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Vitamin D3 Supplements in Winter May Help Protect Against Influenza A

  • Authors: News Author: Laurie Barclay, MD
    CME Author: Désirée Lie, MD, MSEd
  • CME/CE Released: 4/2/2010
  • Valid for credit through: 4/2/2011
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Target Audience and Goal Statement

This article is intended for primary care clinicians, infectious disease specialists, and other specialists who care for children.

The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.

Upon completion of this activity, participants will be able to:

  1. Describe the association between vitamin D3 supplementation and influenza A infection in winter in children.
  2. Identify subgroups of children who benefit more from vitamin D3 supplementation in winter for the prevention of influenza A.


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  • Laurie Barclay, MD

    Freelance writer and reviewer, Medscape, LLC


    Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.


  • Brande Nicole Martin

    CME Clinical Editor, Medscape, LLC


    Disclosure: Brande Nicole Martin has disclosed no relevant financial relationships.

CME Author(s)

  • Désirée Lie, MD, MSEd

    Clinical Professor, Family Medicine, University of California, Irvine, Orange, California; Director of Research and Patient Development, Family Medicine, University of California, Irvine, Medical Center, Rossmoor, California


    Disclosure: Désirée Lie, MD, MSEd, has disclosed the following relevant financial relationship:
    Served as a nonproduct speaker for: "Topics in Health" for Merck Speaker Services

CME Reviewer/Nurse Planner

  • Laurie E. Scudder, MS, NP

    Accreditation Coordinator, Continuing Professional Education Department, Medscape, LLC; Clinical Assistant Professor, School of Nursing and Allied Health, George Washington University, Washington, DC; Nurse Practitioner, School-Based Health Centers, Baltimore City Public Schools, Baltimore, Maryland


    Disclosure: Laurie E. Scudder, MS, NP, has disclosed no relevant financial relationships.

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Vitamin D3 Supplements in Winter May Help Protect Against Influenza A

Authors: News Author: Laurie Barclay, MD CME Author: Désirée Lie, MD, MSEdFaculty and Disclosures

CME/CE Released: 4/2/2010

Valid for credit through: 4/2/2011


April 2, 2010 — Vitamin D3 supplementation during the winter is linked to lower incidence of influenza A, particularly in specific subgroups of schoolchildren, according to the results of a randomized, double-blind, placebo-controlled trial reported online in the March 10 issue of the American Journal of Clinical Nutrition.

"To our knowledge, no rigorously designed clinical trials have evaluated the relation between vitamin D and physician diagnosed seasonal influenza," write Mitsuyoshi Urashima, MD, PhD, from Jikei University School of Medicine, Minato-ku, in Tokyo, Japan, and colleagues. "We investigated the effect of vitamin D supplements on the incidence of seasonal influenza A in schoolchildren."

Schoolchildren were randomly assigned to receive vitamin D3 supplements (1200 IU/day) or placebo from December 2008 through March 2009. The main endpoint of the study was the incidence of influenza A, diagnosed by influenza antigen testing (rapid influenza diagnostic test [RIDT]) on a nasopharyngeal swab specimen.

In the vitamin D3 group, 18 (10.8%) of 167 children had influenza A, as did 31 (18.6%) of 167 children in the placebo group (relative risk [RR], 0.58; 95% confidence interval [CI], 0.34 - 0.99; P = .04). The association of decreased influenza A incidence with vitamin D supplements was stronger in children who had not been taking other vitamin D supplements (RR, 0.36; 95% CI, 0.17 - 0.79; P = .006) and in those who started nursery school after age 3 years (RR, 0.36; 95% CI, 0.17 - 0.78; P = .005).

Among children with a previous diagnosis of asthma, 2 children in the vitamin D3 group vs 12 children in the placebo group had asthma attacks as a secondary outcome (RR, 0.17; 95% CI, 0.04 - 0.73; P = .006).

"This study suggests that vitamin D3 supplementation during the winter may reduce the incidence of influenza A, especially in specific subgroups of schoolchildren," the study authors write. "....Moreover, asthma attacks were also prevented by vitamin D3 supplementation."

Limitations of this study include small sample size, lack of data on serum 25-hydroxyvitamin D or on urinary calcium data, and lack of information on the presence or development of influenza A antibodies.

"Future studies should include a larger sample size of schoolchildren without comorbidities to determine the optimal dose and duration of vitamin D supplementation by measurement of serum 25-hydroxyvitamin D, serum and urinary calcium, and titers of antibody to influenza levels," the study authors conclude.

Jikei University School of Medicine supported this study. The study authors have disclosed no relevant financial relationships.

Am J Clin Nutr. Published online March 10, 2010. Abstract

Additional Resource

More information about seasonal influenza is available on the Center's for Disease Control and Prevention's Web site.

Clinical Context

An inverse association has been shown between serum vitamin D levels and recent upper respiratory tract infections, and vitamin D is dependent on sunlight exposure, which is reduced in the winter. It is uncertain if vitamin D supplementation would reduce the incidence of influenza A infection in children.

This is a double-blind, placebo-controlled, randomized study to examine the effect of vitamin D3 supplementation in children during winter on rates of influenza A infection.

Study Highlights

  • The multicenter study involved 12 hospitals and 8 physicians in private practice in Japan and was conducted for 4 months from winter to early spring.
  • Included were schoolchildren aged 6 to 15 years with or without underlying diseases who started taking the study medication in December and continued to take the medication to the end of March.
  • Excluded were children who had a history of kidney stones, were already taking vitamin D, had allergic reactions to the components of vitamin D, had immunosuppression, or had difficulty swallowing tablets.
  • Children were randomly assigned to either vitamin D3 at 400 IU to be taken 3 times twice daily (total, 1200 IU/day) or placebo.
  • Parents completed prestudy and poststudy questionnaires about medical and demographic data.
  • Each bottle of tablets was consumed in 15 days, and adherence was assessed by direct questioning and pill count.
  • Primary outcome was incidence of influenza A infection diagnosed by RIDT on a nasopharyngeal swab specimen.
  • Secondary outcome was influenza B infection on a nasopharyngeal swab specimen.
  • 430 children/parent pairs met inclusion criteria and were randomly assigned.
  • Mean age of children was 10.2 years, 56% were boys, mean family size was 4.5 persons, 23% had no siblings, and 65% started nursery school or kindergarten at age 3 years or older.
  • 27% had underlying diseases, 26% had bronchial asthma, 56% had a history of asthma, and 24% had a history of atopic dermatitis.
  • Of the 430 children randomly selected, 334 completed the study (50 in the vitamin D3 group and 46 in the placebo group were lost to follow-up).
  • Some participants started taking vitamin D supplements during the study, as this was not prohibited.
  • Influenza A occurred in 49 children overall, and the incidence peaked from the middle to late January.
  • The incidence was 10.8% in the vitamin D3 group and 18.6% in the placebo group (RR, 0.58; P = .04).
  • The difference was significant between day 31 and day 60 after starting the vitamin D3 (RR, 0.41; P = .014), but the difference was not significant between day 61 and the end of the study.
  • The effect was more prominent in children who did not take additional vitamin D supplementation during the study (RR, 0.36; P = .006) and in those who started nursery school at 3 years or older (RR, 0.36; P = .005).
  • Other factors such as sex, age younger or older than 10 years, and having an older sibling did not affect the association.
  • The incidence of influenza B and RIDT-negative influenza-like illness were not significantly different.
  • Rates of asthma attacks were significantly lower in the vitamin D3 group (2 vs 12 children; RR, 0.17; P = .006) vs placebo.
  • The authors concluded that vitamin D3 supplementation in the winter for children could reduce the incidence of influenza A, particularly in asthmatic children and in children who start nursery school at age 3 years and older.

Clinical Implications

  • Vitamin D3 supplementation in winter reduces the incidence of influenza A infection in children.
  • The effect of vitamin D3 supplementation is greater in children who attend nursery school at age 3 years and older and in children with asthma.