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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'abstract': '<jats:title>Abstract</jats:title><jats:sec>\n'
' <jats:title>Background</jats:title>\n'
' <jats:p>Vitamin D supplementation may prevent acute respiratory infections '
'(ARIs). 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<\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'
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'Chandramohan D, Walraven G. Effects of vitamin D supplementation to '
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'trial of vitamin D supplementation to prevent seasonal influenza A in '
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'S. Effect of weekly vitamin D supplements on mortality, morbidity, and '
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'randomised controlled trial. BMJ. 2011;342: d2975.',
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'L, Ekström L, Lindh JD, Andersson J. Vitamin D3 supplementation in '
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'double-blind intervention study. BMJ Open. 2012;2(6):e001663.',
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'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.',
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'Decallonne B, Bouillon R, Decramer M, Janssens W. High doses of vitamin '
'D to reduce exacerbations in chronic obstructive pulmonary disease: a '
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'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.',
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'Florkowski CM, Livesey JH, Camargo CA, Scragg R. Effect of vitamin D3 '
'supplementation on upper respiratory tract infections in healthy adults: '
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'journal-title': 'JAMA'},
{ 'issue': '10',
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'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.',
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{ 'issue': '10',
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'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.',
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'Smieja M. Vitamin D3 and gargling for the prevention of upper '
'respiratory tract infections: a randomized controlled trial. BMC Infect '
'Dis. 2014;14: 273.',
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'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.',
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'JC, Venn A, Gebski V, Whiteman DC, Webb PM, et al. Effect of vitamin D '
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'randomized controlled trial. Food Funct. 2014;5(9):2365–70.',
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'Vitamin D supplementation and upper respiratory tract infections in '
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'2015;27(1):113–9.',
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{ 'issue': '5',
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'Greiller CL, Kilpin K, McLaughlin D, Fletcher G, Mein CA, et al. '
'Double-blind randomised placebo-controlled trial of bolus-dose vitamin '
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{ 'issue': '2',
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'doi-asserted-by': 'publisher',
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'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.',
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'N, Enayat Z, Balayah Z, Syed A, et al. Double-blind randomised '
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'acute respiratory infection in older adults and their carers (ViDiFlu). '
'Thorax. 2015;70(10):953–60.',
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'author': 'S Simpson',
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'Weekly cholecalciferol supplementation results in significant reductions '
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'pilot RCT. BMC Nutr. 2015;1(1): 7.',
'journal-title': 'BMC Nutr'},
{ 'issue': '6',
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'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',
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'doi-asserted-by': 'publisher',
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'SV. Vitamin D supplementation for treatment and prevention of pneumonia '
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{ 'issue': '3',
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'DOI': '10.1001/jama.2017.8708',
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'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',
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'Schwartz RS. High-dose monthly vitamin D for prevention of acute '
'respiratory infection in older long-term care residents: a randomized '
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'journal-title': 'J Am Geriatr Soc'},
{ 'issue': '20',
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'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',
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'doi-asserted-by': 'publisher',
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'year': '2018',
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'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',
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'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.',
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{ 'issue': '4',
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'volume': '22',
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'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.',
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{ 'issue': '9',
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'volume': '6',
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{ 'issue': '6',
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'J, Komoike N, Itagaki M, Miyakawa Y, et al. Randomized trial of vitamin '
'D supplementation to prevent seasonal influenza and upper respiratory '
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{ 'issue': '4',
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'author': 'H Hauger',
'year': '2019',
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'Damsgaard CT. Winter cholecalciferol supplementation at 55°N has little '
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'years: a secondary analysis from a randomized controlled trial. Eur J '
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'to reduce respiratory infections in children and adolescents in Vietnam: '
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'2019;13(2):176–83.',
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'Blauth M, Felson DT, McCloskey EV, Watzl B, Hofbauer LC, et al. Effect '
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'strength-training exercise program on clinical outcomes in older adults: '
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'journal-title': 'JAMA'},
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'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.',
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{ 'issue': '2',
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'Patwardhan V, Padidela R, Khadilkar V. Occurrence of infections in '
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'journal-title': 'J Med Sci'},
{ 'issue': '2',
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