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 CreightonUniversity 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, jcan...@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
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) journal link
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