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Effects of Vitamin D3 Supplementation and Resistance Training on 25-Hydroxyvitamin D Status and Functional Performance of Older Adults: A Randomized Placebo-Controlled Trial.
Aschauer, R, Unterberger, S, Zöhrer, PA, Draxler, A, Franzke, B, Strasser, EM, Wagner, KH, Wessner, B
Nutrients. 2021;(1)
Abstract
Vitamin D status is associated with muscle strength and performance in older adults. To examine the additive effects of vitamin D3 supplementation during resistance training, 100 seniors (65-85 years) participated in a 16-week intervention. Besides a daily dose of 400 mg of calcium, participants received either 800 IU vitamin D3 per day (VDD), 50,000 IU vitamin D3 per month (VDM) or nothing (CON). After the initial loading phase of four weeks, all groups started a 10-week resistance training program. Assessments of 25-hydroxyvitamin D (25(OH)D) status, muscle strength endurance (30-s chair stand and arm curl tests), aerobic capacity (6-min walk test) and functional mobility (gait speed and timed up and go test) were undertaken at baseline, after four weeks and at the end of the study. 25(OH)D status significantly improved in VDD and VDM, but not in CON (time x group: p = 0.021), as 15.2% of CON, 40.0% of VDD and 61.1% of VDM reached vitamin D sufficiency (>30 ng/mL; p = 0.004). Chair stand test, arm curl test, 6-min walk test, gait speed and timed up and go test improved over the whole intervention period (p < 0.05), however only chair stand and arm curl test were selectively affected by resistance training (p < 0.001). Neither muscle strength endurance, nor functional mobility or aerobic capacity were modulated by vitamin D supplementation. Therefore, the mere amelioration of 25(OH)D status of older adults does not lead to an additive effect on muscular performance during RT.
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Influence of vitamin D supplementation on the quality of life of asthma patients: Findings from ACVID randomised clinical trial.
Andújar-Espinosa, R, Aparicio-Vicente, M, Ruiz-López, FJ, Salinero-González, L
Respiratory medicine. 2021;:106484
Abstract
Published data on vitamin D and the quality of life of asthma patients are scarce and disparate. The ACVID clinical trial, published in 2020, showed the efficacy of calcifediol in improving asthma control in asthma patients with vitamin D deficiency. Data on vitamin D and quality of life measured by the Mini-AQLQ questionnaire were analysed: supplemented patients showed improved quality of life compared with a placebo group, and the initial mini-AQLQ scores were improved for both groups.
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Pilot Trial of Vitamin D3 and Calcifediol in Healthy Vitamin D Deficient Adults: Does It Change the Fecal Microbiome?
Shieh, A, Lee, SM, Lagishetty, V, Gottleib, C, Jacobs, JP, Adams, JS
The Journal of clinical endocrinology and metabolism. 2021;(12):3464-3476
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CONTEXT Experimental studies suggest that vitamin D receptor signaling may benefit the gut microbiome. In humans, whether vitamin D supplementation directly alters the gut microbiome is not well studied. OBJECTIVE To determine whether correcting vitamin D deficiency with cholecalciferol (vitamin D3, D3) or calcifediol (25-hydroxyvitamin D3, 25(OH)D3) changes gut microbiome composition. METHODS 18 adults with vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] <20 ng/mL) received 60 µg/day of D3 or 20 µg/day of 25(OH)D3 for 8 weeks. Changes in serum 25(OH)D, 1,25-diydroxyvitamin D (1,25(OH)2D), and 24,25-dihydroxyvitamin D (24,25(OH)2D) were assessed. We characterized composition of the fecal microbiota using 16S rRNA gene sequencing, and examined changes in α-diversity (Chao 1, Faith's Phylogenetic Diversity, Shannon Index), β-diversity (DEICODE), and genus-level abundances (DESeq2). RESULTS Vitamin D3 and 25(OH)D3 groups were similar. After 8 weeks of vitamin D3, mean 25(OH)D and 24,25(OH)2D increased significantly, but 1,25(OH)2D did not (25(OH)D: 17.8-30.1 ng/mL, P = .002; 24,25(OH)2D: 1.1 to 2.7 ng/mL, P =0.003; 1,25(OH)2D: 49.5-53.0 pg/mL, P = .9). After 8 weeks of 25(OH)D3, mean 25(OH)D, 24,25(OH)2D, and 1,25(OH)2D increased significantly (25(OH)D: 16.7-50.6 ng/mL, P < .0001; 24,25(OH)2D: 1.3-6.2 ng/mL, P = .0001; 1,25(OH)2D: 56.5-74.2 pg/mL, P = .05). Fecal microbial α-diversity and β-diversity did not change with D3 or 25D3 supplementation. Mean relative abundance of Firmicutes increased and mean relative abundance of Bacterioidetes decreased from baseline to 4 weeks, but returned to baseline by study completion. DESeq2 analysis did not confirm any statistically significant taxonomic changes. CONCLUSION In a small sample of healthy adults with vitamin D deficiency, restoration of vitamin D sufficiency with vitamin D3 or 25(OH)D3 did not lead to lasting changes in the fecal microbiota.
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Association of serum 25-OH vitamin D₃ with serum IgE and the Pediatric Asthma Severity Score in patients with pediatric asthma.
Mohammadzadeh, I, Darvish, S, Qujeq, D, Hajiahmadi, M, Vaghari-Tabari, M
Allergy and asthma proceedings. 2020;(2):126-133
Abstract
Background: Pediatric asthma is a prevalent disease and has a significant immunologic and inflammatory nature. In recent years, the role of vitamin D₃ in immunologic processes has been studied, and many aspects of this role have been clarified in some human diseases. Objective: The aim of this study was to evaluate the relationship among the vitamin D₃ status, Pediatric Asthma Severity Score (PASS), and inflammatory indicators of pediatric asthma. Methods: Among all of the pediatric patients with asthma and with asthma exacerbation, 100 patients were randomly enrolled in the study and subdivided into three groups according to serum levels of 25-OH vitamin D₃. The control group consisted of 100 sex- and age-matched healthy subjects. Asthma exacerbation severity was evaluated based on the PASS before starting the medical care. The count of the white blood cells, eosinophil count, and serum levels of total immunoglobulin E (IgE) plus 25-OH vitamin D₃ were measured in all the subjects. The obtained data were then compared via proper statistical tests. A p value of <0.05 was considered as statistically significant. Results: The median level of serum IgE was increased in patients with vitamin D₃ deficiency compared with other groups. There was a significant inverse correlation between serum levels of 25-OH vitamin D₃ and IgE in pediatric patients with asthma (r = -0.483, p = 0.001). Furthermore, the serum levels of 25-OH vitamin D₃ also significantly inversely correlated with the PASS (r = -0.285, p = 0.004). Conclusion: Vitamin D₃ deficiency is associated with exacerbation severity and serum IgE levels in patients with pediatric asthma; hence, it can have an important role in pediatric asthma pathogenesis, possibly through IgE.
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Intake of 25-Hydroxyvitamin D3 May Reduce the Severity of Upper Respiratory Tract Infection: Post hoc Analysis of a Randomized, Double-Blind, Placebo-Controlled, Parallel Group Comparison Study.
Shimizu, Y, Ito, Y, Uotsu, N, Yui, K
Nutrients. 2020;(12)
Abstract
To evaluate the effects of 25-hydroxyvitamin D3 (25OHD) on symptoms at the onset of the upper respiratory tract infection (URTI) in subjects with insufficient or deficient serum 25-hydroxyvitamin D levels, we conducted a post hoc analysis of data from a randomized, placebo-controlled study; the subjects received 10 μg of 25OHD per day or a placebo for 16 weeks. The Wisconsin Upper Respiratory Symptom Survey-21 was used to determine URTI. The study endpoints included WURSS-21 scores, number of URTI events, and proportion of medication (antibiotics, antipyretic analgesics) usage. We found that the physical symptom scores for "Runny nose," "Sneezing," and "Head congestion" were significantly lower in the 25OHD group than in the placebo group; for all items except "Breathe easily, "the quality of life" scores were significantly improved in the 25OHD group. There was no significant difference in the number of URTI events or the proportion of medication use between the groups. Collectively, the findings of this study indicate that a sufficient 25OHD intake can reduce physical symptoms at the onset of upper respiratory tract infection, particularly nasal symptoms, and may improve the quality of life at the time of onset.
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"Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study".
Entrenas Castillo, M, Entrenas Costa, LM, Vaquero Barrios, JM, Alcalá Díaz, JF, López Miranda, J, Bouillon, R, Quesada Gomez, JM
The Journal of steroid biochemistry and molecular biology. 2020;:105751
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OBJECTIVE The vitamin D endocrine system may have a variety of actions on cells and tissues involved in COVID-19 progression especially by decreasing the Acute Respiratory Distress Syndrome. Calcifediol can rapidly increase serum 25OHD concentration. We therefore evaluated the effect of calcifediol treatment, on Intensive Care Unit Admission and Mortality rate among Spanish patients hospitalized for COVID-19. DESIGN Parallel pilot randomized open label, double-masked clinical trial. SETTING University hospital setting (Reina Sofia University Hospital, Córdoba Spain.) PARTICIPANTS 76 consecutive patients hospitalized with COVID-19 infection, clinical picture of acute respiratory infection, confirmed by a radiographic pattern of viral pneumonia and by a positive SARS-CoV-2 PCR with CURB65 severity scale (recommending hospital admission in case of total score > 1). PROCEDURES All hospitalized patients received as best available therapy the same standard care, (per hospital protocol), of a combination of hydroxychloroquine (400 mg every 12 h on the first day, and 200 mg every 12 h for the following 5 days), azithromycin (500 mg orally for 5 days. Eligible patients were allocated at a 2 calcifediol:1 no calcifediol ratio through electronic randomization on the day of admission to take oral calcifediol (0.532 mg), or not. Patients in the calcifediol treatment group continued with oral calcifediol (0.266 mg) on day 3 and 7, and then weekly until discharge or ICU admission. Outcomes of effectiveness included rate of ICU admission and deaths. RESULTS Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50 %) p value X2 Fischer test p < 0.001. Univariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment versus without Calcifediol treatment: 0.02 (95 %CI 0.002-0.17). Multivariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment vs Without Calcifediol treatment ICU (adjusting by Hypertension and T2DM): 0.03 (95 %CI: 0.003-0.25). Of the patients treated with calcifediol, none died, and all were discharged, without complications. The 13 patients not treated with calcifediol, who were not admitted to the ICU, were discharged. Of the 13 patients admitted to the ICU, two died and the remaining 11 were discharged. CONCLUSION Our pilot study demonstrated that administration of a high dose of Calcifediol or 25-hydroxyvitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalization due to proven COVID-19. Calcifediol seems to be able to reduce severity of the disease, but larger trials with groups properly matched will be required to show a definitive answer.
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Supplemental 25-Hydroxycholecalciferol Is More Effective than Cholecalciferol in Raising Serum 25-Hydroxyvitamin D Concentrations in Older Adults.
Graeff-Armas, LA, Bendik, I, Kunz, I, Schoop, R, Hull, S, Beck, M
The Journal of nutrition. 2020;(1):73-81
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BACKGROUND There are few studies directly comparing the pharmacokinetics of 25-hydroxycholecalciferol [25(OH)D3] to cholecalciferol (D3). OBJECTIVES The primary objectives were to compare the effectiveness of D3 and 25(OH)D3 in raising 25-hydroxyvitamin D [25(OH)D] serum concentrations and achieving steady state. METHODS This was a randomized, double-blind, active comparator trial of 91 participants (53 females, 38 males), aged 63.3 ± 7.9 y. 25(OH)D3 (10, 15, and 20 µg) and D3 (20 µg) were dosed daily for 6 mo followed by 6 mo of washout. Frequent measurements of serum 25(OH)D were performed. Pharmacokinetic parameters were fitted for each individual and the treatment average was modeled with linear regression using the individual baseline level, sex, and gender as covariates. RESULTS Mean baseline 25(OH)D was similar in all groups (47.1-49.5 nmol/L). Increases in 25(OH)D to steady state were higher in the 25(OH)D3 groups than in the D3 group [least squares (LS) means (95% CI): 50.1 (43.3-58.0), 72.5 (64.3-81.7), 97.4 (86.6-109.6) nmol/L in 10, 15, and 20 µg/d and 38.7 (33.1-45.2) nmol/L in the D3 group; P = 0.0173, P < 0.0001, P < 0.0001]. The rate to reach steady state was similar in all groups, but the time to reach 25(OH)D concentrations of 75 nmol/L was faster in the higher-dosed 25(OH)D3 groups than in the D3 group (7 and 10 d compared with 40 d, P < 0.0001 and P < 0.0001 for 15 and 20 µg/d). The rate of elimination was 59-109% higher in the 25(OH)D3 groups than in the D3 group. The area under the curve (AUC)/µg dose demonstrated that 25(OH)D3 was 3 times as effective as D3 at raising 25(OH)D concentrations. CONCLUSIONS 25(OH)D3 is ∼3 times as effective as D3 at raising 25(OH)D concentrations. Once supplementation is discontinued, the elimination rate of 25(OH)D3 is faster than D3. This trial was registered at clinicaltrials.gov as NCT02333682.
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Influence of genetic variation in the vitamin D pathway on plasma 25-hydroxyvitamin D3 levels and survival among patients with metastatic colorectal cancer.
Yuan, C, Renfro, L, Ambadwar, PB, Ou, FS, McLeod, HL, Innocenti, F, Meyerhardt, JA, Wolpin, BM, Goldberg, RM, Grothey, A, et al
Cancer causes & control : CCC. 2019;(7):757-765
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PURPOSE The relationships of genetic variation in the vitamin D pathway with circulating 25-hydroxyvitamin D3 [25(OH)D] levels and survival remain largely unknown for patients with metastatic colorectal cancer (mCRC). METHODS Among 535 patients participating in a randomized trial of chemotherapy for mCRC, we prospectively measured baseline plasma 25(OH)D and examined 124 tagging single-nucleotide polymorphisms (SNPs) within seven genes in the vitamin D pathway, including five SNPs associated with circulating 25(OH)D levels in previous genome-wide association studies (GWAS). We evaluated whether these SNPs were associated with plasma 25(OH)D levels and patient outcome (overall survival, time to progression, and tumor response), using linear, logistic, and Cox proportional hazards regression. RESULTS We observed a significant association between 25(OH)D levels and an additive genetic risk score determined by the five GWAS-identified SNPs (p = 0.0009). We did not observe any direct association between 25(OH)D-associated SNPs, individually or as a genetic risk score, and patient outcome. However, we found a significant interaction between 25(OH)D levels and rs12785878 genotype in DHCR7 on overall survival (pinteraction = 0.02). CONCLUSION Germline genetic variation in the vitamin D pathway informs baseline 25(OH)D levels among patients with mCRC. The association between 25(OH)D levels and overall survival may vary by DHCR7 genotype. ClinicalTrials.gov Identifier: NCT00003594 ( https://clinicaltrials.gov/ct2/show/NCT00003594 ).
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Rationale for Raising Current Clinical Practice Guideline Target for Serum 25-Hydroxyvitamin D in Chronic Kidney Disease.
Strugnell, SA, Sprague, SM, Ashfaq, A, Petkovich, M, Bishop, CW
American journal of nephrology. 2019;(4):284-293
Abstract
BACKGROUND Vitamin D repletion is recommended for secondary hyperparathyroidism (SHPT) and associated vitamin D insufficiency (VDI) in chronic kidney disease (CKD), but optimal levels of serum total 25-hydroxyvitamin D remain undefined. Clinical practice guidelines target sufficiency, whereas recent data indicate that higher levels are required to control the elevation of intact parathyroid hormone (iPTH) as CKD advances. This secondary analysis of 2 randomized controlled trials seeks to identify the minimum level of mean serum 25-hydroxyvitamin D required to control SHPT arising from VDI in stage 3 or 4 CKD. METHODS Adult subjects (n = 429) with SHPT, VDI, and stage 3 or 4 CKD were stratified by stage and treated daily with either extended-release calcifediol (ERC) or placebo in 2 identical, parallel, randomized, double-blind studies. After treatment for 26 weeks, all subjects were ranked by the level of serum total 25-hydroxyvitamin D and divided into quintiles in order to examine the relationships between the degree of vitamin D repletion and the associated changes in plasma iPTH, serum bone turnover markers, calcium, phosphorus, intact fibroblast growth factor 23 (FGF23) and vitamin D metabolites, estimated glomerular filtration rate (eGFR), and urine calcium:creatinine (Ca:Cr) ratio. RESULTS Progressive increases in serum 1,25-dihydroxyvitamin D and reductions in plasma iPTH and serum bone turnover markers were observed as mean posttreatment serum 25-hydroxyvitamin D rose from 13.9 ng/mL (in Quintile 1) to 92.5 ng/mL (in Quintile 5), irrespective of CKD stage. Mean serum calcium, phosphorus and FGF23, eGFR, and urine Ca:Cr ratio (collectively "safety parameters") did not significantly change from Quintile 1. Suppression of iPTH and bone turnover markers was not observed until serum 25-hydroxyvitamin D rose to at least 50.8 ng/mL (Quintile 3). CONCLUSION ERC therapy produced exposure-dependent reductions in plasma iPTH and bone turnover markers only when mean serum total 25-hydroxyvitamin D reached at least 50.8 ng/mL, indicating that current targets for vitamin D repletion therapy in CKD are too low. Gradual elevation of mean serum 25-hydroxyvitamin D to 92.5 ng/mL was not associated with significant adverse changes in safety parameters.
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Effects of Weekly Supplementation of Cholecalciferol and Calcifediol Among the Oldest-Old People: Findings From a Randomized Pragmatic Clinical Trial.
Ruggiero, C, Baroni, M, Bini, V, Brozzetti, A, Parretti, L, Zengarini, E, Lapenna, M, Antinolfi, P, Falorni, A, Mecocci, P, et al
Nutrients. 2019;(11)
Abstract
Vitamin D inadequacy is pervasive in the oldest-old. Many vitamin D metabolites are available for supplementation, their effects on the recovery of adequate serum levels remain unknown. We investigate the effects of supplementation with cholecalciferol (D3) and calcifediol (25D3) on serum levels of 25(OH)D, 1-25(OH)D, bone and inflammatory markers, ultimately identifying clinical predictors of successful treatment. Sixty-seven oldest-old individuals were randomized to weekly administration of 150 mcg of 25D3 or D3, from hospital admission to 7 months after discharge. Supplementation of 25D3 and D3 were associated with increasing serum levels of 25(OH)D (p < 0.001) and 1-25(OH)D (p = 0.01). Participants on 25D3 experienced a steeper rise than those on D3 (group*time interaction p = 0.01), after adjustment for intact parathyroid hormone (iPTH) levels the differences disappeared (intervention*iPTH interaction p = 0.04). Vitamin D supplementation was associated with a decreasing trend of iPTH and C-reactive protein (CRP) (p < 0.001). Polypharmacy and low handgrip strength were predictors of failure of intervention, independent of vitamin D metabolites. In conclusion, D3 and 25D3 supplementation significantly increase vitamin D serum levels in the oldest-old individuals, with a tendency of 25D3 to show a faster recovery of acceptable iPTH levels than D3. Polypharmacy and low muscle strength weaken the recovery of adequate vitamin D serum levels.