Japanese study is the first clinical trial to test vitamin D against flu; children who took vitamin D were 40 percent less likely to get one kind of flu 03/15/2010
Vitamin D is something of a Cinderella story, with the “sunshine-and-seafood vitamin” rising rapidly from mundane bone builder to nutritional superstar.
In fact, its fundamental importance to myriad body systems was entirely unknown until very recently (To see the amazing range of research in recent years, search our news archive for “vitamin d”).
How might vitamin D manage to fight off the flu?
The Japanese team noted several plausible reasons why vitamin D could reduce the risk of influenza A.
First, vitamin D increases the production of defensive proteins called antimicrobial peptides… specifically in epithelial and other cells where flu viruses often enter the body.
And as we reported last week, there's increasing evidence that vitamin D triggers a key part of the body's second-line, “adaptive” (acquired) immune response.
Last year, American researchers who analyzed data from a survey of nearly 19,000 Americans (NHANES III) found that those with the lowest blood levels of vitamin D reported having significantly more recent colds or cases of the flu (See “Flu and Colds Risk Linked to Vitamin D Lack”).
But interest in this aspect of the essential, hormone-like nutrient first intensified four years ago, after a group of U.S. scientists authored a landmark paper titled “Epidemic influenza and vitamin D” (Cannell JJ et al. 2006).
That team included some of the most experienced vitamin D researchers, such as Harvard's Edward Giovannucci, Cedric Garland of UC San Diego, and Michael Holick of Boston University.
At the moment, the same group's second provocative paper—“On the epidemiology of influenza”—is the most frequently accessed paper in the history of Virology Journal (Cannell JJ et al. 2008).
Together with the epidemiological findings gleaned from the NHANES III survey, the evidence presented in these two papers should inspire more research into vitamin D's role in fighting the flu.
As if to answer the many calls for clinical research, a Japanese team has just published the results of the very first controlled human trial designed to test vitamin D's power to prevent the flu.
And the outcomes were encouraging: “This study suggests that vitamin D3 supplementation during the winter may reduce the incidence of influenza A…” (Urashima M et al. 2010).
Let's examine the details of this study among schoolchildren… which included a sharp drop in asthma attacks among the kids assigned to take vitamin D.
Vitamin D scores against influenza A in Japanese trial
From December 2008 through March 2009, the Japanese team conducted a randomized, double-blind, placebo-controlled trial in 167 children and teens, ranging from six to 15 years of age.
The goal was to compare rates of influenza type A between children assigned to take vitamin D3 supplements and those taking placebo pills.
The vitamin D group took 1200 IU per day, which is six times the U.S. RDA for people from birth through age 50 (200 IU).
After 15 months, influenza type A was diagnosed in 18 of 167 (10.8 percent) of the children in the vitamin D group compared with 31 of 167 (18.6 percent) of the children in the placebo group.
This means that the children assigned high-dose vitamin D supplements were 41 percent less likely to have developed influenza type A.
However, the vitamin D group experienced no reduction in the rates of influenza type B. (The body's immune responses to influenza A and influenza B differ, and the Japanese team thought that this might explain the failure to prevent type B.)
The reduction in influenza A was even greater in children who had not been taking vitamin D supplements before the trial began.
And kids who started nursery school after age three—who presumably were not as likely to have any acquired immunity —enjoyed the same enhanced protection.
Compared with the placebo group, both of these subgroups within the vitamin D group were 63 percent less likely to have developed influenza type A by the end of the trial.
Interestingly, asthmatic children in the vitamin D group were 83 percent less likely to suffer asthma attacks during the trial.
However, children with asthma did not enjoy a reduced risk of flu during the trial, possibly because children with asthma are known to be more susceptible to influenza.
The study had limitations, including its small size and the lack of blood samples to pinpoint the children's blood levels of vitamin D and antibodies to various flu viruses.
But it should prompt larger studies, and as the Japanese team wrote, those investigations should include blood tests to determine the minimum vitamin D blood levels associated with reduced risk of flu.
Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant WB, Madronich S, Garland CF, Giovannucci E. Epidemic influenza and vitamin D. Epidemiol Infect. 2006 Dec;134(6):1129-40. Epub 2006 Sep 7. Review.
Cannell JJ, Zasloff M, Garland CF, Scragg R, Giovannucci E. On the epidemiology of influenza. Virol J. 2008 Feb 25;5:29. Review.
Ginde AA, Mansbach JM, Camargo 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 Feb 23;169(4):384-90.
Gombart AF, Saito T, Koeffler HP. Exaptation of an ancient Alu short interspersed element provides a highly conserved vitamin D-mediated innate immune response in humans and primates. BMC Genomics. 2009 Jul 16;10:321.
Mathews JD, Chesson JM, McCaw JM, McVernon J. Understanding influenza transmission, immunity and pandemic threats. Influenza Other Respi Viruses. 2009 Jul;3(4):143-9. Review.
Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, Ida H. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr. 2010 Mar 10. [Epub ahead of print]
von Essen MR, Kongsbak M, Schjerling P, Olgaard K, Odum N, Geisler C. Vitamin D controls T cell antigen receptor signaling and activation of human T cells. Nat Immunol. 2010 Mar 7. [Epub ahead of print]