Vitamin D and Common Cold

[Guest guest]

Hi Folks - a while back I mentioned this article, about Vitamin D possibly

protecting against the common cold (and being generally good at helping us

ward off infection). Someone wrote back that I posted the wrong URL for the

article, so I'm attaching the whole thing here. Hope you find it

interesting, as I did.

Best,

R

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The Antibiotic Vitamin

Deficiency in vitamin D may predispose people to infection

Janet Raloff

In April 2005, a virulent strain of influenza hit a maximum-security

forensic psychiatric hospital for men that's midway between San Francisco

and Los Angeles. J. Cannell, a psychiatrist there, observed with

increasing curiosity as one infected ward after another was quarantined to

limit the outbreak. Although 10 percent of the facility's 1,200 patients

ultimately developed the flu's fever and debilitating muscle aches, none did

in the ward that he supervised.

WINTER WOES. Cold-weather wear and the sun's angle in the winter sky limit

how much ultraviolet light reaches the skin. This can add up to a deficiency

in production of vitamin D, which might explain why respiratory infections

are common and severe in winter.

" First, the ward below mine was quarantined, then the wards on my right,

left, and across the hall, " Cannell recalls. However, although the 32 men on

his ward at Atascadero (Calif.) State Hospital had mingled with patients

from infected wards before their quarantine, none developed the illness.

Cannell's ward was the only heavily exposed ward left unaffected. Was it by

mere chance, Cannell wondered, that his patients dodged the sickness?

A few months later, Cannell ran across a possible answer in the scientific

literature. In the July 2005 FASEB Journal, F. Gombart of the

University of California, Los Angeles (UCLA) and his colleagues reported

that vitamin D boosts production in white blood cells of one of the

antimicrobial compounds that defends the body against germs.

Immediately, Cannell says, the proverbial lightbulb went on in his head:

Maybe the high doses of vitamin D that he had been prescribing to virtually

all the men on his ward had boosted their natural arsenal of the

antimicrobial, called cathelicidin, and protected them from flu. Cannell had

been administering the vitamin D because his patients, like many other

people in the industrial world, had shown a deficiency.

The FASEB Journal article also triggered Cannell's recollection that

children with rickets, a hallmark of vitamin D deficiency, tend to

experience more infections than do kids without the bone disease. He shared

his flu data with some well-known vitamin D researchers, and they urged him

to investigate further.

On the basis of more than 100 articles that he collected, Cannell and seven

other researchers now propose that vitamin D deficiency may underlie a

vulnerability to infections by the microbes that cathelicidin targets. These

include bacteria, viruses, and fungi, the group notes in a report available

online <http://dx.doi.org/10.1017/S0950268806007175> for the December

Epidemiology and Infection.

This is only a hypothesis, " but a very credible one " that deserves testing,

says immunologist Zasloff of town University in Washington,

D.C.

Behind the hypothesis are recent studies that link vitamin D intake to

revved-up cathelicidin production. These investigations point to an

infection-fighting role for vitamin D, which is produced in skin exposed to

sunlight but is present in few foods.

A study published earlier this year that investigated the relationship

between vitamin D and susceptibility to tuberculosis also bolsters the idea

proposed by Cannell's team. Scientists have already planned a handful of

clinical trials to evaluate the antimicrobial benefits of vitamin D

supplementation.

Zasloff argues that if studies support the hypothesis, " we can imagine one

day treating infections not by giving somebody a drug, but by giving them

safe and simple substances‹like a vitamin. "

Innate protection

Legions of germs come into contact with our bodies every day. Each microbe

seeks a host in which it can multiply. Most would-be invaders, however,

don't succeed; if not barred entry outright, they're destroyed by cellular

recruits called up to participate in local immune militias.

Scientists hadn't been sure what serves as the call to arms for these immune

cells and what triggers the production of their antibiotic arsenal, which

includes several chemical weapons.

Over the past 5 years, a spate of studies began to shed light on the rollout

of one of those munitions‹cathelicidin. Dermatologist and immunologist

L. Gallo of the University of California, San Diego, a coauthor of

many of these studies, explains that cathelicidin " targets the bad guys. " It

kills invaders by punching holes in the external membrane of a microbe,

permitting its innards to leak out.

Molecular geneticist H. White of McGill University in Montreal and his

colleagues were the first to observe that cathelicidin production is ramped

up by vitamin D‹or, more specifically, by the hormone 1,25-D, the vitamin's

active form (SN: 10/9/04, p. 232:

http://www.sciencenews.org/articles/20041009/bob8.asp

<http://www.sciencenews.org/articles/20041009/bob8.asp> ). Through a cascade

of events, vitamin D transforms into a compound, called a prehormone, that

circulates in blood and then is converted locally, as needed, into 1,25-D.

In the nucleus of cells, 1,25-D binds to short sequences of DNA. Known as

response elements, these sequences switch on the activity of adjacent genes.

" We wanted to find out what genes were next to the vitamin D response

elements, " White recalls.

Two of these response elements proved to be neighbors of genes that make

antimicrobial peptides, cathelicidin and beta-defensin 2, the researchers

reported in 2004. When the researchers administered 1,25-D to a variety of

cells, production of beta-defensin 2 increased " modestly, " White told

Science News. In contrast, he says, the gene for making cathelicidin " went

boom! Its induction was very, very strong. "

Almost a year later, while hunting for triggers for cathelicidin production,

Gombart confirmed the McGill finding. His group had been administering

various natural signaling agents to white blood cells, which the immune

system sends out to vanquish germs.

In these cells, " nothing turned on the cathelicidin gene to any degree

except vitamin D. And it really turned that gene on‹just cranked it up, "

Gombart says. " I was completely surprised. "

Independently, dermatologist Mona Ståhle of the Karolinska Institute in

Stockholm reached a similar conclusion when she realized that both vitamin D

and several antimicrobials, including cathelicidin, are produced in the

skin. She says, " It just came to me‹an intuitive thought‹that maybe the sun,

through vitamin D production, might help regulate the skin's antimicrobial

response. "

So, her team administered an ointment containing a drug mimic of 1,25-D to

the skin of four healthy people. The salve hit " the jackpot, right away, "

Ståhle says. In the May 2005 Journal of Investigative Dermatology, her team

reported that where the ointment had been applied, cathelicidin-gene

activity skyrocketed as much as 100-fold. The team also found evidence of a

localized increase in the concentration of cathelicidin.

Tackling TB and more

Those studies, though suggestive, didn't reveal whether vitamin D directly

reduced infection risk in people. Together with Gallo, microbial

immunologist Modlin of UCLA and his colleagues moved closer to that

goal: They evaluated the vitamin's role in fending off the tuberculosis (TB)

germ Mycobacterium tuberculosis.

This group, working independently of Gombart's team, had been focusing on

macrophages, a type of white blood cell deployed by the immune system to

gobble up and destroy germs. These defense cells have features, called

toll-like receptors, that identify biochemical patterns characteristic of

invading microbes. If the receptors sense an invader, they can trigger

cathelicidin production.

Modlin's team showed that before making that antibiotic, those cells briefly

boosted their production of vitamin D receptors and of an enzyme that

converts the vitamin D prehormone into 1,25-D. However, the data suggested

that significant concentrations of 1,25-D would develop only in the presence

of the TB bacteria. This indicated that the microbe, and perhaps other

germs, must be present for the enzyme to maximize its production of 1,25-D,

Modlin says.

His group then tested whether people's blood concentrations of the

prehormone are high enough to drive the production of germ-killing

concentrations of cathelicidin. Black people, because of the sun-filtering

effect of dark pigments in their skin, are far more likely than whites to be

vitamin D deficient (SN: 10/16/04, p. 248:

http://www.sciencenews.org/articles/20041016/bob9.asp

<http://www.sciencenews.org/articles/20041016/bob9.asp> ). Furthermore,

blacks tend to be more susceptible to TB than whites and to develop a more

severe illness when infected.

The team collected blood serum from white people and from blacks. When the

researchers added TB bacteria, macrophages in the serum from black

participants produced 63 percent less cathelicidin‹and were less likely to

kill the germs‹than were macrophages incubated in serum from whites.

The scientists then added vitamin D to the serum from blacks until

concentrations of the prehormone matched those in the serum from whites.

This boosted the macrophages' cathelicidin production and rates of

TB-microbe killing to those seen when such cells were incubated in serum

from whites. Modlin's group reported its findings in the March 24 Science.

The new data may explain the difference between blacks and whites in TB

susceptibility. Modlin says, " We showed that serum from African American

individuals did not support the production of the antibiotic by immune

cells, until the serum received supplemental vitamin D. "

" We're now planning to do a clinical trial and treat African Americans who

are deficient with vitamin D to correct their serum levels [of the

prehormone] and see if this will change their antimicrobial response, "

Modlin says.

Gallo is also planning a new trial. His group will compare the effectiveness

of supplemental vitamin D in elevating cathelicidin concentrations when

administered as oral supplements or as a skin treatment.

The team expects to see the biggest benefit in skin wounds. However, Gallo

predicts that even healthy skin will exhibit somewhat elevated antimicrobial

concentrations, signaling an improved resistance to infection.

Sun exposure‹in moderation‹might also prove therapeutic, Ståhle's team

suggested in the November 2005 Journal of Investigative Dermatology. The

scientists showed that in eight fair-skinned people, a single dose of

ultraviolet-B radiation‹just enough to evoke some skin reddening the next

day‹activated the vitamin D receptor and the cathelicidin gene in the

exposed skin.

Ståhle is now beginning a trial of people with skin infections. A drug

analog of 1,25-D will be applied to see whether it speeds wound healing.

Flu too?

Many other findings also suggested to Cannell's team that flu vulnerability

might be tempered by adequate vitamin D intake. The researchers have

marshaled data, gleaned from 120 or so reports over the past 70 years,

suggesting a link between vitamin D and resistance to infections.

For instance, the researchers point to studies showing that in winter,

colds, flu, and other respiratory diseases are more common and more likely

to be deadly than they are in summer. During winter, ultraviolet-light

exposure tends to be low because people spend more time indoors and the

atmosphere filters out more of the sun's rays, especially at mid and high

latitudes.

Cannell's group cites a 1997 study showing that the rate of pneumonia in

Ethiopian children with rickets, and therefore a likely vitamin D

deficiency, was 13 times as high as in children without that disease. The

researchers also point to five studies since the 1930s that have linked

reduced risks of infectious disease to dietary supplementation with cod

liver oil, a rich source of vitamin D.

Although the arguments in the paper by Cannell's group " are provocative, "

White says, " I find them believable. "

So does Gallo. " There are many microbes out there that rarely-to-never cause

disease in immunocompetent individuals. It's not because the microbes don't

choose to infect us, " he notes. " It's because the body's immune defense

against the microbes is sufficient to control their proliferation. "

It's possible, he says, that a shortfall in vitamin D might seriously

compromise that defense.

Gombart's group is developing rodents in which vitamin D modulates

cathelicidin.

Until such lab animals are available, vitamin D's impact‹even on flu

risk‹ " should be explored in clinical trials, " Zasloff says, because the

treatment poses little risk to people.

Moreover, he argues, the payoff from any positive finding " would be amazing.

Imagine being able to block the spread of epidemic flu with appropriate

doses of this vitamin. "