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Newsletter: Pascal’s wager and pandemic influenza

Posted on: November 1, 2005   by  John Cannell, MD


As we wait for this year’s influenza epidemic, keep in mind we are also waiting for the big one, the pandemic (pan: all, demic: people). A severe influenza A pandemic will kill many more Americans than died in the World Trade Centers, the Iraq war, the Tsunami and Hurricane Katrina combined. Perhaps a million or two in the USA alone. Such a disaster would tear the fabric of our society. Our entire country would resemble New Orleans after Katrina.

Also, it’s only a question of when it will come, not if it will come. Pandemics come every 25 years or so, severe ones every hundred years or so. The last pandemic, the Hong Kong flu, occurred in 1968, killing 34,000 Americans. In 1918, the Spanish flu killed more than 500,000 Americans. So many millions died in other countries, they couldn’t bury the bodies.

The Influenza Pandemic of 1918

Young healthy adults, in the prime of their lives in the morning, drowning in their own inflammation by noon, grossly discolored by sunset, were dead at midnight. An overwhelming immune response to the influenza virus – macrophages releasing large amounts of inflammatory agents called cytokines and chemokines into the lung of the afflicted – resulted in millions of deaths in 1918.

Kobasa D, et al. Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus. Nature. 2004.

Keep in mind, that the Germans recently discovered that vitamin D is intimately involved in reining in the macrophages, holding their cytokine production back, so they don’t overshoot, and kill their owner along with the invader. 1

Your annual flu shot won’t help when the big one hits, the antigenic shift one. Once the pandemic starts, a new vaccine, specific to the new virus must be manufactured and that takes time. You can and should get some antiviral drugs from your doctor in advance. Once the pandemic starts –this year, or ten years from now – the supply of antivirals may be limited and the lines will be long.

“Influenza epidemics above 30 degrees latitude in both hemispheres occurred during the six months of least solar radiation.”It may surprise you that influenza remains an enigma. Current theory holds that influenza infects like measles, one person gets it, gives it to others, in a chain of infectious events. That theory has some problems. For example, Dr. Carolyn Buxton Bridges, of the CDC, recently published a review paper on the transmission of influenza. She noted, “Our review found no human experimental studies published in the English-language literature delineating person-to-person transmission of influenza.”

Bridges CB, et al. Transmission of influenza: implications for control in health care settings. Clin Infect Dis. 2003.

Most experts also think pandemic strains originate in birds or other animals. Dr. Ann Reid and Dr. Jeffery Taubenberger, of the Armed Forces Institute of Pathology recently wrote, “it is important to recognize that the mechanisms by which pandemic strains originate have not been explained yet.” Furthermore, there is a persistent theory that influenza lies dormant in humans, not birds or swine, where it mutates into a killer strain.2

Reid AH, et al. The origin of the 1918 pandemic influenza virus: a continuing enigma. J Gen Virol 2003.

So, get your flu shot for this year’s flu, stock up on some antivirals, and let’s go looking for some ignored facts that might improve your family’s chances when the next pandemic comes. Last month we saw that aggressive treatment of vitamin D deficiency prevented children from getting infections. Dr. Rehman didn’t differentiate between viral and bacterial infections but most of the illnesses vitamin D prevented were probably viral.

Rehman PK. Sub-clinical rickets and recurrent infection. J Trop Pediatr. 1994.

When looking for ignored facts, one should always start with epidemiology, the detective branch of medicine. Epidemiologists look for clues, clues that lead to theories, theories that can be tested, and, if true, save your family’s lives. One of the world’s pioneering epidemiologists died recently, R. Edward Hope-Simpson. He used meticulous, and solitary, detective work to discover that the chickenpox virus was reactivated in adults, causing shingles. Dr. Hope-Simpson became famous.3

In 1979, he turned his attention to influenza A. He studied two remote populations, one in Wales and the other in England. He found that most affected households had only one case of influenza. Furthermore, no serial time intervals could be identified in cumulative household outbreaks, that is, different families didn’t get sick one after another, but around the same time. He discovered other facts that just didn’t fit with the theory that influenza A is primarily spread by person-to-person transmission of this year’s virus.

Hope-Simpson RE. Epidemic mechanisms of type A influenza. J Hyg. 1979.

Then he spent the rest of his life trying to alert us to one of the basic facts of influenza. It is
distinctly seasonal. All theories about its transmission must take into account its seasonality. Hope-Simpson reminded us what Davenport said, “Epidemiological hypotheses must provide satisfactory explanations for all the known findings – not just for a convenient subset of them.”

Going back to 1945, he discovered that influenza epidemics above 30 degrees latitude in both hemispheres occurred during the six months of least solar radiation. Outbreaks in the tropics almost always occur during the rainy season. Hope-Simpson concluded, “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 humans host or their interaction.” That is, something may be regularly reducing our immunity every fall and winter.

Hope-Simpson RE. The role of season in the epidemiology of influenza. J Hyg. 1981.

In 2003, researchers confirmed that influenza epidemics in the tropics occur, with few exceptions, during the rainy season – when vitamin D levels should be falling.4

Furthermore, in his 1981 paper, Hope-Simpson wondered how the same virus could cause influenza outbreaks at exactly the same time (middle of winter) over a six-year period (1969 -1974) in two widely separated areas (Prague, Czechoslovakia, and Cirencester, England). Surely, during the middle of the Cold War, infected people did not arrive at two locations hundreds of miles apart, in the middle of winter, for five years in a row to infect the well people. On thing Prague and Cirencester do have in common, they are both at 50 degrees latitude.

In 1990, researchers confirmed a relative lack of country-to-country transmission, by looking at two countries with heavy tourist traffic between them.

Heinz F, et al. Do influenza epidemics spread to neighbouring countries? J Hyg Epidemiol Microbiol Immunol. 1990.

Hope-Simpson rejected the theory that this year’s virus is only transmitted from actively infected persons to well persons, concluding instead the facts were more consistent with transmission by symptomless carriers who become contagious when the sun is either in the other hemisphere or obscured by the rainy season. He theorized that annual movement of the sun caused a “seasonal stimulus that reactivates latent virus in the innumerable carriers who are everywhere present, so creating the opportunity for epidemics to occur in the wake of its passage.” And thus the celebrated Dr. Hope-Simpson committed heresy.

Everyone knows influenza transmission is direct; the ill people infect the well people. The accepted theory of pandemics is that the virus first spreads in birds, perhaps jumps to a mammal (pigs in 1918), then jumps to humans already infected with a common influenza strain. There it combines and mutates (reassortment) to a hybrid virus in the index case and that single person spreads it to others who spread it to others, etc. No, said Hope-Simpson, the epidemiology just does not fit that theory. Heresy, said the experts.

Hope-Simpson practiced medicine in a small village in southwest England, Cirencester. He went back and looked at 16 years of his medical records and found evidence of 20 influenza outbreaks, spaced over those 16 years. In every outbreak, he found young children were the most frequently affected but in none of the 20 outbreaks did the children appear to be major disseminators of the influenza virus. Furthermore, all ages seemed to get sick around the same time. He concluded, “Such age-patterns are not those caused by a highly infectious immunizing virus surviving by means of direct transmissions from the sick, whose prompt development of the disease continues endless chains of transmissions.”5

No one listened. Everyone knew, and still knows: influenza only occurs when sick people infect well people, who in turn infect other well people. I don’t think so, said Hope-Simpson. In search of more evidence, he went to all the parishes in Gloucestershire, separated by many miles. He looked at burial records for the last 500 years and found evidence of repeated influenza epidemics. He concluded, “In each century, influenzal excess mortalities in Gloucestershire parishes coincided with the date of the relevant influenza epidemic as recorded from widely different parts of Britain.” That is, long before modern rapid transit, everyone in Britain got the flu around the same time! How could one person come down with the flu, infect others, etc, when everyone in Britain got sick at the same time, long before planes trains and automobiles?6

In fact, after studying influenza epidemics in schools, Hoyle and Wickramasinghe also decided that direct spread by infected children could not explain what was happening. They theorized that influenza viral precursors were reaching earth on comets from outer space!7

Content to stay on earth, Hope-Simpson published a detailed theory of influenza’s infectivity in 1987, based on the facts he observed. Right or wrong, Hope-Simpson’s paper is wonderful reading for anyone interested in influenza. Here is a great mind at work. He noted any theory of influenza must explain a number of facts:

  • “Vast explosions of disease which may attack 15% or more of a large community within six weeks and then cease”
  • “Successive outbreaks of type A influenza in small relatively remote communities often coincide closely season after season with those of the country as a whole and, although the virus changes, the identical strains of virus appear contemporaneously in the two situations”
  • “Cessation of epidemics despite abundant available non-immune subjects”
  • “household outbreaks occur all at once, not one after another”
  • “Low secondary attack rates within households”
  • “epidemic patterns of influenza have not changed in four centuries . . . and does not seem to have altered with the increasing speed and complexity of human communications.”

Hope-Simpson RE, Golubev DB. A new concept of the epidemic process of influenza A virus. Epidemiol Infect. 1987.

Hope Simpson proposed that symptomless carriers became infective in response to a seasonal stimulus and then infect others causing simultaneous explosions of disease in widely different areas. Furthermore, he concluded that those who got sick were not particularly contagious. He proposed that the stimulus for infection “is dependent on variations in solar radiation, an extraterrestrial influence unaffected by the rapidity of human travel. The rapidity of influenza spread was as rapid in previous centuries as it is at present because it does not depend on case-to-case transfer.”

He added, “The primary agency mediating seasonal control remains unidentified.” That is, if something is weakening our immune system, every year, as regularly as changing of the leaves and declining vitamin D levels, he didn’t know what it was. Hope-Simpson’s 1987 paper was his last. In 1992, he compiled all his work on influenza into a book. He died in 2003, at the age of 95.

I wish Hope-Simpson could have lived a while longer, to read Dr. Colleen Hayes and her colleagues from the University of Wisconsin-Madison. She is one of the brightest vitamin D researchers out there. In 2003, she reviewed the profound effect vitamin D has on the

Hayes CE, et al. The immunological functions of the vitamin D endocrine system. Cell Mol Biol. 2003.

Yes, as regularly as the flu season, vitamin D levels plummet in the fall and winter. Yes, vitamin D has profound effects on the immune system. Yes vitamin D may be involved in influenza. But is there any direct evidence?

Two animal studies showed vitamin D prevents the flu and one showed it does not. Nothing after 1956. If you obtain and read the first citation below, you’ll see the very first animal paper indicating vitamin D protected rats from influenza was published in Japan during World War II, apparently part of Japan’s biological weapons research. The CIA confiscated the paper after the war.

Young GA, et al. Vitamin D intake and susceptibility of mice to experimental swine influenza virus infection. Proc Soc Exp Biol Med. 1949.

Underdahl NR, Young GA. Effect of dietary intake of fat-soluble vitamins on intensity of experimental swine influenza virus infection in mice. Virology. 1956.

One last thing, when you give flu shots to hemodialysis patients, those taking activated vitamin D develop significantly better immunity.8

Will normal vitamin D levels protect your family against the flu? No one knows. It would be nice if we had a report from a big hospital, were some patients were on vitamin D and some who weren’t and see what happened when the flu struck the hospital. Were the patients on vitamin D less likely to get the flu?

In the meantime, it seems to me the smart thing to do is to take enough real vitamin D (cholecalciferol) or get enough UVB light to get and keep your 25-hydroxy-vitamin D level at about 50 ng/ml. Of course, it is a good idea to keep your level around 50 ng/ml year around even if you don’t fear the coming influenza pandemic. 50 ng/ml is the normal human level and protects the owner from a myriad of chronic diseases.9, 10

Also, don’t depend on high levels in the summer being stored and used in the winter. Vieth believes that the intracellular kinetics of vitamin D metabolism means that declining vitamin D blood levels may cause rapidly declining intracellular levels. That is, declining levels in the autumn may be as dangerous as low levels in the winter.11

Professor Robert Heaney believes healthy blood levels may require up to 4,000 units a day for those with no sun exposure. Most people need to take more in the winter than the summer. Big people need more than little people. African Americans need more than whites. Sunphobes need more than those who enjoy God’s invention.12

Children over 50 pounds need up to 2,000 units a day. Under 50 pounds, about 1,000 units a day. There is no way to know for sure how much you need without a blood test, called a 25-hydroxy-vitamin D. That test should be conducted in the late winter, when your levels are the lowest, and at the beginning of fall, when your levels are the highest. Then you can figure out how much you need to take to keep stable levels. Or adults can simply take 4,000 units a day, every day, except for those late spring, summer, and early fall days when you go into the sun.

It might be a good idea to keep pharmacological doses (50,000 units) of vitamin D next to your antivirals and take a 50,000 unit capsule at the first sign of the flu, although there is not one study to support such a practice. It might help tame those unchained macrophages and save your life or it might not help at all. You can buy 50,000 unit capsules from Bio-Tech-Pharm. Single administrations of ten times that amount have repeatedly been found to be safe and are routinely used in Europe as stoss therapy for vitamin D deficiency. Furthermore, 50,000 units is about what your skin makes after a summer day at the beach.

So, maybe vitamin D will help your family survive the coming influenza pandemic, maybe not. Let’s gamble. Ever heard of the vitamin D variation of Pascal’s wager ?

“If you erroneously believe vitamin D helps influenza, you lose nothing, whereas if you correctly believe vitamin D helps influenza, your family may live. But if you correctly disbelieve in vitamin D, you gain nothing, whereas if you erroneously disbelieve in vitamin D, your family may die.”

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