大剂量维生素能否减少儿童冬季感冒？
流行病学研究发现25-羟维生素D水平低与病毒性上呼吸道感染风险之间存在相关性。然而，冬季补充大剂量（2000IU/d）维生素D与美国儿科学会推荐的标准剂量（400IU/d）维生素D相比，是否有助于预防学龄前儿童冬季病毒性上呼吸道感染仍然未知。
2017年7月18日，《美国医学会杂志》正式发表加拿大多伦多大学、圣迈克尔医院、多伦多儿童医院、多伦多儿童研究所、麦克马斯特大学、安大略临床评估科学研究所、多伦多西奈山医院、美国戴维斯加利福尼亚大学的随机临床研究，比较了加拿大冬季期间补充大剂量（2000IU/d）维生素D与标准剂量（400IU/d）维生素D对学龄前儿童上呼吸道感染的影响，结果发现大剂量组的实验室证实冬季病毒性上呼吸道感染次数高于标准剂量组，无统计学显著差异。因此，维生素D剂量＞400IU/d可能无法预防儿童冬季病毒性上呼吸道感染。
该多中心随机临床研究（TARGet Kids!）于2011年9月13日～2015年6月30日从加拿大安大略省多伦多初级医疗机构研究网络入组703位年龄1～5岁健康儿童（平均年龄2.7岁，男孩占57.7%），在每年冬季（9月至次年5月）随机接受每天口服2000IU维生素D（大剂量组349位）或400IU维生素D（标准剂量组354位）至少4个月。
主要结局为冬季根据父母收集鼻拭经实验室证实的病毒性上呼吸道感染次数。次要结局包括流感和非流感的感染次数、父母报告的上呼吸道疾病次数、至首次上呼吸道感染时间、研究终止时的血清25-羟维生素D水平。
结果，699位（99.4%）完成研究，大剂量组与标准剂量组相比：
每位儿童实验室确诊上呼吸道感染平均次数分别为1.05、1.03（95%置信区间：0.91～1.19、0.90～1.16；组间差异：0.02，95%置信区间：-0.17～0.21）。
实验室确诊感染次数组间差异无统计学意义（发病率比：0.97，95%置信区间：0.80～1.16）。
首次实验室确诊感染中位时间也无显著差异（3.95、3.29个月，95%置信区间：3.02～5.95、2.66～4.14个月）
父母报告的上呼吸道疾病次数也无显著差异（625、600例，发病率比：1.01，95%置信区间：0.88～1.16）
研究终止时血清25-羟维生素D水平分别为48.7ng/mL、36.8ng/mL（95%置信区间：46.9～50.5、35.4～38.2ng/mL）
因此，对于1～5岁健康儿童，每天补充2000IU与400IU维生素D相比，无法减少冬季病毒性上呼吸道感染。这些结果不支持幼儿常规补充大剂量维生素D预防病毒性上呼吸道感染。
JAMA. 2017 Jul 18;318(3):245-254.
Effect of High-Dose vs Standard-Dose Wintertime Vitamin D Supplementation on Viral Upper Respiratory Tract Infections in Young Healthy Children.
Aglipay M, Birken CS, Parkin PC, Loeb MB, Thorpe K, Chen Y, Laupacis A, Mamdani M, Macarthur C, Hoch JS, Mazzulli T, Maguire JL; TARGet Kids! Collaboration.
St Michael's Hospital, Toronto, Ontario, Canada; Hospital for Sick Children, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada; Sick Kids Research Institute, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Institute for Clinical Evaluative Sciences, Toronto, Canada; University of California, Davis, California; Mount Sinai Hospital, Toronto, Ontario, Canada.
This randomized clinical trial compares the effects of 2000 IU vs 400 IU of vitamin D supplementation on the number of upper respiratory tract infections among preschool children during winter months in Canada.
QUESTION: Does high-dose vitamin D supplementation (2000 IU/d) help to prevent wintertime viral upper respiratory tract infections compared with standard-dose vitamin D supplementation (400 IU/d) among preschool children?
FINDINGS: In this multisite randomized clinical trial that included 703 children, the number of wintertime laboratory-confirmed viral upper respiratory tract infections was higher in the high-dose group than the standard-dose group, not a statistically significant difference.
MEANING: Vitamin D dosing higher than 400 IU/d may not be indicated for preventing wintertime viral upper respiratory tract infections in children.
IMPORTANCE: Epidemiological studies support a link between low 25-hydroxyvitamin D levels and a higher risk of viral upper respiratory tract infections. However, whether winter supplementation of vitamin D reduces the risk among children is unknown.
OBJECTIVE: To determine whether high-dose vs standard-dose vitamin D supplementation reduces the incidence of wintertime upper respiratory tract infections in young children.
DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial was conducted during the winter months between September 13, 2011, and June 30, 2015, among children aged 1 through 5 years enrolled in TARGet Kids!, a multisite primary care practice-based research network in Toronto, Ontario, Canada.
INTERVENTIONS: Three hundred forty-nine participants were randomized to receive 2000 IU/d of vitamin D oral supplementation (high-dose group) vs 354 participants who were randomized to receive 400 IU/d (standard-dose group) for a minimum of 4 months between September and May.
MAIN OUTCOME MEASURES: The primary outcome was the number of laboratory-confirmed viral upper respiratory tract infections based on parent-collected nasal swabs over the winter months. Secondary outcomes included the number of influenza infections, noninfluenza infections, parent-reported upper respiratory tract illnesses, time to first upper respiratory tract infection, and serum 25-hydroxyvitamin D levels at study termination.
RESULTS: Among 703 participants who were randomized (mean age, 2.7 years, 57.7% boys), 699 (99.4%) completed the trial. The mean number of laboratory-confirmed upper respiratory tract infections per child was 1.05 (95% CI, 0.91-1.19) for the high-dose group and 1.03 (95% CI, 0.90-1.16) for the standard-dose group, for a between-group difference of 0.02 (95% CI, -0.17 to 0.21) per child. There was no statistically significant difference in number of laboratory-confirmed infections between groups (incidence rate ratio [RR], 0.97; 95% CI, 0.80-1.16). There was also no significant difference in the median time to the first laboratory-confirmed infection: 3.95 months (95% CI, 3.02-5.95 months) for the high-dose group vs 3.29 months (95% CI, 2.66-4.14 months) for the standard-dose group, or number of parent-reported upper respiratory tract illnesses between groups (625 for high-dose vs 600 for standard-dose groups, incidence RR, 1.01; 95% CI, 0.88-1.16). At study termination, serum 25-hydroxyvitamin D levels were 48.7 ng/mL (95% CI, 46.9-50.5 ng/mL) in the high-dose group and 36.8 ng/mL (95% CI, 35.4-38.2 ng/mL) in the standard-dose group.
CONCLUSIONS AND RELEVANCE: Among healthy children aged 1 to 5 years, daily administration of 2000 IU compared with 400 IU of vitamin D supplementation did not reduce overall wintertime upper respiratory tract infections. These findings do not support the routine use of high-dose vitamin D supplementation in children for the prevention of viral upper respiratory tract infections.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01419262.
PMID: 28719693
DOI: 10.1001/jama.2017.8708