Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of aggregate data from randomised controlled trials

{ 'institution': [{'name': 'medRxiv'}], 'indexed': {'date-parts': [[2024, 5, 1]], 'date-time': '2024-05-01T00:06:56Z', 'timestamp': 1714522016889}, 'posted': {'date-parts': [[2020, 7, 17]]}, 'group-title': 'Infectious Diseases (except HIV/AIDS)', 'reference-count': 108, 'publisher': 'Cold Spring Harbor Laboratory', 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'accepted': {'date-parts': [[2020, 11, 25]]}, 'abstract': '<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>A 2017 ' 'meta-analysis of data from 25 randomised controlled trials of vitamin D supplementation for ' 'the prevention of acute respiratory infections revealed a protective effect of the ' 'intervention. Since then, 20 new RCTs have been ' 'completed.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Systematic ' 'review and meta-analysis of data from randomised controlled trials (RCTs) of vitamin D for ' 'ARI prevention using a random effects model. Pre-specified sub-group analyses were done to ' 'determine whether effects of vitamin D on risk of ARI varied according to baseline ' '25-hydroxyvitamin D (25[OH]D) concentration or dosing regimen. We searched MEDLINE, EMBASE, ' 'the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and the ' 'ClinicalTrials.gov registry from inception to 1st May 2020. Double-blind RCTs of ' 'supplementation with vitamin D or calcidiol, of any duration, were eligible if they were ' 'approved by a Research Ethics Committee and if ARI incidence was collected prospectively and ' 'pre-specified as an efficacy outcome. Aggregate data, stratified by baseline 25(OH)D ' 'concentration, were obtained from study authors. The study was registered with PROSPERO (no. ' 'CRD42020190633).</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>We ' 'identified 45 eligible RCTs (total 73,384 participants). Data were obtained for 46,331 ' '(98.0%) of 47,262 participants in 42 studies, aged 0 to 95 years. For the primary comparison ' 'of vitamin D supplementation vs. placebo, the intervention reduced risk of ARI overall (Odds ' 'Ratio [OR] 0.91, 95% CI 0.84 to 0.99; P for heterogeneity 0.01). No statistically significant ' 'effect of vitamin D was seen for any of the sub-groups defined by baseline 25(OH)D ' 'concentration. However, protective effects were seen for trials in which vitamin D was given ' 'using a daily dosing regimen (OR 0.75, 95% CI 0.61 to 0.93); at daily dose equivalents of ' '400-1000 IU (OR 0.70, 95% CI 0.55 to 0.89); and for a duration of ≤12 months (OR 0.82, 95% CI ' '0.72 to 0.93). No significant interaction was seen between allocation to vitamin D vs. ' 'placebo and dose frequency, dose size, or study duration. Vitamin D did not influence the ' 'proportion of participants experiencing at least one serious adverse event (OR 0.97, 95% CI ' '0.86 to 1.09). Risk of bias within individual studies was assessed as being low for all but ' 'three trials. A funnel plot showed left-sided asymmetry (P=0.008, Egger’s ' 'test).</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>Vitamin D ' 'supplementation was safe and reduced risk of ARI, despite evidence of significant ' 'heterogeneity across trials. Protection was associated with administration of daily doses of ' '400-1000 IU vitamin D for up to 12 months. The relevance of these findings to COVID-19 is not ' 'known and requires ' 'investigation.</jats:p></jats:sec><jats:sec><jats:title>Funding</jats:title><jats:p>None</jats:p></jats:sec>', 'DOI': '10.1101/2020.07.14.20152728', 'type': 'posted-content', 'created': {'date-parts': [[2020, 7, 17]], 'date-time': '2020-07-17T17:32:44Z', 'timestamp': 1595007164000}, 'source': 'Crossref', 'is-referenced-by-count': 27, 'title': 'Vitamin D supplementation to prevent acute respiratory infections: systematic review and ' 'meta-analysis of aggregate data from randomised controlled trials', 'prefix': '10.1101', 'author': [ {'given': 'David A', 'family': 'Jolliffe', 'sequence': 'first', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-5071-7654', 'authenticated-orcid': False, 'suffix': 'Jr', 'given': 'Carlos A', 'family': 'Camargo', 'sequence': 'additional', 'affiliation': []}, {'given': 'John D', 'family': 'Sluyter', 'sequence': 'additional', 'affiliation': []}, {'given': 'Mary', 'family': 'Aglipay', 'sequence': 'additional', 'affiliation': []}, {'given': 'John F', 'family': 'Aloia', 'sequence': 'additional', 'affiliation': []}, {'given': 'Davaasambuu', 'family': 'Ganmaa', 'sequence': 'additional', 'affiliation': []}, {'given': 'Peter', 'family': 'Bergman', 'sequence': 'additional', 'affiliation': []}, {'given': 'Arturo', 'family': 'Borzutzky', 'sequence': 'additional', 'affiliation': []}, {'given': 'Camilla T', 'family': 'Damsgaard', 'sequence': 'additional', 'affiliation': []}, {'given': 'Gal', 'family': 'Dubnov-Raz', 'sequence': 'additional', 'affiliation': []}, {'given': 'Susanna', 'family': 'Esposito', 'sequence': 'additional', 'affiliation': []}, {'given': 'Clare', 'family': 'Gilham', 'sequence': 'additional', 'affiliation': []}, {'given': 'Adit A', 'family': 'Ginde', 'sequence': 'additional', 'affiliation': []}, {'given': 'Inbal', 'family': 'Golan-Tripto', 'sequence': 'additional', 'affiliation': []}, {'given': 'Emma C', 'family': 'Goodall', 'sequence': 'additional', 'affiliation': []}, {'given': 'Cameron C', 'family': 'Grant', 'sequence': 'additional', 'affiliation': []}, {'given': 'Christopher J', 'family': 'Griffiths', 'sequence': 'additional', 'affiliation': []}, {'given': 'Anna Maria', 'family': 'Hibbs', 'sequence': 'additional', 'affiliation': []}, {'given': 'Wim', 'family': 'Janssens', 'sequence': 'additional', 'affiliation': []}, {'given': 'Anuradha Vaman', 'family': 'Khadilkar', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ilkka', 'family': 'Laaksi', 'sequence': 'additional', 'affiliation': []}, {'given': 'Margaret T', 'family': 'Lee', 'sequence': 'additional', 'affiliation': []}, {'given': 'Mark', 'family': 'Loeb', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jonathon L', 'family': 'Maguire', 'sequence': 'additional', 'affiliation': []}, {'given': 'Paweł', 'family': 'Majak', 'sequence': 'additional', 'affiliation': []}, {'given': 'David T', 'family': 'Mauger', 'sequence': 'additional', 'affiliation': []}, {'given': 'Semira', 'family': 'Manaseki-Holland', 'sequence': 'additional', 'affiliation': []}, {'given': 'David R', 'family': 'Murdoch', 'sequence': 'additional', 'affiliation': []}, {'given': 'Akio', 'family': 'Nakashima', 'sequence': 'additional', 'affiliation': []}, {'given': 'Rachel E', 'family': 'Neale', 'sequence': 'additional', 'affiliation': []}, {'given': 'Hai', 'family': 'Pham', 'sequence': 'additional', 'affiliation': []}, {'given': 'Christine', 'family': 'Rake', 'sequence': 'additional', 'affiliation': []}, {'given': 'Judy R', 'family': 'Rees', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jenni', 'family': 'Rosendahl', 'sequence': 'additional', 'affiliation': []}, {'given': 'Robert', 'family': 'Scragg', 'sequence': 'additional', 'affiliation': []}, {'given': 'Dheeraj', 'family': 'Shah', 'sequence': 'additional', 'affiliation': []}, {'given': 'Yoshiki', 'family': 'Shimizu', 'sequence': 'additional', 'affiliation': []}, {'given': 'Steve', 'family': 'Simpson-Yap', 'sequence': 'additional', 'affiliation': []}, {'given': 'Geeta Trilok', 'family': 'Kumar', 'sequence': 'additional', 'affiliation': []}, {'given': 'Mitsuyoshi', 'family': 'Urashima', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-5387-1721', 'authenticated-orcid': False, 'given': 'Adrian R', 'family': 'Martineau', 'sequence': 'additional', 'affiliation': []}], 'member': '246', 'reference': [ { 'key': '2020112811101412000_2020.07.14.20152728v3.1', 'doi-asserted-by': 'crossref', 'unstructured': 'Lanham-New SA , Webb AR , Cashman KD , et al. Vitamin D and SARS-CoV-2 ' 'virus/COVID-19 disease. BMJ Nutrition, Prevention & Health 2020.', 'DOI': '10.1136/bmjnph-2020-000089'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.2', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/nu7064240'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.3', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.jsbmb.2012.11.017'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.4', 'doi-asserted-by': 'crossref', 'unstructured': 'Pham H , Rahman A , Majidi A , Waterhouse M , Neale RE . Acute ' 'Respiratory Tract Infection and 25-Hydroxyvitamin D Concentration: A ' 'Systematic Review and Meta-Analysis. International Journal of ' 'Environmental Research and Public Health 2019; 16(17).', 'DOI': '10.3390/ijerph16173020'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.5', 'doi-asserted-by': 'publisher', 'DOI': '10.1017/S0950268809002404'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.6', 'doi-asserted-by': 'publisher', 'DOI': '10.3945/ajcn.2009.29094'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.7', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/j.1365-3156.2010.02578.x'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.8', 'doi-asserted-by': 'publisher', 'DOI': '10.1086/654881'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.9', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.jaci.2010.12.016'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.10', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/bmj.d2975'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.11', 'doi-asserted-by': 'publisher', 'DOI': '10.7326/0003-4819-156-2-201201170-00004'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.12', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S0140-6736(11)61650-4'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.13', 'doi-asserted-by': 'publisher', 'DOI': '10.1542/peds.2011-3029'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.14', 'doi-asserted-by': 'publisher', 'DOI': '10.1001/jama.2012.12505'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.15', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/bmjopen-2012-001663'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.16', 'doi-asserted-by': 'publisher', 'DOI': '10.1097/INF.0b013e31829be0b0'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.17', 'doi-asserted-by': 'crossref', 'unstructured': 'Rees JR , Hendricks K , Barry EL , et al. Vitamin D3 Supplementation and ' 'Upper Respiratory Tract Infections in a Randomized, Controlled Trial. ' 'Clin Infect Dis 2013.', 'DOI': '10.1093/cid/cit549'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.18', 'doi-asserted-by': 'publisher', 'DOI': '10.3945/ajcn.113.063271'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.19', 'doi-asserted-by': 'crossref', 'first-page': '273', 'DOI': '10.1186/1471-2334-14-273', 'article-title': 'Vitamin D3 and gargling for the prevention of upper respiratory tract ' 'infections: a randomized controlled trial', 'volume': '14', 'year': '2014', 'journal-title': 'BMC Infectious Diseases'}, { 'issue': '9', 'key': '2020112811101412000_2020.07.14.20152728v3.20', 'doi-asserted-by': 'crossref', 'first-page': '2365', 'DOI': '10.1039/C4FO00371C', 'article-title': 'Effects of vitamin D supplements on influenza A illness during the 2009 ' 'H1N1 pandemic: a randomized controlled trial', 'volume': '5', 'year': '2014', 'journal-title': 'Food & Function'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.21', 'doi-asserted-by': 'crossref', 'unstructured': 'Grant CC , Kaur S , Waymouth E , et al. Reduced primary care respiratory ' 'infection visits following pregnancy and infancy vitamin D ' 'supplementation: a randomised controlled trial. Acta Paediatr 2014.', 'DOI': '10.1111/apa.12819'}, { 'issue': '2', 'key': '2020112811101412000_2020.07.14.20152728v3.22', 'doi-asserted-by': 'crossref', 'first-page': '120', 'DOI': '10.1016/S2213-2600(14)70255-3', 'article-title': 'Vitamin D3 supplementation in patients with chronic obstructive ' 'pulmonary disease (ViDiCO): a multicentre, double-blind, randomised ' 'controlled trial', 'volume': '3', 'year': '2015', 'journal-title': 'The Lancet Respiratory Medicine'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.23', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/thoraxjnl-2014-206449'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.24', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/thoraxjnl-2015-206996'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.25', 'doi-asserted-by': 'crossref', 'unstructured': 'Simpson SJ , van der Mei I , Stewart N , Blizzard L , Tettey P , Taylor ' 'B. Weekly cholecalciferol supplementation results in significant ' 'reductions in infection risk among the vitamin D deficient: results from ' 'the CIPRIS pilot RCT. BMC Nutrition 2015; 1(7).', 'DOI': '10.1186/2055-0928-1-7'}, { 'issue': '1', 'key': '2020112811101412000_2020.07.14.20152728v3.26', 'doi-asserted-by': 'crossref', 'first-page': '113', 'DOI': '10.1123/pes.2014-0030', 'article-title': 'Vitamin D supplementation and upper respiratory tract infections in ' 'adolescent swimmers: a randomized controlled trial', 'volume': '27', 'year': '2015', 'journal-title': 'Pediatric Exercise Science'}, { 'issue': '6', 'key': '2020112811101412000_2020.07.14.20152728v3.27', 'doi-asserted-by': 'crossref', 'first-page': '634', 'DOI': '10.1164/rccm.201506-1169OC', 'article-title': 'Vitamin D Supplementation and the Risk of Colds in Patients with Asthma', 'volume': '193', 'year': '2016', 'journal-title': 'Am J Respir Crit Care Med'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.28', 'doi-asserted-by': 'crossref', 'unstructured': 'Tachimoto H , Mezawa H , Segawa T , Akiyama N , Ida H , Urashima M. ' 'Improved Control of Childhood Asthma with Low-Dose, Short-Term Vitamin D ' 'Supplementation: A Randomized, Double-Blind, Placebo-Controlled Trial. ' 'Allergy 2016.', 'DOI': '10.1111/all.12856'}, { 'issue': '3', 'key': '2020112811101412000_2020.07.14.20152728v3.29', 'doi-asserted-by': 'crossref', 'first-page': '496', 'DOI': '10.1111/jgs.14679', 'article-title': 'High-Dose Monthly Vitamin D for Prevention of Acute Respiratory ' 'Infection in Older Long-Term Care Residents: A Randomized Clinical ' 'Trial', 'volume': '65', 'year': '2017', 'journal-title': 'J Am Geriatr Soc'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.30', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/bmj.i6583'}, { 'issue': '11', 'key': '2020112811101412000_2020.07.14.20152728v3.31', 'doi-asserted-by': 'crossref', 'first-page': '967', 'DOI': '10.1007/s13312-016-0970-5', 'article-title': 'Vitamin D Supplementation for Treatment and Prevention of Pneumonia in ' 'Under-five Children: A Randomized Double-blind Placebo Controlled Trial', 'volume': '53', 'year': '2016', 'journal-title': 'Indian Pediatr'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.32', 'doi-asserted-by': 'publisher', 'DOI': '10.1001/jama.2017.8708'}, { 'issue': '6', 'key': '2020112811101412000_2020.07.14.20152728v3.33', 'doi-asserted-by': 'crossref', 'first-page': '1088', 'DOI': '10.1093/ibd/izy346', 'article-title': 'Randomized Trial of Vitamin D Supplementation to Prevent Seasonal ' 'Influenza and Upper Respiratory Infection in Patients With Inflammatory ' 'Bowel Disease', 'volume': '25', 'year': '2019', 'journal-title': 'Inflamm Bowel Dis'}, { 'issue': '20', 'key': '2020112811101412000_2020.07.14.20152728v3.34', 'doi-asserted-by': 'crossref', 'first-page': '2086', 'DOI': '10.1001/jama.2018.5729', 'article-title': 'Effect of Vitamin D Supplementation on Recurrent Wheezing in Black ' 'Infants Who Were Born Preterm: The D-Wheeze Randomized Clinical Trial', 'volume': '319', 'year': '2018', 'journal-title': 'JAMA'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.35', 'doi-asserted-by': 'publisher', 'DOI': '10.1182/bloodadvances.2017013979'}, { 'issue': '2', 'key': '2020112811101412000_2020.07.14.20152728v3.36', 'doi-asserted-by': 'crossref', 'first-page': '176', 'DOI': '10.1111/irv.12615', 'article-title': 'Effect of Vitamin D supplementation to reduce respiratory infections in ' 'children and adolescents in Vietnam: A randomized controlled trial', 'volume': '13', 'year': '2019', 'journal-title': 'Influenza Other Respir Viruses'}, { 'issue': '7', 'key': '2020112811101412000_2020.07.14.20152728v3.37', 'doi-asserted-by': 'crossref', 'first-page': '646', 'DOI': '10.1001/jamapediatrics.2018.0602', 'article-title': 'Effect of Higher vs Standard Dosage of Vitamin D3 Supplementation on ' 'Bone Strength and Infection in Healthy Infants: A Randomized Clinical ' 'Trial', 'volume': '172', 'year': '2018', 'journal-title': 'JAMA Pediatrics'}, { 'issue': '4', 'key': '2020112811101412000_2020.07.14.20152728v3.38', 'doi-asserted-by': 'crossref', 'first-page': '491', 'DOI': '10.1007/s12603-017-0952-x', 'article-title': 'Intake of 25-Hydroxyvitamin D3 Reduces Duration and Severity of Upper ' 'Respiratory Tract Infection: A Randomized, Double-Blind, ' 'Placebo-Controlled, Parallel Group Comparison Study', 'volume': '22', 'year': '2018', 'journal-title': 'J Nutr Health Aging'}, { 'issue': '9', 'key': '2020112811101412000_2020.07.14.20152728v3.39', 'doi-asserted-by': 'crossref', 'first-page': 'ofz228', 'DOI': '10.1093/ofid/ofz228', 'article-title': 'Vitamin D and Acute Respiratory Infections-The PODA Trial', 'volume': '6', 'year': '2019', 'journal-title': 'Open Forum Infectious Diseases'}, { 'issue': '4', 'key': '2020112811101412000_2020.07.14.20152728v3.40', 'doi-asserted-by': 'crossref', 'first-page': '1453', 'DOI': '10.1007/s00394-018-1671-8', 'article-title': 'Winter cholecalciferol supplementation at 55 degrees N has little ' 'effect on markers of innate immune defense in healthy children aged 4-8 ' 'years: a secondary analysis from a randomized controlled trial', 'volume': '58', 'year': '2019', 'journal-title': 'European Journal of Nutrition'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.41', 'doi-asserted-by': 'crossref', 'first-page': '311', 'DOI': '10.1093/cid/ciz801', 'article-title': 'Effect of monthly high-dose vitamin D supplementation on acute ' 'respiratory infections in older adults: A randomized controlled trial', 'volume': '71', 'year': '2020', 'journal-title': 'Clin Infect Dis'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.42', 'doi-asserted-by': 'crossref', 'first-page': '359', 'DOI': '10.1056/NEJMoa1915176', 'article-title': 'Vitamin D Supplements and Prevention of Tuberculosis Infection and ' 'Disease', 'volume': '383', 'year': '2020', 'journal-title': 'N Engl J Med'}, { 'issue': '2', 'key': '2020112811101412000_2020.07.14.20152728v3.43', 'doi-asserted-by': 'crossref', 'first-page': '117', 'DOI': '10.4162/nrp.2020.14.2.117', 'article-title': 'Occurrence of infections in schoolchildren subsequent to ' 'supplementation with vitamin D-calcium or zinc: a randomized, ' 'double-blind, placebo-controlled trial', 'volume': '14', 'year': '2020', 'journal-title': 'Nutr Res Pract'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.44', 'unstructured': 'Pham H , Waterhouse M , Baxter C , et al. The effect of vitamin D ' 'supplementation on acute respiratory tract infection in older Australian ' 'adults: an analysis of data from the D-Health Trial: a randomised ' 'controlled trial. The Lancet Diabetes & Endocrinology 2020; in press.'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.45', 'doi-asserted-by': 'publisher', 'DOI': '10.3310/hta24290'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.46', 'unstructured': 'Golan-Tripto I. The Effect of Vitamin D Administration to Premature ' 'Infants on Vitamin D Status and Respiratory Morbidity (NCT02404623). ' 'https://clinicaltrials.gov/ct2/show/NCT02404623.'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.47', 'unstructured': 'Reyes ML , Vizcaya C , Borzutzky A , et al. Study of Vitamin D for the ' 'Prevention of Acute Respiratory Infections in Children (NCT02046577). ' 'https://clinicaltrials.gov/ct2/show/NCT02046577.'}, { 'issue': '1', 'key': '2020112811101412000_2020.07.14.20152728v3.48', 'doi-asserted-by': 'crossref', 'first-page': '138', 'DOI': '10.1186/s13063-019-3184-z', 'article-title': 'Impact of two oral doses of 100,000 IU of vitamin D3 in preschoolers ' 'with viral-induced asthma: a pilot randomised controlled trial', 'volume': '20', 'year': '2019', 'journal-title': 'Trials'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.49', 'unstructured': 'Moreno A. Effect of Supplementation With Vitamin D on the Acute ' 'Bronchitis Prevention During the First Year of Life ' '(NCT01875757).https://clinicaltrials.gov/ct2/show/NCT01875757.'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.50', 'unstructured': 'Camargo CA . Effects of Vitamin D and Omega-3 Fatty Acids on Infectious ' 'Diseases and hCAP18 (VITAL Infection; NCT01758081).'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.51', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/bmj.d5928'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.52', 'doi-asserted-by': 'crossref', 'unstructured': 'Higgins JPT TJ , Chandler J , Cumpston M , Li T , Page MJ , Welch VA ' '(editors). Cochrane Handbook for Systematic Reviews of Interventions ' 'version 6.0 (updated July 2019). Cochrane 2019.', 'DOI': '10.1002/9781119536604'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.53', 'unstructured': 'Harris R , Bradburn M , Deeks J , et al. METAN: Stata module for fixed ' 'and random effects meta-analysis, revised 23 Sep 2010. Statistical ' 'Software Components S456798. 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Vitamin D3 Supplementation and ' 'Upper Respiratory Tract Infections in a Randomized, Controlled Trial. 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Double-blind randomised ' 'controlled trial of vitamin D3 supplementation for the prevention of ' 'acute respiratory infection in older adults and their carers (ViDiFlu). ' 'Thorax 2015.', 'DOI': '10.1136/thoraxjnl-2015-206996'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.88', 'doi-asserted-by': 'crossref', 'unstructured': 'Simpson SJ , van der Mei I , Stewart N , Blizzard L , Tettey P , Taylor ' 'B. Weekly cholecalciferol supplementation results in significant ' 'reductions in infection risk among the vitamin D deficient: results from ' 'the CIPRIS pilot RCT. 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' 'Improved Control of Childhood Asthma with Low-Dose, Short-Term Vitamin D ' 'Supplementation: A Randomized, Double-Blind, Placebo-Controlled Trial. 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The effect of vitamin D ' 'supplementation on acute respiratory tract infection in older Australian ' 'adults: an analysis of data from the D-Health Trial: a randomised ' 'controlled trial. The Lancet Diabetes & Endocrinology 2020; in press.'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.106', 'doi-asserted-by': 'publisher', 'DOI': '10.3310/hta24290'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.107', 'unstructured': 'Golan-Tripto I. The Effect of Vitamin D Administration to Premature ' 'Infants on Vitamin D Status and Respiratory Morbidity (NCT02404623). ' 'https://clinicaltrials.gov/ct2/show/NCT02404623.'}, { 'key': '2020112811101412000_2020.07.14.20152728v3.108', 'unstructured': 'Reyes ML , Vizcaya C , Borzutzky A , et al. Study of Vitamin D for the ' 'Prevention of Acute Respiratory Infections in Children (NCT02046577). 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