Effect Of Vitamin D3 Supplementation Research Articles

Effect of vitamin D3 supplementation on serum 25 (OH)D Levels, hand grip strength, blood sugar levels, and cognitive function in the elderly

ABSTRACTBackground: The aging process in the elderly can be caused by a decrease in vitamin D precursors and reduced Vitamin D levels due to impaired absorption of Vitamin D. Vitamin D plays a role in cognitive function, acts as an immunomodulator affecting blood glucose levels, promotes muscle atrophy, and affects the intranuclear VDR concentration and gene expression of VDR.Objectives: To determine the effect of vitamin D3 supplementation on Serum 25(OH)D levels, hand grip strength, blood sugar levels, and cognitive function in the elderly.Materials and Methods: This study used a quasi-experimental pre-posttest control group design with a total of 60 subjects included and divided into two groups. The treatment group received vitamin D3 at a dosage of 1000 IU/day for three months, while the control group was given a placebo. Blood serum levels were used to obtained serum 25(OH)D and blood sugar level. Hand grip strength values were measured by a hand grip dynamometer, and cognitive function was assessed using the Mini-Mental State Examination (MMSE) Questionnaire. The data was analyzed using the Wilcoxon test, and the bivariate analysis was performed using the Mann-Whitney test.Results: Most subjects were between 60 and 92 years old and had a vitamin D deficiency. Significant (P<0,05) differences were observed in serum 25(OH)D levels, blood sugar levels, and cognitive function following the intervention. The differences in serum 25(OH)D levels were 8,50±6,17, blood sugar levels were -21,68±25,88, and cognitive function was 2,23±3,05. Additionally, hand grip strength increased after the intervention (mean=0,42±4,66) but was not statistically significant (P=0,633).Conclusion: There is an improvement in cognitive function and a decrease in blood glucose levels, along with an increase in 25(OH)D levels after three months of vitamin D supplementation. However, hand grip strength did not significantly increase after supplementation.Keywords: Vitamin D3 Supplementation; serum 25(OH)D; hand grip strength; blood sugar level; cognitive function; elderly.

The effect of vitamin D3 supplementation on the incidence of type 2 diabetes in healthy older adults not at high risk for diabetes (FIND): a randomised controlled trial.

Vitamin D insufficiency is associated with an elevated risk of type 2 diabetes, but evidence from randomised trials on the benefits of vitamin D supplementation is limited, especially for average-risk populations. The Finnish Vitamin D Trial (FIND) investigated the effects of vitamin D3 supplementation at two different doses on the incidence of type 2 diabetes in a generally healthy older adult population. FIND was a 5 year randomised placebo-controlled, parallel-arm trial among 2271 male and female participants aged ≥60 years and ≥65 years, respectively, from a general Finnish population who were free of CVD or cancer and did not use diabetes medications. The study had three arms: placebo, 1600 IU/day of vitamin D3 or 3200 IU/day of vitamin D3. A non-study group statistician carried out sex-stratified simple randomisation in a 1:1:1 ratio, based on computerised random number generation. The participants, investigators and study staff were masked to group assignment. National health registries were used to collect event data. A representative subcohort of 505 participants had more detailed in-person investigations at months 0, 6, 12 and 24. During the mean follow-up of 4.2 years, there were 38 (5.0%), 31 (4.2%) and 36 (4.7%) type 2 diabetes events in the placebo (n=760), 1600 IU/day vitamin D3 (n=744; vs placebo: HR 0.81; 95% CI 0.50, 1.30) and 3200 IU/day vitamin D3 (n=767; vs placebo: HR 0.92, 95% CI 0.58, 1.45) arms, respectively (p-trend=0.73). When the two vitamin D3 arms were combined and compared with the placebo arm, the HR was 0.86 (95% CI 0.58, 1.29). In the analyses stratified by BMI (<25 kg/m2 [n=813, number of type 2 diabetes events=12], 25-30 kg/m2 [n=1032, number of events=38], ≥30 kg/m2 [n=422, number of events=54]), the HRs in the combined vitamin D3 arms vs the placebo were 0.43 (95% CI 0.14, 1.34), 0.97 (0.50, 1.91) and 1.00 (0.57, 1.75), respectively (p-interaction <0.001). In the subcohort, the mean (SD) baseline serum 25-hydroxyvitamin D3 (25(OH)D3) concentration was 74.5 (18.1) nmol/l. After 12 months, the concentrations were 72.6 (17.7), 99.3 (20.8) and 120.9 (22.1) nmol/l in the placebo, 1600 IU/day vitamin D3 and 3200 IU/day vitamin D3 arms, respectively. In the subcohort, no differences were observed in changes in plasma glucose or insulin concentrations, BMI or waist circumference during the 24 month follow-up (p values ≥0.19). Among generally healthy older adults who are not at high risk for diabetes and who have serum 25(OH)D3 levels that are sufficient for bone health, vitamin D3 supplementation did not significantly reduce the risk of developing diabetes. ClinicalTrials.gov NCT01463813.

Effects of vitamin D3 supplementation on lipid profile and renal indices in rat model of drug induced renal injury

Introduction and aim. Renal injury is associated with decreased renal function, hypovitaminosis D, deranged calcium-phos phate metabolism and dyslipidemia, thus increasing risk for chronic kidney disease and cardiovascular diseases. However, re ports on the effects of vitamin D on drug induced renal injury are few. The aim was to investigate the possible role of vitamin D supplementation in reversing deranged lipid profile and renal function post drug induced renal injury. Material and methods. Wister male rats (36) were randomly divided into group 1, 2 and 3 (n=12). Single dose of Adriamycin was given to all except group 1(control) to induce renal injury. Group 2 left untreated, group 3 given vitamin D3 for 28 days. Serum urea, creatinine, total protein, total cholesterol (TC), triglycerides (TG), LDL-C, HDL, apolipoprotein (Apo) A and B were measured. C-reactive protein (CRP) and nitric oxide were assessed in kidney homogenate. Results. Vitamin D3 significantly brought down levels of serum creatinine, TC, LDL CRP, nitric oxide and increased the levels of Apo A, albumin, HDL. Serum urea, TG and Apo B in group 3 were not significantly different after vitamin D3 administration. His tological examination revealed improvement in glomerular messangialisation. Conclusion. Vitamin D3 may improve renal health, through its positive impact on dyslipidemia, inflammation, and oxidative stress in drug induced renal injury.

The effect of vitamin D supplementation on depression: a systematic review and dose–response meta-analysis of randomized controlled trials

Abstract The impact of vitamin D supplementation on depressive symptoms remains uncertain. This study aimed to investigate the dose-dependent effects of vitamin D supplementation on depressive and anxiety symptoms in adults. We systematically searched PubMed, Scopus, and Web of Science up to December 2022 to identify randomized controlled trials evaluating the effects of vitamin D3 supplementation on depression and anxiety symptoms in adults. Using a random-effects model, we calculated the standardized mean difference (SMD) for each 1000 IU/day vitamin D3 supplementation. The GRADE tool assessed the certainty of evidence. Our analysis included 31 trials with 24189 participants. Each 1000 IU/day vitamin D3 supplementation slightly reduced depressive symptoms in individuals with and without depression (SMD: −0.32, 95% CI −0.43 to −0.22; GEADE = moderate). The effect was more pronounced in those with depressive symptoms (SMD: −0.57, 95% CI −0.69 to −0.44; n = 15). The greatest reduction occurred at 8000 IU/day (SMD: −2.04, 95% CI −3.77 to −0.31). Trials with follow-up ⩽8 weeks (SMD: −0.45, 95% CI −0.70 to −0.20; n = 8) and 8 to ⩽24 weeks (SMD: −0.47, 95% CI −0.70 to −0.24; n = 15) showed stronger effects compared to those lasting 24 to ⩽52 weeks (SMD: −0.13, 95% CI −0.28 to 0.02; n = 5) or longer than 52 weeks (SMD: 0.14, 95% CI −0.16 to 0.44; n = 3) (p group difference &lt;0.001). Vitamin D3 supplementation had no significant effects on anxiety symptoms. In summary, this study suggests that vitamin D3 supplementation may effectively reduce depressive symptoms in short term. Further high-quality trials are warranted for a conclusive assessment of its impact on anxiety.

Amelioration of fructose-induced hepatic lipid accumulation by vitamin D3 supplementation and high-intensity interval training in male Sprague‒Dawley rats

BackgroundIntrahepatic lipid accumulation (IHL), a hallmark of metabolic disorders, is closely associated with de novo lipogenesis (DNL). Notably, fructose feeding increased the DNL. Lifestyle modifications resulting from dietary changes and increased physical activity/exercise can decrease the IHL content. We examined the effects of vitamin D3 supplementation (VDS), high-intensity interval training (HIIT), and their combination on the transcription factors and enzymes of the DNL pathway in male Sprague‒Dawley rats fed a high-fructose diet (HFrD).MethodsForty male rats were assigned to 5 groups (n = 8): CS (the control group had a standard diet); CF (the control group had HFrD (10% (w/v) fructose solution in tap water)); and FT (HFrD + HIIT: 10 bouts of 4 min of high-intensity running, corresponding to 85–90% of the maximal speed with 2 min active rest periods of 50% maximal speed, 5 days per week); FD (HFrD + intervention of intraperitoneal injection of 10000 IU/kg/week VDS); FTD (HFrD + HIIT + VDS) that were maintained for 12 weeks. ELISA, the GOD-POD assay, folch, western blotting, and oil red O staining were used to determine insulin, fasting blood glucose (FBG), hepatic triglyceride (TG) and cholesterol levels; SREBP1c, ChREBP-β, ACC1, FASN, p-ACC1, AMPK, p-AMPK, and PKA protein expression; and IHL content, respectively.ResultsBoth HIIT and VDS led to significant increases in the levels of PKA, AMPK, p-AMPK, and p-ACC1, as well as significant decreases in the levels of SREBP1c, ChREBP-β, ACC1, FASN, insulin, FBG, liver TG, liver cholesterol, and IHL. HIIT exhibited superior efficacy over VDS in reducing ChREBP-β, ACC1, insulin, FBG, liver TG and cholesterol, as well as increasing p-ACC1 and PKA. Notably, the combined intervention of HIIT and VDS yielded the most substantial improvements across all the parameters.ConclusionsHFrD causes IHL accumulation and the onset of diabetes, whereas VDS and HIIT, along with their combined effects, prevent the consequences of HFrD.

Bone turnover markers, and growth and bone parameters in infants participating in a vitamin D intervention study.

Amino-terminal propeptide of type 1 procollagen (P1NP) and carboxy-terminal crosslinked telopeptide of type 1 collagen (CTX-I) are markers of bone metabolism. We examined the effect of vitamin D3 supplementation on these markers and their relationship with growth and bone parameters in 12-month-old infants. In a randomized, double-blinded, vitamin D intervention in infants (VIDI) study, 987 infants received daily vitamin D3 supplementation of 10 μg (group-10) or 30 μg (group-30) from age 2 weeks to 24 months. We conducted a secondary analysis of the original VIDI trial. At 12 months of age, P1NP (n = 812) and CTX-I (n = 786) concentrations were analyzed, and anthropometrics and total bone mineral content, volumetric bone mineral density, cross-sectional area and polar moment of inertia of tibia were measured by peripheral quantitative computed tomography. The growth rate in weight and length was calculated from birth to 12 months. The vitamin D dose did not influence mean (SD) levels of CTX-I (group-10: 0.90 (0.31); group-30: 0.89 (0.31) (P > 0.53)). The mean difference of P1NP (CI 95%) comparing group-10 with group-30 was 35 (-103, 33) ng/mL (P = 0.31) in boys and -63 (-4, 130) ng/mL (P = 0.064) in girls. In group-10, girls had higher mean (SD) value of P1NP (1509 (362) ng/mL) than boys (1407 (297) ng/mL) (P = 0.003); no sex differences were observed in group-30 (girls: 1446 (359); boys: 1442 (359), P = 0.91) or CTX-I. P1NP associated positively with the growth rate in length (B (CI 95%) 0.0003 (0.0001, 0.001), P = 0.022) in the whole cohort but not in subgroups divided by the intervention group or sex, adjusted for birth size and parental heights and corrected for multiple testing. P1NP associated positively with the growth rate in weight (0.01 (0.0003, 0.01), P < 0.001). An inverse association was observed between CTX-I and length (cm) in the whole cohort (-0.90 (-1.40, -0.40), P = 0.005) and in group-30 (-1.05 (-1.72, -0.39), P = 0.011). Furthermore, CTX-I associated negatively with weight (SDS) in the whole cohort (-0.33 (-0.55, -0.12), P = 0.015) and the growth rate in weight (-0.43 (-0.66, -0.20), P = 0.005), persisting in group-30 and in boys but not in group-10 or in girls. Neither marker was associated with bone parameters. The observed sex difference in P1NP might suggest that a higher vitamin D dose resulted in a small decrease in bone collagen matrix formation in girls but not in boys. P1NP and CTX-I associate with growth and body size but not with bone mineralization in infancy.

The effect of vitamin D3 supplementation on vitamin D status and associated health outcomes in children

Sufficient vitamin D status is required in childhood for normal skeletal health and the development of muscle and motor function(1). Vitamin D primarily acts through the promotion of calcium absorption from the gut and mobilisation from bone tissue(2). Childrens’ vitamin D dietary intakes are currently below the recommended guidelines within the UK and Ireland suggesting a need for vitamin D3 supplementation to prevent the risk of developing vitamin D deficiency(3). The aim of this study was to examine the effect of 12 weeks’ supplementation with 10µg/d vitamin D3 vs placebo control on vitamin D status and to determine if improved vitamin D status impacted muscle function and cognition in children aged 4-11 years.In the D-VinCHI randomised, double-blind, placebo-controlled trial, healthy children (n = 118; mean age 8.1 ± 1.8 y; 51% girls) were randomly assigned to either placebo or 10µg/day of vitamin D3 for 12 weeks (year-round). Baseline and endpoint measures included anthropometric measures, hand grip strength, balance, and cognitive assessment. Blood samples were analysed for plasma 25hydroxyvitamin D [25(OH)D], and parathyroid hormone. Vitamin D consumption from food sources was assessed via a 13-item food frequency questionnaire.Following the 12-week intervention vitamin D status [25(OH)D concentration] increased in the treatment group from 66.31 ± 17.25 nmol/L to 69.04 ± 16.92 nmol/L. Change in status was significantly different compared to the placebo group within which a decrease in 25(OH)D was observed from 63.67 ± 19.48 to 56.29 ± 18.58 nmol/L, p&lt;0.001. Supplementation with vitamin D3 prevented deficiency of plasma 25(OH)D during the winter months. Vitamin D3supplementation had a positive effect on cognitive function, improving simple movement time from 707 ± 380 to 599 ± 207 milliseconds, compared to the placebo group within which time increased from 680 ± 284 to 728 ± 372 milliseconds, p = 0.017. Vitamin D mean dietary intake from food sources alone was 2.68µg/day. There was no effect of supplementation on muscle function.Vitamin D3 supplementation maintained year-round sufficiency in children and importantly, prevented deficiency during the extended winter months. Vitamin D supplementation may enhance cognitive function via improvements in attention and psychomotor speed. The reported intakes of vitamin D food sources were low and were well below the current dietary reference value for this age group. Further health promotion policies and (bio)fortification strategies should be considered within this age group to maximise vitamin D status for optimal growth and development.

Effects of cholecalciferol supplementation on depressive symptoms, C-peptide, serotonin, and neurotrophin-3 in type 2 diabetes mellitus: A double-blind, randomized, placebo-controlled trial.

The coexistence of depression and type 2 diabetes mellitus (T2DM) can significantly worsen disease prognosis and lower quality of life. Emerging evidence suggests that vitamin D deficiency contributes to the progression of T2DM and is closely associated with the development of depression. The aim of this study was to investigate the effects of cholecalciferol on depression in patients with T2DM, exploring its mechanisms by analyzing its impact on C-peptide, serotonin, and neurotrophin-3 levels. A double-blind, randomized, placebo-controlled clinical trial was conducted at Cipto Mangunkusumo General Hospital, Jakarta, Indonesia, from April 2021 to September 2022. Patients with T2DM and depressive symptoms were randomly assigned to two groups: received 4000 IU of cholecalciferol daily and received a placebo for 12 weeks. Depression was assessed using the Beck Depression Inventory-II (BDI-II) before and 12 weeks after the intervention. The levels of C-peptide, serotonin, and neurotrophin-3 were measured at the end of the fourth week of intervention using the enzyme-linked immunosorbent assay (ELISA) method. Between-group comparisons were made using independent Student t- tests and Mann-Whitney U tests. Paired Student t-tests or Wilcoxon tests were applied for within-group comparisons between pre- and post-intervention. A total of 70 T2DM patients with depression were included in this study, comprising 38 patients in the cholecalciferol group and 32 in the placebo group. C-peptide levels increased significantly in the cholecalciferol group compared to the placebo group (p = 0.006). No significant differences were observed in serotonin and NT-3 levels between the cholecalciferol group compared to the placebo group. The cholecalciferol group had a significantly greater reduction in BDI-II scores compared to the placebo group (p < 0.001). This trial highlights that taking cholecalciferol might help ease mild to moderate depression symptoms in patients with T2DM by enhancing c-peptide levels, though its effects on serotonin and neurotrophin-3 are still unclear.

Effect of cholecalciferol supplementation on PTH and increasing the glomerular filtration rate in kidney transplant patients at King Faisal Specialist Hospital and Research Center

The association between oral cholecalciferol and GFR has been identified in various renal transplant populations around the globe. This study aimed to evaluate the effect of oral cholecalciferol supplementation on the GFR and serum PTH levels, with other parameters in the Saudi kidney transplant population. A retrospective observational study was conducted on a cohort of 174 kidney recipients who underwent transplantation and had serum 25-Hydroxy VD level tests performed (2018-2022) at King Faisal Specialist Hospital and Research Center in Jeddah, KSA. Generalized and linear mixed effects regression models were conducted. The percentage of GFR &gt;60 (25.86% vs 78.16%, P&lt;.0001) and VD insufficiency (&lt; 30 ng/mL) (36.21% vs 6.90%, P&lt;.0001) were significantly different between pre-&amp; post-transplant periods, respectively. After adjustment, significant changes were found in post-transplant GFR, hemoglobin levels, serum creatinine levels, blood urea nitrogen levels, hematocrit levels, PTH levels, and VD 25-Hydroxy from the baseline. Calciferol 1000/2000 IU and 50,000 IU (P&lt;.0001) were significantly more effective in increasing the odds of having GFR &gt;60 as compared to other supplements (P=0.75). VD supplementations may be particularly beneficial in improving kidney function in kidney transplant patients, as this contributes to normalizing GFR levels and creatinine levels and reducing PTH levels.

Vitamin D3 alleviates the damage caused by high-fat and maintains lipid metabolism homeostasis in hepatopancreas by promoting fatty acid β-oxidation of Portunus trituberculatus

The purpose of present study was to evaluate the effects of vitamin D3 supplementation in high-fat diet on growth performance, calcium and phosphorus in tissue, immunity and lipid metabolism, and to explore whether adding vitamin D3 to high-fat diet can alleviate the adverse effects of high-fat diet on swimming crab (Portunus trituberculatus). The three experimental diets were normal fat diet (NFD, 9.35 % fat, 45.53 % protein), high fat diet (HFD, 14.69 % fat, 44.93 % protein) and high fat diet supplemented with 0.47 mg/kg VD3 (HFD+VD), respectively. A total of 108 healthy swimming crabs with an initial body weight of 9.42±0.13 g were selected for an 8-week feeding trial. The results showed that crabs fed with HFD+VD diet exhibited significantly higher percent weight gain (PWG), specific growth rate (SGR), feed efficiency (FE) and molting rate (MR) compared to those fed with HFD diet (P < 0.05). It was observed from hepatopancreas crude lipid content, TG content and hepatopancreas sections that HFD caused hepatopancreatic cell damage and abnormal lipid accumulation (P < 0.05), however, there were no significant differences in hepatopancreas crude fat content, TG content and hepatopancreas section observation between HFD+VD group and NFD group (P > 0.05). Crabs fed HFD diets with or without VD3 significantly down-regulated the expression of genes related to fatty acid transport, such as fabp9 and lpr1 in hepatopancreas (P < 0.05), moreover, the expression of genes related to fatty acid β-oxidation (cpt2 and acox1) were significantly up-regulated and genes related to lipid synthesis (fas and 6pgd) were significantly down-regulated in the hepatopancreas of the crabs fed with HFD+VD diet compared to those fed with HFD diet (P < 0.05). In conclusion, the results of present study indicated that a high-fat diet can cause deformation and rupture of hepatopancreas cells through abnormal lipid accumulation, thereby causing associated inflammation, leading to large calcium and phosphorus deposits in hemolymph and muscle, however, high fat diet supplemented with vitamin VD3 mainly enhanced the β-oxidation of fatty acids, inhibited lipid synthesis, alleviated abnormal lipid accumulation, and thus maintained the balance of lipid metabolism in hepatopancreas cells and promoted growth performance and feed utilization for swimming crab.

Prevalence of vitamin D deficiency and the effect of vitamin D3 supplementation on response to anti-tuberculosis therapy in patients with extrapulmonary tuberculosis

BackgroundWe aimed to assess serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations in extrapulmonary tuberculosis (EPTB) patients and to evaluate the effect of vitamin D3 supplementation on their treatment course.MethodsSerum 25(OH)D3concentrations were measured in 47 newly diagnosed EPTB patients and 42 controls. Vitamin D-deficient EPTB patients were randomly assigned to receive 50,000 IU of vitamin D3 (cholecalciferol) orally once a week for 6 weeks (total 300,000 IU), followed by maintenance doses of 1000 IU a day besides anti-TB drugs or the first line anti-TB treatment only. Follow up serum 25(OH)D3 concentrations were measured after 3 months of starting vitamin D3 supplementation. Both groups were evaluated for clinical, laboratory, and radiological outcomes after treatment.ResultsSerum 25(OH)D3 concentrations were significantly lower among TB cases (17.1 ± 5.5 nmol/L) compared to healthy controls (51.8 ± 27.3 nmol/L), and vitamin D deficiency was observed in all EPTB patients (n = 47). Patients in VD3 supplementation group had significantly higher weight gain and serum albumin level at 2 months and end of treatment, higher hemoglobin concentration at the end of treatment, significantly lower CRP and ESR at 2 months and at the end of treatment. In cases with TB pleurisy, a significant higher rate of full resolution of pleural fluid after 6 months of anti-TB treatment and shorter treatment duration were noted compared to the other group.ConclusionsVitamin D deficiency is prevalent in EPTB patients, in whom, vitamin D supplementation is a useful adjunctive therapy to anti-TB drugs and improves treatment course.

Effects of vitamin D3 supplementation on strength of lower and upper extremities in athletes: an updated systematic review and meta-analysis of randomized controlled trials.

Coaches and athletes are increasingly interested in understanding athletes' serum vitamin D levels, their impact on strength, physical performance, and athletic outcomes. Previous meta-analyses were reported with limited sample size and no significant overall effect was found. Hence, it is crucial to conduct a thorough and up-to-date systematic examination and meta-analysis to elucidate the potential advantages of supplementing with vitamin D3 in enhancing muscle strength for athletes. We performed a thorough investigation, spanning three databases (PubMed, EBSCO, and Cochrane Library), seeking randomized controlled trials (RCTs) in all languages. These trials delved into the influence of vitamin D3 supplementation on the changes of pre- and post-intervention muscle strength in healthy athletes. Our systematic examination and meta-analysis took into account serum 25(OH)D levels exceeding 30 ng/mL as a marker of adequacy. Ten RCTs, comprising 354 athletes (185 in the vitamin D3 group and 169 in the placebo group), fulfilled the inclusion criteria. During the study, 36 athletes were lost to follow-up, leaving 318 athletes (166 in the vitamin D3 group and 152 in the placebo group) with documented complete results. In comparison with the placebo group, there is a significant increase between the changes of pre- and post-intervention serum 25(OH)D levels among athletes following a period of vitamin D3 supplementation (MD 14.76, 95% CI: 8.74 to 20.77, p < 0.0001). Overall effect of four strength measurements including handgrip, one repetition maximum Bench Press (1-RM BP), vertical jump, and quadriceps contraction was not significantly improved (SMD 0.18, 95% CI: -0.02 to 0.37, p = 0.08), but there was a significant increase in quadriceps contraction (SMD 0.57, 95% CI: 0.04 to 1.11, p = 0.04). This updated meta-analysis indicates the potential benefits of vitamin D supplementation for enhancing muscle strength in athletes when analyzing its quantitatively synthesized effects. With limited available studies for the quantitative synthesis, it cannot warrant significant overall enhancements in muscle strength when athletes attain adequate serum 25(OH)D levels through supplementation.

Effect of Vitamin D3 Supplementation on Severe COVID-19: A Meta-Analysis of Randomized Clinical Trials.

Since the beginning of the COVID-19 pandemic, vitamin D has attracted interest due to its immunomodulatory properties. Numerous studies show a correlation between vitamin D levels and COVID-19 cases and mortality. Therefore, we conducted a meta-analysis in order to assess the relationship between vitamin D3 supplementation and COVID-19 severity. We included 13 randomized clinical trials that contained the analyzed endpoints: length of COVID-19 hospitalization, number of intensive care unit (ICU) admissions, length of stay in the ICU, number of cases requiring any supplemental oxygenation, duration of any supplemental oxygenation, number of overall mortality and number of deaths associated with COVID-19. The relative risk with 95% confidence interval (CI) and the mean difference with 95% CI were calculated to compare the effect. A random effects model was used to calculate effect sizes. Our meta-analysis showed a positive effect of vitamin D3 supplementation on ICU admission (RR = 0.73; 95% CI [0.57; 0.95], p = 0.02, I2 = 19.6%) and mortality associated with COVID-19 among patients (RR = 0.56; 95% CI [0.34; 0.91]; p = 0.02; I2 = 0%). Vitamin D3 supplementation may potentially reduce the risk of ICU admission and death associated with COVID-19.

Effects of Vitamin D Supplementation on Central Hemodynamic Parameters and Autonomic Nervous System in Obese or Overweight Individuals.

Previous studies have been inconsistent in demonstrating beneficial cardiovascular effects of vitamin D supplementation. To evaluate the effects of vitamin D3 supplementation on central hemodynamic parameters and autonomic activity in obese/overweight individuals with low vitamin D levels (<30ng/dl). Adults 40-65 years old with body mass index ≥25<40 kg/m2 were enrolled in this prospective, randomized, double-blind clinical trial (NCT05689632). Central hemodynamics was assessed using the oscillometric method (Mobil-O-Graph®), and heart rate variability using a Polar heart rate monitor (Kubios® software). Patients (n=53) received a placebo in the control group (CO, n=25) or vitamin D3 (VD, n=28) 7000 IU/day, and were evaluated before (W0) and after 8 weeks (W8) with a significance level of 0.05. The groups were homogeneous regarding age (51±6 vs 52±6 years, p=0.509) and vitamin D levels (22.8±4.9 vs 21.7±4.5ng/ml, p=0.590). At W8, the VD group had significantly higher levels of vitamin D (22.5 vs 35.6ng/ml, p<0.001). Only the VD group showed a significant reduction in systolic blood pressure (SBP; 123±15 vs 119±14mmHg, p=0.019) and alkaline phosphatase (213±55 vs 202±55mg/dl, p=0.012). The CO group showed an increase in augmentation pressure (AP: 9 vs 12 mmHg, p=0.028) and augmentation index (AIx: 26 vs 35%, p=0.020), which was not observed in the VD group (AP: 8 vs 8 mmHg, AIx: 26 vs 25%, p>0.05). VD group showed an increase in the parasympathetic nervous system index (PNSi) (-0.64±0.94 vs -0.16±1.10, p=0.028) and the R-R interval (866±138 vs 924±161 ms, p= 0.026). In this sample, eight weeks of daily vitamin D supplementation resulted in an improvement in blood pressure levels and autonomic balance.

Effect of vitamin D3 supplementation on blood parameters and liver gene expression in female rats.

To better understand the molecular mechanism responsible for the therapeutic potential of vitamin D, we conducted an analysis of the liver transcriptomes of adult female rats. Adult female rats (n = 18) were divided into three groups, receiving different doses of vitamin D: group I, 0; group II, 1000 U/kg; and group III, 5000 U/kg. Growth, body weight, the weight of main organs, blood haematological and biochemical parameters were evaluated. Gene expression in the liver were analyzed using RNA-seq and qPCR techniques. We observed a lower platelet count (p < 0,008) and a significantly greater (p < 0.02) number of WBCs in rats supplemented with 1000 U/kg than in rats from group III (5000 U/kg). Moreover, we noted a trend (p < 0.06) in total cholesterol concentration, suggesting a linear decrease with increasing doses of vitamin D. RNA-seq analysis did not reveal any differentially expressed genes with FDR < 0.05. However, GSEA revealed significant activation of a number of processes and pathways, including: "metallothionein, and TspO/MBR family", and "negative regulation of tumor necrosis factor production". qPCR analysis revealed significant upregulation of the Mt1, Mt2 and Orm1 genes in animals receiving high doses of vitamin D (p < 0.025, p < 0.025, and p < 0009, respectively). Moreover, Srebp2 and Insig2 were significantly lower in both experimental groups than in the control group (p < 0.003 and p < 0.036, respectively). Our results support the anti-inflammatory, anitioxidant and anticholesterologenic potential of vitamin D but suggest that high doses of vitamin D are needed to obtain significant results in this regard.

Serum Ghrelin and Leptin Concentrations in Patients with Major Depressive Disorder before and after Supplementation with Vitamin D3

Aim. To determine serum concentrations of leptin and ghrelin in patients with major depressive disorder (MDD) before and after vitamin D3 supplementation. Methods. A total of 72 participants were recruited in this study (40 MDD patients and 32 healthy controls). MDD was diagnosed by using Beck’s Depression Inventory (BDI) scale. Blood samples were collected from all participants at the beginning of the study to determine baseline serum 25(OH)D3, leptin, and ghrelin concentrations. Patients were then treated weekly with vitamin D3 (50,000 IU) for 3 months, and blood samples were collected again by the end of the study. Results. At baseline, serum leptin concentrations were significantly higher in MDD patients than in healthy controls. In contrast, serum ghrelin concentrations were significantly lower compared to those in healthy controls. After supplementation with vitamin D3 for three months, MDD patients showed improvements characterized by a decrease in their BDI’s scores and an increase in their serum vitamin D and ghrelin concentrations. No effects of vitamin D3 supplementation were seen on serum leptin concentration. Conclusions. The antidepressant effects of vitamin D3 supplementation could be mediated by ghrelin but not leptin.

Effect of weekly vitamin D supplementation on the severity of atopic dermatitis and type 2 immunity biomarkers in children: A randomized controlled trial.

Vitamin D (VD) deficiency is common among patients with atopic dermatitis (AD) and often associated with severity. However, randomized trials of VD supplementation in AD have had equivocal results, and there is little information regarding the effect of VD supplementation on type 2 immunity in AD patients. To investigate the efficacy of VD supplementation to decrease severity of AD and to alter type 2 immunity biomarkers. We performed a randomized, double-blind, placebo-controlled trial. We randomly assigned 101 children with AD to weekly oral vitamin D3 (VD3) or placebo for 6 weeks. The primary outcome was the change in the Severity Scoring of AD (SCORAD). Mean age of subjects was 6.3 ± 4.0 years, and baseline SCORAD was 32 ± 29. At baseline, 57% of children were VD deficient, with no difference between groups. Change in 25(OH)D was significantly greater with VD3 than placebo (+43.4 ± 34.5 nmol/L vs. +2.3 ± 21.2 nmol/L, p < 0.001). SCORAD change at 6 weeks was not different between VD and placebo (-5.3 ± 11.6 vs. -5.5 ± 9.9, p = 0.91). There were no significant between-group differences in change of eosinophil counts, total IgE, Staphylococcal enterotoxin specific IgE, CCL17, CCL22, CCL27, LL-37 or Staphylococcus aureus lesional skin colonization. Vitamin D receptor (VDR) gene single nucleotide polymorphisms FokI, ApaI and TaqI did not modify subjects' response to VD supplementation. Among children with AD, weekly VD supplementation improved VD status but did not modify AD severity or type 2 immunity biomarkers compared to placebo (ClinicalTrials.gov NCT01996423).

The immune cell transcriptome is modulated by vitamin D3 supplementation in people with a first demyelinating event participating in a randomized placebo-controlled trial

Vitamin D deficiency is a risk factor for developing multiple sclerosis. The PrevANZ trial was conducted to determine if vitamin D3 supplementation can prevent recurrent disease activity in people with a first demyelinating event. As a sub-study of this trial, we investigated the effect of supplementation on peripheral immune cell gene expression. Participants were randomized to 1000, 5000 or 10,000 international units daily of vitamin D3 or placebo. Peripheral blood was collected at baseline and 12 weeks and sent for ribonucleic acid sequencing. Datasets from 55 participants were included. Gene expression was modulated by high dose supplementation. Antigen presentation and viral response pathways were upregulated. Oxidative phosphorylation and immune signaling pathways, including tumor necrosis factor-alpha and interleukin-17 signaling, were downregulated. Overall, vitamin D3 supplementation for 12 weeks modulated the peripheral immune cell transcriptome with induction of anti-inflammatory gene expression profiles. Our results support a dose-dependent effect of vitamin D3 supplementation on immune gene expression.

A study of safety and efficacy of vitamin D3 supplementation in pregnancy

Background: Vitamin D is a lipid-soluble prohormone that is vital for the maintenance of bone and muscle health. Vitamin D deficiency is an unrecognized epidemic, common in all age groups and is associated with preeclampsia, gestational diabetes, preterm birth, early labour and pregnancy loss. Methods: Our study was conducted in Batra hospital and medical research centre, New Delhi from October 2018 to May2019. 126 women were taken, of those seen before 20 weeks of pregnancy who received vitamin D3 supplementation comprised of study group and control group were those who came directly for delivery and without vitamin D3 level done. The outcomes measured were vitamin D3 level at 20 weeks, at delivery, in cord blood and clinical outcomes like pre-eclampsia, gestational diabetes, preterm delivery. Results: Gestational hypertension was seen in 4 (6.3%) of subjects while in control group it was seen in 11 (17.5%), Gestational diabetes was seen in 3 (4.8%) women while it was observed in 10 (15.9%) women of control group. Premature rupture of membranes was seen in 2 (3.2%) women in study group and 8 (12.7%) women of control group. Vitamin D level at the time of delivery in study group was significantly higher than control group (56.84±15.78 versus 18.12±8.97ng/ml). Conclusions: Preterm labor, low birth weight and preeclampsia were uncommon in the subjects and the administered vitamin D3 dose had no adverse effects but more research with larger sample size is strongly urged to assess the safety and effect of vitamin D3 supplementation.

High-dose vitamin D3 supplementation shows no beneficial effects on white blood cell counts, acute phase reactants, or frequency of respiratory infections

BackgroundVitamin D has been suggested to influence the immune system, and vitamin D metabolites and the vitamin D receptor (VDR) are generated and expressed in white blood cells (WBC). Moreover, vitamin D status has been associated with incidence and prognosis of some respiratory tract infections (RTI). Therefore, we investigated the effect of vitamin D3 supplementation on WBC, acute phase reactants (APR), and the risk of developing RTIs.MethodsA double-blinded, randomized, placebo-controlled clinical trial of 307 infertile men with multiple secondary immunological endpoints. The vitamin D3 group (n = 151) initially received 300,000 IU (7,500 µg) cholecalciferol once - followed by 1,400 IU (35 µg) daily for 150 days. The placebo group (n = 156) did not receive active ingredients.ResultsAt baseline, stratification into clinically relevant groups of vitamin D status (< 25; 25–50; 50–75; >75 nmol/L), showed an inverse association with total leucocyte concentrations (7.0 vs. 6.0 vs. 6.0 vs. 5.5 (109/L); p = 0.007), lymphocytes (2.4 vs. 2.1 vs. 2.0 vs. 2.0 (109/L); p = 0.048), CRP (2.0 vs. 1.7 vs. 1.2 vs. 1.2 (mg/L); p = 0.037), and orosomucoid (0.82 vs. 0.77 vs. 0.76 vs. 0.70 (g/L); p = 0.015). After 150 days, no differences were detected in WBC counts or APRs between the vitamin D3 and the placebo group. However, vitamin D3 treated men had a higher prevalence of self-reported RTIs compared with the placebo group (55% vs. 39%; p = 0.005).ConclusionsHigh-dose vitamin D3 supplementation did not alter WBCs or APRs, but a higher prevalence of respiratory infections was observed in the vitamin D3 group. Serum 25(OH)D3 was negatively correlated with most WBCs, indicating that vitamin D status may be linked with inflammation and WBC turnover, but not an important determinant of developing RTIs.Trial registrationNCT01304927 (ClinicalTrials.gov). Registered February 20, 2011.