The antibiotic vitamin: deficiency in vitamin D may predispose people to infection

Science News,  Nov 11, 2006  by Janet Raloff

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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. John 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.

"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, Adrian 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 for an upcoming Epidemiology and Infection.

This is only a hypothesis, "but a very credible one" that deserves testing, says immunologist Michael Zasloff of Georgetown 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 relation ship 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 Richard 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 John 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). 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."