Safety of High-Dose Vitamin D Supplementation: Secondary Analysis of a Randomized Controlled Trial

2019 ◽  
Vol 105 (4) ◽  
pp. 1261-1273 ◽  
Author(s):  
Emma O Billington ◽  
Lauren A Burt ◽  
Marianne S Rose ◽  
Erin M Davison ◽  
Sharon Gaudet ◽  
...  
Keyword(s):  
Vitamin D ◽  
Adverse Events ◽  
Controlled Trial ◽  
Vitamin D Supplementation ◽  
Calcium Excretion ◽  
Hydroxyvitamin D ◽  
Randomized Controlled ◽  
25 Hydroxyvitamin D ◽  
Higher Doses ◽  
Urine Calcium Excretion

Abstract Context More than 3% of adults report vitamin D intakes of 4000 IU/day or more, but the safety of this practice is unknown. Objective The objective of this work is to establish whether vitamin D doses up to 10 000 IU/day are safe and well tolerated. Design The Calgary Vitamin D Study was a 3-year, double-blind, randomized controlled trial. Setting A single-center study was conducted at the University of Calgary, Canada. Participants Participants included healthy adults (n = 373) ages 55 to 70 years with serum 25-hydroxyvitamin D 30 to 125 nmol/L. Interventions Participants were randomly assigned 1:1:1 to vitamin D3 400, 40 000, or 10 000 IU/day. Calcium supplementation was initiated if dietary calcium intake was less than 1200 mg/day. Main Outcome Measures In these prespecified secondary analyses, changes in serum 25-hydroxyvitamin D, calcium, creatinine, 24-hour urine calcium excretion, and incidence of adverse events were assessed. Between-group differences in adverse events were examined using incident rate differences and logistic regression. Results Of 373 participants (400: 124, 4000: 125, 10 000: 124), 49% were male, mean (SD) age was 64 (4) years, and 25-hydroxyvitamin D 78.0 (19.5) nmol/L. Serum calcium, creatinine, and 24-hour urine calcium excretion did not differ between treatments. Mild hypercalcemia (2.56-2.64 mmol/L) occurred in 15 (4%) participants (400: 0%, 4000: 3%, 10 000: 9%, P = .002); all cases resolved on repeat testing. Hypercalciuria occurred in 87 (23%) participants (400: 17%, 4000: 22%, 10 000: 31%, P = .01). Clinical adverse events were experienced by 365 (97.9%) participants and were balanced across treatment arms. Conclusions The safety profile of vitamin D supplementation is similar for doses of 400, 4000, and 10 000 IU/day. Hypercalciuria was common and occurred more frequently with higher doses. Hypercalcemia occurred more frequently with higher doses but was rare, mild, and transient.

scholarly journals Effects of Vitamin D Supplementation on Serum 25-Hydroxyvitamin D Concentrations in Cirrhotic Patients: A Randomized Controlled Trial

Nutrients ◽  
2016 ◽  
Vol 8 (5) ◽  
pp. 278 ◽  
Author(s):  
Stefan Pilz ◽  
Csilla Putz-Bankuti ◽  
Martin Gaksch ◽  
Walter Spindelboeck ◽  
Marius Haselberger ◽  
...  
Keyword(s):  
Vitamin D ◽  
Randomized Controlled Trial ◽  
Controlled Trial ◽  
Vitamin D Supplementation ◽  
Hydroxyvitamin D ◽  
Randomized Controlled ◽  
25 Hydroxyvitamin D ◽  
Cirrhotic Patients

scholarly journals Vitamin D Supplementation and Hemoglobin Levels in Hypertensive Patients: A Randomized Controlled Trial

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Jana B. Ernst ◽  
Andreas Tomaschitz ◽  
Martin R. Grübler ◽  
Martin Gaksch ◽  
Katharina Kienreich ◽  
...  
Keyword(s):  
Vitamin D ◽  
Controlled Trial ◽  
Vitamin D Supplementation ◽  
Epidemiological Evidence ◽  
Hypertensive Patients ◽  
Hydroxyvitamin D ◽  
Randomized Controlled ◽  
25 Hydroxyvitamin D ◽  
The Mean ◽  
Vitamin D Supplement

Epidemiological evidence suggests that circulating 25-hydroxyvitamin D (25OHD) levels are inversely associated with hemoglobin (Hb) levels and anemia risk. We evaluated whether vitamin D supplementation improves Hb levels and reduces anemia risk in hypertensive patients. Two hundred patients with 25OHD levels <75 nmol/L who attended the Styrian Vitamin D Hypertension Trial were included, of whom 188 completed the trial. Patients randomly received 2800 IU vitamin D3 daily or a matching placebo for eight weeks. Initially, the prevalence of anemic status (Hb levels <12.5 g/dL) and deficient 25OHD levels (<30 nmol/L) was 6.5% and 7.5%, respectively. All anemic patients had 25OHD levels >50 nmol/L. The mean (95% confidence interval) vitamin D effect on Hb levels was 0.04 (−0.14 to 0.22) g/dL (P=0.661). Moreover, vitamin D treatment did not influence anemic status significantly (P>0.999). Likewise, vitamin D had no significant effect on Hb levels in the subgroups of anemic patients or in patients with initial 25OHD levels <30 nmol/L. In conclusion, a daily vitamin D supplement of 2800 IU for eight weeks did not improve Hb levels or anemic status in hypertensive patients. Future trials should focus on anemic patients with deficient 25OHD levels (e.g., <30 nmol/L). This trial is registered with clinicaltrials.gov [NCT02136771].

scholarly journals Effects of Vitamin D Supplementation on Surrogate Markers of Fertility in PCOS Women: A Randomized Controlled Trial

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 547
Author(s):  
Elisabeth Lerchbaum ◽  
Verena Theiler-Schwetz ◽  
Martina Kollmann ◽  
Monika Wölfler ◽  
Stefan Pilz ◽  
...  
Keyword(s):  
Vitamin D ◽  
Treatment Effect ◽  
Polycystic Ovary ◽  
Controlled Trial ◽  
Dehydroepiandrosterone Sulfate ◽  
Vitamin D Supplementation ◽  
Double Blind ◽  
Significant Treatment ◽  
Hydroxyvitamin D ◽  
Randomized Controlled

Vitamin D (VD) might play an important role in polycystic ovary syndrome (PCOS) and female fertility. However, evidence from randomized controlled trials (RCT) is sparse. We examined VD effects on anti-Müllerian hormone (AMH) and other endocrine markers in PCOS and non-PCOS women. This is a post hoc analysis of a single-center, double-blind RCT conducted between December 2011 and October 2017 at the endocrine outpatient clinic at the Medical University of Graz, Austria. We included 180 PCOS women and 150 non-PCOS women with serum 25-hydroxyvitamin D (25(OH)D) concentrations <75 nmol/L in the trial. We randomized subjects to receive 20,000 IU of VD3/week (119 PCOS, 99 non-PCOS women) or placebo (61 PCOS, 51 non-PCOS women) for 24 weeks. Outcome measures were AMH, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, dehydroepiandrosterone sulfate, and androstenedione. In PCOS women, we observed a significant treatment effect on FSH (mean treatment effect 0.94, 95% confidence interval [CI] 0.087 to 1.799, p = 0.031) and LH/FSH ratio (mean treatment effect −0.335, 95% CI −0.621 to 0.050, p = 0.022), whereas no significant effect was observed in non-PCOS women. In PCOS women, VD treatment for 24 weeks had a significant effect on FSH and LH/FSH ratio but no effect on AMH levels.

scholarly journals Effects of vitamin D binding protein phenotypes and vitamin D supplementation on serum total 25(OH)D and directly measured free 25(OH)D

2016 ◽  
Vol 174 (4) ◽  
pp. 445-452 ◽  
Author(s):  
Stina T Sollid ◽  
Moira Y S Hutchinson ◽  
Vivian Berg ◽  
Ole M Fuskevåg ◽  
Yngve Figenschau ◽  
...  
Keyword(s):  
Vitamin D ◽  
Binding Protein ◽  
Controlled Trial ◽  
Inverse Correlation ◽  
Vitamin D Supplementation ◽  
Vitamin D Binding Protein ◽  
Baseline Serum ◽  
Hydroxyvitamin D ◽  
Direct Measurements ◽  
25 Hydroxyvitamin D

ObjectiveTo determine the relationship between serum total 25-hydroxyvitamin D (25(OH)D), directly measured free 25(OH)D and calculated free 25(OH)D with regard to vitamin D-binding protein (DBP) phenotypes, sex, BMI, age and season, and their interrelationship to vitamin D supplementation.Design, patients and interventionsA randomized controlled trial with 20 000 IU of vitamin D3per week or placebo for 12 months was designed. A total of 472 subjects, 236 in each of the intervention groups, were included in the analyses.Main outcome measuresBaseline serum concentrations and increases in serum total 25(OH)D, directly measured free 25(OH)D, calculated free 25(OH)D and DBP.ResultsSerum total 25(OH)D and DBP concentrations were significantly lower in subjects with the phenotype Gc2/Gc2 compared to phenotypes with the Gc1S allele, and lower in males compared to females. When using directly measured free 25(OH)D, the differences related to DBP phenotypes and sexes were clearly diminished. All calculated free 25(OH)D concentrations were overestimated compared to the directly measured free 25(OH)D. Serum parathyroid hormone showed an inverse correlation with all vitamin D parameters analyzed. The increases after 12 months of vitamin D supplementation were not significantly different for any of the vitamin D parameters regardless of DBP phenotype, sex or age. Supplementation with vitamin D did not affect serum DBP.ConclusionDirect measurements of free 25(OH)D reduce the differences seen in total 25(OH)D between DBP phenotype groups and sexes, probably caused by differences in DBP concentrations. With conditions affecting serum DBP concentrations, direct measurements of free 25(OH)D should be considered.

scholarly journals Significant Independent Predictors of Vitamin D Deficiency in Inpatients and Outpatients of a Nephrology Unit

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Recep Bentli ◽  
Hulya Taskapan ◽  
Halil Toktaş ◽  
Ozkan Ulutas ◽  
Adnan Ozkahraman ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Female Gender ◽  
Vitamin D Insufficiency ◽  
Vitamin D Supplementation ◽  
Documentary Evidence ◽  
Hydroxyvitamin D ◽  
Nitrogen Levels ◽  
25 Hydroxyvitamin D ◽  
Higher Doses

Aims. Kidney disease was found to be a major risk factor for vitamin D deficiency in a population study of patients hospitalized. The aims of the study were to describe the prevalence of vitamin D deficiency inpatients and outpatients in a nephrology department during fall and to evaluate effect of assessing serum 25-hydroxyvitamin D (25(OH)D) levels and previous supplementation of cholecalciferol on vitamin D status.Methods. We studied 280 subjects in total, between October and January. The subjects were recruited from the following two groups: (a) inpatients and (b) outpatients in nephrology unit. We examined previous documentary evidence of vitamin D supplementation of the patients.Results. The prevalence of vitamin D deficiency among these 280 patients was 62,1% (174 patients). Fifty-three patients (18.9%) had severe vitamin D deficiency, 121 patients (43.2%) moderate vitamin D deficiency, and 66 patients (23.6%) vitamin D insufficiency. In logistic regression analysis female gender, not having vitamin D supplementation history, low serum albumin, and low blood urea nitrogen levels were significant independent predictors of vitamin D deficiency while no association of vitamin D deficiency with diabetes mellitus, serum creatinine, eGFR, and being hospitalized was found.Conclusion. Vitamin D deficiency, seems to be an important problem in both inpatients and outpatients of nephrology. Monitoring serum 25(OH)D concentrations regularly and replacement of vitamin D are important. Women in Turkey are at more risk of deficiency and may therefore need to consume higher doses of vitamin D.

scholarly journals Effect of Vitamin D3 Supplementation vs Placebo on Hospital Length of Stay in Patients with Severe COVID-19: A Multicenter, Double-blind, Randomized Controlled Trial

2020 ◽  
Author(s):  
Igor H. Murai ◽  
Alan L. Fernandes ◽  
Lucas P. Sales ◽  
Ana J. Pinto ◽  
Karla F. Goessler ◽  
...  
Keyword(s):  
Vitamin D ◽  
Length Of Stay ◽  
Controlled Trial ◽  
Hospital Length ◽  
Hospitalized Patients ◽  
Hospital Length Of Stay ◽  
Double Blind ◽  
Hydroxyvitamin D ◽  
Randomized Controlled ◽  
25 Hydroxyvitamin D

ImportancePatients with COVID-19 may exhibit 25-hydroxyvitamin D deficiency, but the beneficial effects of vitamin D3 supplementation in this disease remain to be proven by randomized controlled trials.ObjectiveTo investigate the efficacy and safety of vitamin D3 supplementation in patients with severe COVID-19.Design, Setting, and ParticipantsThis is a multicenter, double-blind, randomized, placebo-controlled trial conducted in two centers (a quaternary hospital and a field hospital) in Sao Paulo, Brazil. The trial included 240 hospitalized patients with severe COVID-19. The study was conducted from June 2, 2020 to October 7, 2020.InterventionsPatients were randomly allocated (1:1 ratio) to receive either a single oral dose of 200,000 IU of vitamin D3 or placebo.Main Outcomes and MeasuresThe primary outcome was hospital length of stay, defined as hospital discharge from the date of randomization or death. Secondary outcomes were mortality, admission to ICU, mechanical ventilation requirement, and serum levels of 25-hydroxyvitamin D, creatinine, calcium, C-reactive protein, and D-dimer.ResultsOf 240 randomized patients (mean age, 56 years; 56% men), 232 (96.7%) were included in the primary analysis. Log-rank test showed that hospital length of stay was comparable between the vitamin D3 supplementation and placebo groups (7.0 days [95% CI, 6.1 to 7.9] and 7.0 days [95% CI, 6.2 to 7.8 days]; hazard ratio, 1.12 [95% CI, 0.9 to 1.5]; P = .379; respectively). The rate of mortality (7.0% vs 5.1%; P = .590), admission to ICU (15.8% vs 21.2%; P = .314), and mechanical ventilation requirement (7.0% vs 14.4%; P = .090) did not significantly differ between groups. Vitamin D3 supplementation significantly increased serum 25-hydroxyvitamin D levels compared to placebo (difference, 24.0 ng/mL [95% CI, 21.0% to 26.9%]; P = .001). No adverse events were observed.Conclusions and RelevanceAmong hospitalized patients with severe COVID-19, vitamin D3 supplementation was safe and increased 25-hydroxyvitamin D levels, but did not reduce hospital length of stay or any other relevant outcomes vs placebo. This trial does not support the use of vitamin D3 supplementation as an adjuvant treatment of patients with COVID-19.Key pointsQuestionCan vitamin D3 supplementation reduce hospital length of stay in hospitalized patients with severe COVID-19?FindingsIn this double-blind, randomized, placebo-controlled trial involving 240 hospitalized patients with severe COVID-19, a single dose of 200,000 IU of vitamin D3 supplementation was safe and effective in increasing 25-hydroxyvitamin D levels, but did not significantly reduce hospital length of stay (hazard ratio, 1.12) or any other clinically-relevant outcomes compared with placebo.MeaningVitamin D3 supplementation does not confer therapeutic benefits among hospitalized patients with severe COVID-19.

scholarly journals Prevention of post-cardiac surgery vitamin D deficiency in children with congenital heart disease: a pilot feasibility dose evaluation randomized controlled trial

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
James Dayre McNally ◽  
◽  
Katie O’Hearn ◽  
Dean A. Fergusson ◽  
Jane Lougheed ◽  
...  
Keyword(s):  
Vitamin D ◽  
Usual Care ◽  
Congenital Heart ◽  
Controlled Trial ◽  
High Dose ◽  
Vitamin D Status ◽  
Hydroxyvitamin D ◽  
Randomized Controlled ◽  
Accrual Rate ◽  
25 Hydroxyvitamin D

Abstract Background The vast majority of children undergoing cardiac surgery have low vitamin D levels post-operative, which may contribute to greater illness severity and worse clinical outcomes. Prior to the initiation of a large phase III clinical trial focused on clinical outcomes, studies are required to evaluate the feasibility of the study protocol, including whether the proposed dosing regimen can safely prevent post-operative vitamin D deficiency in this high-risk population. Methods We conducted a two-arm, double-blind dose evaluation randomized controlled trial in children requiring cardiopulmonary bypass for congenital heart disease. Pre-operatively, participants were randomized to receive cholecalciferol representing usual care (< 1 year = 400 IU/day, > 1 year = 600 IU/day) or a higher dose approximating the Institute of Medicine tolerable upper intake level (< 1 year = 1600 IU/day, > 1 year = 2400 IU/day). The feasibility outcomes were post-operative vitamin D status (primary), vitamin D-related adverse events, accrual rate, study withdrawal rate, blinding, and protocol non-adherence. Results Forty-six children were randomized, and five withdrew prior to surgery, leaving 41 children (21 high dose, 20 usual care) in the final analysis. The high dose group had higher 25-hydroxyvitamin D concentrations both intraoperatively (mean difference + 25.9 nmol/L; 95% CI 8.3–43.5) and post-operatively (mean difference + 17.2 nmol/L; 95% CI 5.5–29.0). Fewer participants receiving high-dose supplementation had post-operative serum 25-hydroxyvitamin D concentrations under 50 nmol/L, compared with usual care (RR 0.31, 95% CI 0.11–0.87). Post-operative vitamin D status was associated with the treatment arm and the number of doses received. There were no cases of hypercalcemia, and no significant adverse events related to vitamin D. While only 75% of the target sample size was recruited (limited funding), the consent rate (83%), accrual rate (1.5 per site month), number of withdrawals (11%), and ability to maintain blinding support feasibility of a larger trial. Conclusions Pre-operative daily high-dose supplementation improved vitamin D status pre-operatively and at time of pediatric ICU admission. The protocol for a more definitive trial should limit enrollment of children with at least 30 days between randomization and surgery to allow adequate duration of supplementation or consider a loading dose. Trial registration ClinicalTrials.gov, NCT01838447. Registered on April 24, 2013

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