Vitamin D2 (Ergocalciferol)

Comment in Nutr Rev. 2025 Oct 15:nuaf182. doi: 10.1093/nutrit/nuaf182. CONTEXT: There is a clear link between ergocalciferol, parathyroid hormone (PTH), phosphorus, and calcium. Various randomized trials have examined the effectiveness of ergocalciferol on vitamins and minerals. However, conflicting results have been reported, and the optimal dose and duration of ergocalciferol remain unclear. OBJECTIVE: This systematic review and meta-analysis of RCTs aim to evaluate the effect of vitamin D2 on PTH, calcium, and phosphorus in humans. DATA SOURCES: A comprehensive literature search was conducted with the assistance of a librarian. Independent reviewers performed searches across multiple databases, including Web of Science, Scopus, PubMed/Medline, and Embase, from their inception until September 20, 2024. DATA EXTRACTION: The random-effects model, based on the DerSimonian and Laird method, was applied to compute pooled estimates of the intervention's impact on the outcomes. DATA ANALYSES: A total of 26 articles were included in the meta-analysis. The pooled analysis, using a random-effects model, demonstrated a significant reduction in serum PTH concentrations (WMD, -12.77 pg/mL, 95% CI, -20.03 to -5.51, P = .001, I2 = 96%, P < .001) and a significant increase in calcium levels (WMD, 0.15 mg/dL, 95% CI, 0.03 to 0.27, P = .011) following vitamin D2 intervention. However, a nonsignificant effect of vitamin D2 on phosphorus concentrations was observed (WMD, 0.166 mg/dL, 95% CI, -0.08 to 0.41, P = .197). CONCLUSION: Vitamin D2 supplementation appears to improve serum calcium levels while decreasing PTH levels. Given the low cost and wide availability of ergocalciferol, it can be recommended, especially for older adults, to help maintain bone strength. © The Author(s) 2025. Published by Oxford University Press on behalf of the International Life Sciences Institute.

BACKGROUND: Inconsistencies exist regarding the influence of vitamin D2 (ergocalciferol) supplementation on serum vitamin D levels. These inconsistencies could be attributed to numerous factors, such as dosage, baseline vitamin D levels, and duration of intervention. Hence, this dose-response meta-analysis of randomized controlled trials was conducted to assess the efficacy of vitamin D2 supplementation on vitamin D levels. METHODS: Relevant studies were searched in PubMed/Medline, Web of Science, Embase, and Scopus, from their inception to 3 January 2023. Variable alterations were considered to calculate the pooled weighted mean difference (WMD) with 95% confidence interval (CI) using the random effects model. RESULTS: Pooled results from 33 study arms demonstrated that Vitamin D2 treatment significantly increases total vitamin D concentrations (WMD: 11.47 ng/mL, 95 %CI: 9.29 to 13.64, p < 0.001), 25(OH)D2 concentrations (WMD: 11.40 ng/mL, 95 %CI: 4.72 to 18.09, p = 0.001), and 1,25(OH)D concentrations (WMD: 5.61 ng/mL, 95 %CI: 0.74 to 10.48, p = 0.024), but decreases 25(OH)D3 concentrations (WMD: -4.63 ng/mL, 95 %CI: -6.46 to -2.81, p < 0.001). In subgroup analyses, increase in total vitamin D concentrations was more significant in vitamin D2 doses >2000 IU/day (WMD: 13.82 ng/mL), studies with duration ≤12 weeks (WMD: 12.53 ng/mL), participants aged ≥60 years (WMD: 14.40 ng/mL), and trials with basal 25(OH)D concentrations <20 ng/mL (WMD: 11.47 ng/mL). CONCLUSIONS: This meta-analysis indicates that the supplementation of vitamin D2 significantly increases the serum concentrations of total vitamin D, 25(OH)D2, and 1,25(OH)D, but decreases 25(OH)D3 concentrations. Careful consideration of patient characteristics, dosage, and treatment duration is recommended for vitamin D2 supplementation.

BACKGROUND: The evidence on whether vitamin D supplementation is effective in decreasing cancers is contradictory. OBJECTIVES: To assess the beneficial and harmful effects of vitamin D supplementation for prevention of cancer in adults. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, Science Citation Index Expanded, and the Conference Proceedings Citation Index-Science to February 2014. We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials. SELECTION CRITERIA: We included randomised trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention in adults who were healthy or were recruited among the general population, or diagnosed with a specific disease. 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), or 1,25-dihydroxyvitamin D (calcitriol)). DATA COLLECTION AND ANALYSIS: Two review authors extracted data independently. We conducted random-effects and fixed-effect model meta-analyses. For dichotomous outcomes, we calculated the risk ratios (RRs). We considered risk of bias in order to assess the risk of systematic errors. We conducted trial sequential analyses to assess the risk of random errors. MAIN RESULTS: Eighteen randomised trials with 50,623 participants provided data for the analyses. All trials came from high-income countries. Most of the trials had a high risk of bias, mainly for-profit bias. Most trials included elderly community-dwelling women (aged 47 to 97 years). Vitamin D was administered for a weighted mean of six years. Fourteen trials tested vitamin D₃, one trial tested vitamin D₂, and three trials tested calcitriol supplementation. Cancer occurrence was observed in 1927/25,275 (7.6%) recipients of vitamin D versus 1943/25,348 (7.7%) recipients of control interventions (RR 1.00 (95% confidence interval (CI) 0.94 to 1.06); P = 0.88; I² = 0%; 18 trials; 50,623 participants; moderate quality evidence according to the

BACKGROUND: Available evidence on the effects of vitamin D on mortality has been inconclusive. In a recent systematic review, we found evidence that vitamin D3 may decrease mortality in mostly elderly women. The present systematic review updates and reassesses the benefits and harms of vitamin D supplementation used in primary and secondary prophylaxis of mortality. OBJECTIVES: To assess the beneficial and harmful effects of vitamin D supplementation for prevention of mortality in healthy adults and adults in a stable phase of disease. SEARCH METHODS: We searched The Cochrane Library, MEDLINE, EMBASE, LILACS, the Science Citation Index-Expanded and Conference Proceedings Citation Index-Science (all up to February 2012). We checked references of included trials and pharmaceutical companies for unidentified relevant trials. SELECTION CRITERIA: Randomised trials that compared any type of vitamin D in any dose with any duration and route of administration versus placebo or no intervention in adult participants. Participants could have been recruited from the general population or from patients diagnosed with a disease in a stable phase. Vitamin D could have been administered as supplemental vitamin D (vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol)) or as an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol) or 1,25-dihydroxyvitamin D (calcitriol)). DATA COLLECTION AND ANALYSIS: Six review authors extracted data independently. Random-effects and fixed-effect meta-analyses were conducted. For dichotomous outcomes, we calculated the risk ratios (RRs). To account for trials with zero events, we performed meta-analyses of dichotomous data using risk differences (RDs) and empirical continuity corrections. We used published data and data obtained by contacting trial authors.To minimise the risk of systematic error, we assessed the risk of bias of the included trials. Trial sequential analyses controlled the risk of random errors possibly caused by cumulative meta-analyses. MAIN RESULTS: We identified 159 randomised clinical trials. Ninety-four trials reported no mortality, and nine trials reported mortality but did not report in which intervention gr

Vitamin D (VD) deficiency (serum 25(OH)D < 50 nmol/L) affects 27.3% of preschool children in Mexico. The purpose of this study was to assess the effect of vitamin D supplementation at different doses on serum 25(OH)D concentrations in preschool children. In a randomized control trial, 222 children 12-30 months old were randomly assigned to one of four treatment groups: (1) Vitamin D2 (Ergocalciferol) 400 IU/day (n = 56); (2) Vitamin D2 (Ergocalciferol) 800 IU/day (n = 55); (3) Vitamin D3 (Cholecalciferol) 1000 IU/day (n = 56); or (4) multiple micronutrients (MM) non-VD (n = 55). Supplements were given five days/wk for three months. Serum 25(OH)D was measured at baseline and after three months. At baseline, mean serum 25(OH)D was 58.9 ± 12.6 nmol/L and 23.4% were VD-deficient. There was a statistically significant increase in serum concentrations of 25(OH)D (range across groups: +8.2 to +17.3 nmol/L). Additionally, the prevalence of vitamin D deficiency decreased after three months: for D2 400 IU, -9.0%; for D2 800 IU, -11.0%; for D3 1000 IU, -18.0%; and for MM non-VD, -2.8% (p < 0.05). No adverse effects were observed. VD supplementation for three months was effective for increasing serum 25(OH)D concentrations and for reducing VD deficiency in preschool children. The highest efficacy was observed by giving 1000 IU D3/d.

OBJECTIVE: To evaluate the efficacy of daily supplementation of 200 mL milk fortified with 240 IU of vitamin D2 (ergocalciferol). DESIGN: Double-blind randomized controlled trial. SETTINGS: School-based study in Delhi between October and December, 2019. PARTICIPANTS: 235 healthy children aged 10-14 years. INTERVENTION: Daily supplementation of 200 mL milk fortified with 240 IU of ergocalciferol in intervention group (n=119) and 200 mL of plain milk in control group (n =116) for 3 months. OUTCOME MEASURES: Change in serum 25 hydroxy vitamin D (25(OH)D), parathyroid hormone (PTH), bone formation and resorption markers, and urinary calcium creatinine ratio (U-Ca/CrR). RESULTS: The mean (SD) baseline serum 25(OH) D level in control and fortification groups was 11.9 (3.8) and 11.4 (3.6) ng/mL (P=0.23), respectively. The serum 25(OH)D levels did not increase post-intervention with the dose used for fortification, but were significantly higher in intervention group as compared to control group [10.8 (3.4) vs 6.7 (3.5) ng/mL; P<0.001]. A higher proportion of secondary hyperparathyroidism was observed post-intervention in control (39%) than in intervention group (13.3%); P<0.001. Serum carboxy-terminal telopeptide levels were similar in both groups but the serum procollagen type1 N-terminal propeptide levels were higher in the control than intervention group (P<0.007), following supplementation. CONCLUSIONS: Supplementation of milk fortified with approximately 240 IU vitamin D2 for three months did not achieve sufficient serum 25(OH)D levels in Indian children with vitamin D deficiency during winter.

Update of doi: 10.1002/14651858.CD015111. RATIONALE: Acute respiratory infections (ARIs) are a leading cause of morbidity and mortality in children under five years of age and contribute to healthcare visits and hospitalisations globally. Vitamin D deficiency is common amongst pregnant women and young children. Given that vitamin D supplementation is safe, affordable, and easy to administer, its potential to reduce ARI-related healthcare visits holds substantial public health relevance. This review evaluates the benefit and harm of vitamin D supplementation in preventing ARI-related healthcare visits in young children, aiming to inform supplementation policies during pregnancy and early childhood. OBJECTIVES: To determine the benefit and harm of vitamin D supplementation for preventing ARIs in children up to five years of age. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, Web of Science, WHO Global Index Medicus, and four clinical trial registries on 18 March 2025. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) comparing vitamin D to placebo, or a higher dose (≥ 1000 IU) versus a lower dose (≤ 1000 IU) administered from early pregnancy through to five years of age. We excluded studies involving children with chronic respiratory or systemic conditions. OUTCOMES: Critical outcomes: 1) healthcare visits made by children for an ARI: (a) the proportion of children with healthcare visits made for ARIs; (b) the mean number of healthcare visits made for ARIs per child; and 2) hypercalcaemia: the number of pregnant women and children with hypercalcaemia. RISK OF BIAS: We assessed risk of bias using the Cochrane risk of bias (RoB) 1 tool for outcomes reported in the summary of findings tables. SYNTHESIS METHODS: We synthesised outcome data using meta-analyses, calculating risk ratios (RR) for dichotomous, and mean differences (MD) for continuous outcomes, each with 95% confidence intervals (CI). Where meta-analysis was not feasible, we summarised the results narratively. We used GRADE to assess the certainty of the evidence for pre-specified outcomes. INCLUDED STUDIES: We included

BACKGROUND: Obesity-associated metabolic syndrome (MetS) is characterized by abdominal adiposity, insulin resistance, and dyslipidemia. Vitamin D deficiency is prevalent in obesity, and supplementation has been hypothesized to modulate body fat distribution and glucolipid metabolism. This meta-analysis compared the metabolic effects of different vitamin D formulations in patients with obesity-associated MetS. METHODS: PubMed, EMBASE, Cochrane Library, Web of Science, and CNKI were searched from inception to the search date. Randomized controlled trials enrolling patients with obesity and/or MetS and evaluating vitamin D2, vitamin D3, or active vitamin D versus placebo/no intervention/low-dose vitamin D for ≥8 weeks were included. Primary outcomes were visceral and subcutaneous fat indices; secondary outcomes included fasting glucose, homeostatic model assessment of insulin resistance, and lipid parameters. Effect sizes were pooled as mean difference (MD) or standardized mean difference (SMD) with 95% confidence intervals (CIs); heterogeneity was assessed using I2. RESULTS: Fifty randomized controlled trials were included. Vitamin D3 and active vitamin D reduced visceral adiposity (SMD -0.35, 95% CI: -0.50 to -0.20; and -0.40, 95% CI: -0.60 to -0.20; I2 = 42%), whereas vitamin D2 showed no significant effect (SMD -0.10, 95% CI: -0.25 to 0.05). Vitamin D3 and active vitamin D improved fasting glucose (MD -0.30 and -0.35 mmol/L) and homeostatic model assessment of insulin resistance (SMD -0.40 and -0.45), and lowered LDL (MD -0.30 and -0.25 mmol/L). Benefits were greater with ≥2000 IU/d, intervention duration ≥6 months, and baseline 25(OH)D <20 ng/mL. The Egger test did not indicate significant publication bias (P = .12). CONCLUSIONS: In obesity-associated MetS, vitamin D3 and active vitamin D, particularly at higher doses and longer durations, are associated with reductions in visceral fat and improvements in glycemic control, insulin resistance, and selected lipid indices; vitamin D2 appears less effective.

BACKGROUND: Vitamin D have been proposed as a supplement to improve cardiometabolic risk factors in obese/overweight children and adolescents. However, findings evidence remains inconsistent. This meta-analysis aimed to assess the effects of vitamin D supplementation on cardiometabolic risk factors in obese/overweight children and adolescents. METHODS: A systematic review of PubMed, Embase, Scopus, Web of Science, Cochrane Library, and Google Scholar up to April 2025 was searched. This study aimed to evaluate the effect of vitamin D supplementation on cardiometabolic factors including anthropometric indices, glycemic state and lipid profile. Data were pooled using a random-effects model to calculate weighted mean differences (WMDs) and 95% confidence intervals (CIs). RESULTS: Nine studies with 440 participants were included. The meta-analysis revealed that vitamin D supplementation no significantly improved BMI, BMI-Z, FBS, insulin, HOMA-IR, QUICKI, TG, TC, and LDL-C. However, it was accompanied with a significant reduction in HDL-C level. Subgroup-analysis showed that vitamin D2 showed a greater reduction in HOMA-IR compared to vitamin D3, though the effect was statistically significant (WMD = -0.51, 95% CI: -1.00 to -0.03; p = 0.038). CONCLUSIONS: The current meta-analysis revealed vitamin D supplementation has no favorable effect on cardiometabolic risk factors. More high-quality and large-scale trials are needed to provide more robust evidence. © 2025. The Author(s).

BACKGROUND: Previous studies have shown that individuals with high body mass index typically require high doses of vitamin D supplementation to correct vitamin D deficiency. However, it is unclear which specific body composition is the determining factor affecting the bioavailability of vitamin D after supplementation. The aim of this study was to determine which body components affect the bioavailability of vitamin D. METHODS: In order to ensure the compliance of the study subjects and avoid the impact of sunlight on vitamin D3 levels, the subjects received multiple intramuscular (i.m.) injections of vitamin D2 until their serum levels of 25-hydroxyvitamin D [25(OH)D] were above 30 ng/mL. All subjects received two i.m. injections of 600,000 IU vitamin D2, and dose adjustments were made every 6 weeks based on whether serum 25(OH)D levels were sufficient. The levels of serum 25(OH)D2 and 25(OH)D3 were determined by liquid chromatography tandem mass spectrometry. The body composition was measured using dual-energy X-ray absorptiometry and corrected using body fat mass index (FMI). Based on the 100% difference in 25(OH)D levels before and after vitamin D supplementation, the sample size was calculated, and 20 subjects would provide over 95% of the power to show the difference. RESULTS: After two dose adjustment, the serum 25(OH)D levels of all subjects were above 30 ng/mL. The subjects were divided into ≤ 1,200,000 IU vitamin D2 (n=10) and ≥ 2,400,000 IU vitamin D2 (n=15) based on the i.m. dose of vitamin D2. The results showed that compared with subjects receiving ≤ 1,200,000 IU vitamin D2, subjects receiving ≥ 2,400,000 IU of vitamin D2 had a higher total body fat mass index (FMI), particularly with higher trunk fat content and high visceral adipose tissue mass. However, the dosage of vitamin D2 supplementation was not related to BMI and lean mass content. CONCLUSION: The body fat content, especially trunk fat content, is the main body component that affects the bioavailability of vitamin D in healthy adults. Healthy adults with high trunk fat content have low bioavailability of vitamin D and require relatively high dose of vitamin D to achieve sufficient levels.

OBJECTIVE: Low vitamin D status is associated with either low muscle mass or impaired muscle function in dialysis patients. However, there is no consensus on how best to correct hypovitaminosis D, defined as serum 25-hydroxyvitamin D level <30 ng/mL, in patients with end-stage kidney disease (ESKD). This study investigated the effect of different vitamin D supplementation regimens on sarcopenia outcomes in dialysis patients. METHODS: This was a prospective randomized controlled trial. ESKD patients treated with maintenance hemodialysis (HD) or peritoneal dialysis with low vitamin D status on a ratio of 1:1, were randomized to either receive oral ergocalciferol utilizing a severity-dependent treatment protocol for low vitamin D status suggested by the Kidney Disease Outcomes Quality Initiative as a control group or a fixed-dose regimen of 20,000 international units/week. The changes in muscle mass were measured by bioimpedance spectroscopy, muscle strength was assessed by a hand grip dynamometer, physical performance was determined by gait speed, and muscle-related biomarkers were examined. RESULTS: A total of 76 dialysis patients were randomized (HD = 43.4%). Baseline characteristics, including age, dialysis vintage, and muscle parameters were similar. After supplementation, the average serum 25-hydroxyvitamin D levels in the severity-dependent and fixed-dose groups were significantly elevated from 14.5 ± 7.3 to 27.2 ± 13.2 ng/mL, P < .001 and from 15.1 ± 6.4 to 28.8 ± 11.5 ng/mL, P < .001, respectively, and did not differ between groups at 6 months (P = .60). Despite comparable energy and protein intake, the mean bioimpedance spectroscopy-derived total body muscle mass normalized to height squared was significantly increased at 6 months in the fixed-dose group (14.5 ± 3.3 to 15.3 ± 3.0 kg/m2, P = .03) compared with the severity-dependent protocol (13.5 ± 2.7 to 13.7 ± 2.9 kg/m2, P = .58). In the subgroup analysis, muscle mass improvement was statistically elevated in peritoneal dialysis patients (P = .01) while unaltered among HD patients (P = .88) in the fixed-dose group. Muscle strength, gait speed, and serum insulin-like growth factor-1 level, as the mediato

BACKGROUND: Numerous studies demonstrate associations between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases. Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population. The benefit-risk ratio of this increase in vitamin D use is not clear, and the optimal vitamin D intake and the role of testing for 25(OH)D for disease prevention remain uncertain. OBJECTIVE: To develop clinical guidelines for the use of vitamin D (cholecalciferol [vitamin D3] or ergocalciferol [vitamin D2]) to lower the risk of disease in individuals without established indications for vitamin D treatment or 25(OH)D testing. METHODS: A multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, identified and prioritized 14 clinically relevant questions related to the use of vitamin D and 25(OH)D testing to lower the risk of disease. The panel prioritized randomized placebo-controlled trials in general populations (without an established indication for vitamin D treatment or 25[OH]D testing), evaluating the effects of empiric vitamin D administration throughout the lifespan, as well as in select conditions (pregnancy and prediabetes). The panel defined "empiric supplementation" as vitamin D intake that (a) exceeds the Dietary Reference Intakes (DRI) and (b) is implemented without testing for 25(OH)D. Systematic reviews queried electronic databases for publications related to these 14 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and guide recommendations. The approach incorporated perspectives from a patient representative and considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations. The process to d

BACKGROUND: Previous studies investigating the effect of oral supplementation of paricalcitol on reactive protein levels in chronic kidney disease (CKD) patients reported inconsistent findings. In this systematic review and meta-analysis, we have analyzed and interpreted the results obtained from previous randomized clinical trials on the effect of paricalcitol on C-reactive protein in CKD patients in the literature. METHODS: MEDLINE, SciVerse Scopus, and Clarivate Analytics Web of Science databases were searched until January 2023 and related articles were obtained through a careful screening process allowing extraction of required data from selected articles. The effect size was calculated using a random effect model and weighted mean differences (WMD) and 95% confidence intervals (CI). Heterogeneity among studies was evaluated using Cochran's Q test and I2. RESULTS: Amongst the 182 articles obtained from the initial search, 4 studies (6 arms) were finally included in the meta-analysis. Pooled analysis shows that C-reactive protein levels significantly decrease after oral supplementation with paricalcitol (WMD: -2.55 mg/L, 95% CI (-4.99 to -0.11; P = 0.04). The studies used in this meta-analysis showed significant heterogeneity (I2 = 66.3% and P = 0.01). CONCLUSION: Oral paricalcitol supplementation in CKD patients can significantly reduce C-reactive protein levels, which may prevent CKD progression. © 2024. The Author(s).

BACKGROUND: Distal symmetric polyneuropathy (DSPN) is the most common chronic complication of type 2 diabetes mellitus (T2DM). DSPN may lead to more serious complications, such as diabetic foot ulcer, amputation, and reduced life expectancy. Observational studies have suggested that vitamin D deficiency may be associated with the development of DSPN in T2DM. However, interventional studies have found that low-dose vitamin D supplementation does not significantly improve neuropathy in DSPN. This study aims to evaluate the efficacy and safety of intramuscular injection of high-dose vitamin D (HDVD) in T2DM with DSPN combined with vitamin D insufficiency. METHODS AND ANALYSIS: We will conduct a multicenter, randomized, double-blinded, and placebo-controlled trial in four large hospitals. All eligible participants will be randomly assigned to either the vitamin D2 supplement or placebo control group and injected intramuscularly monthly for 3 months. Additionally, anthropometric measurements and clinical data will be collected at baseline and 3 months. Adverse events will be collected at 1, 2, and 3 months. The primary outcome measure is the change in the mean Michigan Neuropathy Screening Instrument (MNSI) score at baseline and 3 months post-intervention. We will use the gold-standard liquid chromatography-tandem mass spectrometry method to distinguish between 25(OH)D2 and 25(OH)D3 levels. The MNSN score before the intervention will be used as a covariate to compare the changes between both groups before and after the intervention, and the analysis of covariance will be used to analyze the change in the MNSI score after HDVD supplementation. DISCUSSION: Glycemic control alone does not prevent the progression of DSPN in T2DM. Some studies have suggested that vitamin D may improve DSPN; however, the exact dose, method, and duration of vitamin D supplementation are unknown. Additionally, neuropathy repair requires HDVD supplementation to sustain adequate vitamin D levels. This once-a-month intramuscular method avoids daily medication; therefore, compliance is high. This study will be the first randomized controlled trial in China to analyze the efficacy and safety of H

Comment in J Bone Miner Res. 2024 Mar 4;39(1):1-2. doi: 10.1093/jbmr/zjad012. In a 36-month randomized controlled trial examining the effect of high-dose vitamin D3 on radial and tibial total bone mineral density (TtBMD), measured by high-resolution peripheral quantitative tomography (HR-pQCT), participants (311 healthy males and females aged 55-70 years with dual-energy X-ray absorptiometry T-scores > -2.5 without vitamin D deficiency) were randomized to receive 400 IU (N = 109), 4000 IU (N = 100), or 10,000 IU (N = 102) daily. Participants had HR-pQCT radius and tibia scans and blood sampling at baseline, 6, 12, 24, and 36 months. This secondary analysis examined the effect of vitamin D dose on plasma measurements of the vitamin D metabolome by liquid chromatography-tandem mass spectrometry (LC-MS/MS), exploring whether the observed decline in TtBMD was associated with changes in four key metabolites [25-(OH)D3 ; 24,25-(OH)2 D3 ; 1,25-(OH)2 D3 ; and 1,24,25-(OH)3 D3 ]. The relationship between peak values in vitamin D metabolites and changes in TtBMD over 36 months was assessed using linear regression, controlling for sex. Increasing vitamin D dose was associated with a marked increase in 25-(OH)D3 , 24,25-(OH)2 D3 and 1,24,25-(OH)3 D3 , but no dose-related change in plasma 1,25-(OH)2 D3 was observed. There was a significant negative slope for radius TtBMD and 1,24,25-(OH)3 D3 (-0.05, 95% confidence interval [CI] -0.08, -0.03, p < 0.001) after controlling for sex. A significant interaction between TtBMD and sex was seen for 25-(OH)D3 (female: -0.01, 95% CI -0.12, -0.07; male: -0.04, 95% CI -0.06, -0.01, p = 0.001) and 24,25-(OH)2 D3 (female: -0.75, 95% CI -0.98, -0.52; male: -0.35, 95% CI -0.59, -0.11, p < 0.001). For the tibia there was a significant negative slope for 25-(OH)D3 (-0.03, 95% CI -0.05, -0.01, p < 0.001), 24,25-(OH)2 D3 (-0.30, 95% CI -0.44, -0.16, p < 0.001), and 1,24,25-(OH)3 D3 (-0.03, 95% CI -0.05, -0.01, p = 0.01) after controlling for sex. These results suggest vitamin D metabolites other than 1,25-(OH)2 D3 may be responsible for the bone loss seen in the Calgary Vitamin D Study. Although plasma 1,25-(OH)2 D3 did not change with vitamin D

BACKGROUND: Osteoporosis is a condition where bones become fragile due to low bone density and impaired bone quality. This results in fractures that lead to higher morbidity and reduced quality of life. Osteoporosis is considered a major public health concern worldwide. For this reason, preventive measurements need to be addressed throughout the life course. Exercise and a healthy diet are among the lifestyle factors that can help prevent the disease, the latter including intake of key micronutrients for bone, such as calcium and vitamin D. The evidence on whether supplementation with calcium and vitamin D improves bone mineral density (BMD) in premenopausal women is still inconclusive. In this age group, bone accrual is considered to be the goal of supplementation, so BMD is relevant for the future stages of life. OBJECTIVES: To evaluate the benefits and harms of calcium and vitamin D supplementation, alone or in combination, to increase the BMD, reduce fractures, and report the potential adverse events in healthy premenopausal women compared to placebo. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search was 12 April 2022. SELECTION CRITERIA: We included randomised controlled trials in healthy premenopausal women (with or without calcium or vitamin D deficiency) comparing supplementation of calcium or vitamin D (or both) at any dose and by any route of administration versus placebo for at least three months. Vitamin D could have been administered as cholecalciferol (vitamin D3) or ergocalciferol (vitamin D2). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Outcomes included total hip bone mineral density (BMD), lumbar spine BMD, quality of life, new symptomatic vertebral fractures, new symptomatic non-vertebral fractures, withdrawals due to adverse events, serious adverse events, all reported adverse events and additional withdrawals for any reason. MAIN RESULTS: We included seven RCTs with 941 participants, of whom 138 were randomised to calcium supplementation, 110 to vitamin D supplementation, 271 to vitamin D plus calcium supplementation, and 422 to placebo. Mean age ranged from 18.1 to 42.1 years. Studie

Data on the effect of vitamin D (Vit-D) supplementation on cardiorespiratory fitness (VO2max) are conflicting. A possible source of discrepancies in the literature is the heterogeneity in baseline Vit-D status among participants in previous studies. The main objectives of the present study were to assess the impact of Vit-D supplementation on VO2max and inflammatory status in Vit-D deficient young healthy men. Participants (n = 39, baseline serum Vit-D level < 50 nmol/L) were quasi-randomly assigned to one of the two groups, which, in a double-blind manner, supplemented their diet daily with either Vit-D (8000 IU; VD) or placebo (PLC) and concomitantly performed a 12-week supervised resistance training program. During the 12-week intervention, serum Vit-D concentrations increased 3.9-fold (p < 0.001) in the VD group while no changes occurred in the PLC group. Baseline VO2max did not differ in the two groups and remained unchanged during the intervention. Serum interleukin-10/tumour necrosis factor alpha ratio increased significantly (30%, p = 0.007; effect size 0.399) in VD but not in PLC group. In conclusion, 12-week Vit-D supplementation increases serum 25(OH)D levels and improves inflammatory status, but has no impact on VO2max in Vit-D deficient young men engaged in resistance training.

The publication of our recent randomized controlled trial (RCT) showing that vitamin D could protect the β-cells during the honeymoon phase of type 1 diabetes (T1D) has led to calls for guidance for vitamin D supplementation during the critical phase of type 1 diabetes. Prolonging the partial clinical remission (PR) phase of TID improves glycemic control and reduces long-term complications of T1D. This RCT randomized 36 children and adolescents to either receive vitamin D2 (ergocalciferol, given as 50,000 international units per week for 2 months and then every other week for 10 months) or a placebo. The results showed that vitamin D significantly decreased the temporal rise in both hemoglobin A1c at a mean rate of changes of 0.14% every 3 months versus 0.46% every 3 months for the placebo group (p=0.044); and in the functional marker of PR, the insulin-dose adjusted A1c at a mean rate of change of 0.30% every 3 months versus 0.77% every 3 months for the placebo group, (p=0.015). We recommend a baseline estimation of 25(OH)D concentration at the time of diagnosis of T1D, and to begin vitamin D supplementation if serum 25(OH)D concentration is <30 ng/mL, to maintain serum 25(OH)D concentrations between 30-60 ng/mL. If serum 25(OH)D concentration is >30 ng/mL, monitor vitamin D status with serial 25(OH)D estimations; and initiate vitamin D supplementation if serum 25(OH)D concentrations drop to <30 ng/mL. Continue vitamin D supplementation for at least one year to ensure optimal benefit from vitamin D supplementation during the partial clinical remission phase of type 1 diabetes.