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Pharmacodynamics of Oral Cholecalciferol in Healthy Individuals with Vitamin D Deficiency: A Randomized Open-Label Study.
Fassio, A, Gatti, D, Rossini, M, Benini, C, Fracassi, E, Bertoldo, E, Viapiana, O, Milleri, S, Gatti, M, Adami, G
Nutrients. 2021;(7)
Abstract
Comparative pharmacodynamic (PD) analyses on different dosing schedules for cholecalciferol supplementation are limited. This was an open-label, randomized, parallel-group study involving 75 healthy individuals deficient in vitamin D (baseline 25OHD < 20 ng/mL) receiving oral cholecalciferol with three different dosing regimens: Group A: 10,000 IU/day for 8 weeks followed by 1000 IU/day for 4 weeks; Group B: 50,000 IU/week for 12 weeks and Group C: 100,000 IU every other week for 12 weeks. Regulators of calcium and phosphate homeostasis, bone turnover markers and Wnt inhibitors were measured at baseline, Day 28, 53, 84, and 112. The 1,25OH2D increased at each time point. The increase was greater (p < 0.05) for group A vs. B and C at Day 28, and vs. group B at Day 56. No significant difference among groups was observed for the other biomarkers. The 24,25OH2D remained stable over time. PTH decreased at Day 84 and FGF-23 increased at all time points. CTX-I and PINP increased slightly at Day 28. BALP decreased from Day 56 onward. Dkk-1 increased from Day 56 onward, while sclerostin did not show significant changes. In healthy individuals deficient in vitamin D, vitamin D supplementation exerted effects on multiple regulators of calcium, phosphate and bone metabolism, without marked differences using the three regimens.
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Vitamin D supplementation prior to or during COVID-19 associated with better 3-month survival in geriatric patients: Extension phase of the GERIA-COVID study.
Annweiler, C, Beaudenon, M, Simon, R, Guenet, M, Otekpo, M, Célarier, T, Gautier, J, ,
The Journal of steroid biochemistry and molecular biology. 2021;:105958
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BACKGROUND The objective of this extension phase of the quasi-experimental GERIA-COVID study was to determine whether vitamin D3 supplementation taken prior to or during COVID-19 was associated with better 3-month survival in geriatric patients hospitalized for COVID-19. METHODS Intervention group was defined as all participants supplemented with vitamin D3 prior to or during COVID-19 (n = 67). Supplements were either bolus vitamin D3 (ie, 50,000 IU per month, or 80,000 IU or 100,000 IU or 200,000 IU every 2-3 months), or daily supplementation with 800 IU. Comparator group involved those without vitamin D supplements (n = 28). Outcome was 3-month mortality. Covariables were age, sex, functional abilities, history of malignancies, cardiomyopathy, undernutrition, number of acute health issues, antibiotics use, systemic corticosteroids use, and 25(OH)D concentration. RESULTS 76.1 % (n = 51) of participants survived at 3 months in Intervention group, compared to only 53.6 % (n = 15) in Comparator group (P = 0.03). The fully-adjusted hazard ratio for 3-month mortality was HR = 0.23 [95 %CI: 0.09;0.58](P = 0.002) in Intervention group compared to Comparator group. Intervention group had also longer survival time (log-rank P = 0.008). CONCLUSIONS Vitamin D3 supplementation was associated with better 3-month survival in older COVID-19 patients.
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Vitamin D supplementation: a potential therapeutic agent for metastatic colorectal cancer.
Yuan, C, Ng, K
British journal of cancer. 2020;(8):1205-1206
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Preclinical and epidemiological evidence suggests that vitamin D may have anti-cancer activities in patients with colorectal cancer. A recently completed, randomised Phase 2 trial of vitamin D3 supplementation in patients with metastatic colorectal cancer has shown promising results, and a Phase 3 trial is currently underway.
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The Effects of Cholecalciferol Supplementation on Vitamin D Status Among a Diverse Population of Collegiate Basketball Athletes: A Quasi-Experimental Trial.
Sekel, NM, Gallo, S, Fields, J, Jagim, AR, Wagner, T, Jones, MT
Nutrients. 2020;(2)
Abstract
Vitamin D may play a role in performance and injury risk, yet the required supplementation dosage for collegiate athletes is unclear. The objective of this study was to define the dosage of vitamin D3 supplementation required to beneficially affect serum 25-hydroxyvitamin D (25(OH)D) among a sample of collegiate basketball athletes. This was a quasi-experimental trial, participants were allocated to one of three groups of vitamin D3 daily at the beginning of pre-season training and dependent upon their baseline vitamin D status as follows: insufficient (<75 nmol/L) to 10,000 IU, sufficient (75-125 nmol/L) to 5000 IU and optimal (>125 nmol/L) to no supplementation. Follow-up assessments were completed ~ 5 months later in post season. The majority (n = 13) were allocated to 10,000 IU vs. n = 5 to 5000 IU and n = 2 to no supplementation. The 10,000 IU group showed the greatest change (35.0 ± 27.0 nmol/L) vs. the 5000 IU group (-9.3 ± 9.6 nmol/L) and no supplementation group (-41.6 ± 11.7 nmol/L, p < 0.01). Only 1 participant reached optimal status in the 10,000 IU group. In conclusion, a daily dosage of 10,000 IU vitamin D3 supplementation mitigated the high prevalence of vitamin D deficiency among collegiate basketball players but was insufficient for all to reach sufficient levels.
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High-Dose Cholecalciferol Booster Therapy is Associated with a Reduced Risk of Mortality in Patients with COVID-19: A Cross-Sectional Multi-Centre Observational Study.
Ling, SF, Broad, E, Murphy, R, Pappachan, JM, Pardesi-Newton, S, Kong, MF, Jude, EB
Nutrients. 2020;(12)
Abstract
The worldwide pandemic of 2019 novel coronavirus disease (COVID-19) has posed the most substantial and severe public health issue for several generations, and therapeutic options have not yet been optimised. Vitamin D (in its "parent" form, cholecalciferol) has been proposed in the pharmacological management of COVID-19 by various sources. We aimed to determine whether COVID-19 mortality was affected by serum 25-hydroxyvitamin D (25(OH)D) levels, vitamin D status, or cholecalciferol therapy, and to elucidate any other predictors of COVID-19 mortality. Patients hospitalised with COVID-19 were opportunistically recruited from three UK hospitals, and their data were collected retrospectively. Logistic regression was used to determine any relationships between COVID-19 mortality and potential predictors, including 25(OH)D levels and cholecalciferol booster therapy. A total of 986 participants with COVID-19 were studied, of whom 151 (16.0%) received cholecalciferol booster therapy. In the primary cohort of 444 patients, cholecalciferol booster therapy was associated with a reduced risk of COVID-19 mortality, following adjustment for potential confounders (ORadj 0.13, 95% CI 0.05-0.35, p < 0.001). This finding was replicated in a validation cohort of 541 patients (ORadj 0.38, 95% CI 0.17-0.84, p = 0.018). In this observational study, treatment with cholecalciferol booster therapy, regardless of baseline serum 25(OH)D levels, appears to be associated with a reduced risk of mortality in acute in-patients admitted with COVID-19. Further work with large population studies needs to be carried out to determine adequate serum 25(OH)D levels, as well as multi-dose clinical trials of cholecalciferol therapy to assess maximum efficacy.
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Vitamin D receptor gene polymorphisms affecting changes in visceral fat, waist circumference and lipid profile in breast cancer survivors supplemented with vitamin D3.
Kazemian, E, Amouzegar, A, Akbari, ME, Moradi, N, Gharibzadeh, S, Jamshidi-Naeini, Y, Khademolmele, M, As'habi, A, Davoodi, SH
Lipids in health and disease. 2019;(1):161
Abstract
OBJECTIVE We investigated whether vitamin D receptor (VDR) polymorphisms are associated with circulating metabolic biomarkers and anthropometric measures changes in breast cancer survivors supplemented with vitamin D3. METHODS One hundred sixty-eight breast cancer survivors admitted to Shohaday-e-Tajrish hospital received 4000 IU of daily vitamin D3 supplements for 12 weeks. Anthropometric measurements as well dietary, physical activity and plasma metabolic biomarkers assessments were performed before and after intervention. VDR polymorphisms were considered as the main exposures. Multivariate multiple linear regression analyses were used to determine the association between the VDR single-nucleotide polymorphisms (SNPs) and changes in metabolic and anthropometric measures in response to vitamin D3 supplementation. RESULTS One hundred twenty-five (85%) women had insufficient and inadequate levels of plasma 25-hydroxy vitamin D (25(OH)D) at baseline. Compared to the AA genotype of the ApaI, the aa category showed greater increase in muscle mass [71.3(10.7131.9)] and higher decrease in LDL-C [- 17.9(- 33.6, - 2.3)] levels after adjustment for potential confounders. In addition, the heterozygous genotype (Bb) of the BsmI VDR was associated with higher increase in WC following vitamin D3 supplementation, compared to BB [2.7(0.1,5.3)]. Haplotype score analyses indicate a significant association between inferred haplotypes from BsmI, ApaI, TaqI and FokI, BsmI and Cdx2 VDR polymorphisms and on-study visceral fat changes. CONCLUSIONS Findings of this study showed that genetic variation in the VDR gene was associated with changes in cardio-metabolic parameters in breast cancer survivors, supplemented with vitamin D3, results could provide a novel insight into better understanding of which subset of individuals benefit most from normalization of vitamin D status. TRIAL REGISTRATION This trial has been registered on the Iranian Registry of Clinical Trials (IRCT) under the identification code: IRCT2017091736244N1, registration date: 2017-11-10, http://www.irct.ir/trial/27153 and was approved by the ethics committees of the National Nutrition and Food Technology Research Institute (NNFTRI), Shahid Beheshti University of Medical Sciences (SBMU).
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Randomized trial of daily high-dose vitamin D3 in patients with RRMS receiving subcutaneous interferon β-1a.
Hupperts, R, Smolders, J, Vieth, R, Holmøy, T, Marhardt, K, Schluep, M, Killestein, J, Barkhof, F, Beelke, M, Grimaldi, LME, et al
Neurology. 2019;(20):e1906-e1916
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OBJECTIVE In the phase II, randomized, double-blind, placebo-controlled Supplementation of Vigantol Oil versus Placebo Add-on in Patients with Relapsing-Remitting Multiple Sclerosis (RRMS) Receiving Rebif Treatment (SOLAR) study (NCT01285401), we assessed the efficacy and safety of add-on vitamin D3 in patients with RRMS. METHODS Eligible patients with RRMS treated with SC interferon-β-1a (IFN-β-1a) 44 μg 3 times weekly and serum 25(OH)D levels <150 nmol/L were included. From February 15, 2011, to May 11, 2015, 229 patients were included and randomized 1:1 to receive SC IFN-β-1a plus placebo (n = 116) or SC IFN-β-1a plus oral high-dose vitamin D3 14,007 IU/d (n = 113). The revised primary outcome was the proportion of patients with no evidence of disease activity (NEDA-3) at week 48. RESULTS At 48 weeks, 36.3% of patients who received high-dose vitamin D3 had NEDA-3, without a statistically significant difference in NEDA-3 status between groups (placebo 35.3%; odds ratio 0.93; 95% confidence interval [CI] 0.53-1.63; p = 0.80). Compared with placebo, the high-dose vitamin D3 group had better MRI outcomes for combined unique active lesions (incidence rate ratio 0.68; 95% CI 0.52-0.89; p = 0.0045) and change from baseline in total volume of T2 lesions (difference in mean ranks: -0.074; p = 0.035). CONCLUSIONS SOLAR did not establish a benefit for high-dose vitamin D3 as add-on to IFN-β-1a, based on the primary outcome of NEDA-3, but findings from exploratory outcomes suggest protective effects on development of new MRI lesions in patients with RRMS. CLINICALTRIALSGOV IDENTIFIER NCT01285401. CLASSIFICATION OF EVIDENCE This study provides Class II evidence that for patients with RRMS treated with SC IFN-β-1a, 48 weeks of cholecalciferol supplementation did not promote NEDA-3 status.
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Vitamin D3 supplementation and treatment outcomes in patients with depression (D3-vit-dep).
Hansen, JP, Pareek, M, Hvolby, A, Schmedes, A, Toft, T, Dahl, E, Nielsen, CT
BMC research notes. 2019;(1):203
Abstract
OBJECTIVE To examine whether vitamin D supplementation in patients with depression would result in a reduction in Hamilton D-17 depression score (primary outcome) at 3 and 6 months compared to controls and to explore the correlations between serum vitamin D and symptoms of depression, wellbeing, systolic blood pressure, and waist circumference. In this outpatient multicentre study conducted between 2010 and 2013, patients, 18-65 years old, diagnosed with mild to severe depression were randomly assigned to receive D supplementation 70 micrograms daily or placebo on top of standard treatment. Participants, care givers and those assessing the outcomes were blinded to group assignment. RESULTS At baseline, 23 patients had a normal 25(OH)D level, 22 had insufficiency (< 25 nmol/L), and 17 had deficiency (25-50 nmol/L). No significant reduction in depression was seen after vitamin D supplementation compared to placebo at Hamilton (18.4-18.0; p = 0.73 at 12 weeks). Vitamin D supplementation did not provide a reduction in symptom score among patients with depression. Trial registration The trial was registered in the National Board of Health (EudraCT: 2011-002585-20) and in ClinicalTrials.Gov (NCT01390662).
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Vitamin D Modifies the Incidence of Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation Depending on the Vitamin D Receptor (VDR) Polymorphisms.
Carrillo-Cruz, E, García-Lozano, JR, Márquez-Malaver, FJ, Sánchez-Guijo, FM, Montero Cuadrado, I, Ferra I Coll, C, Valcárcel, D, López-Godino, O, Cuesta, M, Parody, R, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2019;(15):4616-4623
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PURPOSE The biologically active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3 (vit D), has immunoregulatory properties via binding vitamin D receptor (VDR). In a prospective trial, we previously reported a reduction in the incidence of chronic GvHD (cGvHD) among patients who received vit D after allogeneic stem cell transplantation (allo-HSCT; Clinical Trials.gov: NCT02600988). Here we analyze the role of patients and donors' VDR SNPs on the immunomodulatory effect of vit D. PATIENTS AND METHODS Patients undergoing allo-HSCT were included in a prospective phase I/II clinical trial (Alovita) in three consecutive cohorts: control (without vit D), low-dose (1,000 IU/day), and high-dose (5,000 IU/day) groups. Vit D was given from day -5 until +100 after transplant. Genotyping of four SNPs of the VDR gene, FokI, BsmI, ApaI, and TaqI, were performed using TaqMan SNP genotyping assays. RESULTS We observed a decrease in the incidence of overall cGvHD at 1 year after allo-HSCT depending on the use or not of vit D among patients with FokI CT genotype (22.5% vs 80%, P = 0.0004) and among those patients without BsmI/ApaI/TaqI ATC haplotype (22.2% vs 68.8%, P = 0.0005). In a multivariate analysis, FokI CT genotype significantly influenced the risk of cGvHD in patients treated with vit D as compared with the control group (HR 0.143, P interaction < 0.001). CONCLUSIONS Our results show that the immunomodulatory effect of vit D depends on the VDR SNPs, and patients carrying the FokI CT genotype display the highest benefit from receiving vit D after allo-HSCT.
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Clinical characteristics associated with bone mineral density improvement after 1-year alendronate/vitamin d3 or calcitriol treatment: Exploratory results from a phase 3, randomized, controlled trial on postmenopausal osteoporotic women in China.
Liao, EY, Zhang, ZL, Xia, WB, Lin, H, Cheng, Q, Wang, L, Hao, YQ, Chen, DC, Tang, H, Peng, YD, et al
Medicine. 2018;(31):e11694
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Baseline and on-treatment characteristics, including age, obesity, calcium intake, and bone turnover markers, may predict the bone mineral density (BMD) response in women with postmenopausal osteoporosis (PMO) to 1 to 2 years of antiresorptive therapy and/or vitamin D supplementation. This study aimed to explore clinical characteristics associated with 12-month BMD improvement in Chinese women with postmenopausal osteoporosis (PMO).In this post hoc analysis of a previous phase 3 multicenter, randomized controlled trial, Chinese PMO women who were treated with once weekly alendronate 70 mg/vitamin D3 5600 IU (ALN/D5600) or once daily calcitriol 0.25 mcg, and had measurements of 1-year lumbar spine BMD (LS-BMD) and on-treatment bone turnover markers (BTMs) were included in the analysis.In Chinese PMO patients on ALN/D5600, 1-year LS-BMD change was negatively correlated with age (β = -0.00084, P < .01), dietary calcium (β = -0.0017, P = .07), and procollagen type 1 N-terminal propeptide (P1NP) change at month 6 (β = -0.000469, P = .0016), but positively with body mass index (BMI) (β = 0.00128, P = .08); baseline P1NP above the median was associated with a significantly greater BMD percentage change at the lumbar spine (P = .02) and the total hip (P = .0001). In the calcitriol group, a significant 1-year LS-BMD increase was associated with BMI (β = 0.0023, P = .02), baseline P1NP (β = 0.00035, P = .0067), history of prior vertebral fracture(s) (β = 0.034, P < .0001) and baseline serum 25(OH)D level (β = -0.00083, P = .02).The presented findings from Chinese postmenopausal osteoporotic women suggested clinically meaningful baseline and on-treatment characteristics predicting BMD improvement after 1 year of ALN/D5600 treatment, which differed from calcitriol treatment with baseline identifiable associations. The study remained exploratory and further accumulation of evidence is needed.