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1.
Critical Appraisal of Large Vitamin D Randomized Controlled Trials.
Pilz, S, Trummer, C, Theiler-Schwetz, V, Grübler, MR, Verheyen, ND, Odler, B, Karras, SN, Zittermann, A, März, W
Nutrients. 2022;(2)
Abstract
As a consequence of epidemiological studies showing significant associations of vitamin D deficiency with a variety of adverse extra-skeletal clinical outcomes including cardiovascular diseases, cancer, and mortality, large vitamin D randomized controlled trials (RCTs) have been designed and conducted over the last few years. The vast majority of these trials did not restrict their study populations to individuals with vitamin D deficiency, and some even allowed moderate vitamin D supplementation in the placebo groups. In these RCTs, there were no significant effects on the primary outcomes, including cancer, cardiovascular events, and mortality, but explorative outcome analyses and meta-analyses revealed indications for potential benefits such as reductions in cancer mortality or acute respiratory infections. Importantly, data from RCTs with relatively high doses of vitamin D supplementation did, by the vast majority, not show significant safety issues, except for trials in critically or severely ill patients or in those using very high intermittent vitamin D doses. The recent large vitamin D RCTs did not challenge the beneficial effects of vitamin D regarding rickets and osteomalacia, that therefore continue to provide the scientific basis for nutritional vitamin D guidelines and recommendations. There remains a great need to evaluate the effects of vitamin D treatment in populations with vitamin D deficiency or certain characteristics suggesting a high sensitivity to treatment. Outcomes and limitations of recently published large vitamin D RCTs must inform the design of future vitamin D or nutrition trials that should use more personalized approaches.
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2.
Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression.
Markun, S, Gravestock, I, Jäger, L, Rosemann, T, Pichierri, G, Burgstaller, JM
Nutrients. 2021;(3)
Abstract
Vitamin B12 is often used to improve cognitive function, depressive symptoms, and fatigue. In most cases, such complaints are not associated with overt vitamin B12 deficiency or advanced neurological disorders and the effectiveness of vitamin B12 supplementation in such cases is uncertain. The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) is to assess the effects of vitamin B12 alone (B12 alone), in addition to vitamin B12 and folic acid with or without vitamin B6 (B complex) on cognitive function, depressive symptoms, and idiopathic fatigue in patients without advanced neurological disorders or overt vitamin B12 deficiency. Medline, Embase, PsycInfo, Cochrane Library, and Scopus were searched. A total of 16 RCTs with 6276 participants were included. Regarding cognitive function outcomes, we found no evidence for an effect of B12 alone or B complex supplementation on any subdomain of cognitive function outcomes. Further, meta-regression showed no significant associations of treatment effects with any of the potential predictors. We also found no overall effect of vitamin supplementation on measures of depression. Further, only one study reported effects on idiopathic fatigue, and therefore, no analysis was possible. Vitamin B12 supplementation is likely ineffective for improving cognitive function and depressive symptoms in patients without advanced neurological disorders.
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3.
Can vitamin E supplementation affect obesity indices? A systematic review and meta-analysis of twenty-four randomized controlled trials.
Emami, MR, Jamshidi, S, Zarezadeh, M, Khorshidi, M, Olang, B, Sajadi Hezaveh, Z, Sohouli, M, Aryaeian, N
Clinical nutrition (Edinburgh, Scotland). 2021;(5):3201-3209
Abstract
BACKGROUND Several mechanisms have been proposed for the effect of vitamin E on weight loss. Yet various interventional studies with wide ranges of doses and durations have reported contradictory results. METHODS Cochrane Library, PubMed, Scopus, and Embase databases were searched up to December 2020. Meta-analysis was performed using random-effect method. Effect size was presented as weighted mean difference (WMD) and 95% confidence interval (CI). Heterogeneity was evaluated using the I2 index. In order to identification of potential sources of heterogeneity, predefined subgroup and meta regression analyses was conducted. RESULTS A total of 24 studies with 33 data sets were included. There was no significant effect of vitamin E on weight (WMD: 0.15, 95% CI: -1.35 to 1.65, P = 0.847), body mass index (BMI) (WMD = 0.04, 95% CI: -0.29 to 0.37, P = 0.815), and waist circumference (WC) (WMD = -0.19 kg, 95% CI: -2.06 to 1.68, P = 0.842), respectively. However, subgroup analysis revealed that vitamin E supplementation in studies conducted on participants with normal BMI (18.5-24.9) had increasing impact on BMI (P = 0.047). CONCLUSION There was no significant effect of vitamin E supplementation on weight, BMI and WC. However, vitamin E supplementation might be associated with increasing BMI in people with normal BMI (18.5-24.9).
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4.
The effect of vitamin D plus protein supplementation on sarcopenia: A systematic review and meta-analysis of randomized controlled trials.
Gkekas, NK, Anagnostis, P, Paraschou, V, Stamiris, D, Dellis, S, Kenanidis, E, Potoupnis, M, Tsiridis, E, Goulis, DG
Maturitas. 2021;:56-63
Abstract
PURPOSE The exact effect of vitamin D supplementation, either as monotherapy or in combination with protein, on musculoskeletal health in patients with sarcopenia is currently unknown. This study aimed to determine the effect of vitamin D alone or with protein supplementation on muscle strength, mass, and performance in this population. METHODS A comprehensive search was conducted in Medline, Cochrane Central and Scopus databases, up to March 31st, 2020. Data were expressed as standardized mean difference (SMD) with 95 % confidence intervals (CI). I2 index was employed for heterogeneity. RESULTS The initial search identified 1164 studies, eight of which met the eligibility criteria for qualitative and quantitative analysis, yielding a total of 776 patients. Vitamin D (100-1600 IU/day) plus protein (10-44 g/day) supplementation exhibited a beneficial effect on muscle strength, as demonstrated by an improvement in handgrip strength (SMD 0.38 ± 0.07, 95 % CI 0.18-0.47, p = 0.04; I2 76.2 %) and a decrease in the sit-to-stand time (SMD 0.25 ± 0.09, 95 % CI 0.06-0.43, p = 0.007; I2 0%) compared with placebo. However, the effect on muscle mass, assessed by skeletal muscle index, was marginally non-significant (SMD 0.25 ± 0.13, 95 % CI -0.006-0.51, p = 0.05; I2 0%). No effect on appendicular skeletal muscle mass or muscle performance (assessed by walking speed) was observed with vitamin D plus protein. CONCLUSIONS Vitamin D supplementation, combined with protein, improves muscle strength in patients with sarcopenia, but has no effect on muscle mass or performance.
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5.
Vitamin D supplementation reduces the risk of fall in the vitamin D deficient elderly: An updated meta-analysis.
Ling, Y, Xu, F, Xia, X, Dai, D, Xiong, A, Sun, R, Qiu, L, Xie, Z
Clinical nutrition (Edinburgh, Scotland). 2021;(11):5531-5537
Abstract
INTRODUCTION Vitamin D supplementation has been widely recommended to prevent falls. However, considerable controversy exists regarding the association of such supplementation and fall risk. Previous meta-analyses yielded inconsistent results because of differences in the baseline of 25-hydroxyvitamin D [25(OH)D] and dose of vitamin D and use of vitamin D or in combination with calcium in different studies. Furthermore, some studies published recently were not included in the previous meta-analyses. Therefore, an updated and comprehensive meta-analysis is warranted. METHODS We systematically searched several literature databases including PubMed and the Embase from inception to September 2020. The protocol for this meta-analysis was registered with PROSPERO (CRD42021226380). Randomized clinical trials (RCTs) reporting the effect of vitamin D supplementation alone or with calcium on fall incidence were selected from studies. Qualitative and quantitative information was extracted; the random-effects model was conducted to pool the data for fall; statistical heterogeneity was assessed using the I2 test and potential for publication bias was assessed qualitatively by a visual estimate of the funnel plot and quantitatively by calculation of the Begg's test and the Egger's test. RESULTS Of the citations retrieved, 31 eligible studies involving 57 867 participants met inclusion criteria, reporting 17 623 falls. A total of 21 RCTs of vitamin D alone and 10 RCTs of vitamin D plus calcium were included in the meta-analysis. The meta-analysis of 21 RCTs (51 984 participants) of vitamin D supplementation alone (daily or intermittent doses of 400-60 000 IU) did not show a reduced risk of falls (The risk ratio [RR] 1.00, 95% confidence intervals [CI] 0.95 to 1.05) compared to placebo or no treatment. Subgroup analyses showed that the baseline of serum 25(OH)D concentration less than 50 nmol/L resulted in a reduction of fall risk (RR 0.77, 95% CI 0.61 to 0.98). In contrast, the meta-analysis of 10 RCTs (5883 participants) of combined supplementation of vitamin D (daily doses of 700-1000 IU) and calcium (daily doses of 1000-1200 mg) showed a 12% reduction in the risk of fall (RR 0.88, 95% CI 0.80 to 0.97). CONCLUSIONS The combination of vitamin D and calcium have beneficial effects on prevention falls in old adults. Although vitamin D supplementation alone has no effect on fall risk in old adults with 25(OH)D levels higher than 50 nmol/L, vitamin D supplementation alone does have a benefit on prevention of falls in old adults with 25(OH)D levels lower than 50 nmol/L.
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6.
Prenatal Vitamins and the Risk of Offspring Autism Spectrum Disorder: Systematic Review and Meta-Analysis.
Friel, C, Leyland, AH, Anderson, JJ, Havdahl, A, Borge, T, Shimonovich, M, Dundas, R
Nutrients. 2021;(8)
Abstract
Prenatal nutrition is associated with offspring autism spectrum disorder (herein referred to as autism), yet, it remains unknown if the association is causal. Triangulation may improve causal inference by integrating the results of conventional multivariate regression with several alternative approaches that have unrelated sources of bias. We systematically reviewed the literature on the relationship between prenatal multivitamin supplements and offspring autism, and evidence for the causal approaches applied. Six databases were searched up to 8 June 2020, by which time we had screened 1309 titles/abstracts, and retained 12 articles. Quality assessment was guided using Newcastle-Ottawa in individual studies, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) for the body of evidence. The effect estimates from multivariate regression were meta-analysed in a random effects model and causal approaches were narratively synthesised. The meta-analysis of prenatal multivitamin supplements involved 904,947 children (8159 cases), and in the overall analysis showed no robust association with offspring autism; however, a reduced risk was observed in the subgroup of high-quality observational studies (RR 0.77, 95% CI (0.62, 0.96), I2 = 62.4%), early pregnancy (RR 0.76, 95% CI (0.58; 0.99), I2 = 79.8%) and prospective studies (RR 0.69, 95% CI (0.48, 1.00), I2 = 95.9%). The quality of evidence was very low, and triangulation was of limited utility because alternative methods were used infrequently and often not robustly applied.
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7.
Can vitamin D be considered an adiponectin secretagogue? A systematic review and meta-analysis.
Nikooyeh, B, Neyestani, TR
The Journal of steroid biochemistry and molecular biology. 2021;:105925
Abstract
There is some evidence for ameliorating effect of vitamin D on glycemic and lipidemic status which are likely to be mediated through other molecules including adiponectin. However, the overall results have been controversial. This study was conducted to evaluate the effect of vitamin D supplementation on serum adiponectin concentration. MEDLINE, PubMed, Embase, Cochrane Library, and Google Scholar were searched and 402 studies were found in a preliminary search. After screening of titles and abstracts nine studies were selected. Pooled data showed no significant effect on adiponectin concentrations (mean difference (MD) 0.37, 95 % CI: -0.1 to 0.87). However, there was a significant effect in a subgroup of participants who had diabetes (MD: 0.03, 95 % CI: 0.00 to 0.05, p = 0.029). The treatment effect on adiponectin concentrations was significant in those trials that used supplementation on a daily basis (MD: 0.03, 95 % CI: 0.00 to 0.05, p = 0.028) and vitamin D plus calcium (MD: 0.04, 95 % CI: 0.01 to 0.07, p = 0.014). The meta-regression revealed a significant association between BMI and age of participants at baseline and the treatment effect (B, -0.144, 95 % CI: -0.276 to -0.011, p = 0.033 and B, -0.043, 95 % CI: -0.075 to -0.012, p = 0.006). The results of this meta-analysis study indicates that vitamin D may be considered an adiponectin secretagogue in subjects with diabetes and this effect may be potentiated if vitamin D intake is on daily basis and in combination with calcium but can be weakened by increasing BMI.
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8.
Vitamin D can safely reduce asthma exacerbations among corticosteroid-using children and adults with asthma: a systematic review and meta-analysis of randomized controlled trials.
Chen, Z, Peng, C, Mei, J, Zhu, L, Kong, H
Nutrition research (New York, N.Y.). 2021;:49-61
Abstract
Previous studies have failed to draw a consistent conclusion over the effect of vitamin D administration on asthma. We hypothesized that vitamin D supplementation could improve the clinical efficacy of corticosteroids in patients with asthma as measured by exacerbations, Asthma Control Test (ACT) score, and lung function in order to maintain asthma control. We searched Web of Science, PubMed, the Cochrane Library, and ScienceDirect up through January 20, 2021 for randomized controlled trials analyzing the effect of vitamin D supplementation on asthma exacerbation. Studies were limited to patients with moderate to severe asthma who were treated with corticosteroids. We identified 12 studies involving 1,543 participants in this meta-analysis. Vitamin D supplementation significantly reduced the risk of asthma exacerbation (pooled risk ratio (RR) 0.70, 95% confidence interval (CI), 0.59, 0.83; P < .05). The pooled RR of the ACT score was 0.04 (95% CI, -0.19, 0.27; P > .05). The pooled standardized mean difference in vitamin D levels was 1.07 (95% CI, 0.77, 1.38; P < .05), and in the percentage of forced expiratory volume in one second was -0.02 (95% CI, -0.13, 0.09; P > .05). The pooled RR of adverse events was 1.06 (95% CI, 0.89, 1.25; P > .05). We performed subgroup analysis and meta-regression of serum vitamin D levels but found no source of heterogeneity. Vitamin D supplementation safely reduced the rate of asthma exacerbation but did not improve ACT score or lung function among patients with asthma treated with corticosteroids.
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9.
Effect of Vitamin D Supplementation in Early Life on Children's Growth and Body Composition: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Ma, K, Wei, SQ, Bi, WG, Weiler, HA, Wen, SW
Nutrients. 2021;(2)
Abstract
BACKGROUND Vitamin D deficiency during pregnancy or infancy is associated with adverse growth in children. No systematic review has been conducted to summarize available evidence on the effect of vitamin D supplementation in pregnancy and infancy on growth and body composition in children. OBJECTIVE We aim to summarize the available evidence on the effect of vitamin D supplementation in pregnancy and infancy on child growth and body composition. METHOD A systematic review and meta-analysis were performed on the effects of vitamin D supplementation during early life on children's growth and body composition (bone, lean and fat). A literature search of randomized controlled trials (RCTs) was conducted to identify relevant studies on the effects of vitamin D supplementation during pregnancy and infancy on children's body composition (bone, lean and fat) in PubMed, EMBASE and Cochrane Library from inception to 31 December 2020. A Cochrane Risk Assessment Tool was used for quality assessment. The comparison was vitamin D supplementation vs. placebo or standard care. Random-effects and fixed-effect meta-analyses were conducted. The effects are presented as mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS A total of 3960 participants from eleven randomized controlled trials were eligible for inclusion. Vitamin D supplementation during pregnancy was associated with higher triceps skinfold thickness (mm) (MD 0.33, 95% CI, 0.12, 0.54; I2 = 34%) in neonates. Vitamin D supplementation during pregnancy or infancy was associated with significantly increased length for age z-score in infants at 1 year of age (MD 0.29, 95% CI, 0.03, 0.54; I2 = 0%), and was associated with lower body mass index (BMI) (kg/m2) (MD -0.19, 95% CI -0.34, -0.04; I2 = 0%) and body mass index z-score (BMIZ) (MD -0.12, 95% CI -0.21, -0.04; I2 = 0%) in offspring at 3-6 years of age. Vitamin D supplementation during early life was not observed to be associated with children's bone, lean or fat mass. CONCLUSION Vitamin D supplementation during pregnancy or infancy may be associated with reduced adiposity in childhood. Further large clinical trials of the effects of vitamin D supplementation on childhood body composition are warranted.
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10.
Association of 25-hydroxyvitamin D level with survival outcomes in female breast cancer patients: A meta-analysis.
Li, C, Li, H, Zhong, H, Li, X
The Journal of steroid biochemistry and molecular biology. 2021;:105947
Abstract
Conflicting results have been reported on the association of blood vitamin D level with prognosis in women with breast cancer. This meta-analysis aimed to evaluate the association between blood 25-hydroxyvitamin D level and survival outcomes in female breast cancer patients. Two authors independently searched PubMed and Embase databases from their inception to August 25, 2020. Prospective or retrospective cohort studies evaluating the association between blood 25-hydroxyvitamin D level and survival outcomes in women with breast cancer were included. Outcome measures included overall survival (OS), breast cancer-specific survival (BCSS), and disease-free survival (DFS). Twelve studies involving 8574 female breast cancer patients were identified and analyzed. When compared the lowest with the highest category of 25-hydroxyvitamin D level, the pooled adjusted hazard ratio (HR) was 1.57 (95 % confidence interval [CI] 1.35-1.83) for OS, 1.98 (95 % CI 1.55-2.53) for DFS, and 1.44 (95 % CI 1.14-1.81) for BCSS. This meta-analysis indicates that lower blood 25-hydroxyvitamin D level is significantly associated with reduced survival among female breast cancer patients. Additional clinical trials are required to investigate whether vitamin D supplement can improve survival outcomes in these patients.