseline and post supplementation was noted. Conclusion In accordance with the level of treatment, various oral cholecalciferol regimens improved serum 25(OH)D levels in all the subjects, but the 2000 IU/day achieved the best results while being safe. Daily supplementation with 2000 IU of oral cholecalciferol does meet the RDA requirement of achieving serum 25(OH)D of &amp;gt;30ng/ml in 94% subjects. Whether RDA of 600 IU/day, recommended by IOM is sufficient to combat VD deficiency in our population, is debatable. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSAT173 Weekly Supplementation with Vitamin D3 reduces 1,25(OH)2 vitamin D3 Measured by Mass Spectrometry, and increases Fibroblast-like growth factor 23 (FGF23) in Individuals with and without Primary Hyperparathyroidism (PHPT)

Abstract Introduction Vitamin D deficiency is a very common condition, which has been associated with more severe presentations of PHPT. It has been suggested that the Vitamin D replacement improves this prognosis, but there are few data regarding its effect on mineral homeostasis. The aim of this research was to evaluate the effects of weekly Vitamin D supplementation on the mineral metabolism in this population.Material and methods: In this prospective case-control trial, we evaluated the effects of 14,000 IU/week of oral Vitamin D3, for 12 weeks, on albumin-adjusted total Calcium (TCa), Parathormone (PTH), 25 hydroxyvitamin D3 (25OHD), intact FGF23 and 1,25dihydroxyvitamin D3 (1,25(OH)2D), in addition to other biochemical markers. Volunteers with active PHPT (n=55) and paired controls (n=64) collected fasting blood samples before and after 12 weeks of the Vitamin D supplementation. 1,25(OH)2D was measured by liquid chromatography and mass spectrometry, and other hormones by commercial immunometric assays. P&amp;lt;0.05 was considered significant. Results At baseline there were no differences between groups regarding 25OHD, FGF23 and clearance of creatinine. As expected, the concentrations of TCa, PTH, 1,25(OH)2D were higher in the PHPT. After supplementation, TCa and PTH did not change despite the significant increase on 25OHD in both groups, more markedly in the controls (from 22.7±6.1 to 31.5±6.8 ng/mL in PHPT; and from 20.4±5.8 to 32.5±6.4 ng/mL in controls). FGF23 levels significantly increased after supplementation in both groups, more markedly in the PHPT. (from 47.9 ± 27.1 to 76.3 ± 33.3 pg/mL in PHPT and from 40.5 ± 13.9 to 59.8±19.8 pg/mL in controls). A significant reduction in the concentrations of 1,25(OH)2D was seen in both groups, (time effect p-value&amp;lt;0.001), with more intensity in the PHPT group (time x group effect p-value=0.015) (from 94.8±34.6 to 68.9±25.3 pg/mL in PHPT and from 68.7±23.5 to 56.4±20.7pg/mL in controls). The delta of 1,25(OH)2D was inversely correlated with the delta of FGF23 in both the PHPT (r=-0.302, p-value=0.028) and control (r=-0.278, p-value=0.027) groups. Conclusion In both patient groups (with and without PHPT), weekly administration of 14,000IU of Vitamin D3 reduced 1,25(OH)2D concentrations measured by mass spectrometry, probably due to the inhibition of 1α-hydroxylase induced by the increase in FGF23. This phenomenon could explain the absence of hypercalcemia after supplementation, even in individuals with active PHPT, appearing to be a protective mechanism against Vitamin D excess. Future studies are needed to see if this increase in FGF23 could explain the paradoxical effects observed with the high bolus doses of vitamin D described by others.*This research received public grants from FAPESP (Fundação de Amparo a Pesquisa do Estado de Sao Paulo), with technical support from Laboratorio Fleury Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Oral vitamin D modulates the epidermal expression of the vitamin D receptor and cathelicidin in children with atopic dermatitis.

Although vitamin D (VD) is known to have multiple effects on the skin and immunity, its effects on atopic dermatitis (AD) severity remain unclear. We investigated whether oral cholecalciferol (VD3) supplementation changes stratum corneum expression of the vitamin D receptor (vdr), and the epidermal alarmins Cathelicidin Antimicrobial Peptide (camp/LL-37) and Thymic Stromal Lymphopoietin (tslp) in children with AD. We conducted an open-label supplementation study with weekly oral VD3 for six weeks in children with AD. Serum 25-hydroxyvitamin D (25OHD), lesional Staphylococcus aureus colonization, and AD severity evaluated by SCORAD index were evaluated before and after supplementation. Tape stripping (TS) was performed on non-lesional and lesional skin to measure mRNA expression of vdr, camp, and tslp through RT-qPCR and LL-37 peptide by ELISA. Twenty-two children with moderate-severe AD received weekly oral VD3 for six weeks. Total serum 25OHD increased from 45.1 ± 23 to 93.5 ± 24.3 nmoL/L (p < 0.0001), while SCORAD decreased from 41.4 ± 13.5 to 31.5 ± 15.8 (p < 0.0001). After treatment, epidermal gene expression of camp increased significantly in non-lesional (p = 0.014) and lesional (p = 0.0007) tape stripping samples, while vdr only increased in lesional skin samples (p < 0.0001). LL-37 peptide increased significantly only in lesional skin samples (p = 0.008). Gene expression of tslp did not change after oral VD3 treatment. In children with AD, oral VD3 supplementation was associated with improved VD status and AD severity, as well as increased VDR and Cathelicidin expression in lesional skin, which provide mechanistic clues on its effects.

Effects of long-term vitamin D supplementation on metabolic profile in middle-aged and elderly patients with type 2 diabetes

To evaluate the effects of long-term vitamin D supplementation on metabolic profiles in middle-aged to elderly patients with type 2 diabetes (T2D), a randomized controlled trial was conducted among patients with T2D aged 50–70 years. A total of 270 patients underwent randomization with 135 being allocated to the vitamin D group and 135 to the control group, and participants in the vitamin D group received oral vitamin D3 (800 IU/day) for 30 months. Serum 25(OH)D and metabolic variables were measured at baseline, and after 6, 12, 18, and 30 months of intervention. After 30 months, the vitamin D group showed a greater increase in serum 25(OH)D than the control group (12.39 ± 6.99 vs 5.35 ± 5.29 ng/ml, P < 0.001). Meanwhile, changes in the levels of fasting insulin, HOMA-IR, non-high-density-lipoprotein cholesterol (non-HDL-C), high-sensitivity C-reactive protein (hs-CRP), and uric acid differed significantly between the two groups (all P < 0.05). Stratified analysis indicated that change in uric acid differed significantly between the two groups in subgroup with baseline 25(OH)D ≥ 20 ng/ml (P = 0.042) or subgroup with female patients (P = 0.034). And the change in fasting blood glucose (FBG) differed significantly between the vitamin D group (−0.30 ± 2.52 mmol/L) and the control group (0.49 ± 1.78 mmol/L, P = 0.049) among patients achieving 25(OH)D concentrations of 30 ng/ml at the end of this trial. A significant difference in the change of triglyceride was observed between the two groups among patients with obesity at baseline [0.05(−0.59, 0.23) vs 0.41(−0.01, 0.80) mmol/L, P = 0.023]. These findings suggested that long-term vitamin D supplementation significantly reduced fasting insulin, HOMA-IR, and serum concentrations of non-HDL-C, hs-CRP, and uric acid among middle-aged to elderly patients with T2D. And vitamin D status, gender, and baseline obesity may modify the effects of vitamin D supplementation.

Sixteen-Week Vitamin D3 Supplementation Increases Peripheral T Cells in Overweight Black Individuals: Post hoc Analysis of a Randomized, Double-Blinded, Placebo-Controlled Trial.

Background: Vitamin D is considered to modulate T-cell function, which has been implicated in the treatment of inflammatory conditions. However, there is limited knowledge on the effects of vitamin D and its influences on circulating T-cell profiles in humans, particularly in overweight Black individuals who are more likely to be vitamin D insufficient (serum 25(OH)D concentrations of ≤20 ng/mL). Thus, this study tested the hypothesis that vitamin D supplementation modulates T-cell composition, which is in a dose-dependent manner. Methods: A 16-week randomized, double-blinded, placebo-controlled trial of vitamin D3 supplementation was undertaken in 70 overweight/obese Black people (mean age = 26 years, 82% female) with 25 hydroxyvitamin D ≤ 20 ng/mL at baseline. Subjects were randomly assigned a supervised monthly oral vitamin D3 equivalent to approximately 600 IU/day (n = 17), 2000 IU/day (n = 18), 4000 IU/day (n = 18), or a placebo (n = 17). Fresh peripheral whole blood was collected and CD3+, CD4+ and CD8+ cell counts and percentages were determined by flow cytometry at baseline and at 16 weeks, among 56 subjects who were included in the analyses. Results: A statistically significant increase in CD3+% in the 2000 IU/day vitamin D3 supplementation group, and increases in CD4+% in the 2000 IU/day and 4000 IU/day vitamin D3 supplementation groups were observed (p-values < 0.05) from the changes in baseline to 16 weeks. Further adjustments for age, sex and BMI showed that 2000 IU/day vitamin D3 supplementation increased in CD3+ count, CD3%, CD4 count, and CD4%, as compared to the placebo group (p-values < 0.05). Moreover, the highest serum 25(OH)D quantile group had the highest CD3% and CD4%. Conclusions: Sixteen-week vitamin D3 supplementation increases peripheral blood T-cell numbers and percentages in overweight/obese Black patients with vitamin D insufficiency. This resulting shift in circulating T-cell composition, particularly the increase in T helper cells (CD4+ cells), suggests that vitamin D supplementation may improve immune function in Black individuals.

Sunlight Exposure vs Oral Vitamin D Supplementation for Prevention of Vitamin D Deficiency in Infancy: A Randomized Controlled Trial

To compare the efficacy of sunlight exposure and oral vitamin D3 supplementation to achieve vitamin D sufficiency in infants at 6 months of age. Open-label randomized controlled trial. Public hospital in Northern India (28.7°N). Breastfed infants at 6-8 weeks of age. Randomized to receive sunlight exposure (40% body surface area for a minimum of 30 minutes/week) or oral vitamin D3 supplementation (400 IU/day) till 6 months of age. Primary - proportion of infants having vitamin D sufficiency (>20 ng/mL). Secondary - proportion of infants developing vitamin D deficiency (<12ng/mL) and rickets in both the groups at 6 months of age. Eighty (40 in each group) infants with mean (SD) age 47.8 (4.5) days were enrolled. The proportion of infants with vitamin D sufficiency increased after intervention in the vitamin D group from 10.8% to 35.1% (P=0.01) but remained the same in sunlight group (13.9%) and was significant on comparison between both groups (P=0.037). The mean (SD) compliance rate was 72.9 (3.4) % and 59.7 (23.6) % in the vitamin D and sunlight group, respectively (P=0.01). The geometric mean (95% CI) serum 25(OH) D levels in the vitamin D and sunlight group were 16.23 (13.58-19.40) and 11.89 (9.93-14.23) ng/mL, respectively; (P=0.02), after adjusting baseline serum 25(OH)D with a geometric mean ratio of 1.36 (1.06-1.76). Two infants in sunlight group developed rickets. Oral vitamin D3 supplementation is more efficacious than sunlight in achieving vitamin D sufficiency in breastfed infants during the first 6 months of life due to better compliance.

39-Year-Old Woman With Severe Weakness

39-Year-Old Woman With Severe Weakness

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.

Effects of Different Routes and Forms of Vitamin D Administration on Mesenteric Lymph Node CD4+ T Cell Polarization and Intestinal Injury in Obese Mice Complicated with Polymicrobial Sepsis.

This study compared the efficacies of enteral cholecalciferol and/or intravenous (IV) calcitriol administration on mesenteric lymph node (MLN) cluster-of-differentiation-4-positive (CD4+) T cell distribution and intestinal barrier damage in obese mice complicated with sepsis. Mice were fed a high-fat diet for 16 weeks and then sepsis was induced by cecal ligation and puncture (CLP). Mice were divided into the following sepsis groups: without vitamin D (VD) (S); with oral cholecalciferol 1 day before CLP (G); with IV calcitriol 1 h after CLP (V); and with both cholecalciferol before and IV calcitriol after CLP (GV). All mice were sacrificed at 12 or 24 h after CLP. The findings show that the S group had a higher T helper (Th)17 percentage than the VD-treated groups at 12 h after CLP. The V group exhibited a higher Th1 percentage and Th1/Th2 ratio than the other groups at 24 h, whereas the V and GV groups had a lower Th17/regulatory T (Treg) ratio 12 h post-CLP in MLNs. In ileum tissues, the VD-treated groups had higher tight junction protein and cathelicidin levels, and higher mucin gene expression than the S group at 24 h post-CLP. Also, aryl hydrocarbon receptor (AhR) and its associated cytochrome P450 1A1 and interleukin 22 gene expressions were upregulated. In contrast, levels of lipid peroxides and inflammatory mediators in ileum tissues were lower in the groups with VD treatment after CLP. These results suggest that IV calcitriol seemed to have a more-pronounced effect on modulating the homeostasis of Th/Treg subsets in MLNs. Both oral cholecalciferol before and IV calcitriol after CLP promoted cathelicidin secretion, alleviated intestinal inflammation, and ameliorated the epithelial integrity in obese mice complicated with sepsis possibly via VD receptor and AhR signaling pathways.

Efficacy and safety of various oral regimens (three oral doses) and schedules (daily v. monthly) of cholecalciferol in North Indian adults with low vitamin D status: evidence from a randomised controlled trial.

Vitamin D (VD) deficiency (serum 25 hydroxy vitamin D (25(OH)D) concentration of < 20 ng/ml), in endemic proportions, demands a supplementation strategy with optimal dosing regimens. A randomised parallel-group, active-controlled trial was conducted among apparently healthy, VD-deficient subjects, aged 18-60 years who received 600 μg/d (Group A), 1000 μg/d (Group B), 2000 μg/d (Group C) and 60000 μg/month (Group D) of oral cholecalciferol. The intervention was carried in two phases (I and II) of 12 weeks each, with same dose, separated by a washout phase of 12 weeks. Serum 25(OH)D, intact parathyroid hormones (iPTH), Ca, phosphorous (PO4), alkaline phosphatase (ALP) and spot urine Ca/Cr were measured at baseline, 12, 24 and 36 weeks following the intervention, and adverse events were recorded at each occurrence and at 12, 24 and 36 weeks. A statistically significant time-group interaction was found in serum 25(OH)D concentration (P < 0·05). Serum 25(OH)D concentration increased significantly from baseline to 12 weeks (P < 0·05) in all the groups with no change at 24 weeks but further increase at 36 weeks (P < 0·05). At the end of the study, Group C had maximum increment in serum 25(OH)D concentration, while as Groups C and D (95 %, and 90 %) had higher proportion of subjects VD sufficient than Groups A and B (65 % and 78 %) (P < 0·05). No significant time-dose interactions were observed in serum iPTH, Ca, PO4 and ALP or urine Ca/Cr ratio. Three subjects (two in Group C and one in Group D) developed transient hypercalciuria. Supplementation with daily 2000 μg or monthly 60000 μg of oral cholecalciferol among adults seems optimal and safe.

Modulation of cardiometabolic risk and CardioRenal syndrome by oral vitamin D3 supplementation in Black and White Southern Sahara residents with chronic kidney disease Stage 3: focus on racial and ethnic disparities

Objectives Several studies have shown that cholecalciferol supplementation (25OHD-S) in chronic kidney disease (CKD) improves kidney injury by reducing fibrosis-related vascular calcification and declining apoptosis-linked nephron damage. Methods The oral 25OHD-S was evaluated in 60,000 IU/month/36 weeks versus in 2000 IU/d/24 weeks in CKD Stage 3 with serum 25OHD level < 20 ng/mL. The study was undertaken on 156 black subjects and 150 white subjects Southern Sahara (SS). All biomarkers of cardiometabolic (CMet) and cardiorenal (CRenal) syndrome, Renin-angiotensin-aldosterone system (RAAS) profile, secondary hyperparathyroidism (SHPT), N-terminal pro B-type natriuretic peptide (NT-proBNP), Troponin T (cTnT) and atherogenicity risk were assessed by biochemical methods. Estimate glomerular filtration rate (eGFR) by chronic CKD-EPI equation formula. Total serum vitamin D by liquid chromatography-tandem mass spectrometry (MS). Results Vitamin D deficiency alters in the same manner CMet, CRenal, and others biomarkers in both groups SS; however, these disorders are more acute in blacks compared to whites SS. Oral 25OHD-S a highlighted improvement of eGFR drop, SHPT decrease, decline proteinuria, and cardiac failure risk (NT-proBNP and cTnT) attenuation. Concomitantly, 25OHD-S normalizes Renin, Aldosterone, and Angiotensin System (RAAS) activity. Nevertheless, homocysteine and Lp (a) do not modulate by 25OHD-S. Conclusions The oral vitamin D3 supplementation, according the dose, and the treatment duration does not like in black-skinned people versus to white-skinned inhabitants, while the 02 groups are native to the same Saharan environment. It emerge that a high intermittent dose through an extensive supplementation (60,000 IU/36 weeks) was more effective in black subjects. At opposite, a lower dose during a short period supplementation is sufficient (2000 IU/24 weeks) in white subjects.

Effect of vitamin D on endothelial and ventricular function in chronic heart failure patients: A prospective, randomized, placebo-controlled trial.

Background:Low 25-hydroxyvitamin D (25OHD) levels are common in patients with chronic heart failure (HF) and are associated with increased mortality risk. This study aimed to establish the safety and efficacy of oral vitamin D3 (cholecalciferol) supplementation and its effect on endothelial and ventricular function in patients with stable HF.Methods:This study was an investigator-initiated, multicenter, prospective, randomized, placebo-controlled trial. Seventy-three HF patients with 25OHD levels < 75 nmol/L (30 ng/mL) were randomized to receive 4000 IU vitamin D daily or a placebo for 6 months. The primary endpoint was a change in endothelial function between the baseline and after 6 months as assessed using EndoPAT. Secondary endpoints included changes in echocardiographic parameters and differences in quality of life (6-min walking test and New York Heart Association functional status) at 6 months.Results:There were no adverse events in either group during the study period. Vitamin D supplementation did not improve endothelial dysfunction (EndoPAT: baseline, 1.19 ± 0.4 vs 6 months later, 1.22 ± 0.3, P = .65). However, patients’ blood pressure, 6-min walking distance, and EQ-5D questionnaire scores improved after vitamin D treatment. In addition, a significant reduction in the left atrial diameter was observed.Conclusion:A daily vitamin D dose of 4000 IU for chronic HF appears to be safe. This dosage did not improve endothelial function but did improve the 6-min walk distance, symptoms, and left atrial diameter at 6 months.

Efficacy of Alendronate in Preventing Periprosthetic Bone Loss after Implantation of a Primary Hip Endoprosthesis

Total hip arthroplasty (THA) is now the gold standard for the surgical treatment of coxarthrosis. The appearance of bone loss after implantation of the hip endoprosthesis over time reduces the primary stability of the implant and leads to progressive looseningof the implant, or periprosthetic fracture, which are considered to be the most common causes of hip revision.&#x0D; The aim of this study is to evaluate the value of alendronate application in reducing periprosthetic osteolysis reduction after implantation of total cementless hip endoprosthesis.&#x0D; The study analyzed 50 patients operated on with implantation of a cementless total hip arthroplasty (THA). The first group of 25 patients recieved oral alendronate, calcium and vitamin D3 postoperatively. The second group of 25 patients were examined and followed postoperatively without any therapy.&#x0D; Patients were examined by RTG and DXA methods at 6, 12 and 18 months.&#x0D; The study showed a difference in the values of bone mineral density (BMD) and bone mineral content (BMC) in the interval of 6,12 and 18 months, using the DXA method.&#x0D; Alendronate therapy after total hip implantation reduces periprosthetic bone loss, maintains bone mineralization and strengthens the implant

839 Early biomarker identification for immune sensitization and prevention with oral vitamin D3

Reaction to chemical irritants is a common cause of dermatology consultation and a challenge for topical medication utility. Cholecalciferol (D3) mitigates inflammation from experimental sunburn in humans and chemical injury in mice. To investigate the clinical utility of D3 for chemical injury in humans, we conducted a double-blinded, placebo-controlled trial. 28 healthy subjects had 3x8mm2 of arm skin exposed to 0.0016% topical nitrogen mustard (NM) under occlusion. 2 weeks later, subjects were randomized to receive 200,000 IU oral D3 or placebo after repeat NM exposure on the other arm. By proteomic analysis of skin biopsies, placebo subjects have 22% more differentially expressed inflammatory proteins (DEP) than D3 subjects after 3 days and 650% after 6 weeks. PCA of RNAseq separates samples by exposure yet shows 2 intervention-independent subclusters in NM exposure 2. One shows a normal skin profile (NS) and the other shows immune memory cell enrichment, suggesting immune sensitization (S). S subjects show more inflammation than NS by skin erythema (p<0.01), edema (p=0.05), and histopathologic score (p<1e-4). S and NS D3 subjects express fewer DEPs than placebo at 3 days (S:41%;NS:82%) and 6 weeks (S:86%;NS:100%). Subgroup analysis of exposure 1 identifies early S-associated biomarkers. After exposure 2, NS subjects express no S markers if given D3 vs 75% if given placebo. Results identify biomarkers of sensitization that may have predictive clinical utility and demonstrate that oral D3 mitigates chemically-induced inflammation for up to 6-weeks. Thus, D3 may have preventative properties against chemical sensitization and serve as a low-risk treatment and prevention in those undergoing repetitive chemical exposure.

Role of C3a as a Novel Regulator of 25(OH)D3 to 1α,25-Dihydroxyvitamin D3 Metabolism in Upper Airway Epithelial Cells.

In patients with chronic rhinosinusitis with nasal polyps, primary human sinonasal epithelial cell (HSNEC) 1α-hydroxylase levels are reduced, as is their ability to metabolize 25-hydroxycholecalciferol [25(OH)D3] to its active metabolite, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3]. In this study, we sought to identify the factor responsible for the regulation of HSNEC metabolism of 25(OH)D3, focusing on C3 and C3a. Multiple inhaled irritants trigger the release of complement components, C3 and C3a, leading to suppression of 1α-hydroxylase levels in HSNECs. Recombinant C3a was able to decrease 1α-hydroxylase and impair 25(OH)D3 to 1,25(OH)2D3 metabolism, while addition of a C3a receptor antagonist restored conversion. Conversely, 1,25(OH)2D3 suppressed Aspergillus fumigatus-induced C3 and C3a levels in HSNEC supernatant. Given the ability of 1,25(OH)2D3 to modulate LL37 in other cell types, we examined its regulation in HSNECs and relationship to C3a. 1,25(OH)2D3 stimulated the secretion of LL37, whereas A. fumigatus and C3a suppressed it. Conversely, LL37 reduced the release of C3/C3a by HSNECs. Lastly, oral steroid use and in vitro dexamethasone application both failed to increase 1α-hydroxylase or reduce C3a levels. In summary, in this article, we describe for the first time a novel relationship between complement activation and local vitamin D metabolism in airway epithelial cells. The presence of elevated C3/C3a in patients with asthma and/or chronic rhinosinusitis with nasal polyps may account for their impaired HSNEC 25(OH)D3 to 1,25(OH)2D3 metabolism and explain why they receive limited therapeutic benefit from oral vitamin D3 supplementation.

COMPARISON OF THE EFFICACY OF DULOXETINE VERSUS DULOXETINE PLUS ORAL VITAMIN D IN TREATING PERIPHERAL DIABETIC NEUROPATHY

Painful diabetic peripheral neuropathy (PDPN) is a common complication of diabetes mellitus that affects the quality of life. Duloxetine and vitamin D have been used for its management, but there is limited literature comparing the efficacy of these drugs. In this study, we aimed to compare Duloxetine alone versus Duloxetine in combination with vitamin D for treating PDPN. An open-labeled randomized controlled trial was conducted at King Edward Medical University, Mayo Hospital, Lahore, for a duration of 6 months, starting from July 1, 2021, to December 31, 2021. The study included 78 patients aged 20 to 60 years suffering from PDPN as per inclusion and exclusion criteria. Participants were randomly assigned to two groups, with 39 participants in each group. Group A was given Duloxetine 60mg OD, and Group B was given Duloxetine 60mg OD plus oral Vitamin D3 2000IU daily for 8 weeks. Patients were assessed before the start of treatment and followed up after 8 weeks in the outpatient department to measure the mean reduction in pain score using the Visual Analogue Scale. All the collected data was analyzed using SPSS 26.0. The mean age of the participants was 44.46 ± 6.51 years. Of the 78 participants, 51 were female, and 27 were male. 89.8% of patients tolerated the drugs well with no side effects. Only 6.4% of patients complained of tiredness, and 3.8% experienced constipation. The mean VAS before treatment and at the end of the 8th week was 7.41 ± 0.98 and 3.48 ± 1.01, respectively. There was a marked reduction in pain after using both regimens, which was statistically significant (p-value &lt; 0.001). The mean VAS before and after the treatment in Group A was 7.46 ± 0.99 and 4.17 ± 0.72, respectively. In Group B, the mean VAS before and after the treatment was 7.35 ± 0.978 and 2.79 ± 0.832, respectively. This reduction was statistically significant compared to the two groups (p-value &lt; 0.001). The combination of Duloxetine and vitamin D proved superior to the Duloxetine group and is a recommended regimen according to our results. Further studies with more extensive data from multiple centers are required to establish the guidelines.

La vitamina-D para la prevención de fracturas osteoporóticas.

Introduction: The objective of this study was to show the initial results of an oral vitamin-D and calcium supplementation program in patients who had suffered a hip fracture for the prevention of subsequent fractures considered osteoporotic. Method: Prospective comparative cohorts study in patients older than 65 operated for hip fracture. The patients were divided into two groups according to the serum level of vitamin-D at admission: 1) hypovit-D group, 58 patients who were prescribed oral vitamin-D and calcium at discharge; 2) control group, 13 patients with a normal level of vitamin-D who did not have that supplementation. Results: The sample size could not be completed due to the scarcity of patients with normal vitamin-D levels. The subsequent fracture rate in the following two years was 20.7% in the hypovit-D group and 15.4% in control group, with no significant difference (p = 0.664). Conclusion: provisionally, with the available data, oral vitamin-D and calcium supplementation have not shown effectiveness in preventing a subsequent hip fracture.

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.