Epidemiology and Infection

Review Article

Epidemic influenza and vitamin D

J. J. CANNELL a1c1, R. VIETH a2, J. C. UMHAU a3, M. F. HOLICK a4, W. B. GRANT a5, S. MADRONICH a6, C. F. GARLAND a7 and E. GIOVANNUCCI a8
a1 Atascadero State Hospital, 10333 El Camino Real, Atascadero, CA, USA
a2 Mount Sinai Hospital, Pathology and Laboratory Medicine, Department of Medicine, Toronto, Ontario, Canada
a3 Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD
a4 Departments of Medicine and Physiology, Boston University School of Medicine, Boston, MA, USA
a5 SUNARC, San Francisco, CA, USA
a6 Atmospheric Chemistry Division, National Center for Atmospheric Research, Boulder, CO, USA
a7 Department of Family and Preventive Medicine, University of California San Diego, La Jolla, CA, USA
a8 Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA, USA

Article author query
cannell jj   [PubMed][Google Scholar] 
vieth r   [PubMed][Google Scholar] 
umhau jc   [PubMed][Google Scholar] 
holick mf   [PubMed][Google Scholar] 
grant wb   [PubMed][Google Scholar] 
madronich s   [PubMed][Google Scholar] 
garland cf   [PubMed][Google Scholar] 
giovannucci e   [PubMed][Google Scholar] 


In 1981, R. Edgar Hope-Simpson proposed that a ‘seasonal stimulus’ intimately associated with solar radiation explained the remarkable seasonality of epidemic influenza. Solar radiation triggers robust seasonal vitamin D production in the skin; vitamin D deficiency is common in the winter, and activated vitamin D, 1,25(OH)2D, a steroid hormone, has profound effects on human immunity. 1,25(OH)2D acts as an immune system modulator, preventing excessive expression of inflammatory cytokines and increasing the ‘oxidative burst’ potential of macrophages. Perhaps most importantly, it dramatically stimulates the expression of potent anti-microbial peptides, which exist in neutrophils, monocytes, natural killer cells, and in epithelial cells lining the respiratory tract where they play a major role in protecting the lung from infection. Volunteers inoculated with live attenuated influenza virus are more likely to develop fever and serological evidence of an immune response in the winter. Vitamin D deficiency predisposes children to respiratory infections. Ultraviolet radiation (either from artificial sources or from sunlight) reduces the incidence of viral respiratory infections, as does cod liver oil (which contains vitamin D). An interventional study showed that vitamin D reduces the incidence of respiratory infections in children. We conclude that vitamin D, or lack of it, may be Hope-Simpson's ‘seasonal stimulus’.

(Accepted August 5 2006)
(Published Online September 7 2006)

c1 Atascadero State Hospital, 10333 El Camino Real, Atascadero, CA 93422, USA. (Email: jcannell@dmhash.state.ca.us)