Epidemic Influenza And Vitamin D‏

http://www.medicalnewstoday.com/articles/51913.php

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.