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Vitamin D Level, Respiratory Tract Infections, and Controlled Trials

Vitamin D Level, Respiratory Tract Infections, and Controlled Trials Proponents of evidence-based medicine argue that conclusions of treatment effects should be based on controlled trials and not on observational studies. Nevertheless, based on the correlation between serum vitamin D level and infections, Ginde et al1 proposed that vitamin D supplementation may reduce the incidence of upper respiratory tract infections. Nutrition is associated with a wide range of lifestyle variables, and there is a great risk of residual confounding caused by inadequate adjustments for complex social and environmental exposures acting over a person’s life.2 Residual confounding may explain, for example, the divergent findings in observational studies and controlled trials on vitamin E.2 Therefore, great caution should be exercised when interpreting correlations between serum vitamin D levels and health outcomes. Furthermore, certain randomized controlled trials on multivitamin supplements are relevant when considering the effect of vitamin D supplementation on respiratory tract infections. If a multivitamin supplement has no effect on infections, it seems justified to conclude that there is a lack of effect by each constituent of the supplement. In contrast, if a multivitamin supplement does have an effect, we cannot draw any specific conclusions because the effect can be caused by any single substance or the combination of several of them together. In this respect, the implications are quite different when the result of a multivitamin trial is positive or negative. Two multivitamin trials with 748 and 652 elderly participants included 160 and 200 IU/d of vitamin D in their supplements.3,4 The supplements had no effect on the incidence of upper or lower respiratory tract infections.3,4 Thus, following this logic, these trials indicate that increasing vitamin D intake has no effect on the incidence of respiratory tract infections in the elderly people studied. Finally, the comment by Ginde et al1 on vitamin C is somewhat inaccurate. Although regular vitamin C (ascorbic acid) supplementation has not reduced the incidence of the common cold in ordinary people, it has consistently reduced the duration of colds that occurred during the supplementation period. In adults, the reduction in common cold duration was 8% and in children it was 13%.5 Therefore, we concluded in our Cochrane review that the therapeutic effects of vitamin C should be further studied, in particular in children because no therapeutic trials with children have been carried out, although the effect of regular vitamin C has been greater in them.5 Correspondence: Dr Hemilä, Department of Public Health, University of Helsinki, Mannerheimintie 172, PO Box 41, Helsinki FIN-00014, Finland (harri.hemila@helsinki.fi). References 1. Ginde AAMansbach JMCamargo CA Jr 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 (4) 384- 390PubMedGoogle ScholarCrossref 2. Lawlor DADavey Smith GBruckdorfer KRKundu DEbrahim S Those confounded vitamins: what can we learn from the differences between observational versus randomised trial evidence? Lancet 2004;363 (9422) 1724- 1727PubMedGoogle ScholarCrossref 3. Liu BA McGeer A McArthur MA et al. Effect of multivitamin and mineral supplementation on episodes of infection in nursing home residents: a randomized, placebo-controlled study [correction published in J Am Geriatr Soc. 2007;55(3):478]. J Am Geriatr Soc 2007;55 (1) 35- 42PubMedGoogle ScholarCrossref 4. Graat JMSchouten EGKok FJ Effects of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons: a randomized controlled trial. JAMA 2002;288 (6) 715- 721PubMedGoogle ScholarCrossref 5. Douglas RMHemilä HChalker ETreacy B Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev 2007 Jul 18; (3) CD000980PubMedGoogle Scholar http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Vitamin D Level, Respiratory Tract Infections, and Controlled Trials

Archives of Internal Medicine , Volume 169 (15) – Aug 10, 2009

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Publisher
American Medical Association
Copyright
Copyright © 2009 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinternmed.2009.246
Publisher site
See Article on Publisher Site

Abstract

Proponents of evidence-based medicine argue that conclusions of treatment effects should be based on controlled trials and not on observational studies. Nevertheless, based on the correlation between serum vitamin D level and infections, Ginde et al1 proposed that vitamin D supplementation may reduce the incidence of upper respiratory tract infections. Nutrition is associated with a wide range of lifestyle variables, and there is a great risk of residual confounding caused by inadequate adjustments for complex social and environmental exposures acting over a person’s life.2 Residual confounding may explain, for example, the divergent findings in observational studies and controlled trials on vitamin E.2 Therefore, great caution should be exercised when interpreting correlations between serum vitamin D levels and health outcomes. Furthermore, certain randomized controlled trials on multivitamin supplements are relevant when considering the effect of vitamin D supplementation on respiratory tract infections. If a multivitamin supplement has no effect on infections, it seems justified to conclude that there is a lack of effect by each constituent of the supplement. In contrast, if a multivitamin supplement does have an effect, we cannot draw any specific conclusions because the effect can be caused by any single substance or the combination of several of them together. In this respect, the implications are quite different when the result of a multivitamin trial is positive or negative. Two multivitamin trials with 748 and 652 elderly participants included 160 and 200 IU/d of vitamin D in their supplements.3,4 The supplements had no effect on the incidence of upper or lower respiratory tract infections.3,4 Thus, following this logic, these trials indicate that increasing vitamin D intake has no effect on the incidence of respiratory tract infections in the elderly people studied. Finally, the comment by Ginde et al1 on vitamin C is somewhat inaccurate. Although regular vitamin C (ascorbic acid) supplementation has not reduced the incidence of the common cold in ordinary people, it has consistently reduced the duration of colds that occurred during the supplementation period. In adults, the reduction in common cold duration was 8% and in children it was 13%.5 Therefore, we concluded in our Cochrane review that the therapeutic effects of vitamin C should be further studied, in particular in children because no therapeutic trials with children have been carried out, although the effect of regular vitamin C has been greater in them.5 Correspondence: Dr Hemilä, Department of Public Health, University of Helsinki, Mannerheimintie 172, PO Box 41, Helsinki FIN-00014, Finland (harri.hemila@helsinki.fi). References 1. Ginde AAMansbach JMCamargo CA Jr 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 (4) 384- 390PubMedGoogle ScholarCrossref 2. Lawlor DADavey Smith GBruckdorfer KRKundu DEbrahim S Those confounded vitamins: what can we learn from the differences between observational versus randomised trial evidence? Lancet 2004;363 (9422) 1724- 1727PubMedGoogle ScholarCrossref 3. Liu BA McGeer A McArthur MA et al. Effect of multivitamin and mineral supplementation on episodes of infection in nursing home residents: a randomized, placebo-controlled study [correction published in J Am Geriatr Soc. 2007;55(3):478]. J Am Geriatr Soc 2007;55 (1) 35- 42PubMedGoogle ScholarCrossref 4. Graat JMSchouten EGKok FJ Effects of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons: a randomized controlled trial. JAMA 2002;288 (6) 715- 721PubMedGoogle ScholarCrossref 5. Douglas RMHemilä HChalker ETreacy B Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev 2007 Jul 18; (3) CD000980PubMedGoogle Scholar

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Aug 10, 2009

Keywords: respiratory tract infections,vitamin d

References