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All Studies   Meta Analysis    Recent:   

Optimal methods of vitamin D supplementation to prevent acute respiratory infections: a systematic review, dose–response and pairwise meta-analysis of randomized controlled trials

Wang et al., Nutrition Journal, doi:10.1186/s12937-024-00990-w
Aug 2024  
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Vitamin D for COVID-19
8th treatment shown to reduce risk in October 2020
 
*, now with p < 0.00000000001 from 122 studies, recognized in 9 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,800+ studies for 95 treatments. c19early.org
Systematic review and meta-analysis of 43 RCTs involving 49,320 participants showing lower risk of acute respiratory infections (ARIs) with vitamin D treatment for trials using daily doses of 400–1200 IU/day. Trials shorter than four months yielded the strongest results. No significant effects were observed for bolus dosing, longer trial durations, and overall.
18 meta analyses show significant improvements with vitamin D treatment for mortality1-13, mechanical ventilation1,6,7,12,14,15, ICU admission1,3,6,7,10,12,14-17, hospitalization5,12, severity2,4,6,11,18, and cases8,17,18.
Currently there are 122 vitamin D treatment for COVID-19 studies, showing 36% lower mortality [28‑43%], 19% lower ventilation [-3‑36%], 45% lower ICU admission [28‑58%], 19% lower hospitalization [9‑29%], and 17% fewer cases [9‑24%].
Wang et al., 14 Aug 2024, peer-reviewed, 11 authors. Contact: lianglbh@126.com, schl@bjmu.edu.cn.
This PaperVitamin DAll
Randomized trial of influence of vitamin D on the prevention and improvement of symptomatic COVID-19
Huan Wang, Liyuan Tao, Liyan Cui, Yahong Chen, Dongyang Liu, Lixiang Xue, Yuping Yang, Yang Lv, Fuchun Zhang, Tiancheng Wang, Xiaoxiao Wang, Wanqiong Yuan, Hao Liu, Jie Huang, Yanfang Jiang, Na Liu, Lijuan Yang, Yunjing Hu, Yanfang Li, Yuling Gao, Haiyan Li, Baohua Li, Chunli Song
Scientific Reports, doi:10.1038/s41598-024-66267-8
We aimed to investigate the preventive effect of vitamin D2 on COVID-19 and the improvement of symptoms after COVID-19 infection. The study recruited 228 health care workers who tested negative PCR or antigen for COVID-19. Subjects were randomly allocated to vitamin D2 or non-intervention at a ratio 1:1. Subjects recorded PCR or antigen tests and the symptoms of COVID-19 twice a week during the follow-up visit. The concentration of serum 25-hydroxyvitamin D (25(OH)D), C-reaction protein (CRP), complement component C1q and inflammatory cytokines were measured. The rates of COVID-19 infection were 50.5% in the vitamin D2 group and 52.4% in the non-intervention group (P = 0.785). There was no difference in the COVID-19 symptoms between the two groups. The mean 25(OH)D level significantly increased from 14.1 to 31.1 ng/mL after administration (P < 0.001). The difference between the two groups was not significant for the concentrations of CRP, C1q and inflammatory cytokines on the thirtieth day of the trial. According to the second level of vitamin D, there was a 14.3% difference in positive infection rates between the vitamin D adequate (> 30 ng/mL) and deficient groups (< 20 ng/mL). Adequate vitamin D had a tendency to prevent COVID-19. Trial registration: ClinicalTrials.gov NCT05673980, dated: 12/2022.
Author contributions All authors read and approved the final manuscript. Chunli Song, Baohua Li, Haiyan Li, Yahong Chen, Dongyang Liu, Yuping Yang, Yang Lv and Fuchun Zhang designed this research. Chunli Song directed the whole study. Drafting of the manuscript: Huan Wang and Liyuan Tao. Statistical analysis: Liyuan Tao, Xiaoxiao Wang and Huan Wang. Critical revision of the manuscript for important intellectual content: All authors. Acquisition, analysis, or interpretation of data: Huan Wang, Wanqiong Yuan, Hao Liu, Jie Huang. Obtained funding: Chunli Song. Administrative, technical, or material support: Liyan Cui, Lixiang Xue, Tiancheng Wang, Yanfang Jiang, Na Liu, Yanfang Li, Yuling Gao. Supervision: Chunli Song, Baohua Li amd Haiyan Li. Competing interests The authors declare no competing interests.
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This study aimed to identify the optimal methods of vitamin D ' 'supplementation.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Methods</jats:title>\n' ' <jats:p>PubMed, Embase, Cochrane Central Register of Controlled Trials, Web ' 'of Science, and the ClinicalTrials.gov registry were searched from database inception through ' 'July 13, 2023. Randomized-controlled trials (RCTs) were included. Data were pooled using ' 'random-effects model. The primary outcome was the proportion of participants with one or more ' 'ARIs.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Results</jats:title>\n' ' <jats:p>The analysis included 43 RCTs with 49320 participants. Forty RCTs ' 'were considered to be at low risk for bias. The main pairwise meta-analysis indicated there ' 'were no significant preventive effects of vitamin D supplementation against ARIs (risk ratio ' '[RR]: 0.99, 95% confidence interval [CI]: 0.97 to 1.01, ' '<jats:italic>I</jats:italic><jats:sup><jats:italic>2</jats:italic></jats:sup>\u2009=\u2009' '49.6%). The subgroup dose–response meta-analysis indicated that the optimal vitamin D ' 'supplementation doses ranged between 400–1200\xa0IU/day for both summer-sparing and ' 'winter-dominant subgroups. The subgroup pairwise meta-analysis also revealed significant ' 'preventive effects of vitamin D supplementation in subgroups of daily dosing (RR: 0.92, 95% ' 'CI: 0.85 to 0.99, ' '<jats:italic>I</jats:italic><jats:sup><jats:italic>2</jats:italic></jats:sup>\u2009=\u2009' '55.7%, number needed to treat [NNT]: 36), trials duration\u2009&lt;\u20094\xa0months (RR: ' '0.81, 95% CI: 0.67 to 0.97, ' '<jats:italic>I</jats:italic><jats:sup><jats:italic>2</jats:italic></jats:sup>\u2009=\u2009' '48.8%, NNT: 16), summer-sparing seasons (RR: 0.85, 95% CI: 0.74 to 0.98, ' '<jats:italic>I</jats:italic><jats:sup><jats:italic>2</jats:italic></jats:sup>\u2009=\u2009' '55.8%, NNT: 26), and winter-dominant seasons (RR: 0.79, 95% CI: 0.71 to 0.89, ' '<jats:italic>I</jats:italic><jats:sup><jats:italic>2</jats:italic></jats:sup>\u2009=\u2009' '9.7%, NNT: 10).</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Conclusion</jats:title>\n' ' <jats:p>Vitamin D supplementation may slightly prevent ARIs when taken daily ' 'at doses between 400 and 1200\xa0IU/d during spring, autumn, or winter, which should be ' 'further examined in future clinical trials.</jats:p>\n' ' </jats:sec>', 'DOI': '10.1186/s12937-024-00990-w', 'type': 'journal-article', 'created': {'date-parts': [[2024, 8, 14]], 'date-time': '2024-08-14T07:02:39Z', 'timestamp': 1723618959000}, 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Optimal methods of vitamin D supplementation to prevent acute respiratory infections: a ' 'systematic review, dose–response and pairwise meta-analysis of randomized controlled trials', 'prefix': '10.1186', 'volume': '23', 'author': [ {'given': 'Chih-Hung', 'family': 'Wang', 'sequence': 'first', 'affiliation': []}, {'given': 'Lorenzo', 'family': 'Porta', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ting-Kai', 'family': 'Yang', 'sequence': 'additional', 'affiliation': []}, {'given': 'Yu-Hsiang', 'family': 'Wang', 'sequence': 'additional', 'affiliation': []}, {'given': 'Tsung-Hung', 'family': 'Wu', 'sequence': 'additional', 'affiliation': []}, {'given': 'Frank', 'family': 'Qian', 'sequence': 'additional', 'affiliation': []}, {'given': 'Yin-Yi', 'family': 'Han', 'sequence': 'additional', 'affiliation': []}, {'given': 'Wang-Huei', 'family': 'Sheng', 'sequence': 'additional', 'affiliation': []}, {'given': 'Shyr-Chyr', 'family': 'Chen', 'sequence': 'additional', 'affiliation': []}, {'given': 'Chien-Chang', 'family': 'Lee', 'sequence': 'additional', 'affiliation': []}, {'given': 'Shan-Chwen', 'family': 'Chang', 'sequence': 'additional', 'affiliation': []}], 'member': '297', 'published-online': {'date-parts': [[2024, 8, 14]]}, 'reference': [ { 'key': '990_CR1', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.eclinm.2021.100986', 'volume': '37', 'author': 'X Jin', 'year': '2021', 'unstructured': 'Jin X, Ren J, Li R, Gao Y, Zhang H, Li J, Zhang J, Wang X, Wang G. 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A ' 'randomized controlled trial of vitamin D3 supplementation for the ' 'prevention of symptomatic upper respiratory tract infections. Epidemiol ' 'Infect. 2009;137(10):1396–404.', 'journal-title': 'Epidemiol Infect'}, { 'issue': '5', 'key': '990_CR29', 'doi-asserted-by': 'publisher', 'first-page': '809', 'DOI': '10.1086/654881', 'volume': '202', 'author': 'I Laaksi', 'year': '2010', 'unstructured': 'Laaksi I, Ruohola JP, Mattila V, Auvinen A, Ylikomi T, Pihlajamäki H. ' 'Vitamin D supplementation for the prevention of acute respiratory tract ' 'infection: a randomized, double-blinded trial among young Finnish men. J ' 'Infect Dis. 2010;202(5):809–14.', 'journal-title': 'J Infect Dis'}, { 'issue': '10', 'key': '990_CR30', 'doi-asserted-by': 'publisher', 'first-page': '1148', 'DOI': '10.1111/j.1365-3156.2010.02578.x', 'volume': '15', 'author': 'S Manaseki-Holland', 'year': '2010', 'unstructured': 'Manaseki-Holland S, Qader G, Isaq Masher M, Bruce J, Zulf Mughal M, ' 'Chandramohan D, Walraven G. Effects of vitamin D supplementation to ' 'children diagnosed with pneumonia in Kabul: a randomised controlled ' 'trial. Trop Med Int Health. 2010;15(10):1148–55.', 'journal-title': 'Trop Med Int Health'}, { 'issue': '5', 'key': '990_CR31', 'doi-asserted-by': 'publisher', 'first-page': '1255', 'DOI': '10.3945/ajcn.2009.29094', 'volume': '91', 'author': 'M Urashima', 'year': '2010', 'unstructured': 'Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, Ida H. Randomized ' 'trial of vitamin D supplementation to prevent seasonal influenza A in ' 'schoolchildren. Am J Clin Nutr. 2010;91(5):1255–60.', 'journal-title': 'Am J Clin Nutr'}, { 'key': '990_CR32', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/bmj.d2975', 'volume': '342', 'author': 'GT Kumar', 'year': '2011', 'unstructured': 'Kumar GT, Sachdev HS, Chellani H, Rehman AM, Singh V, Arora H, Filteau ' 'S. Effect of weekly vitamin D supplements on mortality, morbidity, and ' 'growth of low birthweight term infants in India up to age 6 months: ' 'randomised controlled trial. BMJ. 2011;342: d2975.', 'journal-title': 'BMJ'}, { 'issue': '5', 'key': '990_CR33', 'doi-asserted-by': 'publisher', 'first-page': '1294', 'DOI': '10.1016/j.jaci.2010.12.016', 'volume': '127', 'author': 'P Majak', 'year': '2011', 'unstructured': 'Majak P, Olszowiec-Chlebna M, Smejda K, Stelmach I. Vitamin D ' 'supplementation in children may prevent asthma exacerbation triggered by ' 'acute respiratory infection. J Allergy Clin Immunol. 2011;127(5):1294–6.', 'journal-title': 'J Allergy Clin Immunol'}, { 'issue': '6', 'key': '990_CR34', 'doi-asserted-by': 'publisher', 'first-page': 'e001663', 'DOI': '10.1136/bmjopen-2012-001663', 'volume': '2', 'author': 'P Bergman', 'year': '2012', 'unstructured': 'Bergman P, Norlin AC, Hansen S, Rekha RS, Agerberth B, Björkhem-Bergman ' 'L, Ekström L, Lindh JD, Andersson J. Vitamin D3 supplementation in ' 'patients with frequent respiratory tract infections: a randomised and ' 'double-blind intervention study. BMJ Open. 2012;2(6):e001663.', 'journal-title': 'BMJ Open'}, { 'issue': '3', 'key': '990_CR35', 'doi-asserted-by': 'publisher', 'first-page': 'e561', 'DOI': '10.1542/peds.2011-3029', 'volume': '130', 'author': 'CA Camargo Jr', 'year': '2012', 'unstructured': 'Camargo CA Jr, Ganmaa D, Frazier AL, Kirchberg FF, Stuart JJ, Kleinman ' 'K, Sumberzul N, Rich-Edwards JW. Randomized trial of vitamin D ' 'supplementation and risk of acute respiratory infection in Mongolia. ' 'Pediatrics. 2012;130(3):e561-567.', 'journal-title': 'Pediatrics'}, { 'issue': '2', 'key': '990_CR36', 'doi-asserted-by': 'publisher', 'first-page': '105', 'DOI': '10.7326/0003-4819-156-2-201201170-00004', 'volume': '156', 'author': 'A Lehouck', 'year': '2012', 'unstructured': 'Lehouck A, Mathieu C, Carremans C, Baeke F, Verhaegen J, Van Eldere J, ' 'Decallonne B, Bouillon R, Decramer M, Janssens W. High doses of vitamin ' 'D to reduce exacerbations in chronic obstructive pulmonary disease: a ' 'randomized trial. Ann Intern Med. 2012;156(2):105–14.', 'journal-title': 'Ann Intern Med'}, { 'issue': '9824', 'key': '990_CR37', 'doi-asserted-by': 'publisher', 'first-page': '1419', 'DOI': '10.1016/S0140-6736(11)61650-4', 'volume': '379', 'author': 'S Manaseki-Holland', 'year': '2012', 'unstructured': 'Manaseki-Holland S, Maroof Z, Bruce J, Mughal MZ, Masher MI, Bhutta ZA, ' 'Walraven G, Chandramohan D. Effect on the incidence of pneumonia of ' 'vitamin D supplementation by quarterly bolus dose to infants in Kabul: a ' 'randomised controlled superiority trial. Lancet. 2012;379(9824):1419–27.', 'journal-title': 'Lancet'}, { 'issue': '13', 'key': '990_CR38', 'doi-asserted-by': 'publisher', 'first-page': '1333', 'DOI': '10.1001/jama.2012.12505', 'volume': '308', 'author': 'DR Murdoch', 'year': '2012', 'unstructured': 'Murdoch DR, Slow S, Chambers ST, Jennings LC, Stewart AW, Priest PC, ' 'Florkowski CM, Livesey JH, Camargo CA, Scragg R. Effect of vitamin D3 ' 'supplementation on upper respiratory tract infections in healthy adults: ' 'the VIDARIS randomized controlled trial. JAMA. 2012;308(13):1333–9.', 'journal-title': 'JAMA'}, { 'issue': '10', 'key': '990_CR39', 'doi-asserted-by': 'publisher', 'first-page': '1055', 'DOI': '10.1097/INF.0b013e31829be0b0', 'volume': '32', 'author': 'P Marchisio', 'year': '2013', 'unstructured': 'Marchisio P, Consonni D, Baggi E, Zampiero A, Bianchini S, Terranova L, ' 'Tirelli S, Esposito S, Principi N. Vitamin D supplementation reduces the ' 'risk of acute otitis media in otitis-prone children. Pediatr Infect Dis ' 'J. 2013;32(10):1055–60.', 'journal-title': 'Pediatr Infect Dis J'}, { 'issue': '10', 'key': '990_CR40', 'doi-asserted-by': 'publisher', 'first-page': '1384', 'DOI': '10.1093/cid/cit549', 'volume': '57', 'author': 'JR Rees', 'year': '2013', 'unstructured': 'Rees JR, Hendricks K, Barry EL, Peacock JL, Mott LA, Sandler RS, ' 'Bresalier RS, Goodman M, Bostick RM, Baron JA. Vitamin D3 ' 'supplementation and upper respiratory tract infections in a randomized, ' 'controlled trial. Clin Infect Dis. 2013;57(10):1384–92.', 'journal-title': 'Clin Infect Dis'}, { 'key': '990_CR41', 'doi-asserted-by': 'publisher', 'DOI': '10.1186/1471-2334-14-273', 'volume': '14', 'author': 'EC Goodall', 'year': '2014', 'unstructured': 'Goodall EC, Granados AC, Luinstra K, Pullenayegum E, Coleman BL, Loeb M, ' 'Smieja M. Vitamin D3 and gargling for the prevention of upper ' 'respiratory tract infections: a randomized controlled trial. BMC Infect ' 'Dis. 2014;14: 273.', 'journal-title': 'BMC Infect Dis'}, { 'issue': '4', 'key': '990_CR42', 'doi-asserted-by': 'publisher', 'first-page': '396', 'DOI': '10.1111/apa.12819', 'volume': '104', 'author': 'CC Grant', 'year': '2015', 'unstructured': 'Grant CC, Kaur S, Waymouth E, Mitchell EA, Scragg R, Ekeroma A, Stewart ' 'A, Crane J, Trenholme A, Camargo CA Jr. Reduced primary care respiratory ' 'infection visits following pregnancy and infancy vitamin D ' 'supplementation: a randomised controlled trial. Acta Paediatr. ' '2015;104(4):396–404.', 'journal-title': 'Acta Paediatr'}, { 'issue': '1', 'key': '990_CR43', 'doi-asserted-by': 'publisher', 'first-page': '156', 'DOI': '10.3945/ajcn.113.063271', 'volume': '99', 'author': 'B Tran', 'year': '2014', 'unstructured': 'Tran B, Armstrong BK, Ebeling PR, English DR, Kimlin MG, van der Pols ' 'JC, Venn A, Gebski V, Whiteman DC, Webb PM, et al. Effect of vitamin D ' 'supplementation on antibiotic use: a randomized controlled trial. Am J ' 'Clin Nutr. 2014;99(1):156–61.', 'journal-title': 'Am J Clin Nutr'}, { 'issue': '9', 'key': '990_CR44', 'doi-asserted-by': 'publisher', 'first-page': '2365', 'DOI': '10.1039/C4FO00371C', 'volume': '5', 'author': 'M Urashima', 'year': '2014', 'unstructured': 'Urashima M, Mezawa H, Noya M, Camargo CA Jr. Effects of vitamin D ' 'supplements on influenza A illness during the 2009 H1N1 pandemic: a ' 'randomized controlled trial. Food Funct. 2014;5(9):2365–70.', 'journal-title': 'Food Funct'}, { 'issue': '1', 'key': '990_CR45', 'doi-asserted-by': 'publisher', 'first-page': '113', 'DOI': '10.1123/pes.2014-0030', 'volume': '27', 'author': 'G Dubnov-Raz', 'year': '2015', 'unstructured': 'Dubnov-Raz G, Rinat B, Hemilä H, Choleva L, Cohen AH, Constantini NW. ' 'Vitamin D supplementation and upper respiratory tract infections in ' 'adolescent swimmers: a randomized controlled trial. Pediatr Exerc Sci. ' '2015;27(1):113–9.', 'journal-title': 'Pediatr Exerc Sci'}, { 'issue': '5', 'key': '990_CR46', 'doi-asserted-by': 'publisher', 'first-page': '451', 'DOI': '10.1136/thoraxjnl-2014-206449', 'volume': '70', 'author': 'AR Martineau', 'year': '2015', 'unstructured': 'Martineau AR, MacLaughlin BD, Hooper RL, Barnes NC, Jolliffe DA, ' 'Greiller CL, Kilpin K, McLaughlin D, Fletcher G, Mein CA, et al. ' 'Double-blind randomised placebo-controlled trial of bolus-dose vitamin ' 'D3 supplementation in adults with asthma (ViDiAs). Thorax. ' '2015;70(5):451–7.', 'journal-title': 'Thorax'}, { 'issue': '2', 'key': '990_CR47', 'doi-asserted-by': 'publisher', 'first-page': '120', 'DOI': '10.1016/S2213-2600(14)70255-3', 'volume': '3', 'author': 'AR Martineau', 'year': '2015', 'unstructured': 'Martineau AR, James WY, Hooper RL, Barnes NC, Jolliffe DA, Greiller CL, ' 'Islam K, McLaughlin D, Bhowmik A, Timms PM, et al. Vitamin D3 ' 'supplementation in patients with chronic obstructive pulmonary disease ' '(ViDiCO): a multicentre, double-blind, randomised controlled trial. ' 'Lancet Respir Med. 2015;3(2):120–30.', 'journal-title': 'Lancet Respir Med'}, { 'issue': '10', 'key': '990_CR48', 'doi-asserted-by': 'publisher', 'first-page': '953', 'DOI': '10.1136/thoraxjnl-2015-206996', 'volume': '70', 'author': 'AR Martineau', 'year': '2015', 'unstructured': 'Martineau AR, Hanifa Y, Witt KD, Barnes NC, Hooper RL, Patel M, Stevens ' 'N, Enayat Z, Balayah Z, Syed A, et al. 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;70(10):953–60.', 'journal-title': 'Thorax'}, { 'issue': '1', 'key': '990_CR49', 'doi-asserted-by': 'publisher', 'DOI': '10.1186/2055-0928-1-7', 'volume': '1', 'author': 'S Simpson', 'year': '2015', 'unstructured': 'Simpson S, 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 Nutr. 2015;1(1): 7.', 'journal-title': 'BMC Nutr'}, { 'issue': '6', 'key': '990_CR50', 'doi-asserted-by': 'publisher', 'first-page': '634', 'DOI': '10.1164/rccm.201506-1169OC', 'volume': '193', 'author': 'LC Denlinger', 'year': '2016', 'unstructured': 'Denlinger LC, King TS, Cardet JC, Craig T, Holguin F, Jackson DJ, Kraft ' 'M, Peters SP, Ross K, Sumino K, et al. Vitamin D supplementation and the ' 'risk of colds in patients with asthma. Am J Respir Crit Care Med. ' '2016;193(6):634–41.', 'journal-title': 'Am J Respir Crit Care Med'}, { 'issue': '11', 'key': '990_CR51', 'doi-asserted-by': 'publisher', 'first-page': '967', 'DOI': '10.1007/s13312-016-0970-5', 'volume': '53', 'author': 'P Gupta', 'year': '2016', 'unstructured': 'Gupta P, Dewan P, Shah D, Sharma N, Bedi N, Kaur IR, Bansal AK, Madhu ' 'SV. Vitamin D supplementation for treatment and prevention of pneumonia ' 'in under-five children: a randomized double-blind placebo controlled ' 'trial. Indian Pediatr. 2016;53(11):967–76.', 'journal-title': 'Indian Pediatr'}, { 'issue': '3', 'key': '990_CR52', 'doi-asserted-by': 'publisher', 'first-page': '245', 'DOI': '10.1001/jama.2017.8708', 'volume': '318', 'author': 'M Aglipay', 'year': '2017', 'unstructured': 'Aglipay M, Birken CS, Parkin PC, Loeb MB, Thorpe K, Chen Y, Laupacis A, ' 'Mamdani M, Macarthur C, Hoch JS, et al. Effect of high-dose vs ' 'standard-dose wintertime vitamin D supplementation on viral upper ' 'respiratory tract infections in young healthy children. JAMA. ' '2017;318(3):245–54.', 'journal-title': 'JAMA'}, { 'issue': '3', 'key': '990_CR53', 'doi-asserted-by': 'publisher', 'first-page': '496', 'DOI': '10.1111/jgs.14679', 'volume': '65', 'author': 'AA Ginde', 'year': '2017', 'unstructured': 'Ginde AA, Blatchford P, Breese K, Zarrabi L, Linnebur SA, Wallace JI, ' 'Schwartz RS. High-dose monthly vitamin D for prevention of acute ' 'respiratory infection in older long-term care residents: a randomized ' 'clinical trial. J Am Geriatr Soc. 2017;65(3):496–503.', 'journal-title': 'J Am Geriatr Soc'}, { 'issue': '20', 'key': '990_CR54', 'doi-asserted-by': 'publisher', 'first-page': '2086', 'DOI': '10.1001/jama.2018.5729', 'volume': '319', 'author': 'AM Hibbs', 'year': '2018', 'unstructured': 'Hibbs AM, Ross K, Kerns LA, Wagner C, Fuloria M, Groh-Wargo S, Zimmerman ' 'T, Minich N, Tatsuoka C. Effect of vitamin D supplementation on ' 'recurrent wheezing in black infants who were born preterm: the D-wheeze ' 'randomized clinical trial. JAMA. 2018;319(20):2086–94.', 'journal-title': 'JAMA'}, { 'issue': '9', 'key': '990_CR55', 'doi-asserted-by': 'publisher', 'first-page': '969', 'DOI': '10.1182/bloodadvances.2017013979', 'volume': '2', 'author': 'MT Lee', 'year': '2018', 'unstructured': 'Lee MT, Kattan M, Fennoy I, Arpadi SM, Miller RL, Cremers S, McMahon DJ, ' 'Nieves JW, Brittenham GM. Randomized phase 2 trial of monthly vitamin D ' 'to prevent respiratory complications in children with sickle cell ' 'disease. Blood Adv. 2018;2(9):969–78.', 'journal-title': 'Blood Adv'}, { 'issue': '7', 'key': '990_CR56', 'doi-asserted-by': 'publisher', 'first-page': '646', 'DOI': '10.1001/jamapediatrics.2018.0602', 'volume': '172', 'author': 'J Rosendahl', 'year': '2018', 'unstructured': 'Rosendahl J, Valkama S, Holmlund-Suila E, Enlund-Cerullo M, Hauta-Alus ' 'H, Helve O, Hytinantti T, Levälahti E, Kajantie E, Viljakainen H, et al. ' 'Effect of higher vs standard dosage of vitamin D3 supplementation on ' 'bone strength and infection in healthy infants: a randomized clinical ' 'trial. JAMA Pediatr. 2018;172(7):646–54.', 'journal-title': 'JAMA Pediatr'}, { 'issue': '4', 'key': '990_CR57', 'doi-asserted-by': 'publisher', 'first-page': '491', 'DOI': '10.1007/s12603-017-0952-x', 'volume': '22', 'author': 'Y Shimizu', 'year': '2018', 'unstructured': 'Shimizu Y, Ito Y, Yui K, Egawa K, Orimo H. Intake of 25-hydroxyvitamin ' 'D3 reduces duration and severity of upper respiratory tract infection: a ' 'randomized, double-blind, placebo-controlled, parallel group comparison ' 'study. J Nutr Health Aging. 2018;22(4):491–500.', 'journal-title': 'J Nutr Health Aging'}, { 'issue': '9', 'key': '990_CR58', 'doi-asserted-by': 'publisher', 'first-page': 'ofz228', 'DOI': '10.1093/ofid/ofz228', 'volume': '6', 'author': 'JF Aloia', 'year': '2019', 'unstructured': 'Aloia JF, Islam S, Mikhail M. Vitamin D and acute respiratory ' 'infections-the PODA trial. Open Forum Infect Dis. 2019;6(9):ofz228.', 'journal-title': 'Open Forum Infect Dis'}, { 'issue': '6', 'key': '990_CR59', 'doi-asserted-by': 'publisher', 'first-page': '1088', 'DOI': '10.1093/ibd/izy346', 'volume': '25', 'author': 'S Arihiro', 'year': '2019', 'unstructured': 'Arihiro S, Nakashima A, Matsuoka M, Suto S, Uchiyama K, Kato T, Mitobe ' 'J, Komoike N, Itagaki M, Miyakawa Y, et al. Randomized trial of vitamin ' 'D supplementation to prevent seasonal influenza and upper respiratory ' 'infection in patients with inflammatory bowel disease. Inflamm Bowel ' 'Dis. 2019;25(6):1088–95.', 'journal-title': 'Inflamm Bowel Dis'}, { 'issue': '4', 'key': '990_CR60', 'doi-asserted-by': 'publisher', 'first-page': '1453', 'DOI': '10.1007/s00394-018-1671-8', 'volume': '58', 'author': 'H Hauger', 'year': '2019', 'unstructured': 'Hauger H, Ritz C, Mortensen C, Mølgaard C, Metzdorff SB, Frøkiær H, ' 'Damsgaard CT. Winter cholecalciferol supplementation at 55°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. Eur J ' 'Nutr. 2019;58(4):1453–62.', 'journal-title': 'Eur J Nutr'}, { 'issue': '2', 'key': '990_CR61', 'doi-asserted-by': 'publisher', 'first-page': '176', 'DOI': '10.1111/irv.12615', 'volume': '13', 'author': 'M Loeb', 'year': '2019', 'unstructured': 'Loeb M, Dang AD, Thiem VD, Thanabalan V, Wang B, Nguyen NB, Tran HTM, ' 'Luong TM, Singh P, Smieja M, et al. Effect of Vitamin D supplementation ' 'to reduce respiratory infections in children and adolescents in Vietnam: ' 'a randomized controlled trial. Influenza Other Respir Viruses. ' '2019;13(2):176–83.', 'journal-title': 'Influenza Other Respir Viruses'}, { 'issue': '18', 'key': '990_CR62', 'doi-asserted-by': 'publisher', 'first-page': '1855', 'DOI': '10.1001/jama.2020.16909', 'volume': '324', 'author': 'HA Bischoff-Ferrari', 'year': '2020', 'unstructured': 'Bischoff-Ferrari HA, Vellas B, Rizzoli R, Kressig RW, da Silva JAP, ' 'Blauth M, Felson DT, McCloskey EV, Watzl B, Hofbauer LC, et al. Effect ' 'of vitamin D supplementation, omega-3 fatty acid supplementation, or a ' 'strength-training exercise program on clinical outcomes in older adults: ' 'the DO-HEALTH randomized clinical trial. JAMA. 2020;324(18):1855–68.', 'journal-title': 'JAMA'}, { 'issue': '2', 'key': '990_CR63', 'doi-asserted-by': 'publisher', 'first-page': '311', 'DOI': '10.1093/cid/ciz801', 'volume': '71', 'author': 'CA Camargo', 'year': '2020', 'unstructured': 'Camargo CA, Sluyter J, Stewart AW, Khaw KT, Lawes CMM, Toop L, Waayer D, ' 'Scragg R. Effect of monthly high-dose vitamin D supplementation on acute ' 'respiratory infections in older adults: a randomized controlled trial. ' 'Clin Infect Dis. 2020;71(2):311–7.', 'journal-title': 'Clin Infect Dis'}, { 'issue': '4', 'key': '990_CR64', 'doi-asserted-by': 'publisher', 'first-page': '359', 'DOI': '10.1056/NEJMoa1915176', 'volume': '383', 'author': 'D Ganmaa', 'year': '2020', 'unstructured': 'Ganmaa D, Uyanga B, Zhou X, Gantsetseg G, Delgerekh B, Enkhmaa D, Khulan ' 'D, Ariunzaya S, Sumiya E, Bolortuya B, et al. Vitamin D supplements for ' 'prevention of tuberculosis infection and disease. N Engl J Med. ' '2020;383(4):359–68.', 'journal-title': 'N Engl J Med'}, { 'issue': '2', 'key': '990_CR65', 'doi-asserted-by': 'publisher', 'first-page': '117', 'DOI': '10.4162/nrp.2020.14.2.117', 'volume': '14', 'author': 'R Mandlik', 'year': '2020', 'unstructured': 'Mandlik R, Mughal Z, Khadilkar A, Chiplonkar S, Ekbote V, Kajale N, ' 'Patwardhan V, Padidela R, Khadilkar V. Occurrence of infections in ' 'schoolchildren subsequent to supplementation with vitamin D-calcium or ' 'zinc: a randomized, double-blind, placebo-controlled trial. Nutr Res ' 'Pract. 2020;14(2):117–26.', 'journal-title': 'Nutr Res Pract'}, { 'issue': '10', 'key': '990_CR66', 'doi-asserted-by': 'publisher', 'first-page': '1', 'DOI': '10.3310/hta24100', 'volume': '24', 'author': 'C Rake', 'year': '2020', 'unstructured': 'Rake C, Gilham C, Bukasa L, Ostler R, Newton M, Peto Wild J, Aigret B, ' 'Hill M, Gillie O, Nazareth I, et al. High-dose oral vitamin D ' 'supplementation and mortality in people aged 65–84 years: the VIDAL ' 'cluster feasibility RCT of open versus double-blind individual ' 'randomisation. 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Lancet ' 'Diabetes Endocrinol. 2021;9(2):69–81.', 'journal-title': 'Lancet Diabetes Endocrinol'}, { 'issue': '5', 'key': '990_CR69', 'doi-asserted-by': 'publisher', 'first-page': '803', 'DOI': '10.1016/j.jmii.2022.01.003', 'volume': '55', 'author': 'YN Huang', 'year': '2022', 'unstructured': 'Huang YN, Chi H, Chiu NC, Huang CY, Li ST, Wang JY, Huang DT. A ' 'randomized trial of vitamin D supplementation to prevent seasonal ' 'influenza and enterovirus infection in children. J Microbiol Immunol ' 'Infect. 2022;55(5):803–11.', 'journal-title': 'J Microbiol Immunol Infect'}, { 'issue': '4', 'key': '990_CR70', 'doi-asserted-by': 'publisher', 'first-page': '423', 'DOI': '10.1016/j.arcmed.2022.04.003', 'volume': '53', 'author': 'MA Villasis-Keever', 'year': '2022', 'unstructured': 'Villasis-Keever MA, López-Alarcón MG, Miranda-Novales G, Zurita-Cruz JN, ' 'Barrada-Vázquez AS, González-Ibarra J, Martínez-Reyes M, Grajales-Muñiz ' 'C, Santacruz-Tinoco CE, Martínez-Miguel B, et al. 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' 'Washington (DC): National Academies Press (US), National Academy of ' 'Sciences; 2011.'}, { 'issue': '4', 'key': '990_CR77', 'doi-asserted-by': 'publisher', 'first-page': '1833', 'DOI': '10.1007/s00394-023-03124-w', 'volume': '62', 'author': 'A Zittermann', 'year': '2023', 'unstructured': 'Zittermann A, Trummer C, Theiler-Schwetz V, Pilz S. Long-term ' 'supplementation with 3200 to 4000 IU of vitamin D daily and adverse ' 'events: a systematic review and meta-analysis of randomized controlled ' 'trials. Eur J Nutr. 2023;62(4):1833–44.', 'journal-title': 'Eur J Nutr'}, { 'issue': '1', 'key': '990_CR78', 'doi-asserted-by': 'publisher', 'first-page': '48', 'DOI': '10.1111/nure.12090', 'volume': '72', 'author': 'RP Heaney', 'year': '2014', 'unstructured': 'Heaney RP. Guidelines for optimizing design and analysis of clinical ' 'studies of nutrient effects. 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Pediatrics. 2011;127(1):e180–7.', 'journal-title': 'Pediatrics'}, { 'key': '990_CR81', 'doi-asserted-by': 'publisher', 'DOI': '10.3389/fimmu.2022.1023903', 'volume': '13', 'author': 'LS Kümmel', 'year': '2022', 'unstructured': 'Kümmel LS, Krumbein H, Fragkou PC, Hünerbein BL, Reiter R, Papathanasiou ' 'KA, Thölken C, Weiss ST, Renz H, Skevaki C. Vitamin D supplementation ' 'for the treatment of COVID-19: a systematic review and meta-analysis of ' 'randomized controlled trials. 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