Large-scale study supports potential role in boosting immune system, affirming prior indications 06/01/2009
A new epidemiological study in nearly 19,000 Americans indicates that lack of adequate vitamin D may leave people vulnerable to the common cold… and the flu.
In the largest and most nationally representative study of possible links between vitamin D and respiratory infections, a team from Colorado and Massachusetts found that people with the lowest blood vitamin D levels reported having significantly more recent colds or cases of the flu (Ginde AA et al. 2009).
The risks were even higher for those with chronic respiratory disorders, such as asthma and emphysema.
“The findings of our study support an important role for vitamin D in prevention of common respiratory infections, such as colds and the flu,” said lead author Adit Ginde, MD, MPH of UC Denver. “Individuals with common lung diseases, such as asthma or emphysema, may be particularly susceptible to respiratory infections from vitamin D deficiency” (MGH 2009).
While vitamin C has been promoted for the prevention of colds, the only scientific evidence that supports its effectiveness shows that it may shorten their duration slightly. And there's no evidence that vitamin C or any other nutrient prevents or treats the flu.
In contrast, evidence has accumulated in recent years suggesting that vitamin D may play a key role in the “innate” immune system, which attacks viruses and other microbes by means other than those triggered by vaccines.
Circumstantial evidence has implicated the wintertime deficiency of vitamin D, which the body produces in response to sunlight, in the seasonal increase in colds and flu; and small studies have suggested an association between low blood levels of vitamin D and a higher risk of respiratory infections.
What the study found
The current study analyzed data from the Third National Health and Nutrition Examination Survey (NHANES III), conducted by the National Center for Health Statistics. Participants were interviewed in their homes regarding their health and nutrition, and most participants also received a physical examination that included collection of blood and other samples for laboratory analysis.
The research team analyzed blood levels of 25-hydroxyvitamin D—the best measure of vitamin D status—from almost 19,000 adult and adolescent NHANES III participants, selected to be representative of the overall U.S. population.
Study participants with the lowest vitamin D blood levels- less than 10 nanograms per milliliter (ng/mL) of blood - were about 40 percent more likely to report having a recent respiratory infection than were those with vitamin D levels of 30 ng/mL or higher.
The association was seen in all seasons and was even stronger among participants with a history of asthma or chronic obstructive pulmonary disease (COPD), including emphysema.
Asthma patients with the lowest vitamin D levels were five times more likely to have had a recent respiratory infection; while among COPD patients, respiratory infections were twice as common among those with vitamin D deficiency.
According to senior author Carlos Camargo, MD, DrPH, “A respiratory infection in someone with otherwise healthy lungs usually causes a few days of relatively mild symptoms. But respiratory infections in individuals with an underlying lung disease can cause serious attacks of asthma or COPD that may require urgent office visits, emergency department visits or hospitalizations. So the impact of preventing infections in these patients could be very large” (MGH 2009).
The authors stressed that the study's results need to be confirmed in clinical trials before vitamin D can be recommended to prevent colds and flu.
“We are planning clinical trials to test the effectiveness of vitamin D to boost immunity and fight respiratory infection, with a focus on individuals with asthma and COPD, as well as children and older adults—groups that are at higher risk for more severe illness,” Ginde says (MGH 2009).
And he added the most important point, regardless of the fate of vitamin D in clinical trials against colds and flu: “While it's too early to make any definitive recommendations, many Americans also need more vitamin D for its bone and general health benefits. Clinicians and laypeople should stay tuned as this exciting area of research continues to expand” (MGH 2009).
Why would vitamin D deter respiratory viruses?
John Cannell, M.D. is one of several researchers examining the potential role of vitamin D in immunity.
Three years back, Dr. Cannell and leading researchers from Harvard, Boston University, Mount Sinai Hospital Toronto, and UC San Diego published an intriguing reexamination of influenza's causes, titled “Epidemic influenza and vitamin D.”
This briefer explanation of the hypothesis that flu manifests in the absence of adequate vitamin D—an idea supported by the study we report today—comes from a question-answer column in the May 2009 issue of his Vitamin D Newsletter:
Dr. Cannell,How does Vitamin D work in the immune system?Philip,Texas
“Two systems exist in your body to fight infections, the innate or immediate system and the acquired or adaptive immune system that makes antibodies.
“Recent evidence indicates seasonal impairments of the antimicrobial peptide (AMPs) systems are crucial to impaired innate immunity, impairments caused by seasonal fluctuations in 25-hydroxyvitamin D [25(OH)D] levels. The evidence that vitamin D has profound effects on innate immunity is rapidly growing.
“Unlike adaptive immunity, innate immunity is that branch of host defense that is ‘hard-wired' to respond rapidly to microorganisms using genetically encoded effectors that are ready for activation by an antigen before the body has ever encountered that antigen.
“Of the effectors, the best studied are the antimicrobial peptides (AMPs). Both epithelial tissues and phagocytic blood cells produce AMPs; they exhibit rapid and broad-spectrum antimicrobial activity against bacteria, fungi, and viruses. In general, they act by rapidly and irreversibly damaging the lipoprotein membranes of microbial targets, including enveloped viruses, like influenza.
“Antimicrobial peptides protect mucosal epithelial surfaces by creating a hostile antimicrobial barricade. The epithelia secrete them constitutively into the thin layer of fluid that lies above the apical surface of the epithelium but below the viscous mucous layer.
“To effectively access the epithelium, a microbe must first infiltrate the mucous barrier and then survive assault by the AMPs present in this fluid. Should microbes breach this constitutive cordon, their binding to the epithelium rapidly mobilizes the expression of high concentrations of specific inducible AMPs, which provide a backup antimicrobial shield.
“The crucial role of vitamin D in the innate immune system was discovered only very recently. Both epithelial cells and macrophages [microbe-eating white blood cells] increase expression of the antimicrobial [compound] cathelicidin upon exposure to microbes, an expression that is dependent upon the presence of vitamin D. Pathogenic microbes stimulate the production of an enzyme that converts 25(OH)D to 1,25(OH)2D, a seco-steroid hormone. This in turn rapidly activates a suite of genes involved in pulmonary defense.
“In the macrophage [microbe-eating white blood cell], the presence of vitamin D also appears to suppress the pro-inflammatory cytokines. Thus, vitamin D appears to both enhance the local capacity of the epithelium to produce endogenous antibiotics and at the same time dampen certain destructive arms of the immune response, especially those responsible for the signs and symptoms of acute inflammation, such as the cytokine storms operative when influenza kills quickly.
“Because humans obtain most vitamin D from sun exposure and not from diet, a varying percentage of the population is vitamin D deficient, at any time, during any season, at any latitude, although the percentage is higher in the winter, in the aged, in the obese, in the sun-deprived, in the dark-skinned, and in more poleward [northern] populations.
“However, seasonal variation of vitamin D levels even occur around the equator and widespread vitamin D deficiency can occur at equatorial latitudes, probably due to sun avoidance, rainy seasons, and air pollution.
“For example, a study of Hong Kong infants showed about half had 25(OH)D levels less than 20 ng/mL in the winter. Even in the summer, few of the infants had levels higher than 30 ng/mL, which many experts now think is well below the lower limit of the optimal range.
“As 25(OH)D levels affect innate immunity, then a varying percentage of most populations even equatorial ones will have impaired innate immunity at any given time, together with distinct seasonal variations in that percentage. The effects such impairments have on influenza transmission are unknown.”
- Ginde AA, Liu MC, Camargo CA Jr. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch Intern Med. 2009 Mar 23;169(6):626-32.
- Massachusetts General Hospital (MGH). February 23, 2009. Vitamin D deficiency may increase risk of colds, flu. Accessed online at http://www.massgeneral.org/about/pressrelease.aspx?id=1103
- 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.