Vitamin D and respiratory tract infections

A link between vitamin D and respiratory tract infections has been hypothesised. According to the hypothesis, vitamin D deficiency may predispose to infection. Evidence supporting the hypothesis derives from some scientific studies and the observation that outbreaks of respiratory infections occur predominantly during months associated with lower exposure to the sun. Evidence against the hypothesis has also been reported. The Institute of Medicine concluded in a 2011 report that the existing data were "not consistently supportive of a causal role" for the vitamin in reducing the risk of infection. However, more recent studies show that Vitamin D provides a protective role in reducing the incidence of respiratory infection.

Ultraviolet radiation and vitamin D

An inverse association between exposure to the sun and upper respiratory tract infections was first proposed in 1926 by Smiley, who theorized that seasonality of infection was caused by “disordered vitamine metabolism in the human...directly due to a lack of solar radiation during the dark months of winter.”[1] Studies of Dutch[2] and Russian[3] subjects have also indicated a correlation of ultraviolet light exposure and relative absence of infection. However, the seasonality of infections such as influenza may also be explicable by other factors. For example, low absolute humidity favours the survival of the influenza virus.[4] A review by authors from the University of Maryland School of Pharmacy suggested that while low-dose vitamin D supplementation was unlikely to be harmful, "sensible sun exposure" was "an inexpensive and enjoyable way" to ensure healthy levels of vitamin D.[5]

Evidence

Evidence both for and against an association of vitamin D and respiratory infections has been reported. Early studies of vitamin D and mice came to different conclusions, with one group reporting a link and the other no link between deficiency and infection.[5] More recent studies of humans have also had divergent results. A study published in the Archives of Internal Medicine found that people with the lowest blood vitamin D levels reported having significantly more recent colds or cases of the flu chronic respiratory disorders, especially those who had pre-existing respiratory ailments.[6][7] A report in the American Journal of Clinical Nutrition reported that children who took vitamin D3 supplements daily in winter were 42% less likely to get infected with seasonal flu than those who were given a placebo.[8][9] Mongolian schoolchildren who drank vitamin D fortified milk during winter reported having fewer colds than those who received non-fortified milk.[10] Another study found no effect of vitamin D supplementation on the incidence or severity of upper respiratory tract infections.[11] Authors of one of the positive studies also stressed that their results would need to be confirmed in clinical trials before vitamin D could be recommended to prevent infections.[6]

The Institute of Medicine released a comprehensive, peer-reviewed report on calcium and vitamin D in 2011. The conclusion of the report was that the existing studies did not provide strong or consistent evidence for a link between vitamin D deficiency and respiratory tract infections. The authors stated that data from randomised controlled trials would be needed, showing a dose response to vitamin D supplementation, before recommendations could be considered.[12]

However, a 2017 individual-participant meta-analysis of 25 randomized controlled trials (11,321 total participants) concluded "Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit."[13] Doses used in the constituent studies that used daily dosing ranged from 300-4000 IU/day (7.5-100 µg/day).

Vitamin D supplementation

Proponents of the vitamin D hypothesis have recommended dietary supplements (5,000 International Units (IU)/day for adults and 1,000 IU/day for every 25 pounds of body weight in children) and suggested that larger doses (2,000 IU/kg/day for 3–4 days) could be used to treat influenza.[14][15] It has been noted that large doses of vitamin D can lead to hypercalcemia and that "single megadoses" of vitamin D, while not especially harmful, may be associated with an increased risk of bone fractures.[5] The authors of this review suggested that supplementation should be offered only to those with verified deficiencies or to promote muscular and skeletal health in elderly patients.[5]

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See also

References
  1. Smiley DF. Seasonal factors in the incidence of the acute respiratory infections. Am J Hyg 1926;6:621-6, p. 626
  2. Termorshuizen F, Wijga A, Gerritsen J, Neijens HJ, van Loveren H (October 2004). "Exposure to solar ultraviolet radiation and respiratory tract symptoms in 1-year-old children". Photodermatol Photoimmunol Photomed. 20 (5): 270–1. doi:10.1111/j.1600-0781.2004.00110.x. PMID 15379879.
  3. Gigineĭshvili GR, Il’in NI, Suzdal’nitskiĭ RS, Levando VA. The use of UV irradiation to correct the immune system and decrease morbidity in athletes [in Russian]. Vopr Kurortol Fizioter Lech Fiz Kult 1990 May-Jun:30-3.
  4. Shaman J, Kohn M (March 2009). "Absolute humidity modulates influenza survival, transmission, and seasonality" (PDF). Proc. Natl. Acad. Sci. U.S.A. 106 (9): 3243–8. doi:10.1073/pnas.0806852106. PMC 2651255. PMID 19204283.
  5. Haines, S. T.; Park, S. K. (2012). "Vitamin D Supplementation: What's Known, What to Do, and What's Needed". Pharmacotherapy. 32 (4): 354–382. doi:10.1002/phar.1037. PMID 22461123.
  6. Ginde AA, Mansbach JM, Camargo CA (February 2009). "Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey". Arch. Intern. Med. 169 (4): 384–90. doi:10.1001/archinternmed.2008.560. PMC 3447082. PMID 19237723.
  7. massgeneral press release http://www.massgeneral.org/about/pressrelease.aspx?id=1103
  8. food consumer newsite http://www.foodconsumer.org/newsite/2/other_diseases/vitamin_d_as_effective_as_vaccine_in_preventing_flu_1403100231.html Archived 2013-05-13 at the Wayback Machine
  9. "Archived copy". Archived from the original on 2010-10-12. Retrieved 2013-06-27.CS1 maint: archived copy as title (link)
  10. Camargo; et al. (August 2012). "Randomized Trial of Vitamin D Supplementation and Risk of Acute Respiratory Tract Infection in Mongolia". Pediatrics. 130 (3): e561–7. doi:10.1542/peds.2011-3029. PMID 22908115.
  11. Li-Ng, M.; Aloia, J. F.; Pollack, S.; Cunha, B. A.; Mikhail, M.; Yeh, J.; Berbari, N. (2009). "A randomized controlled trial of vitamin D3 supplementation for the prevention of symptomatic upper respiratory tract infections". Epidemiology and Infection. 137 (10): 1396–1404. doi:10.1017/S0950268809002404. PMID 19296870.
  12. DIETARY REFERENCE INTAKES FOR CALCIUM AND VITAMIN D Committee to Review Dietary Reference Intakes for Vitamin D and Calcium, Food and Nutrition Board. A. Catharine Ross, Christine L. Taylor, Ann L. Yaktine, and Heather B. Del Valle, Editors. Institute of Medicine of the National Academies, 2011.
  13. Martineau AR, Jolliffe DA, Greenberg L, Aloia JF, Bergman P, Dubnov-Raz G, Esposito S, Ganmaa D, Ginde AA, Goodall EC, Grant CC, Janssens W, Jensen ME, Kerley CP, Laaksi I, Manaseki-Holland S, Mauger D, Murdoch DR, Neale R, Rees JR, Simpson S, Stelmach I, Trilok Kumar G, Urashima M, Camargo CA, Griffiths CJ, Hooper RL. Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis. Health Technol Assess. 2019 Jan;23(2):1-44. doi: 10.3310/hta23020. PubMed PMID: 30675873; PubMed Central PMCID: PMC6369419.
  14. Cannell JJ, Vieth R, Umhau JC, et al. (December 2006). "Epidemic influenza and vitamin D". Epidemiol. Infect. 134 (6): 1129–40. doi:10.1017/S0950268806007175. PMC 2870528. PMID 16959053.
  15. Cannell JJ, Zasloff M, Garland CF, Scragg R, Giovannucci E (2008). "On the epidemiology of influenza". Virol. J. 5: 29. doi:10.1186/1743-422X-5-29. PMC 2279112. PMID 18298852.
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