Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials
Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials
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DOI：
10.1101/2020.07.14.20152728
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发表时间：
2021-05-01
影响因子：
44.5
通讯作者：
Martineau, Adrian R.
中科院分区：
文献类型：
--
作者：
Jolliffe, David A.;Camargo, Carlos A., Jr.;Martineau, Adrian R.
背景2017年对25个维生素D补充剂预防急性呼吸道感染(ARIS)的随机对照试验(RCT)的数据进行的荟萃分析揭示了这种干预的保护作用。我们的目的是在最新的荟萃分析中检验维生素D补充剂和ARIS预防之间的联系。方法在这项系统性综述和荟萃分析中，我们搜索了MEDLINE、Embase、Cochrane中央对照试验注册中心、Web of Science和ClinicalTrials.gov注册中心，检索了从数据库建立到2020年5月1日的研究。维生素D-3、维生素D-2或25-羟基维生素D(25[OH]D)补充剂与安慰剂或低剂量维生素D对照的双盲随机对照试验，只要得到了研究伦理委员会的批准，如果ARI的发生率被前瞻性收集并预先指定为疗效结果，则符合条件。报告初级随机对照试验长期随访结果的研究被排除在外。汇总的研究水平数据，按基线25(OH)D浓度和年龄分层，从研究作者那里获得。使用每个试验中有一个或多个ARI的参与者的比例，我们进行了随机效应荟萃分析，以获得合并优势比(OR)和95%的CI，以估计与安慰剂相比，补充维生素D对发生一个或多个ARI(主要结果)的风险的影响。亚组分析以评估补充维生素D对急性呼吸窘迫综合征风险的影响是否根据基线25(OH)D浓度(75.0nmol/L)、维生素D剂量(每日相当于2000IU)、给药频率(每天与每周或每月一次至每三个月一次)、试验持续时间(12个月)、登记时年龄(=65.00岁)以及是否有呼吸道疾病(例如，仅限哮喘、仅限慢性阻塞性肺病或不受限制)而变化。使用Cochrane协作偏倚风险工具评估偏倚风险。研究结果：我们鉴定了1528篇文章，其中46篇随机对照试验(RCT)(75541名参与者)符合条件。在43项研究中，49419名参与者(年龄0-95岁)中的48488人(98.1%)获得了主要结果的数据。维生素D补充组的参与者有一个或多个ARI的比例(23364名参与者中的14332[61.3%])明显低于安慰剂组(22802名参与者中的14217[62.3%])，OR为0.92(95%可信区间0.86-0.99；37项研究；I-2=35.6%，p(异质性)=0.018)。对于基线25(OH)D浓度定义的任何亚组，补充维生素D对发生一个或多个ARI的风险没有显著影响。然而，在每日剂量当量为400-1000IU的试验中观察到补充维生素D的保护作用(OR0.78[95%CI 0.65-0.94]；19项研究；I-2=53.5%，p(异质性)=0.003；10项研究；I-2=31.2%，p(异质性)=0.16)，持续12个月或更短(0.82[0.72-0.93]；29项研究；I-2=38.1%，p(异质性)=0.021)，以及1.00-15.99岁的参与者(0.71[0.57-0.9]；15项研究；I-2=46.0%，p(异质性)=0.027)。维生素D补充组与安慰剂组之间的分配与剂量、剂量频率、研究持续时间或年龄之间没有显著的交互作用。此外，与安慰剂组相比，维生素补充组中至少发生一次严重不良事件的参与者的比例没有显著差异(0.97[0.86-1.07]；36项研究；I-2=0.0%，p(异质性)=0.99)。除了三个试验外，所有单独研究中的偏倚风险都被评估为低风险。尽管有证据表明在各个试验中存在显著的异质性，但补充维生素D是安全的，总体上与安慰剂相比，ARI的风险降低了，尽管风险降低幅度很小。保护与每天服用400-1000IU剂量最多12个月，登记年龄1.00-15.99岁有关。这些发现与新冠肺炎的相关性尚不清楚，需要进一步调查。版权所有(C)2021爱思唯尔有限公司。保留所有权利。
Background A 2017 meta-analysis of data from 25 randomised controlled trials (RCTs) of vitamin D supplementation for the prevention of acute respiratory infections (ARIs) revealed a protective effect of this intervention. We aimed to examine the link between vitamin D supplementation and prevention of ARIs in an updated meta-analysis.Methods For this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov registry for studies listed from database inception to May 1, 2020. Double-blind RCTs of vitamin D-3, vitamin D-2, or 25-hydroxyvitamin D (25[OH]D) supplementation for any duration, with a placebo or low-dose vitamin D control, were eligible if they had been approved by a research ethics committee, and if ARI incidence was collected prospectively and prespecified as an efficacy outcome. Studies reporting results of long-term follow-up of primary RCTs were excluded. Aggregated study-level data, stratified by baseline 25(OH)D concentration and age, were obtained from study authors. Using the proportion of participants in each trial who had one or more ARIs, we did a random-effects meta-analysis to obtain pooled odds ratios (ORs) and 95% CIs to estimate the effect of vitamin D supplementation on the risk of having one or more ARIs (primary outcome) compared with placebo. Subgroup analyses were done to estimate whether the effects of vitamin D supplementation on the risk of ARI varied according to baseline 25( OH)D concentration (75.0 nmol/L), vitamin D dose (daily equivalent of 2000 IU), dosing frequency (daily vs weekly vs once per month to once every 3 months), trial duration (12 months), age at enrolment (= 65.00 years), and presence versus absence of airway disease (ie, asthma only, COPD only, or unrestricted). Risk of bias was assessed with the Cochrane Collaboration Risk of Bias Tool. The study was registered with PROSPERO, CRD42020190633.Findings We identified 1528 articles, of which 46 RCTs (75 541 participants) were eligible. Data for the primary outcome were obtained for 48 488 (98.1%) of 49 419 participants (aged 0-95 years) in 43 studies. A significantly lower proportion of participants in the vitamin D supplementation group had one or more ARIs (14 332 [61.3%] of 23 364 participants) than in the placebo group (14 217 [62.3%] of 22 802 participants), with an OR of 0.92 (95% CI 0.86-0.99; 37 studies; I-2 =35.6%, p(heterogeneity)=0.018). No significant effect of vitamin D supplementation on the risk of having one or more ARIs was observed for any of the subgroups defined by baseline 25(OH)D concentration. However, protective effects of supplementation were observed in trials in which vitamin D was given in a daily dosing regimen (OR 0.78 [95% CI 0.65-0.94]; 19 studies; I-2=53 .5%, p(heterogeneity)=0.003), at daily dose equivalents of 400-1000 IU (0.70 [0.55-0.89]; ten studies; I-2=31.2%, p(heterogeneity)=0.16), for a duration of 12 months or less (0.82 [0.72-0.93]; 29 studies; I-2=38 .1%, p(heterogeneity)=0.021), and to participants aged 1.00-15.99 years at enrolment (0.71 [0.57-0.90]; 15 studies; I-2=46.0%, p(heterogeneity)=0.027). No significant interaction between allocation to the vitamin D supplementation group versus the placebo group and dose, dose frequency, study duration, or age was observed. In addition, no significant difference in the proportion of participants who had at least one serious adverse event in the vitamin supplementation group compared with the placebo group was observed (0.97 [0.86-1.07]; 36 studies; I-2=0.0%, p(heterogeneity)=0.99). Risk of bias within individual studies was assessed as being low for all but three trials.Interpretation Despite evidence of significant heterogeneity across trials, vitamin D supplementation was safe and overall reduced the risk of ARI compared with placebo, although the risk reduction was small. Protection was associated with administration of daily doses of 400-1000 IU for up to 12 months, and age at enrolment of 1.00-15.99 years. The relevance of these findings to COVID-19 is not known and requires further investigation. Copyright (c) 2021 Elsevier Ltd. All rights reserved.