CoChat
Sign Up
Cited by 33Vitamin D Research StudiesInfluenza Virus Research StudiesRespiratory viral infections research

Association between vitamin D and influenza: meta-analysis and systematic review of randomized controlled trials

Open access
Zhu, Zhixin, Zhu, Xiaoxia, Gu, Lanfang, Zhan, Yancen, Chen, Liang, Li, Xiuyang·2022·Frontiers in Nutrition
DOI 10.3389/fnut.2021.799709PMC PMC8777486
Open this paper in CoChat — free account

Abstract

Background: Vitamin D supplementation improves the immune function of human body and can be a convenient way to prevent influenza. However, evidence on the protective effect of vitamin D supplementation on influenza from Randomized Controlled Trials (RCTs) is inconclusive. Methods: RCTs regarding the association between vitamin D supplementation and influenza were identified by searching PubMed, Cochrane library, Embase and Chinese Biomedical Database (CBM) from inception until present (last updated on 10 November 2021). Studies that reported dosages and durations of vitamin D supplementation and number of influenza infections could be included. Heterogeneity was assessed using Cochran's Q test and I2 statistics, the meta-analysis was conducted by using a random-effects model, the pooled effects were expressed with risk ratio (RR) with 95% confidence interval (95% CI). Results: 10 trials including 4859 individuals were ultimately eligible after scanning. There was no evidence of a significant heterogeneity among studies (I2 = 27%, P = 0.150). Meta-regression analysis finding indicated that country, latitude, average age, economic level, follow-up period and average daily vitamin D intake did not cause the statistical heterogeneity. The study finding indicates that substitution with vitamin D significantly reduces the risk of influenza infections (RR = 0.78, 95% CI:0.64–0.95). No evidence of publication bias was observed. Omission of any single trial had little impact on the pooled risk estimates. Conclusions: The meta-analysis produced a corroboration that vitamin D supplement has a preventive effect on influenza. Strategies for preventing influenza can be optimized by vitamin D supplementation.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fnut.2021.799709

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • There are still limited meta-analyses on the role of nutrient supplementation in preventing COVID-19 and influenza.

    “Additionally, there are still limited meta-analyses on the role of nutrient supplementation in preventing COVID-19 and influenza.”

    From Comparative effectiveness of oral nutritional supplements in preventing respiratory tract infections among adults: a systematic review and network meta-analysis (2025) · cites this paper as [18]

    The Discussion (page unavailable) says no previous meta-analysis had examined the same question of vitamin D supplementation and influenza, and that earlier respiratory-infection meta-analyses did not analyze influenza as a subgroup. This supports a gap for vitamin D and influenza, but the paper does not address whether meta-analyses are limited for other nutrients or for COVID-19 prevention. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 42

  1. [2]Osterholm MT Kelley NS Sommer A Belongia EA. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis. (2012) 12: 36– 44. 10.1016/S1473-3099(11)70295-X 22032844 · DOI · Paper page
  2. [3]Zhou J Du J Huang L Wang Y Shi Y Lin H. Preventive effects of vitamin D on seasonal influenza a in infants: a multicenter, randomized, open, controlled clinical trial. Pediatr Infect Dis J. (2018) 37: 749– 54. 10.1097/INF.0000000000001890 29315160 · DOI
  3. [4]Aglipay M Birken CS Parkin PC Loeb MB Thorpe K Chen Y. Effect of high-dose vs standard-dose wintertime Vitamin D supplementation on viral upper respiratory tract infections in young healthy children. JAMA. (2017) 318: 245– 54. 10.1001/jama.2017.8708 28719693 PMC5817430 · DOI
  4. [5]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: 1255– 60. 10.3945/ajcn.2009.29094 20219962 · DOI
  5. [6]Urashima M Mezawa H Noya M Camargo CA. Effects of vitamin D supplements on influenza A illness during the 2009 H1N1 pandemic: a randomized controlled trial. Food Function. (2014) 5: 2365- 70. 10.1039/C4FO00371C 25088394 · DOI
  6. [7]Arihiro S Nakashima A Matsuoka M Suto S Uchiyama K Kato T. 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: 1088– 95. 10.1093/ibd/izy346 30601999 PMC6499936 · DOI
  7. [8]Loeb M Dang AD Thiem VD Thanabalan V Wang B Nguyen NB. Effect of Vitamin D supplementation to reduce respiratory infections in children and adolescents in Vietnam: a randomized controlled trial. Influenza Other Respi Viruses. (2019) 13: 176– 83. 10.1111/irv.12615 30328294 PMC6379634 · DOI
  8. [9]Ginde AA Mansbach JM Camargo CA. Association between Serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. (2009) 169: 384– 90. 10.1001/archinternmed.2008.560 19237723 PMC3447082 · DOI
  9. [10]Karatekin G Kaya A Salihoglu Ö Balci H Nuhoglu A. Association of subclinical vitamin D deficiency in newborns with acute lower respiratory infection and their mothers. Eur J Clin Nutr. (2009) 63: 473– 7. 10.1038/sj.ejcn.1602960 18030309 · DOI
  10. [11]Laaksi I Ruohola JP Tuohimaa P Auvinen A Haataja R Pihlajamäki H. An association of serum vitamin D concentrations <40 nmol/L with acute respiratory tract infection in young Finnish men. Am J Clin Nutr. (2007) 86: 714– 7. 10.1093/ajcn/86.3.714 17823437 · DOI
  11. [12]Roth D Shah R Black R Baqui A. Vitamin D status and acute lower respiratory infection in early childhood in Sylhet, Bangladesh. Acta Paediatr Int J Paediatr. (2010) 99: 389– 93. 10.1111/j.1651-2227.2009.01594.x 19900174 · DOI
  12. [13]Wayse V Yousafzai A Mogale K Filteau S. Association of subclinical vitamin D deficiency with severe acute lower respiratory infection in Indian children under 5 y. Eur J Clin Nutr. (2004) 58: 563– 7. 10.1038/sj.ejcn.1601845 15042122 · DOI
  13. [14]McNally JD Leis K Matheson LA Karuananyake C Sankaran K Rosenberg AM. Vitamin D deficiency in young children with severe acute lower respiratory infection. Pediatr Pulmonol. (2009) 44: 981– 8. 10.1002/ppul.21089 19746437 · DOI
  14. [15]Roth DE Jones AB Prosser C Robinson JL Vohra S. Vitamin D status is not associated with the risk of hospitalization for acute bronchiolitis in early childhood. Eur J Clin Nutr. (2009) 63: 297– 9. 10.1038/sj.ejcn.1602946 17971825 · DOI
  15. [16]Jpt H AD Jac S. Cochrane Handbook for systematic reviews of interventions version 5.1.0 (updated March 2011). Wiley-Blackwell. (2011).
  16. [17]Moher D Liberati A Tetzlaff J Altman DG Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol. (2009) 62: 1006– 12. 10.1016/j.jclinepi.2009.06.005 19631508 · DOI · Paper page
  17. [18]Higgins JP Green S. Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Book Series (2008). p. 1– 649. 10.1002/978047071218431643080 · DOI · Paper page
  18. [19]Atkins D Best D Briss PA Eccles M Falck-Ytter Y Flottorp S. Grading quality of evidence and strength of recommendations. The BMJ. (2004) 328: 1490. 10.1136/bmj.328.7454.1490 15205295 PMC428525 · DOI · Paper page
  19. [20]Higgins JP Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. (2002) 21: 1539– 58. 10.1002/sim.1186 12111919 · DOI · Paper page
  20. [21]Ioannidis JP Patsopoulos NA Evangelou E. Uncertainty in heterogeneity estimates in meta-analyses. BMJ (Clinical research ed). (2007) 335: 914– 6. 10.1136/bmj.39343.408449.80 17974687 PMC2048840 · DOI · Paper page
  21. [24]Altman DG MD Bryant TN Gardner MJ. Statistics with Confidence Second Edition. (2000).
  22. [25]Godan Hauptman A Lukić-Grlić A Vraneš J Milošević M Gagro A. The effect of standard-dose wintertime vitamin D supplementation on influenza infection in immunized nursing home elderly residents. Croat Med J. (2021) 62: 495– 503. 10.3325/cmj.2021.62.495 34730890 PMC8596483 · DOI
  23. [26]Murdoch DR Slow S Chambers ST Jennings LC Stewart AW Priest PC. Effect of vitamin D 3 supplementation on upper respiratory tract infections in healthy adults: The VIDARIS randomized controlled trial. JAMA. (2012) 308: 1333– 9. 10.1001/jama.2012.12505 23032549 · DOI
  24. [27]Jorde R Witham M Janssens W Rolighed L Borchhardt K de Boer IH. Vitamin D supplementation did not prevent influenza-like illness as diagnosed retrospectively by questionnaires in subjects participating in randomized clinical trials. Scandinav J Infect Dis. (2012) 44(2): 126- 32. 10.3109/00365548.2011.621446 22026455 PMC3917712 · DOI
  25. [28]Rees JR Hendricks K Barry EL Peacock JL Mott LA Sandler RS. Vitamin D3 supplementation and upper respiratory tract infections in a randomized, controlled trial. Clin Infect Dis. (2013) 57: 1384– 92. 10.1093/cid/cit549 24014734 PMC3805175 · DOI
  26. [29]Rondanelli M Miccono A Lamburghini S Avanzato I Riva A Allegrini P. Self-care for common colds: the pivotal role of vitamin D, vitamin C, zinc, and echinacea in three main immune interactive clusters (physical barriers, innate and adaptive immunity) involved during an episode of common colds - practical advice on dosages and on the time to take these nutrients/botanicals in order to prevent or treat common colds. Evid-Based Complement Altern Med. (2018) 2018: 1– 36. 10.1155/2018/5813095 29853961 PMC5949172 · DOI
  27. [30]Szymczak I Pawliczak R. The Active Metabolite of Vitamin D3 as a Potential Immunomodulator. Scand J Immunol. (2016) 83: 83– 91. 10.1111/sji.12403 26678915 · DOI
  28. [31]Hewison M. Vitamin D and immune function: an overview. Proc Nutr Soc. (2012) 71: 50– 61. 10.1017/S0029665111001650 21849106 · DOI
  29. [32]Charan J Goyal JP Saxena D Yadav P. Vitamin D for prevention of respiratory tract infections: a systematic review and meta-analysis. J Pharmacol Pharmacother. (2012) 3: 300– 3. 10.4103/0976-500X.103685 23326099 PMC3543548 · DOI · Paper page
  30. [33]Mao S Huang S. Vitamin D supplementation and risk of respiratory tract infections: a meta-analysis of randomized controlled trials. Scand J Infect Dis. (2013) 45: 696– 702. 10.3109/00365548.2013.803293 23815596 · DOI
  31. [34]Vuichard Gysin D Dao D Gysin CM Lytvyn L Loeb M. Effect of vitamin D3 supplementation on respiratory tract infections in healthy individuals: a systematic review and meta-analysis of randomized controlled trials. PLoS ONE. (2016) 11: e0162996. 10.1371/journal.pone.0162996 27631625 PMC5025082 · DOI
  32. [35]Xiao L Xing C Yang Z Xu S Wang M Du H. Vitamin D supplementation for the prevention of childhood acute respiratory infections: a systematic review of randomised controlled trials. Br J Nutr. (2015) 114: 1026– 34. 10.1017/S000711451500207X 26310436 · DOI
  33. [36]Bergman P Lindh ÅU Björkhem-Bergman L Lindh JD. Vitamin D and respiratory tract infections: a systematic review and meta-analysis of randomized controlled trials. PLoS ONE. (2013) 8: e65835. 10.1371/journal.pone.0065835 23840373 PMC3686844 · DOI · Paper page
  34. [37]Cannell JJ Vieth R Umhau JC Holick MF Grant WB Madronich S. Epidemic influenza and vitamin D. Epidemiol Infect. (2006) 134: 1129– 40. 10.1017/S0950268806007175 16959053 PMC2870528 · DOI
  35. [38]Kimlin MG Olds WJ Moore MR. Location and Vitamin D synthesis: Is the hypothesis validated by geophysical data? J Photochem Photobiol B Biol. (2007) 86: 234– 9. 10.1016/j.jphotobiol.2006.10.004 17142054 · DOI
  36. [39]Holick M Matsuoka L Wortsman jage vitamin D solar. ultraviolet. Lancet. (1989) 334: 1104– 5. 10.1016/S0140-6736(89)91124-0 2572832 · DOI
  37. [40]Vásárhelyi B Sátori A Olajos F Szabó A Beko G. Low vitamin D levels among patients at Semmelweis University: retrospective analysis during a one-year period. Orvosi Hetil. (2011) 152: 1272– 7. 10.1556/OH.2011.29187 21803724 · DOI
  38. [41]Xu C Fang VJ Perera RA Kam AM Ng S Chan YH. Serum 25-Hydroxyvitamin D was not associated with influenza virus infection in children and adults in Hong Kong, 2009-2010. J Nutr. (2016) 146: 2506– 12. 10.3945/jn.116.234856 27798334 · DOI
  39. [42]Greiller CL Martineau AR. Modulation of the immune response to respiratory viruses by vitamin D. Nutrients. (2015) 7: 4240– 70. 10.3390/nu7064240 26035247 PMC4488782 · DOI
  40. [43]Sato M Hosoya M Wright PF. Differences in serum cytokine levels between influenza virus A and B infections in children. Cytokine. (2009) 47: 65– 8. 10.1016/j.cyto.2009.05.003 19497758 · DOI
  41. [44]Goncalves-Mendes N Talvas J Dualé C Guttmann A Corbin V Marceau G. Impact of vitamin D supplementation on influenza vaccine response and immune functions in deficient elderly persons: a randomized placebo-controlled trial. Front Immunol. (2019) 10: 65. 10.3389/fimmu.2019.00065 30800121 PMC6375825 · DOI
  42. [45]Lee MD Lin CH Lei WT Chang HY Lee HC Yeung CY. Does vitamin D deficiency affect the immunogenic responses to influenza vaccination? A systematic review and meta-analysis. Nutrients. (2018) 10: 409. 10.3390/nu10040409 29587438 PMC5946194 · DOI

Cited by

Sorted by citations

Authors
Zhu, Z., Zhu, X., Gu, L., Zhan, Y., Chen, L., & Li, X.
Affiliations
Second Affiliated Hospital of Zhejiang University (CN)
Corresponding author
Li, Xiuyang
ORCID
Venue
Frontiers in Nutrition
Publisher
Frontiers Media SA
Published
2022-01-07
Volume
8
Pages
799709-799709
ISSN
2296-861X (ISSN-L)
DOI
10.3389/fnut.2021.799709
PMC
PMC8777486
OpenAlex
W4205847097
Cited by
33
References
2
Citations by year
2026: 4 · 2025: 12 · 2024: 5 · 2023: 7 · 2022: 5
FWCI
1.19
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Nutrition (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Science and Technology Department of Zhejiang Province
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
  • Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
  • Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
Keywords
vitamin D supplementation, influenza, influenza prevention, immune function, vitamin D deficiency, randomized controlled trials

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review