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#124 Vitamin D and Respiratory Tract Infections: Does the sun’s vitamin chase the cold?

Can regular vitamin D supplementation reduce the frequency, duration, or severity of respiratory tract infection (RTI)?

Regular use of vitamin D does not reduce the frequency, duration, or severity of RTI in western populations. Infrequent benefits seen in a few studies are at high risk of bias and/or involved children with profound deficiency (example 17.5 nmol/L) in developing countries.   

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Three systematic reviews1-3 with 4-11 Randomized Controlled Trials (RCTs) with 1,668-5,660 patients. Vitamin D supplementation:  
  • Statistically significantly reduced RTI in two meta-analyses [Odds Ratio 0.64 (0.49-0.84)1 and 0.58 (0.42-0.81)2] but not another [Relative Risk 0.98 (0.93-1.03)].3 
    • Why the difference? Numerous large biases, especially the former two: Using odds ratios for common problems exaggerates effects, including selectively reported outcomes, combining unrelated studies, including secondary analyses, inconsistent results, and publication bias.1,2   
  • Examining individual RCTs: 
    • Any RTI:  
      • 162 US adults: No difference.4 
      • 164 Finnish military recruits: No difference.5 
      • 140 Immuno-compromised patients: Improved non-validated RTI score (not clinically interpretable).6  
      • 247 Mongolian children with profound vitamin D deficiency (level=17.5 nmol/L): 0.35 less RTI over three months.7  
    • Cold and Flu (mostly cold): 
      • 322 New Zealander adults: No effect in any outcome.8   
        • This is the highest quality study.   
    • Flu:  
      • 430 Japanese children mean age 10: No difference.9   
    • Pneumonia:  
      • 453 Afghanistan children age <3 years: Reduced risk of one repeat pneumonia but not multiple pneumonias.10   
      • 3,060 Afghanistan children age <1 year: No difference (suggesting earlier results spurious).11  
    • Three RCTs of other conditions looked at RTI secondarily: 
      • Two found no difference,12,13 but the weakest (smallest RCT with grossly under-reported RTI examined retrospectively) found possible reduced cold/flu frequency.14   
  • Cohort studies suggest patients with low vitamin D levels get more RTI.15 
    • However, low vitamin D status is associated with many ills from weight gain to mortality but vitamin D RCTs rarely find clinical improvements.16,17   
    • Vitamin D is likely a surrogate marker for ill health.16 
  • Cold prevention likely lies with physical interventions like hand-washing.18 

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  • Frank Martino MD CCFP
  • G. Michael Allan MD CCFP

1. Bergman P, Lindh AU, Björkhem-Bergman L, et al. PLoS One. 2013 Jun 19; 8(6):e65835.

2. Charan J, Goyal JP, Saxena D, et al. J Pharmacol Pharmacother. 2012; 3(4):300-3.

3. Mao S, Huang S. Scand J Infect Dis. 2013; 45(9):696-702.

4. Li-Ng M, Aloia JF, Pollack S, et al. Epidemiol Infect. 2009; 137(10):1396-404.

5. Laaksi I, Ruohola JP, Mattila V, et al. J Infect Dis. 2010; 202(5):809-14.

6. Bergman P, Norlin AC, Hansen S, et al. BMJ Open. 2012; 2:e001663.

7. Camargo CA, Ganmaa D, Frazier AL, et al. Pediatrics. 2012; 130;e561-7.

8. Murdoch DR, Slow S, Chambers ST, et al. JAMA. 2012; 308(13):1333-9.

9. Urashima M, Segawa T, Okazaki M, et al. Am J Clin Nutr. 2010; 91(5):1255-60.

10. Manaseki-Holland S, Qader G, Isaq Masher M, et al. Trop Med Int Health. 2010; 15(10):1148-55.

11. Manaseki-Holland S, Maroof Z, Bruce J, et al. Lancet. 2012; 379(9824):1419-27.

12. Avenell A, Cook JA, Maclennan GS, et al. Age Ageing. 2007; 36(5):574-7.

13. Rees JR, Hendricks K, Barry EL, et al. Clin Infect Dis. 2013; 57(10):1384-92.

14. Aloia JF, Li-Ng M. Epidemiol Infect. 2007; 135(7):1095-6.

15. Ginde AA, Mansbach JM, Camargo CA Jr. Arch Intern Med. 2009; 169(4):384-90.

16. Autier P, Boniol M, Pizot C, et al. Lancet Diabetes Endocrinol. 2014; 2(1):76-89.

17. Theodoratou E, Tzoulaki I, Zgaga L, et al. BMJ. 2014 Apr 1; 348:g2035.

18. Allan GM, Arroll B. CMAJ. 2014; 186(3):190-9.

Authors do not have any conflicts to disclose.