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Effects of vitamin D supplementation on markers for cardiovascular disease and type 2 diabetes: an individual participant data meta-analysis of randomized controlled trials.

ABSTRACT: Background:Evidence from randomized controlled trials (RCTs) for the causal role of vitamin D on noncommunicable disease outcomes is inconclusive. Objective:The aim of this study was to investigate whether there are beneficial or harmful effects of cholecalciferol (vitamin D3) supplementation according to subgroups of remeasured serum 25-hydroxyvitamin D [25(OH)D] on cardiovascular and glucometabolic surrogate markers with the use of individual participant data (IPD) meta-analysis of RCTs. Design:Twelve RCTs (16 wk to 1 y of follow-up) were included. For standardization, 25(OH)D concentrations for all participants (n = 2994) at baseline and postintervention were re-measured in bio-banked serum samples with the use of a certified liquid chromatography-tandem mass spectrometry method traceable to a reference measurement procedure. IPD meta-analyses were performed according to subgroups of remeasured 25(OH)D. Main outcomes were blood pressure and glycated hemoglobin (HbA1c). Secondary outcomes were LDL, HDL, and total cholesterol and triglycerides; parathyroid hormone (PTH); fasting glucose, insulin, and C-peptide; and 2-h glucose. In secondary analyses, other potential effect modifiers were studied. Results:Remeasurement of 25(OH)D resulted in a lower mean 25(OH)D concentration in 10 of 12 RCTs. Vitamin D supplementation had no effect on the main outcomes of blood pressure and HbA1c. Supplementation resulted in 10-20% lower PTH concentrations, irrespective of the 25(OH)D subgroups. The subgroup analyses according to achieved 25(OH)D concentrations showed a significant decrease in LDL-cholesterol concentrations after vitamin D supplementation in 25(OH)D subgroups with <75, <100, and <125 nmol of -0.10 mmol/L (95% CI: -0.20, -0.00 mmol/L), -0.10 mmol/L (95% CI: -0.18, -0.02 mmol/L), and -0.07 mmol/L (95% CI: -0.14, -0.00 mmol/L), respectively. Patient features that modified the treatment effect could not be identified. Conclusions:For the main outcomes of blood pressure and HbA1c, the data support no benefit for vitamin D supplementation. For the secondary outcomes, in addition to its effect on PTH, we observed indications for a beneficial effect of vitamin D supplementation only on LDL cholesterol, which warrants further investigation. This trial was registered at www.clinicaltrials.gov as NCT02551835.

SUBMITTER: Swart KM

PROVIDER: S-EPMC6248392 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Effects of vitamin D supplementation on markers for cardiovascular disease and type 2 diabetes: an individual participant data meta-analysis of randomized controlled trials.

Swart Karin Ma KM Lips Paul P Brouwer Ingeborg A IA Jorde Rolf R Heymans Martijn W MW Grimnes Guri G Grübler Martin R MR Gaksch Martin M Tomaschitz Andreas A Pilz Stefan S Eiriksdottir Gudny G Gudnason Vilmundur V Wamberg Louise L Rejnmark Lars L Sempos Christopher T CT Durazo-Arvizu Ramón A RA Dowling Kirsten G KG Hull George G Škrabáková Zuzana Z Kiely Mairead M Cashman Kevin D KD van Schoor Natasja M NM

The American journal of clinical nutrition 20180601 6

<h4>Background</h4>Evidence from randomized controlled trials (RCTs) for the causal role of vitamin D on noncommunicable disease outcomes is inconclusive.<h4>Objective</h4>The aim of this study was to investigate whether there are beneficial or harmful effects of cholecalciferol (vitamin D3) supplementation according to subgroups of remeasured serum 25-hydroxyvitamin D [25(OH)D] on cardiovascular and glucometabolic surrogate markers with the use of individual participant data (IPD) meta-analysis ...[more]

PMID: 29868916

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Project description:BackgroundThe clinical benefit of aspirin for the primary prevention of cardiovascular disease (CVD) in diabetes remains uncertain. To evaluate the efficacy and safety of aspirin for the primary prevention of cardiovascular outcomes and all-cause mortality events in people with diabetes, we conducted an updated meta-analysis of published randomised controlled trials (RCTs) and a pooled analysis of individual participant data (IPD) from three trials.MethodsRandomised controlled trials of aspirin compared with placebo (or no treatment) in participants with diabetes with no known CVD were identified from MEDLINE, Embase, Cochrane Library, and manual search of bibliographies to January 2019. Relative risks with 95% confidence intervals were used as the summary measures of associations.ResultsWe included 12 RCTs based on 34,227 participants with a median treatment duration of 5.0 years. Comparing aspirin use with no aspirin, there was a significant reduction in risk of major adverse cardiovascular events (MACE)0.89 (0.83-0.95), with a number needed to treat (NNT)of 95 (95% CI 61 to 208) to prevent one MACE over 5 years average follow-up. Evidence was lacking of heterogeneity and publication bias among contributing trials for MACE. Aspirin use had no effect on other endpoints including all-cause mortality; however, there was a significant reduction in stroke for aspirin dosage ≤ 100 mg/day 0.75 (0.59-0.95). There were no significant effects of aspirin use on major bleeding and other bleeding events, though some of the estimates were imprecise. Pooled IPD from the three trials (2306 participants) showed no significant evidence of an effect of aspirin on any of the outcomes evaluated; however, aspirin reduced the risk of MACE in non-smokers 0.70 (0.51-0.96) with a NNT of 33 (95% CI 20 to 246) to prevent one MACE.ConclusionsAspirin has potential benefits in cardiovascular primary prevention in diabetes. The use of low dose aspirin may need to be individualised and based on each individual's baseline CVD and bleeding risk. Systematic review registration PROSPERO: CRD42019122326.

Project description:BACKGROUND:A previous aggregate data meta-analysis of randomised controlled trials showed that vitamin D supplementation reduces the rate of asthma exacerbations requiring treatment with systemic corticosteroids. Whether this effect is restricted to patients with low baseline vitamin D status is unknown. METHODS:For this systematic review and one-step and two-step meta-analysis of individual participant data, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science for double-blind, placebo-controlled, randomised controlled trials of vitamin D3 or vitamin D2 supplementation in people with asthma that reported incidence of asthma exacerbation, published between database inception and Oct 26, 2016. We analysed individual participant data requested from the principal investigator for each eligible trial, adjusting for age and sex, and clustering by study. The primary outcome was the incidence of asthma exacerbation requiring treatment with systemic corticosteroids. Mixed-effects regression models were used to obtain the pooled intervention effect with a 95% CI. Subgroup analyses were done to determine whether effects of vitamin D on risk of asthma exacerbation varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration, age, ethnic or racial origin, body-mass index, vitamin D dosing regimen, use of inhaled corticosteroids, or end-study 25(OH)D levels; post-hoc subgroup analyses were done according to sex and study duration. This study was registered with PROSPERO, number CRD42014013953. FINDINGS:Our search identified 483 unique studies, eight of which were eligible randomised controlled trials (total 1078 participants). We sought individual participant data for each and obtained it for seven studies (955 participants). Vitamin D supplementation reduced the rate of asthma exacerbation requiring treatment with systemic corticosteroids among all participants (adjusted incidence rate ratio [aIRR] 0·74, 95% CI 0·56-0·97; p=0·03; 955 participants in seven studies; high-quality evidence). There were no significant differences between vitamin D and placebo in the proportion of participants with at least one exacerbation or time to first exacerbation. Subgroup analyses of the rate of asthma exacerbations treated with systemic corticosteroids revealed that protective effects were seen in participants with baseline 25(OH)D of less than 25 nmol/L (aIRR 0·33, 0·11-0·98; p=0·046; 92 participants in three studies; moderate-quality evidence) but not in participants with higher baseline 25(OH)D levels (aIRR 0·77, 0·58-1·03; p=0·08; 764 participants in six studies; moderate-quality evidence; pinteraction=0·25). p values for interaction for all other subgroup analyses were also higher than 0·05; therefore, we did not show that the effects of this intervention are stronger in any one subgroup than in another. Six studies were assessed as being at low risk of bias, and one was assessed as being at unclear risk of bias. The two-step meta-analysis did not reveal evidence of heterogeneity of effect (I2=0·0, p=0·56). INTERPRETATION:Vitamin D supplementation reduced the rate of asthma exacerbations requiring treatment with systemic corticosteroids overall. We did not find definitive evidence that effects of this intervention differed across subgroups of patients. FUNDING:Health Technology Assessment Program, National Institute for Health Research (reference number 13/03/25).

Project description:Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect.Design Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials.Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015.Eligibility criteria for study selection Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome.Results 25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality.Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit.Systematic review registration PROSPERO CRD42014013953.

Project description:BACKGROUND:Estimation of the dietary requirements for vitamin D is crucial from a public health perspective in providing a framework for the prevention of vitamin D deficiency. It has been shown that pooling individual participant-level data (IPD) from selected randomised controlled trials (RCTs) of white children and adults facilitated the generation of more accurate estimates of the vitamin D requirement. Recent RCT data suggest the vitamin D requirement of dark-skinned, particularly black, individuals, an at-risk group of vitamin D deficiency, is greater than those of white counterparts. Thus, we wished to develop a study protocol for the conduct of an IPD-level meta-analysis of vitamin D requirements using data from appropriate vitamin D RCTs in dark-skinned population subgroups. METHODS:The study protocol details the steps needed within such an IPD meta-analysis which will include its registration, constituent systematic review to identify all appropriate RCTs on the basis of pre-specified eligibility criteria, the associated data collection, handling, and synthesis, as well as checking the integrity of the IPD, followed by implementation of a one/two-stage IPD meta-analysis and derivation of vitamin D requirement estimates. DISCUSSION:As dark-skinned population subgroups are at increased risk of vitamin D deficiency, further investigation of dietary recommendations for vitamin D in these subgroups is needed. We strongly believe that application of an IPD-based meta-analysis is a highly strategic approach by which to undertake some of this further investigation. Such IPD-based analysis, however, will need collaboration across the principal investigators of the identified RCTs meeting with the eligibility criteria, and the availability of this study protocol will be important to highlight the potential of IPD-based analysis for estimation of the dietary requirement for vitamin D for this particular population subgroup as well as for other at-risk target populations. SYSTEMATIC REVIEW REGISTRATION:PROSPERO International Prospective Register of Systematic Reviews (registration number: CRD42018092343).

Project description:BackgroundMeta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNSs) reduce child stunting and wasting. Identification of subgroups who benefit most from SQ-LNSs may facilitate program design.ObjectivesWe aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child growth outcomes.MethodsWe conducted a 2-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 37,066). We generated study-specific and subgroup estimates of SQ-LNS compared with control and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons.ResultsSQ-LNS provision decreased stunting (length-for-age z score < -2) by 12% (relative reduction), wasting [weight-for-length (WLZ) z score < -2] by 14%, low midupper arm circumference (MUAC) (<125 mm or MUAC-for-age z score < -2) by 18%, acute malnutrition (WLZ < -2 or MUAC < 125 mm) by 14%, underweight (weight-for-age z score < -2) by 13%, and small head size (head circumference-for-age z score < -2) by 9%. Effects of SQ-LNSs generally did not differ by study-level characteristics including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact, or average compliance with SQ-LNS. Effects of SQ-LNSs on stunting, wasting, low MUAC, and small head size were greater among girls than among boys; effects on stunting, underweight, and low MUAC were greater among later-born (than among firstborn) children; and effects on wasting and acute malnutrition were greater among children in households with improved (as opposed to unimproved) sanitation.ConclusionsThe positive impact of SQ-LNSs on growth is apparent across a variety of study-level contexts. Policy-makers and program planners should consider including SQ-LNSs in packages of interventions to prevent both stunting and wasting.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592.

Project description:BackgroundPrevious observational studies have supported the hypothesis that vitamin D supplementation protects against stroke. However, several current intervention studies contradict this observation. Therefore, we conducted a meta-analysis to investigate further the association between vitamin D supplementation and the risk of stroke.MethodsThis meta-analysis was conducted in accordance with the PRISMA statement and included all the randomized controlled trials (RCTs) that analyzed the relationship between vitamin D supplementation and the risk of stroke. A literature search strategy was established, and the following Medical Search Terms (MeSH) were used: "vitamin D," "Calcitriol," "Calcifediol," "Cholecalciferol," "25-Hydroxyvitamin D 2," "ergocalciferols," "stroke," and stroke-derived terms. We searched for articles published before January 2022 in several databases, namely, PubMed, Web of Science, EMBASE, and The Cochrane Library. We also reviewed references included in relevant published meta-analyses and searched the http://www.ClinicalTrials.gov website for additional RCTs. The Q test and I 2 were utilized to assess the degree of heterogeneity among the studies. Review Manager 5.3 and STATA16.0 software programs were used to assess the literature quality and perform statistical analyses.ResultsIn total, twenty-four RCTs (86,202 participants) were included. There was no statistical heterogeneity among the RCTs (I 2 = 0.0%, P = 0.94) included in this meta-analysis. We determined that vitamin D supplementation was not associated with a reduced risk of stroke compared with the placebo (RR = 1.02, 95% CI: 0.93-1.13, P = 0.65). In total, 10 studies only included women, and 14 studies included women and men among the 24 RCTs. Therefore, we performed a subgroup analysis based on sex. After the subgroup analysis, the effect remained statistically insignificant (mixed-sex group: RR = 1.06, 95% CI: 0.93-1.22, P = 0.37, women group: RR = 0.98, 95% CI: 0.86-1.13, P = 0.80). The results were generally comparable, based on age, body mass index (BMI), follow-up period, baseline 25-hydroxyvitamin D (25(OH)D) levels, the designated endpoint, latitude, vitamin D dosage, type of vitamin D administered, and an absence or presence of concurrent calcium supplementation (P > 0.05).ConclusionOur study revealed that additional vitamin D supplementation did not reduce the risk of stroke. Therefore, additional RCTs of similar design should not be encouraged to assess any association between vitamin D supplementation and reduced stroke risk.

Dataset Information

Effects of vitamin D supplementation on markers for cardiovascular disease and type 2 diabetes: an individual participant data meta-analysis of randomized controlled trials.

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Effects of vitamin D supplementation on markers for cardiovascular disease and type 2 diabetes: an individual participant data meta-analysis of randomized controlled trials.

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