Epidemic Influenza And Vitamin D
Date: 15 Sep 2006 - 0:00 PDT
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
