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1.
The Effect of Vitamin D Supplementation on its Metabolism and the Vitamin D Metabolite Ratio.
Francic, V, Ursem, SR, Dirks, NF, Keppel, MH, Theiler-Schwetz, V, Trummer, C, Pandis, M, Borzan, V, Grübler, MR, Verheyen, ND, et al
Nutrients. 2019;(10)
Abstract
25-hydroxyvitamin D (25(OH)D) is commonly measured to assess vitamin D status. Other vitamin D metabolites such as 24,25-dihydroxyvitamin D (24,25(OH)2D) provide additional insights into vitamin D status or metabolism. Earlier studies suggested that the vitamin D metabolite ratio (VMR), calculated as 24,25(OH)2D/25(OH)D, could predict the 25(OH)D increase after vitamin D supplementation. However, the evidence for this additional value is inconclusive. Therefore, our aim was to assess whether the increase in 25(OH)D after supplementation was predicted by the VMR better than baseline 25(OH)D. Plasma samples of 106 individuals (25(OH)D < 75 nmol/L) with hypertension who completed the Styrian Vitamin D Hypertension Trial (NC.T.02136771) were analyzed. Participants received vitamin D (2800 IU daily) or placebo for 8 weeks. The treatment effect (ANCOVA) for 25(OH)D3, 24,25(OH)2D3 and the VMR was 32 nmol/L, 3.3 nmol/L and 0.015 (all p < 0.001), respectively. Baseline 25(OH)D3 and 24,25(OH)2D3 predicted the change in 25(OH)D3 with comparable strength and magnitude. Correlation and regression analysis showed that the VMR did not predict the change in 25(OH)D3. Therefore, our data do not support routine measurement of 24,25(OH)2D3 in order to individually optimize the dosage of vitamin D supplementation. Our data also suggest that activity of 24-hydroxylase increases after vitamin D supplementation.
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2.
Self-Directed Oral Vitamin D Supplementation in Professional Ballet Dancers: A Randomized Controlled Trial Pilot Study.
Rowan, FE, Benjamin-Laing, H, Kennedy, A, De Medici, A, Beasley, I, Haddad, FS
Journal of dance medicine & science : official publication of the International Association for Dance Medicine & Science. 2019;(3):91-96
Abstract
Inadequate levels of vitamin D may lead to poor performance in professional dancers. Therefore, dietary supplementation may be essential in this population. This longitudinal pilot study to a randomized controlled trial assessed dancer compliance with self-directed oral vitamin D supplementation. Seventy-one dancers, 41 females and 30 males with a mean age of 31.1 years, were recruited from The Royal Ballet, London. Baseline serum 25(OH)D levels were measured and dancers were interviewed, examined, and provided with oral supplements for the winter period, November 2011 to March 2012. Dancers with normal serum 25(OH)D levels were provided with maintenance supplements (1,000 IU/ day) and those with insufficient or deficient serum 25(OH)D levels were given a loading dose of 60,000 IU weekly for 2 and 6 weeks, respectively. Serum 25(OH) D levels were measured at 1 and 2 years and dancers were sampled for compliance with instructions. Mean compliance during loading and maintenance was 86% and 50%, respectively. Mean serum 25(OH)D levels at start and end of the study period were 79.3 ± 31.6 nmol/L and 78.68 ± 19.8 nmol/L, respectively. Only one-third of dancers with insufficient (N = 5) and deficient (N = 5) serum vitamin D levels improved to normal values. It is concluded that professional ballet dancers demonstrate good compliance with self-directed loading doses of vitamin D supplementation but poor compliance with maintenance doses. Poor maintenance compliance may have accounted for the low rates of serum vitamin D level improvement among dancers with insufficient or deficient levels.
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3.
Vitamin D: A Micronutrient Regulating Genes.
Carlberg, C
Current pharmaceutical design. 2019;(15):1740-1746
Abstract
BACKGROUND At sufficient sun exposure, humans can synthesize vitamin D3 endogenously in their skin, but today's lifestyle makes the secosteroid a true vitamin that needs to be taken up by diet or supplementation with pills. The vitamin D3 metabolite 1α,25-dihydroxyvitamin D3 acts as a nuclear hormone activating the transcription factor vitamin D receptor (VDR). METHODS This review discusses the biological effects of micronutrient vitamin D ranging from calcium homeostasis and bone formation to the modulation of innate and adaptive immunity. RESULTS Since normal human diet is sufficient in vitamin D, the need for efficient vitamin D3 synthesis in the skin acts as an evolutionary driver for its lightening during the migration out of Africa towards North. Via activating the VDR, vitamin D has direct effects on the epigenome and the expression of more than 1000 genes in most human tissues and cell types. CONCLUSIONS The pleiotropic action of vitamin D in health and disease prevention is explained through complex gene regulatory events of the transcription factor VDR.
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4.
Effect of 16-weeks vitamin D replacement on calcium-phosphate homeostasis in overweight and obese adults.
Mesinovic, J, Mousa, A, Wilson, K, Scragg, R, Plebanski, M, de Courten, M, Scott, D, Naderpoor, N, de Courten, B
The Journal of steroid biochemistry and molecular biology. 2019;:169-175
Abstract
This randomised placebo-controlled trial aimed to determine the effect of 16-weeks cholecalciferol supplementation on calcium-phosphate homeostasis and bone mineral density (BMD) in overweight and obese adults. Fifty-four vitamin D-deficient (25OHD<50 nmol/L), overweight and obese adults (mean age 32 ± 8.5 years) were included in the trial. Participants were randomly assigned to receive either a bolus oral dose of 100,000 IU cholecalciferol followed by 4000 IU cholecalciferol/d or a matching placebo for 16 weeks. Before and after the intervention, serum calcium, phosphate, 25-hydroxyvitamin D [25(OH)D], intact parathyroid hormone (iPTH) and C-terminal plasma fibroblast growth factor-23 (cFGF-23) concentrations were measured. Whole-body BMD was assessed using dual-energy X-ray absorptiometry (DXA) and diet and sun exposure were assessed using self-administered questionnaires. There were no significant differences in baseline characteristics between the vitamin D and placebo group. After 16-weeks of vitamin D supplementation, mean changes in 25(OH)D concentration were higher in the vitamin D group (57 nmol/L 95% CI 49, 65) compared with placebo (2 nmol/L 95% CI -4, 8), P < 0.001. Additionally, iPTH concentrations declined in the vitamin D group (-1.19 pmol/L 95% CI -1.9, -0.47) compared with placebo (0.14 pmol/L 95% CI -0.49, 0.77), P = 0.006. There were no significant differences in calcium, phosphate, iPTH and cFGF-23 concentrations and whole-body BMD between vitamin D and placebo at follow-up. Inverse correlations were observed between mean change in serum iPTH and cFGF-23 in the vitamin D group only (r=-0.41, P = 0.029). In individuals with greater vitamin D deficiency at baseline (25(OH)D < 30 nmol/L), there was a significant increase in mean whole-body BMD (0.01 g/cm2, 95% CI 0.001, 0.025) however, the mean change in BMD was not different between vitamin D and placebo groups in this sub-group analysis. We conclude that cholecalciferol supplementation for 16 weeks increases serum 25(OH)D concentrations and reduces iPTH concentrations in overweight and obese, but otherwise healthy adults with vitamin D deficiency, and has no effect on calcium, phosphate and iFGF-23 concentrations and whole-body BMD.
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5.
Vitamin D in the prevention of exacerbations of asthma in preschoolers (DIVA): protocol for a multicentre randomised placebo-controlled triple-blind trial.
Jensen, ME, Ducharme, FM, Alos, N, Mailhot, G, Mâsse, B, White, JH, Sadatsafavi, M, Khamessan, A, Tse, SM, Alizadehfar, R, et al
BMJ open. 2019;(12):e033075
Abstract
INTRODUCTION Preschoolers have the highest rate of emergency visits and hospitalisations for asthma exacerbations of all age groups, with most triggered by upper respiratory tract infections (URTIs) and occurring in the fall or winter. Vitamin D insufficiency is highly prevalent in Canadian preschoolers with recurrent asthma exacerbations, particularly in winter. It is associated with more URTIs and, in patients with asthma, more oral corticosteroid (OCS) use. Although evidence suggests that vitamin D supplements significantly decrease URTIs and asthma exacerbations requiring OCS, there is insufficient data in preschoolers. This study aims to determine the impact of vitamin D3 supplementation on exacerbations requiring OCS, in preschoolers with recurrent URTI-induced asthma exacerbations. METHODS AND ANALYSIS This is a phase III, randomised, triple-blind, placebo-controlled, parallel-group multicentre trial of vitamin D3 supplementation in children aged 1-5 years, with asthma triggered by URTIs and a recent history of frequent URTIs and OCS use. Children (n=865) will be recruited in the fall and early winter and followed for 7 months. They will be randomised to either the (1) intervention: two oral boluses of 100 000 international unit (IU) vitamin D3 (3.5 months apart) with 400 IU vitamin D3 daily; or (2) control: identical placebo boluses with daily placebo. The primary outcome is the number of exacerbations requiring OCS per child, documented by medical and pharmacy records. Secondary outcomes include number of laboratory-confirmed viral URTIs, exacerbation duration and severity, parent functional status, healthcare use, treatment deintensification, cost and safety. ETHICS AND DISSEMINATION This study has received ethical approval from all sites. Results will be disseminated via international conferences and manuscripts targeting paediatricians and respirologists, and to families of asthmatic children via our Quebec parents-partners outreach programme. If proven effective, findings may markedly influence the management of URTI-induced asthma in high-morbidity preschoolers and could be directly implemented into practice with an update to clinical guidelines. TRIAL REGISTRATION NUMBER NCT03365687.
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6.
Efficacy of risedronate with cholecalciferol on bone mineral density in Korean patients with osteoporosis.
Park, SY, Kang, MI, Park, HM, Rhee, Y, Moon, SH, Yoon, HK, Koh, JM, Chang, JS, Kim, IJ, Won, YY, et al
Archives of osteoporosis. 2019;(1):3
Abstract
UNLABELLED The efficacy of once-weekly risedronate with and without cholecalciferol in bone mineral density (BMD) in Korean patients with osteoporosis was compared. After 12 months, both spine and hip BMD increased significantly in both groups, but there was no significant difference between two groups. INTRODUCTION This study investigated the efficacy and safety of once-weekly risedronate with and without cholecalciferol in BMD in Korean patients with osteoporosis. METHODS This was a prospective, 12-month, randomized, open-labeled, actively controlled trial involving 41 hospitals. A total of 841 subjects with osteoporosis were randomized to once-weekly risedronate (35 mg) and cholecalciferol (5600 IU) in a single pill (RSD+, n = 642) or once-weekly risedronate (35 mg) alone (RSD, n = 199). BMD was measured via dual-energy X-ray absorptiometry at the lumbar spine and hip, and the serum levels of 25-hydroxy vitamin D (25(OH) D), parathyroid hormone (PTH), and alkaline phosphatase (ALP) were assayed at baseline and after 12 months of treatment. RESULTS After 12 months, the lumbar spine, femoral neck, and total hip BMD increased significantly in both groups; there was no significant difference between two groups. Women in the RSD+ group exhibited significantly increased lumbar spine BMD, and subjects with previous fracture history in the RSD+ group had significantly increased total hip BMD compared with the RSD group. The serum 25(OH) D level increased significantly in the RSD+ group. The serum PTH level decreased in the RSD+ group but increased in the RSD group. The serum ALP level significantly decreased in both groups; there was no significant difference between two groups. CONCLUSIONS A once-weekly pill containing risedronate and cholecalciferol had the equivalent antiresorptive efficacy on BMD compared with risedronate alone and improved 25(OH) D serum levels after 12 months of treatment without significant adverse events in Korean patients with osteoporosis.
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7.
Genetic Variation of the Vitamin D Binding Protein Affects Vitamin D Status and Response to Supplementation in Infants.
Enlund-Cerullo, M, Koljonen, L, Holmlund-Suila, E, Hauta-Alus, H, Rosendahl, J, Valkama, S, Helve, O, Hytinantti, T, Viljakainen, H, Andersson, S, et al
The Journal of clinical endocrinology and metabolism. 2019;(11):5483-5498
Abstract
CONTEXT Single nucleotide polymorphisms (SNPs) of the vitamin D binding protein encoding the GC (group component) gene affect 25-hydroxyvitamin D (25OHD) concentrations, but their influence on vitamin D status and response to vitamin D supplementation in infants is unknown. OBJECTIVE To study GC genotype-related differences in 25OHD concentrations and the response to supplementation during a vitamin D intervention study in infants. DESIGN In this randomized controlled trial, healthy term infants received vitamin D3 (10 or 30 μg/d) from 2 weeks to 24 months of age. GC SNPs rs2282679, rs4588, rs7041, and rs1155563 were genotyped. rs4588/7041 diplotype and haplotypes of rs2282679, rs4588, and rs7041 (Haplo3SNP) and of all four SNPs (Haplo4SNP) were determined. MAIN OUTCOME MEASURES 25OHD measured in cord blood at birth and at 12 and 24 months during intervention. RESULTS A total of 913 infants were included. Minor allele homozygosity of all studied GC SNPs, their combined haplotypes, and rs4588/rs7041 diplotype 2/2 were associated with lower 25OHD concentrations at all time points in one or both intervention groups [analysis of covariance (ANCOVA) P < 0.043], with the exception of rs7041, which did not affect 25OHD at birth. In the high-dose supplementation group receiving 30 μg/d vitamin D3, but not in those receiving 10 µg/d, genotype of rs2282679, rs4588, and rs7041; diplotype; and Haplo3SNP significantly affected intervention response (repeated measurement ANCOVA Pinteraction < 0.019). Minor allele homozygotes had lower 25OHD concentrations and smaller increases in 25OHD throughout the intervention. CONCLUSIONS In infants, vitamin D binding protein genotype affects 25OHD concentration and efficiency of high-dose vitamin D3 supplementation.
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8.
Effects of cholecalciferol supplementation on inflammatory markers and muscle damage indices of soccer players after a simulated soccer match.
Parsaie, N, Ghavamzadeh, S, Cheraghi, M
Nutrition (Burbank, Los Angeles County, Calif.). 2019;:37-43
Abstract
OBJECTIVES Soccer-induced muscle damage and inflammation lead to a reduction in athletic performance. The aim of this study was to determine whether supplementation with cholecalciferol would reduce inflammation and muscle damage in soccer players after a simulated soccer match. METHODS Twenty-two soccer players (median age 27 y, interquartile range 5 y) were divided randomly into two groups, as follows: a cholecalciferol group (n = 11) and a placebo group (n = 11). Cholecalciferol supplements (50 000 IU/wk) or placebos were administered to the groups by an independent co-worker. After 8 wk, the athletes participated in a simulated soccer match, and perceived exertion and heart rates were measured during the trial. Blood samples were obtained presupplementation, postsupplementation, immediately after, and 2- and 24-h postexercise for measurement of lactate dehydrogenase, creatine phosphokinase, C-reactive protein (CRP), and interleukin (IL)-6. RESULTS The intervention group demonstrated a significant increase in serum 25-hydroxyvitamin D levels (53.93, 10.68 ng/mL, P < 0.0001), which is the best indicator of vitamin D levels in the body, with no change in the circulating markers of muscle damage and CRP (P ˃ 0.05) but showed increased IL-6 (P = 0.034). In addition, the ratings of perceived exertion and heart rates were not altered by vitamin D compared with placebo ingestion (P = 0.155 versus P = 0.261; P = 0.600 versus P = 0.983). CONCLUSION The study showed that 50 000 IU/wk of cholecalciferol supplementation for 8 wk increased the 25-hydroxyvitamin D levels, with no effect on muscle damage indices or CRP. However, The IL-6 concentration was generally higher in the intervention group.
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9.
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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10.
Effect of vitamin D3 supplementation in pregnancy on risk of pre-eclampsia - Randomized controlled trial.
Ali, AM, Alobaid, A, Malhis, TN, Khattab, AF
Clinical nutrition (Edinburgh, Scotland). 2019;(2):557-563
Abstract
BACKGROUND Vitamin D plays pivotal role in decidualization and implantation of the placenta. Recent researches have shown that low level of vitamin D3 "25-hydroxyvitamin D (25[OH]D)" in serum is a risk factor for pre-eclampsia. Latest evidence supports role of vitamin D3 deficiency treatment in reducing the risk of pre-eclampsia. The aim of this study is to determine the effect of antenatal supplementation of vitamin D3 on the risk of pre-eclampsia and to explore the dose effect in attaining the vitamin D3 normal level. METHOD An open labelled randomized controlled study was conducted on 179 pregnant women presenting in King Fahad Medical City antenatal clinic from Oct 2012-Oct 2015. Patients with age less than 20 years or more than 40 years, pregnancy with fetal anomalies, history of hypertension, pre-eclampsia, recurrent miscarriage, chronic renal or hepatic disease and malignancy were excluded from the study. Serum 25[OH]D was analysed during the first trimester (between 6 and 12 weeks of pregnancy). Patients with vitamin D3 deficiency (serum levels <25 nmol/L) were included in the study and randomized for vitamin D3 supplementation 400 IU (Group 1) versus 4000 IU (Group 2). Both groups were compared for the prevalence of pre-eclampsia and dose effect on vitamin D level. RESULTS Of 179 gravidae enrolled, 164 completed the trial. Mean maternal 25[OH]D was significantly increased in group 2 from 16.3 ± 5 nmol/mL to 72.3 ± 30.9 nmol/mL compared with group 1 from 17.5 ± 6.7 nmol/mL to 35.3 ± 20.7 nmol/mL (p > 0.0001). The relative risk reduction (RRR) for attaining ≥75 nmol/L before delivery was significantly higher (RRR 93.2 [CI 79-98] when treated with 4000 IU. The total incidence of pre-eclampsia in the study population was 4.3%. In comparison to group 1, the group 2 reported fewer pre-eclampsia events during the study period (8.6% versus 1.2%; p < 0.05). The total number of IUGRs was lesser in the group 2 (9.6%) versus group 1 (22.2%); p = 0.027. However, other obstetric outcomes were comparable between both groups. CONCLUSION Vitamin D supplementation in the deficient group reduces the risk of pre-eclampsia and IUGR in a dose dependant manner. However larger clinical trials are essential to investigate optimum dosage of vitamin D3 in this group.