{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T15:46:41Z","timestamp":1785685601088,"version":"3.56.0"},"reference-count":111,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T00:00:00Z","timestamp":1688947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Vitamin\u2009D plays an important role in immune function, and the deficiency thereof has been associated with several infections, most notably respiratory tract infections. However, data from intervention studies investigating the effect of high-dose vitamin D supplementation on infections have been inconclusive.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>The aim of this study was to evaluate the level of evidence regarding the efficacy of vitamin D supplementation above the standard dose (400\u2009IU) in preventing infections in apparently healthy children\u2009&amp;lt;\u20095\u2009years of age.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Data Sources<\/jats:title>\n                  <jats:p>PubMed, Scopus, Science Direct, Web of Science, Google Scholar, CINAHL, and MEDLINE electronic databases were searched between August 2022 and November 2022. Seven studies met the inclusion criteria.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Data Extraction<\/jats:title>\n                  <jats:p>Meta-analyses of outcomes in more than one study were performed using Review Manager software. Heterogeneity was evaluated using the I2 statistic. Randomized controlled trials in which vitamin D was supplemented at\u2009&amp;gt;\u2009400\u2009IU compared with placebo, no treatment, or standard dose were included.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Data Analysis<\/jats:title>\n                  <jats:p>Seven trials that enrolled a total of 5748 children were included. Odds ratios (ORs) with 95%CIs were calculated using random- and fixed-effects models. There was no significant effect of high-dose vitamin D supplementation on the incidence of upper respiratory tract infection (OR, 0.83; 95%CI, 0.62\u20131.10). There was a 57% (95%CI, 0.30\u20130.61), 56% (95%CI, 0.27\u20130.07), and 59% (95%CI, 0.26\u20130.65) reduction in the odds of influenza\/cold, cough, and fever incidence, respectively, with daily supplementation of vitamin D\u2009&amp;gt;\u20091000\u2009IU. No effect was found on bronchitis, otitis media, diarrhea\/gastroenteritis, primary care visits for infections, hospitalizations, or mortality.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>High-dose vitamin D supplementation provided no benefit in preventing upper respiratory tract infections (moderate certainty of evidence) but reduced the incidence influenza\/cold (moderate certainty of evidence), cough, and fever (low certainty of evidence). These findings are based on a limited number of trials and should be interpreted with caution. Further research is needed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Systematic Review Registration<\/jats:title>\n                  <jats:p>PROSPERO registration number CRD42022355206.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/nutrit\/nuad082","type":"journal-article","created":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T00:15:57Z","timestamp":1689034557000},"page":"579-599","source":"Crossref","is-referenced-by-count":12,"title":["High-dose oral vitamin D supplementation for prevention of\u00a0infections in children aged 0 to 59 months: a systematic review and meta-analysis"],"prefix":"10.1093","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7435-4520","authenticated-orcid":false,"given":"Janet Adede","family":"Carboo","sequence":"first","affiliation":[{"name":"Centre of Excellence for Nutrition (CEN), North-West University , Potchefstroom, North West Province, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin Claire","family":"Dolman-Macleod","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Nutrition (CEN), North-West University , Potchefstroom, North West Province, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6609-0238","authenticated-orcid":false,"given":"Linda","family":"Malan","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Nutrition (CEN), North-West University , Potchefstroom, North West Province, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2457-6456","authenticated-orcid":false,"given":"Martani Johanni","family":"Lombard","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Nutrition (CEN), North-West University , Potchefstroom, North West Province, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,7,10]]},"reference":[{"key":"2024041208003260400_nuad082-B1","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1210\/er.2018-00126","article-title":"Skeletal and extraskeletal actions of vitamin D: current evidence and outstanding questions","volume":"40","author":"Bouillon","year":"2019","journal-title":"Endocr Rev"},{"key":"2024041208003260400_nuad082-B2","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/1472-6823-13-14","article-title":"Factors affecting vitamin D status in different populations in the city of S\u00e3o Paulo, Brazil: the S\u00e3o PAulo vitamin D Evaluation Study (SPADES)","volume":"13","author":"Maeda","year":"2013","journal-title":"BMC Endocr Disord"},{"key":"2024041208003260400_nuad082-B3","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.ijpp.2017.11.005","article-title":"Vitamin D's role in health and disease: how does the present inform our understanding of the past?","volume":"23","author":"Lockau","year":"2018","journal-title":"Int J Paleopathol"},{"key":"2024041208003260400_nuad082-B4","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.jaut.2017.07.007","article-title":"Modulation of inflammatory and immune responses by vitamin D","volume":"85","author":"Colotta","year":"2017","journal-title":"J Autoimmun"},{"key":"2024041208003260400_nuad082-B5","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.jsbmb.2018.09.003","article-title":"The serum vitamin D metabolome: what we know and what is still to discover","volume":"186","author":"Tuckey","year":"2019","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2024041208003260400_nuad082-B6","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.jsbmb.2017.11.014","article-title":"Why should we measure free 25(OH) vitamin D?","volume":"180","author":"Tsuprykov","year":"2018","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2024041208003260400_nuad082-B7","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/s2213-8587(13)70165-7","article-title":"Vitamin D status and ill health: a systematic review","volume":"2","author":"Autier","year":"2014","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2024041208003260400_nuad082-B8","doi-asserted-by":"publisher","first-page":"1911","DOI":"10.1210\/jc.2011-0385","article-title":"Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline [published correction appears in J Clin Endocrinol Metab. 2011;96:3908]","volume":"96","author":"Holick","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"2024041208003260400_nuad082-B9","author":"National Kidney Foundation. 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