In early April of 2005, after a particularly rainy spring, an influenza
epidemic (epi: upon, demic: people) exploded through the maximum-security
hospital for the criminally insane where I have worked for the last ten years.
It was not the pandemic (pan: all, demic: people) we all fear, just an epidemic.
The world is waiting and governments are preparing for the next pandemic. A
severe influenza pandemic will kill many more Americans than died in the World
Trade Centers, the Iraq war, the Vietnam War, and Hurricane Katrina combined,
perhaps a million people in the USA alone. Such a disaster would tear the fabric
of American society. Our entire country might resemble the Superdome or Bourbon
Street after Hurricane Katrina.
It's only a question of when a pandemic will come, not if it will come.
Influenza A pandemics come every 30 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 Great Flu Epidemic killed more than 500,000 Americans.
So many millions died in other countries, they couldn't bury the bodies. 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.
Their body's own broad-spectrum natural antibiotics, called antimicrobial
peptides, seemed nowhere to be found. An overwhelming immune response to the
influenza virus - white blood cells releasing large amounts of inflammatory
agents called cytokines and chemokines into the lungs of the doomed - resulted
in millions of deaths in 1918.
As I am now a psychiatrist, and no longer a general practitioner, I was not
directly involved in fighting the influenza epidemic in our hospital. However,
our internal medicine specialists worked overtime as they diagnosed and treated
a rapidly increasing number of stricken patients. Our Chief Medical Officer
quarantined one ward after another as more and more patients were gripped with
the chills, fever, cough, and severe body aches that typifies the clinical
presentation of influenza A.
Epidemic influenza kills a million people in the world every year by causing
pneumonia, "the captain of the men of death." These epidemics are often
explosive; the word influenza comes from Italian (Medieval Latin ?nfluentia) or
influence, because of the belief that the sudden and abrupt epidemics were due
to the influence of some extraterrestrial force. One seventeenth century
observer described it well when he wrote, "suddenly a Distemper arose, as if
sent by some blast from the stars, which laid hold on very many together: that
in some towns, in the space of a week, above a thousand people fell sick
together."
I guess our hospital was under luckier stars as only about 12% of our patients
were infected and no one died. However, as the epidemic progressed, I noticed
something unusual. First, the ward below mine was infected, and then the ward on
my right, left, and across the hall - but no patients on my ward became ill. My
patients had intermingled with patients from infected wards before the
quarantines. The nurses on my unit cross-covered on infected wards. Surely, my
patients were exposed to the influenza A virus. How did my patients escape
infection from what some think is the most infectious of all the respiratory
viruses?
My patients were no younger, no healthier, and in no obvious way different from
patients on other wards. Like other wards, my patients are mostly African
Americans who came from the same prisons and jails as patients on the infected
wards. They were prescribed a similar assortment of powerful psychotropic
medications we use throughout the hospital to reduce the symptoms of psychosis,
depression, and violent mood swings and to try to prevent patients from killing
themselves or attacking other patients and the nursing staff. If my patients
were similar to the patients on all the adjoining wards, why didn't even one of
my patients catch the flu?
A short while later, a group of scientists from UCLA published a remarkable
paper in the prestigious journal, Nature. The UCLA group confirmed two other
recent studies, showing that a naturally occurring steroid hormone - a hormone
most of us take for granted - was, in effect, a potent antibiotic. Instead of
directly killing bacteria and viruses, the steroid hormone under question
increases the body's production of a remarkable class of proteins, called
antimicrobial peptides. The 200 known antimicrobial peptides directly and
rapidly destroy the cell walls of bacteria, fungi, and viruses, including the
influenza virus, and play a key role in keeping the lungs free of infection. The
steroid hormone that showed these remarkable antibiotic properties was plain old
vitamin D.
All of the patients on my ward had been taking 2,000 units of vitamin D every
day for several months or longer. Could that be the reason none of my patients
caught the flu? I then contacted Professors Reinhold Vieth and Ed Giovannucci
and told them of my observations. They immediately advised me to collect data
from all the patients in the hospital on 2,000 units of vitamin D, not just the
ones on my ward, to see if the results were statistically significant. It turns
out that the observations on my ward alone were of borderline statistical
significance and could have been due to chance alone. Administrators at our
hospital agreed, and are still attempting to collect data from all the patients
in the hospital on 2,000 or more units of vitamin D at the time of the epidemic.
Four years ago, I became convinced that vitamin D was unique in the vitamin
world by virtue of three facts. First, it's the only known precursor of a potent
steroid hormone, calcitriol, or activated vitamin D. Most other vitamins are
antioxidants or co-factors in enzyme reactions. Activated vitamin D - like all
steroid hormones - damasks the genome, turning protein production on and off, as
your body requires. That is, vitamin D regulates genetic expression in hundreds
of tissues throughout your body. This means it has as many potential mechanisms
of action as genes it damasks.
Second, vitamin D does not exist in appreciable quantities in normal human
diets. True, you can get several thousand units in a day if you feast on
sardines for breakfast, herring for lunch and salmon for dinner. The only people
who ever regularly consumed that much fish are peoples, like the Inuit, who live
at the extremes of latitude. The milk Americans depend on for their vitamin D
contains no naturally occurring vitamin D; instead, the U.S. government requires
fortified milk to be supplemented with vitamin D, but only with what we now know
to be a paltry 100 units per eight-ounce glass.
The vitamin D steroid hormone system has always had its origins in the skin, not
in the mouth. Until quite recently, when dermatologists and governments began
warning us about the dangers of sunlight, humans made enormous quantities of
vitamin D where humans have always made it, where naked skin meets the
ultraviolet B radiation of sunlight. We just cannot get adequate amounts of
vitamin D from our diet. If we don't expose ourselves to ultraviolet light, we
must get vitamin D from dietary supplements.
The third way vitamin D is different from other vitamins is the dramatic
difference between natural vitamin D nutrition and the modern one. Today, most
humans only make about a thousand units of vitamin D a day from sun exposure;
many people, such as the elderly or African Americans, make much less than that.
How much did humans normally make? A single, twenty-minute, full body exposure
to summer sun will trigger the delivery of 20,000 units of vitamin D into the
circulation of most people within 48 hours. Twenty thousand units, that's the
single most important fact about vitamin D. Compare that to the 100 units you
get from a glass of milk, or the several hundred daily units the U.S. government
recommend as "Adequate Intake." It's what we call an "order of magnitude"
difference.
Humans evolved naked in sub-equatorial Africa, where the sun shines directly
overhead much of the year and where our species must have obtained tens of
thousands of units of vitamin D every day, in spite of our skin developing heavy
melanin concentrations (racial pigmentation) for protecting the deeper layers of
the skin. Even after humans migrated to temperate latitudes, where our skin
rapidly lightened to allow for more rapid vitamin D production, humans worked
outdoors. However, in the last three hundred years, we began to work indoors; in
the last one hundred years, we began to travel inside cars; in the last several
decades, we began to lather on sunblock and consciously avoid sunlight. All of
these things lower vitamin D blood levels. The inescapable conclusion is that
vitamin D levels in modern humans are not just low - they are aberrantly low.
About three years ago, after studying all I could about vitamin D, I began
testing my patient's vitamin D blood levels and giving them literature on
vitamin D deficiency. All their blood levels were low, which is not surprising
as vitamin D deficiency is practically universal among dark-skinned people who
live at temperate latitudes. Furthermore, my patients come directly from prison
or jail, where they get little opportunity for sun exposure. After finding out
that all my patients had low levels, many profoundly low, I started educating
them and offering to prescribe them 2,000 units of vitamin D a day, the U.S.
government's "Upper Limit."
Could vitamin D be the reason none of my patients got the flu? In the last
several years, dozens of medical studies have called attention to worldwide
vitamin D deficiency, especially among African Americans and the elderly, the
two groups most likely to die from influenza. Cancer, heart disease, stroke,
autoimmune disease, depression, chronic pain, depression, gum disease, diabetes,
hypertension, and a number of other diseases have recently been associated with
vitamin D deficiency. Was it possible that influenza was as well?
Then I thought of three mysteries that I first learned in medical school at the
University of North Carolina: (1) although the influenza virus exists in the
population year-round, influenza is a wintertime illnesses; (2) children with
vitamin D deficient rickets are much more likely to suffer from respiratory
infections; (3) the elderly in most countries are much more likely to die in the
winter than the summer (excess wintertime mortality), and most of that excess
mortality, although listed as cardiac, is, in fact, due to influenza.
Could vitamin D explain these three mysteries, mysteries that account for
hundreds of thousands of deaths every year? Studies have found the influenza
virus is present in the population year-around; why is it a wintertime illness?
Even the common cold got its name because it is common in cold weather and rare
in the summer. Vitamin D blood levels are at their highest in the summer but
reach their lowest levels during the flu and cold season. Could such a simple
explanation explain these mysteries?
The British researcher, Dr. R. Edgar Hope-Simpson, was the first to document the
most mysterious feature of epidemic influenza, its wintertime surfeit and
summertime scarcity. He theorized that an unknown "seasonal factor" was at work,
a factor that might be affecting innate human immunity. Hope-Simpson was a
general practitioner who became famous in the late 1960's after he discovered
the cause of shingles. British authorities bestowed every prize they had on him,
not only because of the importance of his discovery, but because he made the
discovery own his own, without the benefit of a university appointment, and
without any formal training in epidemiology (the detective branch of medicine
that methodically searches for clues about the cause of disease).
After his work on shingles, Hope-Simpson spent the rest of his working life
studying influenza. He concluded a "seasonal factor" was at work, something that
was regularly and predictably impairing human immunity in the winter and
restoring it in the summer. He discovered that communities widely separated by
longitude, but which shared similar latitude, would simultaneously develop
influenza. He discovered that influenza epidemics in Great Britain in the 17th
and 18th century occurred simultaneously in widely separated communities, before
modern transportation could possibly explain its rapid dissemination.
Hope-Simpson concluded a "seasonal factor" was triggering these epidemics.
Whatever it was, he was certain that the deadly "crop" of influenza that sprouts
around the winter solstice was intimately involved with solar radiation.
Hope-Simpson predicted that, once discovered, the "seasonal factor" would
"provide the key to understanding most of the influenza problems confronting
us."
Hope-Simpson had no way of knowing that vitamin D has profound effects on human
immunity, no way of knowing that it increases production of broad-spectrum
antimicrobial peptides, peptides that quickly destroy the influenza virus. We
have only recently learned how vitamin D increases production of antimicrobial
peptides while simultaneously preventing the immune system from releasing too
many inflammatory cells, called chemokines and cytokines, into infected lung
tissue.
In 1918, when medical scientists did autopsies on some of the fifty million
people who died during the 1918 flu pandemic, they were amazed to find destroyed
respiratory tracts; sometimes these inflammatory cytokines had triggered the
complete destruction of the normal epithelial cells lining the respiratory
tract. It was as if the flu victims had been attacked and killed by their own
immune systems. This is the severe inflammatory reaction that vitamin D has
recently been found to prevent.
I subsequently did what physicians have done for centuries. I experimented,
first on myself and then on my family, trying different doses of vitamin D to
see if it has any effects on viral respiratory infections. After that, as the
word spread, several of my medical colleagues experimented on themselves by
taking three-day courses of pharmacological doses (2,000 units per kilogram per
day) of vitamin D at the first sign of the flu. I also asked numerous colleagues
and friends who were taking physiological doses of vitamin D (5,000 units per
day in the winter and less, or none, in the summer) if they ever got colds or
the flu, and, if so, how severe the infections were. I became convinced that
physiological doses of vitamin D reduce the incidence of viral respiratory
infections and that pharmacological doses significantly ameliorate the symptoms
of some viral respiratory infections if taken early in the course of the
illness. However, such observations are so personal, so likely to be biased,
that they are worthless science.
As I waited for the hospital to finish collecting data from all the patients
taking vitamin D at the time of the outbreak - to see if it really reduced the
incidence of influenza - I decided to research the literature thoroughly,
finding all the clues in the world's medical literature that indicated if
vitamin D played any role in preventing influenza or other viral respiratory
infections. I worked on the paper for over a year, writing it with Professor
Edward Giovannucci of Harvard, Professor Reinhold Vieth of the University of
Toronto, Professor Michael Holick of Boston University, Professor Cedric Garland
of U.C., San Diego, as well as Dr. John Umhau of the National Institute of
Health, Sasha Madronich of the National Center for Atmospheric Research, and Dr.
Bill Grant at the Sunlight, Nutrition and Health Research Center. After numerous
revisions, we submitted our paper to the same widely respected journal where Dr.
Hope-Simpson published most of his work several decades ago.
Epidemiology and Infection, known as The Journal of Hygiene in
Hope-Simpson's day, recently published our
paper. The editor, Professor Norman Noah, knew Dr. Hope-Simpson and helped
tremendously with the paper. In the paper, we detailed our theory that vitamin D
is Hope-Simpson's long forgotten "seasonal stimulus." We proposed that annual
fluctuations in vitamin D levels explain the seasonality of influenza. The
periodic seasonal fluctuations in 25-hydroxy-vitamin D levels, which cause
recurrent and predictable wintertime vitamin D deficiency, predispose human
populations to influenza epidemics. We raised the possibility that influenza is
a symptom of vitamin D deficiency in the same way that an unusual form of
pneumonia (pneumocystis carinii) is a symptom of AIDS. That is, we theorized
that George Bernard Shaw was right when he said, "the characteristic microbe of
a disease might be a symptom instead of a cause."
In the paper, we propose that vitamin D explains the following 14
observations:
1. Why the flu predictably occurs in the months following the winter solstice,
when vitamin D levels are at their lowest,
2. Why it disappears in the months following the summer solstice,
3. Why influenza is more common in the tropics during the rainy season,
4. Why the cold and rainy weather associated with El Nino Southern Oscillation
(ENSO), which drives people indoors and lowers vitamin D blood levels, is
associated with influenza,
5. Why the incidence of influenza is inversely correlated with outdoor
temperatures,
6. Why children exposed to sunlight are less likely to get colds,
7. Why cod liver oil (which contains vitamin D) reduces the incidence of viral
respiratory infections,
8. Why Russian scientists found that vitamin D-producing UVB lamps reduced colds
and flu in schoolchildren and factory workers,
9. Why Russian scientists found that volunteers, deliberately infected with a
weakened flu virus - first in the summer and then again in the winter - show
significantly different clinical courses in the different seasons,
10. Why the elderly who live in countries with high vitamin D consumption, like
Norway, are less likely to die in the winter,
11. Why children with vitamin D deficiency and rickets suffer from frequent
respiratory infections,
12. Why an observant physician (Rehman), who gave high doses of vitamin D to
children who were constantly sick from colds and the flu, found the treated
children were suddenly free from infection,
13. Why the elderly are so much more likely to die from heart attacks in the
winter rather than in the summer,
14. Why African Americans, with their low vitamin D blood levels, are more
likely to die from influenza and pneumonia than Whites are.
Although our paper discusses the possibility that physiological doses of vitamin
D (5,000 units a day) may prevent colds and the flu, and that physicians might
find pharmacological doses of vitamin D (2,000 units per kilogram of body weight
per day for three days) useful in treating some of the one million people who
die in the world every year from influenza, we remind readers that it is only a
theory. Like all theories, our theory must withstand attempts to be disproved
with dispassionately conducted and well-controlled scientific experiments.
However, as vitamin D deficiency has repeatedly been associated with many of the
diseases of civilization, we point out that it is not too early for physicians
to aggressively diagnose and adequately treat vitamin D deficiency. We recommend
that enough vitamin D be taken daily to maintain 25-hydroxy vitamin D levels at
levels normally achieved through summertime sun exposure (50 ng/ml). For many
persons, such as African Americans and the elderly, this will require up to
5,000 units daily in the winter and less, or none, in the summer, depending on
summertime sun exposure.
By: J. J. Cannell
Acknowldegement: We wish to thank Professor Norman Noah of the London School of
Hygiene and Tropical Medicine, Professor Robert Scragg of the University of
Auckland and Professor Robert Heaney of Creighton University for reviewing the
manuscript and making many useful suggestions.
-- Dr. John Cannell, Atascadero State Hospital, 10333 El Camino Real,
Atascadero, CA 93422, USA, 805 468-2061, jcannell@dmhash.state.ca.us
-- Professor Reinhold Vieth, Mount Sinai Hospital, Pathology and Laboratory
Medicine, Department of Medicine, Toronto, Ontario, Canada
-- Dr. John Umhau, Laboratory of Clinical and Translational Studies, National
Institute on Alcohol Abuse and Alcoholism, National Institutes of Health,
Bethesda, MD
-- Professor Michael Holick, Departments of Medicine and Physiology, Boston
University School of Medicine, Boston, MA, USA
-- Dr. Bill Grant, SUNARC, San Francisco, CA
-- Dr. Sasha Madronich, Atmospheric Chemistry Division, National Center for
Atmospheric Research, Boulder, CO, USA
-- Professor Cedric Garland, Department of Family and Preventive Medicine,
University of California San Diego, La Jolla, CA
-- Professor Edward Giovannucci, Departments of Nutrition and Epidemiology,
Harvard School of Public Health, Boston, MA
http://www.vitamindcouncil.com
Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant WB, Madronich S, Garland CF, and
Giovanucci E. Epidemic Influenza and Vitamin D. Epidemiol Infect. 2006 Sep
7;:1-12 (Epub ahead of print)
Link Here.