Epidemic Influenza And Vitamin D3

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

Main Category: Complementary Medicine / Alternative Medicine
Also Included In: Flu / Cold / SARS;  Infectious Diseases / Bacteria 
/ Viruses;  Swine Flu
Article Date: 15 Sep 2006 - 0:00 PDT

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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 
<http://journals.cambridge.org/download.php?file=%2FHYG%2FS0950268806007175a.pdf&code=b8b8a5129561fd1881bc6fe8a66d382c>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, [email protected]
-- 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>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)
<http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=469543>journal
 
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