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1.
Vitamin D deficiency and treatment versus risk of infection in end-stage renal disease patients under dialysis: a systematic review and meta-analysis.
Su, G, Liu, Z, Qin, X, Hong, X, Liu, X, Wen, Z, Lindholm, B, Carrero, JJ, Johnson, DW, Brusselaers, N, et al
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2019;(1):146-156
Abstract
BACKGROUND Infections are common and can be fatal in patients undergoing long-term dialysis. Recent studies have shown conflicting evidence associating infection with vitamin D status or use of vitamin D and have not been systematically reviewed in this population. METHODS We searched PubMed, Web of Science, Cochrane Library, Embase and three Chinese databases from inception until December 2017 for interventional [non-randomized or randomized controlled trials (RCTs)], cohort and case-control studies on levels of serum 25-hydroxyvitamin D [25(OH)D] or use of vitamin D [supplemental nutritional vitamin D or vitamin D receptor activator (VDRA)] and infection (any infection, infection-required hospitalization or infection-related death or composite) in long-term dialysis patients. We conducted a meta-analysis on the relative risk (RR) of infection and level of 25(OH)D or use of vitamin D. RESULTS Of 2440 reports identified, 17 studies met inclusion criteria, all with moderate quality, with 6 cohort studies evaluating 25(OH)D serum concentrations (n = 5714) and 11 (2 RCTs and 9 observational studies) evaluating the use of vitamin D (n = 92 309). The risk of composite infection was 39% lower {relative risk [RR] 0.61 [95% confidence interval (CI) 0.41-0.89]} in the subjects with high or normal levels of 25(OH)D than in those with low levels. When compared with those who did not use vitamin D, the pooled adjusted risk for composite infection was 41% lower in those who used vitamin D [RR 0.59 (95% CI 0.43-0.81)]. CONCLUSIONS High or normal serum levels of 25(OH)D and the use of vitamin D, particularly VDRA, were each associated with a lower risk of composite infection in long-term dialysis patients.
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2.
Vitamin D supplementation and musculoskeletal health.
Bouillon, R, Lips, P, Bilezikian, JP
The lancet. Diabetes & endocrinology. 2019;(2):85-86
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3.
Native vitamin D in pre-dialysis chronic kidney disease.
Cardoso, MP, Pereira, LAL
Nefrologia. 2019;(1):18-28
Abstract
Chronic kidney disease patients have a high prevalence of vitamin D insufficiency/deficiency. Vitamin D deficiency has been associated with a variety of bone, metabolic and cardiovascular disorders. However, the role of native vitamin D supplementation (ergocalciferol, cholecalciferol or calcifediol) remains unclear in chronic kidney disease (CKD), particularly in the pre-dialytic phase. Several international guidelines have been developed on CKD-Mineral and Bone Disorder, but the optimal strategy for native vitamin D supplementation and its clinical benefit remains a subject of debate in the scientific community. This paper aims to review the available literature, including randomized clinical trials that evaluated the effects of native vitamin D supplementation on pre-dialysis CKD on biochemical and clinically relevant outcomes.
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4.
Vitamin D in the ICU: More sun for critically ill adult patients?
Langlois, PL, D'Aragon, F, Manzanares, W
Nutrition (Burbank, Los Angeles County, Calif.). 2019;:173-178
Abstract
Critical illness in patients is characterized by systemic inflammation and oxidative stress. Vitamin D has a myriad of biological functions relevant to this population, including immunomodulation by the alteration of cytokine production and nuclear factor loop amplification. Low serum levels have consistently been found in observational studies conducted on critically ill patients, but the causality with mortality and worse outcomes has not been confirmed. The current focus is on interventional trials, whereas the pharmacokinetic profile of vitamin D administration remains sparse and the optimal strategy has not been confirmed. So far, high-dose oral or enteral supplementation is the most studied strategy. The largest randomized controlled trial published so far, the VITdAL-ICU (Effect of High-dose Vitamin D3 on Hospital Length of Stay in Critically Ill Patients with Vitamin D Deficiency) trial, showed no benefits on mortality in its primary analysis. However, secondary analysis suggested improvement in those patients with severe deficiency (i.e., 25-dihydroxyvitaminD <12 ng/mL). Smaller trials investigated intramuscular and intravenous administration and found interesting intermediate biochemical findings, including increased cathelicidins, but were not powered to investigate relevant clinical outcomes in the critically ill. The latest meta-analysis, which was recently published, does not support benefits of vitamin D supplementation in the heterogeneous population of critically ill patients. The European guidelines, published in the last year, suggest supplementing severely deficient patients with levels <12.5 ng/mL within the first week after ICU admission. However, other societies do not support such supplementation in their older recommendations. Large trials are currently recruiting ICU patients and could elucidate potential clinical benefits of vitamin D therapy in the critically ill.
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5.
A narrative review on effects of vitamin D on main risk factors and severity of Non-Alcoholic Fatty Liver Disease.
Sangouni, AA, Ghavamzadeh, S, Jamalzehi, A
Diabetes & metabolic syndrome. 2019;(3):2260-2265
Abstract
The global prevalence of Non-alcoholic fatty liver disease (NAFLD) is increasing rapidly. Many studies have been conducted on the treatment of NAFLD; nevertheless, there is still no approved drug treatment for this disease. Although the pathogenesis of NAFLD is not fully understood, but inflammation, insulin resistance, oxidative stress, obesity and dyslipidemia are among the main causes. Epidemiological studies have shown that hypovitaminosis D is associated with these factors causing NAFLD. In addition, rate of Vitamin D deficiency has been shown to be directly related to the severity of NAFLD. Accordingly, it is believed that vitamin D may help to treatment of NAFLD by improving the above-mentioned risk factors. The purpose of this review is to survey the recent advances in the field of Vitamin D efficacy on risk factors and the severity of NAFLD based on existing evidence, especially the clinical efficiency of vitamin D supplementation in patients with NAFLD.
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6.
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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7.
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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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.
Circulating Vitamin D and Colorectal Cancer Risk: An International Pooling Project of 17 Cohorts.
McCullough, ML, Zoltick, ES, Weinstein, SJ, Fedirko, V, Wang, M, Cook, NR, Eliassen, AH, Zeleniuch-Jacquotte, A, Agnoli, C, Albanes, D, et al
Journal of the National Cancer Institute. 2019;(2):158-169
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Abstract
BACKGROUND Experimental and epidemiological studies suggest a protective role for vitamin D in colorectal carcinogenesis, but evidence is inconclusive. Circulating 25-hydroxyvitamin D (25(OH)D) concentrations that minimize risk are unknown. Current Institute of Medicine (IOM) vitamin D guidance is based solely on bone health. METHODS We pooled participant-level data from 17 cohorts, comprising 5706 colorectal cancer case participants and 7107 control participants with a wide range of circulating 25(OH)D concentrations. For 30.1% of participants, 25(OH)D was newly measured. Previously measured 25(OH)D was calibrated to the same assay to permit estimating risk by absolute concentrations. Study-specific relative risks (RRs) for prediagnostic season-standardized 25(OH)D concentrations were calculated using conditional logistic regression and pooled using random effects models. RESULTS Compared with the lower range of sufficiency for bone health (50-<62.5 nmol/L), deficient 25(OH)D (<30 nmol/L) was associated with 31% higher colorectal cancer risk (RR = 1.31, 95% confidence interval [CI] = 1.05 to 1.62); 25(OH)D above sufficiency (75-<87.5 and 87.5-<100 nmol/L) was associated with 19% (RR = 0.81, 95% CI = 0.67 to 0.99) and 27% (RR = 0.73, 95% CI = 0.59 to 0.91) lower risk, respectively. At 25(OH)D of 100 nmol/L or greater, risk did not continue to decline and was not statistically significantly reduced (RR = 0.91, 95% CI = 0.67 to 1.24, 3.5% of control participants). Associations were minimally affected when adjusting for body mass index, physical activity, or other risk factors. For each 25 nmol/L increment in circulating 25(OH)D, colorectal cancer risk was 19% lower in women (RR = 0.81, 95% CI = 0.75 to 0.87) and 7% lower in men (RR = 0.93, 95% CI = 0.86 to 1.00) (two-sided Pheterogeneity by sex = .008). Associations were inverse in all subgroups, including colorectal subsite, geographic region, and season of blood collection. CONCLUSIONS Higher circulating 25(OH)D was related to a statistically significant, substantially lower colorectal cancer risk in women and non-statistically significant lower risk in men. Optimal 25(OH)D concentrations for colorectal cancer risk reduction, 75-100 nmol/L, appear higher than current IOM recommendations.
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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.