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Vitamin D and respiratory tract infections

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Associations have been shown between vitamin D levels and several respiratory tract infections suggesting that vitamin D deficiency may predispose to infection. Outbreaks of respiratory infections occur predominantly during months associated with lower exposure to the sun. The Institute of Medicine concluded in a 2011 report that the existing data were "not consistently supportive of a causal role" for vitamin D in reducing the risk of infection. Other studies suggest that vitamin D supplementation can provide a protective role in reducing the incidence or severity of respiratory infections.[1][2]

Vitamin D deficiency has long been associated with tuberculosis.[3][4] Beneficial effects of supplemental vitamin D for patients with COPD have also been shown.[5]

Ultraviolet radiation and vitamin D

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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.”[6] Studies of Dutch[7] and Russian[8] 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.[9] 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.[10]

Evidence

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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.[10] More recent studies of humans have also had divergent results. 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[11] 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.[12] Mongolian schoolchildren who drank vitamin D fortified milk during winter reported having fewer colds than those who received non-fortified milk.[13] Another study found no effect of vitamin D supplementation on the incidence or severity of upper respiratory tract infections. 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.[14]

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.[15]

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." Doses used in the constituent studies that used daily dosing ranged from 300 to 4000 IU/day (7.5-100 μg/day).[1]

Vitamin D supplementation

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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.[16][17] 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.[10] 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.[10] Benefits have not been shown in children with asthma.[18]

References

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  1. ^ a b Martineau AR, Jolliffe DA, Greenberg L, Aloia JF, Bergman P, Dubnov-Raz G, et al. (January 2019). "Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis". Health Technology Assessment. 23 (2): 1–44. doi:10.3310/hta23020. PMC 6369419. PMID 30675873.
  2. ^ Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, et al. (February 2017). "Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data". BMJ. 356: i6583. doi:10.1136/bmj.i6583. PMC 5310969. PMID 28202713.
  3. ^ Luong K, Nguyen LT (June 2011). "Impact of vitamin D in the treatment of tuberculosis". The American Journal of the Medical Sciences. 341 (6): 493–8. doi:10.1097/MAJ.0b013e3182070f47. PMID 21289501. S2CID 18802134.
  4. ^ Nnoaham KE, Clarke A (February 2008). "Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis". International Journal of Epidemiology. 37 (1): 113–9. CiteSeerX 10.1.1.513.3969. doi:10.1093/ije/dym247. PMID 18245055.
  5. ^ Jolliffe DA, Greenberg L, Hooper RL, Mathyssen C, Rafiq R, de Jongh RT, Camargo CA, Griffiths CJ, Janssens W, Martineau AR (April 2019). "Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials". Thorax. 74 (4): 337–345. doi:10.1136/thoraxjnl-2018-212092. PMID 30630893.
  6. ^ Smiley DF. Seasonal factors in the incidence of the acute respiratory infections. Am J Hyg 1926;6:621-6, p. 626
  7. ^ 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. S2CID 6674965.
  8. ^ 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.
  9. ^ 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. Bibcode:2009PNAS..106.3243S. doi:10.1073/pnas.0806852106. PMC 2651255. PMID 19204283.
  10. ^ a b c d Haines ST, Park SK (April 2012). "Vitamin D supplementation: what's known, what to do, and what's needed". Pharmacotherapy. 32 (4): 354–82. doi:10.1002/phar.1037. PMID 22461123. S2CID 25985630.
  11. ^ 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". Archives of Internal Medicine. 169 (4): 384–90. doi:10.1001/archinternmed.2008.560. PMC 3447082. PMID 19237723.
  12. ^ Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, Ida H (May 2010). "Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren". The American Journal of Clinical Nutrition. 91 (5): 1255–60. doi:10.3945/ajcn.2009.29094. PMID 20219962.
  13. ^ 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. S2CID 3092825.
  14. ^ 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.
  15. ^ 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.
  16. ^ 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.
  17. ^ 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.
  18. ^ Yakoob MY, Salam RA, Khan FR, Bhutta ZA (November 2016). "Vitamin D supplementation for preventing infections in children under five years of age". The Cochrane Database of Systematic Reviews. 2016 (11): CD008824. doi:10.1002/14651858.cd008824.pub2. PMC 5450876. PMID 27826955.
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