Posted on 11/10/2006 4:08:52 PM PST by blam
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. 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.
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. iStockphoto
"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 the December 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 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 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: 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 Robert 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). 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."
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Alright, thanks for the information djf
Hey!
Free Republic is an endless source of "stuff" - as George Carlin would say
Faster then Google or Dr. Kildare
Yes it is, and there are a lot of well informed Freepers in sleepers here!
Someday you, too, will be a geezer and have little better to do than research medical stuff on the net!
Good luck!
Vitamin D may cut pancreatic cancer risk by nearly half
Eureka Alert ^ | 09.12.06 | Warren Froelich
Posted on 09/14/2006 9:10:47 PM CDT by Coleus
PHILADELPHIA -- Consumption of Vitamin D tablets was found to cut the risk of pancreatic cancer nearly in half, according to a study led by researchers at Northwestern and Harvard universities. The findings point to Vitamin D's potential to prevent the disease, and is one of the first known studies to use a large-scale epidemiological survey to examine the relationship between the nutrient and cancer of the pancreas. The study, led by Halcyon Skinner, Ph.D., of Northwestern, appears in the September issue of Cancer Epidemiology Biomarkers & Prevention.
The study examined data from two large, long-term health surveys and found that taking the U.S. Recommended Daily Allowance of Vitamin D (400 IU/day) reduced the risk of pancreatic cancer by 43 percent. By comparison, those who consumed less than 150 IUs per day experienced a 22 percent reduced risk of cancer. Increased consumption of the vitamin beyond 400 IUs per day resulted in no significant increased benefit.
"Because there is no effective screening for pancreatic cancer, identifying controllable risk factors for the disease is essential for developing strategies that can prevent cancer," said Skinner. "Vitamin D has shown strong potential for preventing and treating prostate cancer, and areas with greater sunlight exposure have lower incidence and mortality for prostate, breast, and colon cancers, leading us to investigate a role for Vitamin D in pancreatic cancer risk. Few studies have examined this association, and we did observe a reduced risk for pancreatic cancer with higher intake of Vitamin D."
Skinner, currently in the Department of Population Health Sciences at the University of Wisconsin School of Medicine and Public Health, and his colleagues analyzed data from two long-term studies of health and diet practices, conducted at Harvard University. They looked at data on 46,771 men aged 40 to 75 years who took part in the Health Professionals Follow-up Study, and 75,427 women aged 38 to 65 years who participated in the Nurses' Health Study. Between the two studies, they identified 365 cases of pancreatic cancer. The surveys are considered valuable for their prospective design, following health trends instead of looking at purely historical information, high follow-up rates and the ability to enable researchers like Skinner to incorporate data from two independent studies.
Pancreatic cancer is a rapidly fatal disease and the fourth-leading cause of death from cancer in the United States. This year, the American Cancer Society estimates that 32,000 new cases of cancer will be diagnosed. About the same number of people will die this year from the disease. It has no known cure, and surgical treatments are not often effective. Except for cigarette smoking, no environmental factors or dietary practices have been linked to the disease.
In addition to Vitamin D, the researchers also measured the association between pancreatic cancer and the intakes of calcium and retinol (Vitamin A). Calcium and retinol intakes showed no association with pancreatic cancer risk, although retinol is an antagonist of Vitamin D's ability to influence mineral balances and bone integrity. For that reason, further research is necessary to determine if Vitamin D ingestion from dietary sources, like eggs, liver and fatty fish or fortified dairy products, or through sun exposure might be preferable to multi-vitamin supplements, which contain retinol.
The potential benefits of vitamin D for pancreatic cancer were only recently established by other laboratory studies. Normal and cancerous pancreas tissue contain high levels of the enzyme that converts circulating 25-hydroxyvitamin D into 1,25-dihydroxyvitamin D, the vitamin's active form. Other studies have shown an anti-cell proliferation effect of 1,25-dihydroxyvitamin D, potentially inhibiting tumor cells. "In concert with laboratory results suggesting anti-tumor effects of Vitamin D, our results point to a possible role for Vitamin D in the prevention and possible reduction in mortality of pancreatic cancer. Since no other environmental or dietary factor showed this risk relationship, more study of Vitamin D's role is warranted," Skinner said.
Great article..thnx for the ping.
Health bump.
I have lived in Asia for over a decade, and though my Chinese friends think myself, my wife and my child are overweight (by their standards we are; by US standards we look like Twiggy), they marvel at how infrequently we get colds and flu compared to them.
One thing we do, especially my little one, is we drink milk--lots of it, and we are not afraid of being in the sun. In fact, living in a major urban area, whenever we have the chance of going out to a park on a sunny day, it is like going to Disneyland.
Contrast that with our Chinese friends, especially women. They typically don't drink much milk (that is changing), go to great links to avoid exposure to the sun (the women especially will stay out of sunlight) and get the flu much more often than we do.
Yes, this is anecdotal, at least insofar as my family and I are concerned.
But one thing that is not in doubt: Virulent flus almost always emerge from China--especially south China. Is it possible that there is a cultural aspect to this reality? Namely, that Chinese aversion of milk (if it has vitamin D) and aversion to the sun (which naturally creates vitamin D for us) leads to a vitamin D deficiency and, thus, reduced immunity to the flu?
Very interesting. Maybe some of those tb sanitariums which were located in the mountains did some good. I think the patients used to sit on the porches. Were the porches on the south side of the building?
If you get plenty of sun wouldn't you automatically get plenty of Vit D? Unless your skin is dark or you use lots of sunscreen.
What are the side effects of too much Vitamin D? Daily supplements could be abused if too much D is harmful.
I don't know...If someone finds out, please ping me.
I've also read that people (mostly women) who take calcium for osterporosis(sp)are wasting their time if they don't also take a sufficent amount of vitamin-D.
Blam is a busy little booger, isn't he?
Interesting set of articles; I have been taking 25mg of Toprol to control mild hypertension for 11 months using 6 ounces of milk to wash it down.
I haven't had an infection in the whole time, but then, I don't know how much vitamin D is in 6 oz of whole milk.
It sounds odd to state that a deficiency is being increased.
Cod liver oil as a tonic has been prescribed and recommended for decades for all manner of illness, my Grandma was always right, ugh - nasty tasting stuff, though.
I'm 6 feet tall and weigh 145 pounds, I'm not worried about getting fat.
I have been this size since I was 19 except for two short gains caused by overeating, weight-lifting and later snack binging.
The snack one put me up to 170 and I had to buy a new shirt, slacks and belt. Hate belts, love my size 30-32 pants and now I wear one shirt that I have had for about thirty years on special occasions (ugly thing).
At 66, I imagine that after all is said and done that I will be buried in that shirt in another 20 years or so.
Daily Vitamin D
Minimum 400IU
Optimum 400 -800 IU
Overdose 2000IU
http://www.archure.net/salus/vitamins.html
VITAMIN D EXCESS
Taking very high daily doses of vitamin D over several months can cause toxicity and a high calcium level in the blood (hypercalcemia)
Early symptomsoms are loss of appetite, nausea, and vomiting, followed by excessive thirst, weakness, nervousness, and high blood pressure.
Because the calcium level is high, calcium may be deposited throughout the body, particularly in the kidneys, blood vessels, lungs, and heart.
The kidneys may be permanently damaged and malfunction. As a result, urination increases, protein passes into the urine, and the level of urea (a waste product) increases in the blood. Kidney failure may result.
http://www.merck.com/mmhe/sec12/ch154/ch154c.html#sec12-ch154-ch154c-116
I'm probably going to take only 200iu daily because some foods are vitamin-D fortified already and I eat a lot of (deep-sea) tuna.
Perhaps a poor choose of wording. I meant that deficiency is probably more widespread in the population because so many people are covering up from the sun. Thus, increased prevalence of vitamin D deficiency because so many people follow the latest health fads.
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