Vitamin D and Influenza

The hallmark clue to vitamin D deficiency disease is an associated seasonal and latitudinal variability in incidence and morbidity. Multiple sclerosis, almost absent close to the equator, increases in frequency the further from the equator one lives. Heart disease is worse in the dark, winter months, with blood pressure increasing as vitamin D stores in the body decrease. Similar associations are seen in the list of suspected diseases caused by, or closely associated with, low vitamin D, including diabetes mellitus, most forms of cancer, hypertension, myocardial infarcts, inflammatory bowel disease and, of course, osteomalacia, or softening of the bones. However, until last December, no one dared to point their finger at the most obvious suspect of all, influenza and the common cold.

In its December 2006 issue, Epidemiology and Infection published a paper about vitamin D that is a must-read for everyone in our profession.1 John Cannell, of the Vitamin D Council, is the lead author listed, but the co-authors are all prominent vitamin D researchers. No subservient grad students are on this list. The co-authors include all the big names: Vieth of Mt. Sinai in Toronto, Umhau of NIH, Holick of Boston University, Grant of SUNARC, Madronich of the National Center of Atmospheric Research, Garland of UC San Diego, and Giovannucci of the Harvard School of Public Health. They all stepped forward, with Cannell, and pointed out what should have been obvious all along—decreasing vitamin D levels during the winter months trigger the seasonal cycle of cold and flu.

The Later Work of R. Edgar Hope-Simpson (1908-2003)

The paper begins by summarizing the later work of R. Edgar Hope-Simpson, an English general practitioner and a self-educated epidemiologist who has long been famous for his work in the 1940s and early 1950s. He figured out the cause of shingles, linking it to the varicella virus through epidemiological analysis. In his later years, but still a quarter of a century ago, he turned his attention to influenza.

"In 1981," to quote Cannell, "R. Edgar Hope-Simpson proposed that a 'seasonal stimulus' intimately associated with solar radiation explained the remarkable seasonality of epidemic influenza." Hope- Simpson's 1992 book, The Transmission of Epidemic Influenza, summarized his findings and made an eloquent plea for scientists to identify this "stimulus." As Amazon.com currently lists this book for $122, eloquent or not, it's not in my shopping cart. To quote Cannell, quoting Hope-Simpson:

"Hope-Simpson was the first to document that influenza-A epidemics in temperate latitudes peak in the month following the winter solstice. In both hemispheres, influenza rates rise significantly for about 2 months on either side of its peak. 'Outbreaks are globally ubiquitous and epidemic loci move smoothly to and fro across the surface of the earth almost every year in a sinuous curve that runs parallel with the midsummer curve of vertical solar radiation, but lags about six months behind it … Latitude alone broadly determines the timing of the epidemics in the annual cycle, a relationship that suggests a rather direct effect of some component of solar radiation acting positively or negatively upon the virus, the human host, or their interaction … The nature of the seasonal stimulus remains undiscovered.'"

Although Hope-Simpson suspected a seasonal trigger associated with changing ultraviolet light exposure, he didn't live long enough to identify it as vitamin D. Cannell and colleagues nominate vitamin D deficiency as the mysterious trigger. They argue for this nomination by pointing out a series of circumstantial clues. While Hope-Simpson suspected that some part of human physiology responded to ultraviolet light affecting immunity, he didn't have the benefit of our current knowledge of vitamin D biochemistry. If he had, he would surely have figured this out for himself. We now know that:

  • Vitamin D has profound and multiple effects on human immunity.
  • Vitamin D levels fluctuate over the year, more so in the higher latitudes, and deficiency is common, more so in the winter. Yet, seasonal variations in vitamin D status occur even in tropical and subtropical latitudes.
  • Vitamin D deficiency is common, especially among the elderly in the winter. As compared to 20-year-olds, the elderly only make about 25 percent of the vitamin D needed after exposure to the same amount of sunlight.
  • Influenza occurrence parallels vitamin D deficiency in time and space.

If you are interested in the details of how vitamin D deficiency weakens immune function and enjoy brandishing words such chemokines, defensins, and cathelicidins in conversation, I definitely encourage you to read the original papers. Suffice to say, researchers have now elucidated much of the chemistry involved.

Norwegians, who get less sun exposure than any other Europeans, appear somewhat exempt from the annual wintertime flu epidemic and have a smaller wintertime spike in mortality. The explanation is simple. Norwegians take so much fish oil they have the highest wintertime vitamin D levels of any European nation.

Disease from Outer Space?

Solar flare activity on the sun affects influenza outbreaks here on Earth. Hope-Simpson was the first to notice this association. Such an outlandish idea justifiably has had its share of disbelievers. Although one proposed explanation suggests viral invasions from outer space, we now understand what is going on. Solar flare activity increases high altitude ozone, which, in turn, absorbs more solar radiation and so decreases the amount of ultraviolet light that actually reaches the Earth's surface. Current analysis says ultraviolet exposure may drop as much as 13 percent during maximum solar flare activity, something that fluctuates on an 11-year cycle. This fluctuation produces a proportional decrease in global vitamin D status. Extraterrestrial events may explain the cycles of more and less aggressive influenza epidemics. Wow!

Race Relations

Melanin in the skin lowers vitamin D production. No one doubts that African Americans have lower vitamin D levels than white Americans. This fact likely contributes to the explanation as to why African American children get pneumonia twice as often as Caucasian children. Low vitamin D levels may also be a factor in higher death rates from respiratory infections and pneumonia in African Americans.

Don't Volunteer

There are a number of trials in which people were injected with attenuated flu vaccine and then watched to see how many of them got feverish. It's not clear what incentives researchers employed to find these study participants; I would not rush to volunteer for this one. Anyway, it turns out that injecting people with the flu virus produces very different results depending on when and where you perform the experiment. If you run the experiment in the winter, eight times as many test subjects get a fever than if you run the same test in summer. The further north you run the experiment, the more people get sick at any time of the year.

More Examples

Cannell points out no end of interesting trivia that associates vitamin D deficiency with upper respiratory infections. For example, children with rickets, the classic vitamin D deficiency illness in which inadequate calcium is absorbed to build bones, are 11 times more likely to have lower respiratory infections than matched controls without rickets.

Another example is a 1990 Russian study in which athletes were treated with ultraviolet radiation twice a year for three years. Compared to a matched control group, the treated athletes developed half the respiratory infections, recovered faster, and had higher levels of salivary immunoglobulin.

These days, we promote fish oils for their anti-inflammatory action. Years ago, the focus was different; fish oil was an anti-infective, given to reduce incidence of respiratory infections. Controlled studies from way back in the 1930s show fish oil, which supplied a decent dose of vitamin D, reduced respiratory infections by 50 percent.

By this point, you should be getting the idea. You should download and read Cannell's paper. http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=469543

Read the full paper and then sit down and contemplate those basic lessons we learned in naturopathic philosophy. Recall that debate between germ theory and fertile field that was so elementary to our medical education. As naturopaths, we view the concept that a fertile field is necessary for disease to occur and this remains an ongoing and central theme to our approach to preventing and treating disease. Yet, one rarely hears mention of fertile fields in modern medical literature. Rather, the focus always is on germs, the infectious agents responsible for causing disease. Cannell's paper lays out a perfect example and explanation for the fertile field. Both the cause and the cure for seasonal influenza are lifestyle. Inadequate exposure to one of the most basic elements of nature's cure—sunlight, weakens the body, leaving it vulnerable to disease.

Will vitamin D be the cure for the common cold? Or at least prevent the common cold? The jury still is out, but the evidence is good enough that the question has been asked.

 

Every year, we all field patient questions about flu shots. This study must now inform how we answer those questions. Flu shots expose a person to a weak relative of the soon-to-arrive flu virus, stimulating the immune system to respond and acquire immunity. This has benefit as long as the drug makers pick the right virus strain for the vaccine. Vitamin D, in contrast, prevents flu by stimulating innate immunity and prevents flu infection, regardless of what strain arrives this year. Flu vaccine attempts to fight the germ. Vitamin D removes the fertile field. This is what naturopathic medicine is about.