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by J. J. Cannell
15 September 2006
from
MedicalNewsToday Website
Spanish version
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:
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although the influenza virus
exists in the population year-round, influenza is a
wintertime illnesses
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children with vitamin D
deficient rickets are much more likely to suffer from
respiratory infections
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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,
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Professor Edward Giovannucci of
Harvard
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Professor Reinhold Vieth of the
University of Toronto
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Professor Michael Holick of
Boston University
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Professor Cedric Garland of U.C.,
San Diego
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Dr. John Umhau of the National
Institute of Health
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Sasha Madronich of the National
Center for Atmospheric Research
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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:
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Why the flu predictably occurs
in the months following the winter solstice, when vitamin D
levels are at their lowest
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Why it disappears in the months
following the summer solstice
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Why influenza is more common in
the tropics during the rainy season
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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
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Why the incidence of influenza
is inversely correlated with outdoor temperatures
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Why children exposed to sunlight
are less likely to get colds
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Why cod liver oil (which
contains vitamin D) reduces the incidence of viral
respiratory infections
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Why Russian scientists found
that vitamin D-producing UVB lamps reduced colds and flu in
schoolchildren and factory workers
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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
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Why the elderly who live in
countries with high vitamin D consumption, like Norway, are
less likely to die in the winter
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Why children with vitamin D
deficiency and rickets suffer from frequent respiratory
infections
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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
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Why the elderly are so much more
likely to die from heart attacks in the winter rather than
in the summer
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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.
Acknowledgement
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.
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Dr. John Cannell, Atascadero
State Hospital, 10333 El Camino Real, Atascadero, CA 93422,
USA, 805 468-2061,
jcannell@dmhash.state.ca.us
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Professor Reinhold Vieth, Mount
Sinai Hospital, Pathology and Laboratory Medicine,
Department of Medicine, Toronto, Ontario, Canada
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Dr. John Umhau, Laboratory of
Clinical and Translational Studies, National Institute on
Alcohol Abuse and Alcoholism, National Institutes of Health,
Bethesda, MD
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Professor Michael Holick,
Departments of Medicine and Physiology, Boston University
School of Medicine, Boston, MA, USA
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Dr. Bill Grant, SUNARC, San
Francisco, CA
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Dr. Sasha Madronich, Atmospheric
Chemistry Division, National Center for Atmospheric
Research, Boulder, CO, USA
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Professor Cedric Garland,
Department of Family and Preventive Medicine, University of
California San Diego, La Jolla, CA
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Professor Edward Giovannucci,
Departments of Nutrition and Epidemiology, Harvard School of
Public Health, Boston, MA
http://www.vitamindcouncil.com
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