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HeatherAdministrator

Reged: 12/09/02
Posts: 7668
Loc: Seattle, WA
Gut Check - The bacteria in your intestines are welcome guests new
      #69097 - 05/10/04 01:33 PM

Gut Check - The bacteria in your intestines are welcome guests

John Travis

New York and London are famous for both their congestion and the diverse origins of their residents. But if you're looking for the ultimate teeming metropolis of immigrants, check out the large intestine. In people, some 500 to 1,000 kinds of bacteria reside in this part of the gastrointestinal (GI) tract, and these gut microbes outnumber all the cells in your body, perhaps by as much as a factor of 10.

"The density of this society is mind-boggling," says Jeffrey I. Gordon of Washington University School of Medicine in St. Louis.

It's a society overlooked by most microbiologists, who generally stick to the myriad bacteria that cause disease. Yet some scientists argue that it's shortsighted to ignore what they call the microflora living in our intestines.

"What these bacteria do definitely makes a very significant contribution to our health—or lack thereof," says Mark Schell of the University of Georgia in Athens, who studies an intestinal microbe called Bifodobacterium longum.

Shell and a few other researchers have recently begun to probe exactly what individual microbes do for or to the intestine.

Consider Bacteriodes thetaiotaomicron. Although not as well known, it's more than 1,000 times as abundant in the guts of people and mice as the extensively studied bacterium Escherichia coli. Some researchers have proposed that in return for a steady food supply, B. thetaiotaomicron breaks down indigestible complex carbohydrates into easily absorbed sugars and produces other substances, such as vitamins, that benefit its host.

There may be much more to this microbe-host relationship, however. About a decade ago, Gordon chose B. thetaiotaomicron as a prototypical germ for studying how microbes influence the GI tract. This bacterium normally becomes a predominant member of the intestinal community about the time an animal is weaned from its mother's milk. Gordon's research team has discovered that the microbe can turn on specific intestinal genes, promote the growth of blood vessels necessary for the gut's function, and trigger production of a chemical that may kill competing bacteria. Investigators are now asking just how much gut bacteria regulate the developing and adult human body.

"Bacteria do an awful lot for us and with us," says Gordon. "Most people's views of bacteria are of menacing, disease-promoting entities. Au contraire, I think that most of our encounters with bacteria are mutually beneficial, friendly, and part of our normal biology. . . . They've insinuated themselves into our biology and coevolved with us."

Sweet-talking germ

Perhaps the best way to understand the significance of intestinal microorganisms is to see what happens when an animal doesn't have them. During the past 50 years, researchers have created germfree mice and rats by delivering the animals by cesarean section into sterile environments and maintaining them there. "It's a very demanding technology," says Gordon. Scientists have generally used such germfree animals to study how particular pathogens cause diseases.

One of the most striking aspects of a germfree rodent is that it must consume about 30 percent more calories to maintain its body weight than a typical rodent does. Germfree animals are also unusually susceptible to infections, presumably because the microflora in a normal gut ward off foreign pathogens.

As a way to study animals hosting a simplified society of gut bacteria, Gordon and his colleagues have introduced B. thetaiotaomicron into germfree mice. Their first significant discovery was that the bacterium could change what sugars the intestine makes.

The surfaces of intestinal cells of typical mice are coated with complex sugars containing the simple sugar fucose and B. thetaiotaomicron consumes the fucose for energy. In germfree mice, however, fucose production ceases around the time of weaning.

If B. thetaiotaomicron colonizes a germfree mouse before weaning, however, normal fucose synthesis continues throughout life, the researchers found. Through a still undiscovered signal, the microbe apparently induces the intestinal cells to make one of its favorite foods. The bacterium even has a fucose sensor that informs it when this food source is scarce, according to Gordon and his colleagues.

The capacity of B. thetaiotaomicron to instruct intestinal cells to make fucose was just a hint of things to come. To get a more comprehensive picture of the bacterium's influence, Gordon's group turned to microchip-size devices, called DNA microarrays, that monitor the activity of thousands of genes at once (SN: 3/8/97, p. 144).

With such instruments, the scientists took a snapshot of the gene activity in the mouse intestine. By comparing tissue from germfree mice and mice hosting B. thetaiotaomicron, the team found that the presence of the bacterium significantly reduces or boosts the activity of about 100 of the approximately 25,000 rodent genes in the microarray survey.

Some of the intestinal genes triggered by the microbe help mammals absorb and metabolize sugars and fats, Gordon and his colleagues reported in 2001. Other activated genes fortify the cellular barrier that prevents bacteria, both dangerous and friendly, from sneaking out of the intestine into other tissues and the bloodstream. And yet other affected genes determine how the intestine detoxifies compounds and how the gut matures.

"We were amazed at the breadth of normal intestinal functions affected by a single microbe," says study coauthor Lora V. Hopper. Gordon adds, "It's difficult to anticipate the full range of host functions that might be manipulated by these microbes."

The genetic activity that the researchers didn't see in the bacteria-colonized mice was interesting, too. Even though the originally germfree mice had never encountered B. thetaiotaomicron before, there was no increase in activity of the genes underlying an immune or inflammatory response. That's a reflection of the microbe's still mysterious skill at convincing a host that it's a friendly visitor and not a danger, says Gordon.

Raising fences

Among the intestinal genes activated by B. thetaiotaomicron is one suspected to stimulate the growth of new blood vessels. The finding spurred Gordon's group to investigate the microbe's control over the system of blood vessels that runs through the GI tract. These blood vessels are crucial to a body's absorption of nutrients.

The researchers discovered that their germfree mice have a poorly formed network of the capillaries that normally supply the inner intestinal surface with its blood supply. This could partly explain the difficulty that germfree animals have absorbing nutrients.

The team also found that it could stimulate germfree mice to grow a normal network of intestinal capillaries by exposing the animals to either a full complement of microflora or just B. thetaiotaomicron. The investigators reported the finding in the Nov. 26, 2002 Proceedings of the National Academy of Sciences.

This is a vivid illustration that the physical development of the gut can depend on the microbes that normally inhabit animals, says Gordon. The researchers also found cells in the mouse gut that seems to work with the microbes to spur vessel growth.

In the small intestine, so-called Paneth cells normally secrete antimicrobial compounds (SN: 8/26/00, p. 135: Available to subscribers at http://www.sciencenews.org/20000826/fob8.asp). This keeps the intestine healthy by protecting other cells that continually replenish the gut lining. Gordon's team created germfree versions of mutant mice that lack Paneth cells and found that B. thetaiotaomicron couldn't trigger the maturation of blood vessels in such rodents. While most investigators have regarded Paneth cells simply as defenders against invading bacteria, it makes sense that these cells mediate interactions between a host and its natural microflora, says Gordon. "What better cell to respond to the presence or absence of a microbe?" he remarks.

The Paneth cell is at the heart of another microbe-intestine interaction uncovered recently by Gordon's group. One of the intestinal genes triggered in germfree mice by B. thetaiotaomicron encodes a protein called angiogenin 4 or Ang4. Cancer researchers are particularly interested in this protein, because they have evidence that it nourishes tumors by creating new blood vessels. Gordon's team suspected that Ang4 plays a role in the intestinal blood vessel maturation that they had documented earlier. Indeed, it turned out that Paneth cells make Ang4 and secrete it when they detect bacteria.

While the suspicion that Ang4 makes intestinal blood vessels has not yet been proven, it looks like the protein has a more certain role. It can kill several bacteria and fungi that cause diseases in mammals, Gordon, Hooper, and their colleagues report in the March Nature Immunology. In contrast, B. thetaiotaomicron and other common residents of the mouse intestines are largely resistant to Ang4.

"One interpretation of the interaction between host defense and the resident flora is that the resident bacteria that are resistant to Paneth-cell secretions stimulate these host-defense mechanisms to prevent competition by nonresident bacteria. The host in turn benefits by decreasing its exposure to potential pathogens," says Tomas Ganz of the University of California, Los Angeles in a commentary accompanying the March report.

Hooper agrees that the normal inhabitants of the gut may use Paneth cells and Ang4 to raise what she calls an "electric fence" to keep out competing microbes. Beyond fending off foreign pathogens, such fences may also keep typical intestinal microbes within the gut. "Anything can become a pathogen if it crosses the fence," she says.

Eating leftovers

Scientists have estimated that the hundreds of bacterial species within the human gut may together possess as many unique genes as a person does, and perhaps far more. "How much of our biology is dependent on metabolic traits encoded in the collective genomes of our microbial partners?" asks Gordon.

Investigators have begun to address that question. For example, Schell recently worked with scientists at the Nestlé Research Center in Lausanne, Switzerland, to unravel some of the genetic secrets of B. longum. This microbe typically colonizes the intestines of a newborn mammal, thrives during the breast-feeding period, and then subsides after weaning, when B. thetaiotaomicron and other bacteria take hold. Nestlé incorporates B. longum into some of its products, such as infant formulas and yogurts, to promote gastrointestinal health.

In the Oct. 29, 2002 Proceedings of the National Academy of Sciences, Schell and his colleagues unveiled the entire DNA sequence of B. longum and identified a large roster of genes for enzymes that break apart sugars and other edible substances. Some of these enzymes may degrade complex sugars found in breast milk, speculates Schell. Others, such as ones that apparently break down plant gums, may help the bacterium survive later in its host's life when B. longum is in the minority in the intestines.

The bacterium appears to break down substances that B. thetaiotaomicron and other Bacteriodes can't handle. "It seems to be more specialized for the leftovers of metabolism," says Schell. In a strategy similar to Gordon's, investigators at Nestlé are now using germfree mice to evaluate B. longum's impact on intestinal genes.

Gordon's team is drawing its own insights from the group's recent deciphering of B. thetaiotaomicron's genome. Among that microbe's nearly 4,800 genes, several hundred encode proteins that bind carbohydrates, enzymes that degrade bonds between sugars, or enzymes that create new sugars, the investigators reported in the March 28 Science. And the activity of many of these genes appears to be regulated by genes encoding molecules related to known environmental sensors, suggesting that the microbe can monitor the contents of the intestines and quickly deploy the molecular machinery needed for it to digest nutrients.

"This organism has a sweet tooth. It knows how to process carbohydrates," says Gordon.

Over the next 5 to 10 years, predicts Schell, researchers will decode the genomes of many more intestinal microbes. Investigators may also begin to address such issues as whether a person's diet changes his or her intestinal microflora. "I think the gut population of a vegetarian is clearly going to be different" from that of a meat eater, says Schell.

Gordon offers an even more provocative question: Do intestinal microbes influence a person's weight? "Over time, could relatively minor differences in the ability to extract nutrients in some individuals predispose them to obesity?" he asks.

The complicated nation of bacteria within our intestines is a "window into our biology and how we've evolved as a species," concludes Gordon.

http://www.sciencenews.org/articles/20030531/bob9.asp

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Heather is the Administrator of the IBS Message Boards. She’s the author of Eating for IBS and The First Year: IBS, and the CEO of Heather's Tummy Care. Join her IBS Newsletter. Meet Heather on Facebook!

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HeatherAdministrator

Reged: 12/09/02
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Loc: Seattle, WA
Aloe, cascara sagrada, and senna laxtives can cause cathartic colon new
      #73372 - 05/25/04 03:24 PM

Aloe, cascara sagrada, and senna laxtives can cause cathartic colon

Cathartic Colon

Cathartic colon is the anatomic and physiologic change in the colon that occurs with chronic use of stimulant laxatives (> 3 times per week for at least 1 year). Signs and symptoms of cathartic colon include bloating, a feeling of fullness, abdominal pain, and incomplete fecal evacuation. Radiologic studies show an atonic and redundant colon. Chronic use of stimulant laxatives can lead to serious medical consequences such as fluid and electrolyte imbalance, steatorrhea, protein-losing gastroenteropathy, osteomalacia, and vitamin and mineral deficiencies. When the drug is discontinued, radiographic and functional changes in the colon may only partially return to normal because of drug-induced neuromuscular damage to the colon.

Anthranoid laxatives (aloe, cascara sagrada, and senna) are derived from naturally occurring plants and are considered to be stimulant laxatives. Short-term use of stimulant laxatives may be safe, but abuse of these drugs can cause melanosis coli and possibly increases the risk of colonic cancer. Melanosis coli, a benign condition, is characterized by dark pigmentation of the colonic mucosa that usually develops 9 months after initiating the use of these drugs and disappears just as quickly after the drug is discontinued.

http://www.medscape.com/viewarticle/437034_7




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Heather is the Administrator of the IBS Message Boards. She’s the author of Eating for IBS and The First Year: IBS, and the CEO of Heather's Tummy Care. Join her IBS Newsletter. Meet Heather on Facebook!

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HeatherAdministrator

Reged: 12/09/02
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Safety of aloe a concern new
      #73375 - 05/25/04 03:26 PM

Safety of Aloe a Concern

Some Notes on Aloe Vera

Beth Lulinski, R.D.
Cathy Kapica, Ph.D., R.D.

Aloe, a popular houseplant, has a long history as a multipurpose folk remedy. Commonly known as Aloe vera, the plant can be separated into two basic products: gel and latex. Aloe vera gel is the leaf pulp or mucilage, a thin clear jelly-like substance obtained from the parenchymal tissue that makes up the inner portion of the leaves [1]. The gel contains carbohydrate polymers, such as glucomannans or pectic acid, plus various other organic and inorganic compounds. Aloe latex, commonly referred to as "aloe juice," is a bitter yellow exudate from the pericyclic tubules just beneath the outer skin of the leaves. For pharmaceutical use as a laxative, the juice is often dried to produce "aloe" granules that are dark brown from exposure to air. The terms "gel" and "juice" are not clearly defined by manufacturers and often are confused by consumers.

The mechanical separation process is not always complete, so aloe latex can be found in some aloe gels. It is desirable to make the gel as pure as possible, because aloe latex contains the anthraquinone glycosides aloin A and B, which are potent laxatives [2]. The processed products are difficult to keep stable, a problem that can cause differences in product potency. Many products advertise special stabilizing procedures, but the best source of aloe gel would be direct from a broken leaf of the plant.

Aloe gel has been used for topical treatment of wounds, minor burns, and skin irritations. American consumers are most familiar with aloe's use in skin-care products, but aloe can also be used as a beverage. Aloe products for internal use have been promoted for constipation, coughs, wounds, ulcers, diabetes, cancer, headaches, arthritis, immune-system deficiencies, and many other conditions. However, the only substantiated internal use is as a laxative [3-6]. The anthroquinones and anthrones in the aloe latex probably produce their laxative effect by increasing colonic peristalsis and increasing the intestinal water content by opening chloride channels of the colonic membrane to cause a net reduction of liquid absorption by the colon [4]. The anthroquinone glycosides reach the colon mostly undigested, although some are metabolized by enzymes produced by intestinal bacteria. The result includes more frequent stools with softer consistency. In most of the studies on the laxative effects of aloe, the aloe was not used alone but in combination with other laxatives, such as celandin or psyllium. Aloe's side effects can include abdominal pain, diarrhea, and electrolyte imbalances, especially at higher doses.

Few studies have tested whether taking aloe gel internally can influence wound-healing. One study has demonstrated improved wound healing in mice, which the authors attributed to increased capillary blood flow to the injured areas [7]. During the 1970s, two FDA advisory panels concluded that there was insufficient evidence that aloe vera gel was useful for treating minor burns, cuts, or abrasions, or for treating minor vaginal irritations [8].

One study of 5,000 subjects found a positive effect of lowering risk factors in patients with heart disease. The study showed that by adding Isabgol (which increases the bulk of feces) and aloe vera gel to the diet, there was a marked reduction in total lipids, total serum cholesterol, serum triglycerides, fasting and post-meal blood sugar levels in diabetics, and an increase in HDL [9]. Our January 1998 MEDLINE search found no other studies on blood lipids, heart disease risk, and aloe. Some research has shown decreasing fasting blood sugar in diabetic animals given aloe [10-13]. Further studies are needed to explore these issues in humans.

False advertising claims for aloe are common, especially on the Internet. Some Web pages are making bold claims and using testimonials promoting it for treating the AIDS virus, arthritis, or other chronic and debilitating conditions [14,15]. These claims have not been substantiated by scientific studies.

The safety of aloe is another concern. Genotoxicity studies show that aloe-containing laxatives pose cancer risk to humans when used as directed [4]. Aloe extract can be taken orally as a dietary supplement, but does not have FDA approval for use as a drug [16]. Currently, aloe is a Category I over-the-counter stimulant laxative, meaning that it is generally recognized as safe and effective if used appropriately for this purpose [17]. The FDA recommends further testing and safety data for aloe. Some deaths have been reported of cancer patients who were treated with aloe vera intravenously by a physician whose license was subsequently revoked [16,18-20]. Injection of aloe vera is illegal in the United States, but desperate people can go to other countries where there is less regulation for unproven treatments.

Key Points
Aloe latex is a harsh stimulant laxative that has FDA approval for OTC use as a laxative ingredient.
Products derived from aloe gel and intended for internal use have not been proven effective against any disease.
The effectiveness of aloe skin-care products is uncertain.
References
1. Tyler V. The Honest Herbal: A Sensible Guide to the Use of Herbs and Related Remedies, Third Edition. Binghamton, NY: Pharmaceutical Products Press; 1993.
2. Tyler V. Herbs of Choice: The Therapeutic Use of Phytomedicinals. Binghamton, NY: Pharmaceutical Products Press; 1994.
3. Odes H.S., Madar Z. A double-blind trial of a celandin, aloevera and psyllium laxative preparation in adult patients with constipation. Digestion 49:65-71, 1991.
4. Brusick D, Mengs U. Assessment of the genotoxic risk from laxative senna products. Environmental and Molecular Mutagenesis 29:1-9, 1997.
5. Ishii Y, Tanizawa H, Takino Y. Studies of aloe. V. Mechanism of cathartic effect (4). Biological and Pharmaceutical Bulletin 17:651-3, 1994.
6. Grindlay D, Reynolds T. The Aloe vera phenomenon: A review of the properties and modern uses of the leaf parenchyma gel. Journal of Ethnopharmacology 16(2-3):117-151, 1986.
7. Davis RH, Leitner MG, Russo JM, Byrne ME. Wound healing. Oral and topical activity of aloe vera. Journal of the American Podiatric Medical Association 79:559-562, 1989.
8. Hecht A. The Overselling of aloe vera. FDA Consumer 15(6):26-29, 1981.
9. Agarwal OP. Prevention of atheromatous heart disease. Angiology 36:485-492, 1985.
10. Ghannam N and others. The antidiabetic activity of aloes: Preliminary clinical and experimental observations. Hormone Research 24:288-294, 1986.
11. Ajabnoor MA. Effect of aloes on blood glucose levels in normal and alloxan diabetic mice. Journal of Ethnopharmacology 28:215-220, 1990.
12. Al-Awadi F, Fatania H, Shamte U. The effect of a plants mixture extract on liver gluconeogenesis in streptozotocin induced diabetic rats. Diabetes Research 18:163-168, 1991.
13. Roman-Ramos R and others. Experimental study of the hypoglycemic effect of some antidiabetic plants. Archivos de Investigacion Medica 22(1):87-93, 1991.
14. Premium Aloe Company Web site, June 22, 1998.
15. Nature's Choice Aloe Vera Online Catalog, June 22, 1998.
16. Smith L., Struck D. The aloe vera trail: Investigation of four patient deaths leads officials to company based in Maryland. Washington Post. Oct 11,1997; Sec. C, 1:2.
17. Schultz W. Proposed Rules. Federal Register. Sep 2, 1997; Vol 62(169):46223-46227.
18. Smith L., Blum J. Police probe death of second patient treated by Manassas Doctor. Washington Post. Sept 26, 1997; SecB, 1:2.
19. Smith L., Lipton E. Panel suspends the license of VA physician; Doctor's aloe therapy suspected in 3 deaths. Washington Post. Sept 27, 1997; Sec.A, 1:2.
20. Smith L. Judge rejects case against Doctor's aide; Man allegedly gave aloe vera injections. Washington Post. Nov 18,1997; Sec.B, 3:2.

About the Authors

Ms. Lulinski is a medical nutritionist.

Dr. Kapica is Assistant Professor of Nutrition and Clinical Dietetics, Finch University of Health Sciences/The Chicago Medical School.

Thomas J. Wheeler, Ph.D., and Manfred Kroger, Ph.D., helped edit this article.

http://www.quackwatch.org/01QuackeryRelatedTopics/DSH/aloe.html


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Heather is the Administrator of the IBS Message Boards. She’s the author of Eating for IBS and The First Year: IBS, and the CEO of Heather's Tummy Care. Join her IBS Newsletter. Meet Heather on Facebook!

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HeatherAdministrator

Reged: 12/09/02
Posts: 7668
Loc: Seattle, WA
Calcium Seems to Protect Against Colorectal Cancer new
      #83756 - 06/27/04 02:04 PM

Calcium Seems to Protect Against Colorectal Cancer

Supplements effective at reducing polyps that can lead to tumors, study says

By Kathleen Doheny
HealthDay Reporter

TUESDAY, June 15 (HealthDayNews) -- Taking calcium supplements helps prevent polyps in the colon, a risk factor for colorectal cancer.

And the supplements seem to offer the most protection against the advanced polyps most strongly associated with invasive colorectal cancer, according to a new study.

"In an earlier publication, we showed a reduction in polyps [with calcium intake]," said Dr. John A. Baron, a professor of medicine at Dartmouth Medical School, and senior author of the study that appears in the June 16 issue of the Journal of the National Cancer Institute.

"There was less than a 20 percent reduction, overall," he added. "Now, we find when we look at more advanced [polyps], it is a much more marked reduction, suggesting that calcium might have a more pronounced effect in preventing advanced [polyps]."

For advanced polyps, calcium might reduce the risk of colorectal cancer 35 percent to 45 percent, Baron said.

An estimated 106,370 new cases of colon cancer and 40,570 cases of rectal cancer will be diagnosed this year in the United States, according to the American Cancer Society, and about 56,730 deaths will result.

Most colon and rectal cancers begin as a polyp, a growth of tissue into the center of the colon or rectum. Removing polyps, also known as adenomas, early may prevent them from becoming cancerous, according to the Cancer Society.

In new the study, Baron's team analyzed data from 913 patients enrolled in the Calcium Polyp Prevention Study. Patients took either a 1,200 milligram supplement of calcium or a placebo, and had a follow-up colonoscopy -- an exam of the colon -- one and four years after they began the calcium therapy.

Compared with those on a placebo, people taking calcium supplements had fewer of all types of polyps. But the protective effect was most pronounced for the kind of advanced lesions that are most strongly associated with colon cancer. The risk for advanced polyps was reduced by about 35 percent, Baron said.

While it's not known exactly how the calcium may help prevent the polyps, researchers speculate that calcium prevents the irritating and cancer-promoting effect of bile acids and other fats in the bowel.

In an accompanying editorial in the journal, Ulrike Peters, now an assistant faculty member at the Fred Hutchinson Cancer Research Center in Seattle, but formerly a research fellow at the National Cancer Institute, writes that the beneficial effects of calcium supplements still have not been proven. But the protective role of calcium against colon cancer "looks very promising," she said.

For now, she added, those wanting to reduce their risk of colon cancer should follow the dietary recommendation for calcium -- 1,200 milligrams a day for those over 50 years of age, and 1,000 milligrams for those 19 to 50.

"We cannot really tell if there is a difference right now between [calcium from] supplementation and from food," she said. "That needs further investigation.

Dr. Arthur Schatzkin, lead author of the editorial and chief of the nutritional epidemiology branch of the NCI, agreed. "For a variety of health reasons people should try to make sure they are getting adequate intakes of calcium." Calcium helps with bone strength, for one thing. But he cautioned that "...we haven't proved that calcium prevents colon cancer."

Added Baron: "As always, talk to your doctor. It is really thought that calcium supplements are safe, but don't think you can take something like this and forget everything else. Remember, this is just one aspect of what might be done."

He advised people to get colorectal cancer screening tests, such as colonoscopies and occult blood testing. "Exercise is probably beneficial," he added, in helping to reduce colorectal cancer risk.

More information

To learn more about colorectal cancer, visit the National Cancer Institute.


SOURCES: John A. Baron, M.D., professor of medicine, Dartmouth Medical School, Lebanon, N.H.; Ulrike Peters, Ph.D., formerly research fellow at the National Cancer Institute, now assistant faculty member, Fred Hutchinson Cancer Research Center, Seattle; Arthur Schatzkin, M.D., D.P.H., chief, nutritional epidemiology branch, National Cancer Institute, National Institutes of Health, Bethesda, Md.;

June 16, 2004, Journal of the National Cancer Institute

Copyright © 2004 ScoutNews LLC. All rights reserved.


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HeatherAdministrator

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Prebiotics for improved gut health new
      #88774 - 07/11/04 03:15 PM

FoodInfo Online Features

15 October 2001

Prebiotics for improved gut health

Glenn R Gibson

Food Microbial Sciences Unit, School of Food Biosciences,
The University of Reading, UK


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The bacterial microbiota in the human large intestine is thought to compromise 95% of the total cells in the body, representing 1012 cells/g dry weight contents. Through the activities of the resident microflora, the colon plays a major role in host nutrition and welfare (Gibson and Roberfroid 1999). Dietary modulation of the human gut flora can be of great benefit to health. In recent years, the functional food concept has moved away from mineral and vitamin supplementation towards the situation where improved gut (microbial) functionality is the main current driving force. The colon is the most intensely populated region of the gastrointestinal tract (Figure 1) and is therefore the main target for such dietary intervention.

The gastrointestinal tract is a sterile environment at birth and bacterial colonisation begins during the delivery process (organisms are transferred to the newborn gut from the maternal faecal or vaginal flora and/or the environment). Initial bacteria to colonise the colon are facultatively anaerobic organisms, such as Escherichia coli and streptococci. These first colonisers metabolise any traces of oxygen in the gut, thereby reducing the environment into one of strong anaerobic conditions. The bacteria that then further colonise the gut depend largely upon the feeding profile of the infant. The breast fed infant has bifidobacteria as the numerically predominant genus, whereas formula feeds give rise to a more complex, adult-like, gut flora with clostridia, bacteroides, bifidobacteria and streptococci as prevalent genera (Salminen et al. 1998). A major reason for these differences is that breast milk contains a ‘bifidus’ factor, which stimulates growth of bifidobacteria; this is a glycoprotein containing glucose, galactose, fructose, and N-acetyl glucosamine. Breast fed infants generally have less gastrointestinal problems than their formula-fed counterparts and this may well be attributed to the powerful anti-pathogen effects exerted by bifidobacteria. The final phase of microflora acquisition occurs at weaning, when a complex microflora develops. Currently, there is much interest in modulating the constituents of infant formulae, such that bifidobacteria are much more effectively stimulated.

The resident gut microbiota ferments substances, mainly provided by the diet, that cannot be digested by the host in the small gut. These include, resistant starch, non-starch polysaccharides (dietary fibre), oligosaccharides, proteins, amino acids, etc. In a typical adult, around 80 g of food ingested each day reaches the large intestine and is therefore susceptible to fermentation by the gut flora. The two main types of fermentation that are carried out in the gut are saccharolytic and proteolytic. The main end products of carbohydrate metabolism are, the short chain fatty acids, acetate, propionate, and butyrate. These may be further metabolised systemically or locally to provide energy generation for the host. The end products of proteolytic fermentation include, phenolic compounds, amines, and ammonia, all of which are toxic. The proximal colon (right side) is essentially a site of saccharolytic fermentation, whereas the more distal (left side) sees more proteolytic fermentation. This is probably a major reason why many gastrointestinal disorders (including colon cancer, ulcerative colitis) predominate distally.

Dietary modulation of the human gut flora has been carried out for many years. In humans, there are positive aspects to the gut fermentation, which may improve certain aspects of host health. The microflora contains certain bacteria that can be perceived as health promoting, as well as pathogenic. For instance, bifidobacteria and lactobacilli may help to improve resistance to gut infections by inhibiting the growth of harmful microorganisms (that may onset both acute and chronic gut disorder), reduce blood lipid levels, improve the immune response, and be involved in protection against gut cancers (Gibson and Roberfroid 1999; Sanders 1998). The definitive health outcomes, and their mechanisms of effect, are being gradually uncovered and there is currently much interest in increasing numbers and activities of these bacteria in the large gut, preferably at the expense of more harmful species. The manner in which this can be achieved is through dietary supplementation.

The use of probiotics has been widely supported. In this case, foodstuffs such as fermented milk products containing viable cultures perceived as beneficial (e.g. lactobacilli, bifidobacteria) are used to proliferate populations in the colon. Probiotics are defined as live microbial feed supplements, which beneficially affect the host animal by improving its intestinal microbial balance (Fuller 1989). To be effective, probiotics must be capable of being prepared in a viable manner and on large scale (e.g. for industrial purposes), whilst during use and under storage the probiotic should remain viable and stable, be able to survive in the intestinal ecosystem, and the host animal should gain beneficially from harbouring the probiotic. Clearly, the organisms used should be generally regarded as safe.

Whilst records indicate that probiotics have been ingested by humans for thousands of years, the work of Metchnikoff in the Pasteur Institute at the start of the 20th Century was probably the first realistic look at their use. He observed that Bulgarian peasants who consumed fermented dairy products exhibited longevity (Metchnikoff, 1907). In his thesis ‘The Prolongation of Life’ he attributed this to their elevated intake of so called soured milks – what we now recognise as probiotics.

Many probiotic products now exist in Europe. The most popular food vehicles are fermented milks, other drinks, or as lyophilised forms. Examples include: Danone’s Actimel (containing Lactobacillus casei Immunitas) or Bio (containing bifidobacteria); Yakult (L. casei Shirota); Nestle’s LC1 (L. johnsonii); and Seven Seas’ Multibionta (containg Bifidobacterium bifidum, B. longum, and L. acidophilus).

An alternative approach has been investigated where the commensal bifidobacteria and/or lactobacilli are selectively promoted by the intake of certain non-viable substrates, known as prebiotics. Gibson and Roberfroid (1995) first described a prebiotic as a “non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, and thus improves host health.” As diet is the main factor controlling the intestinal microflora, it is possible to modulate the microflora composition through foods. A prebiotic substrate is selectively utilised by beneficial components of the indigenous gut flora but does not promote growth of potential pathogens, such as toxin producing clostridia, proteolytic bacteroides, and toxigenic Escherichia coli. In this manner, a “healthier” microflora composition is obtained, whereby the bifidobacteria and/or lactobacilli become predominant in the intestine and exert possible health-promoting effects (similar to the situation that prevails in the breast fed infant gut). For a dietary substrate to be classed as a prebiotic, three criteria are required:

1) the substrate must not be hydrolysed or absorbed in the stomach or small intestine;

2) it must be selective for beneficial commensal bacteria in the colon, such as the bifidobacteria;

3) the substrate should induce beneficial luminal/systemic effects within the host.

The premise behind prebiotics is therefore to stimulate certain indigenous bacteria in the gut, rather than introducing exogenous species, as is the case with probiotics. Ingesting a diet containing non-digestible carbohydrates that are selectively fermented by indigenous beneficial bacteria, is the prebiotic principal. Any dietary component that reaches the colon intact is a potential prebiotic, however much of the interest in the development of prebiotics is aimed at non-digestible oligosaccharides, such as fructooligosaccharides (FOS), trans-galactooligosaccharides (TOS), isomaltooligosaccharides (IMO), xylooligosaccharides (XOS), soyoligosaccharides (SOS), glucooligosaccharides (GOS), and lactosucrose. In Europe, FOS, GOS and lactulose have been shown to be prebiotics, through numerous volunteer trials, as evidence by their ability to change the gut flora composition after a short feeding period (Gibson et al. 2000). The Japanese market is more widespread.

As prebiotics exploit the use non-viable dietary components to improve gut health, the range of foods into which they can be added is much wider than that for probiotics, where culture viability needs to be maintained. This has the advantage that heat stability, or exposure to oxygen is not an issue. As such, virtually any carbohydrate containing food is susceptible to supplementation. Examples are shown in Table 1.

On the contrary, it may be possible to intake prebiotics more naturally through the diet. Many fruit and vegetables contain prebiotic oligosaccharides, such as FOS. Examples are onion, garlic, banana, asparagus, leek, and Jerusalem artichoke. However, the likely situation is that levels are too low to have any significant effect. Our (unpublished) data indicate that at least 4g/d, but more preferably 8g/d of FOS, would be needed to significantly elevate bifidobacteria in the human gut. Hence, there exists much value in the approach of dietary fortification. However, it is important to ensure that the prebiotic effect is maintained in the food product. Figure 2 shows data from a recent volunteer trial carried out at the University of Reading (Tuohy et al. 2001). Here, shortbread containing 7g/d FOS was fed to human subjects and the effects upon faecal bacteria determined as compared to a placebo (FOS not added). The nature of the trial was a crossover approach in that volunteers took active and placebo shortbread, but neither they nor the investigators were aware of which was ingested. Moreover, the bacteriology was carried out using a (culture independent) probing approach that relied upon differences in 16SrRNA profiles for the confirmation of identity. The data clearly show that the use of FOS exerted a profound effect upon bifidobacteria.

It is the case that many new products are being, and have been, developed that exploit the prebiotic approach. As mentioned, their use is more widespread than for probiotics. Hence, it is likely that the eventual market value will outstrip that of the live microbial approach (currently estimated at over 1 billion euro p.a. in Europe). There is therefore a huge potential for the use of functional foods, and in particular prebiotics in the food industry. However, it is important that new product developments have satisfactory scientific evidence to back their claims. One difficulty in the past has been the limitations imposed by cultural microbiology when applied to a complex ecosystem, such as the human gut.

Gut microbiology is conventionally carried out by plating faecal microorganisms onto selective agars designed to recover numerically predominant groups. However, the agars used are only semi-selective, do not recover non-culturable bacteria (which may represent over 50% of the overall diversity), and allow operator subjectivity in terms of microbial characterisation, which is usually based on limited phenotypic procedures. As such, alternative mechanisms, based around molecular principles, to more effectively characterise the microflora involved in fermentation studies, need to be applied. The use of such methods gives a much clearer picture of the gut microbiota and the effects of prebiotics. Traditional methods of bacterial enumeration are therefore being replaced with these molecular techniques (Tannock 1999; Vaughan et al. 2000). One such method is fluorescent in situ hybridisation (FISH) using specific rRNA probes, as employed in the study mentioned above (see Figure 3). The application of post-genomic principles in gut microbial studies will help fully explore human gut microflora diversity, develop reliable model systems, test a new generation of purpose designed prebiotic molecules with enhanced functionality, and determine the effectiveness of dietary intervention in the clinical situation.

In terms of new developments, it is important that the definitive health bonuses associated with prebiotic intake be determined. This is especially relevant given the broad applicability of their use. It is likely that prevention of acute gastroenteritis through fortification of certain gut microbiota components is an important aspect. Moreover, improved protection from more chronic gut disorders that have been associated with bacteria (inflammatory bowel disease, colon cancer, irritable bowel syndrome) may also be possible. It may also be the case that certain target populations, such as infants, the elderly, hospitalised persons, are more susceptible to the approach. Finally, the use of synbiotics, where both probiotics and prebiotics are combined, may offer the dual benefits of both approaches, whilst the use of a selective substrate may help long term persistence of the live microorganisms.

References

Franks, A.H., Harmsen, H.J., Raangs, G.C., Jansen, G.J., Schut, F. and Welling, G.W. (1998) Variations of bacterial populations in human faeces measured by fluorescent in situ hybridization with group-specific 16S rRNA-targeted oligonucleotide probes. Applied and Environmental Microbiology 64, 3336-3345.

Fuller, R. (1989) Probiotics in man and animals. Journal of Applied Bacteriology 66, 365-378.

Gibson, G.R., Berry Ottaway, P. and Rastall, R.A. (2000) Prebiotics: New Developments in Functional Foods. Chandos Publishing Limited, Oxford.

Gibson, G.R. and Roberfroid, M.B. (1995) Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. Journal of Nutrition 125, 1401-1412.

Gibson, G.R. and Roberfroid, M.B. (1999) Colonic Microbiota, Nutrition and Health. Kluwer Academic Publishers, Dodrecht.

Metchnikoff, E. (1907) The Prolongation of Life. William Heinemann, London.

Salminen, S., Bouley, C., Boutron-Ruault, M-C., Cummings, J.H., Franck, A., Gibson, G.R., Isolauri, E., Moreau, M.C., Roberfroid, M.B. and Rowland, I.R. (1998) Functional food science and gastrointestinal physiology and function. British Journal of Nutrition 80, S147-S171.

Sanders, M.A. (1998) Overview of functional foods: emphasis on probiotic bacteria. International Dairy Journal 8, 341-347.

Tannock, G.W. (1999) A fresh look at the intestinal microflora. In Probiotics A Critical Review, pp.5-14 [GW Tannock, editor] Wymondham: Horizon Scientific Press.

Tuohy, K.M., Kolida, S., Lustenberger, A. and Gibson, G.R. (2001) The prebiotic effects of biscuits containing partially hydrolyzed guar gum and fructooligosaccharides – A human volunteer study. British Journal of Nutrition – in press.

Vaughan, E.E., Schut, F., Heilig, H.G.H.J., Zoetendal, E.G., deVos, W.M. and Akkermans, A.D.L. (2000) A molecular view of the intestinal ecosystem. Current Issues in Intestinal Microbiology 1, 1-12.


About the author

Glenn Gibson is Professor of Food Microbiology and Head of Food Microbial Sciences Unit at The University of Reading. Prior to this he was with the Institute of Food Research, Reading and MRC Dunn Laboratories, Cambridge. The Research Unit runs numerous projects on gut microbiology and food safety. Specific interests include, the bacteriology of acute and chronic gut disorders (e.g. gastroenteritis, ulcerative colitis, bowel cancer) and the use of molecular approaches to facilitate characteisation/enumeration of microorganisms. The group are extensively researching prebiotics and probiotics as dietary microflora management tools - in gut model systems and through human studies.

© IFIS Publishing 2004 - All Rights Reserved

http://www.foodsciencecentral.com/library.html#ifis/3731


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Probiotics, dead or alive, can relieve gut disease new
      #102661 - 08/30/04 02:38 PM

Probiotics, dead or alive, can relieve gut disease


02/02/2004 - Probiotics, the bacteria thought to help gut health disorders, allergies and even some forms of cancer, contain immune system-stimulating DNA, which makes them just as effective when inactivated as when consumed as live microorganisms in dairy products, say US researchers.

The findings, reported in this month’s Gastroenterology (DOI:10.1053/j.gastro.2003.11.019), offer considerable potential for food makers previously restricted to adding bacteria to fermented foods like yoghurt.
The study, by researchers at the University of California, San Diego School of Medicine and the Shaare Zedek Medical Center in Jerusalem, Israel, also reveals a mechanism that can be used to determine and to select which probiotic bacteria are best for patients with IBD.

The addition of probiotic bacteria has until now been limited to dairy products such as yoghurt because it was thought that they needed to be live to have any effect. Adding live bacteria to other foods would result in fermentation, changing the taste, texture and freshness on an hourly basis.

But the new research suggests that the metabolic activity of probiotics is not in fact key to their protective effect.

The researchers used gamma radiation to reduce the metabolic activity of probiotic bacteria to a minimum. Previous studies, using heat to inactivate the bacteria, destroyed the cellular structure and beneficial aspects.

The irradiated probiotics were given to mice with experimentally induced colitis, which is similar to human IBD. The irradiated probiotics effectively improved the colitis symptoms, as did the administration of viable, ‘live’ bacteria to another group of mice with colitis. This indicated that inactivated probiotics were as effective as live probiotics.

The scientists say that the beneficial, anti-inflammatory activities seen with the inactivated probiotics could be the product of the innate immune system, the body’s instant response to invasion by pathogens.

The European probiotics market is forecast to more than triple in value from €34.6 million currently to €118.5 million in 2010, according to recent statistics from Frost & Sullivan. But the market research firm also estimated that its gut health cousin, prebiotics, would be helped by much wider scope in applications, as prebiotic ingredients are easily formulated into a number of different foods, including baked goods and even drinks.

The new research could however open a vast range of new application areas to probiotics too. Gut health is currently driving sales of functional foods in Europe, according to a Datamonitor report, outpacing those foods targeting consumers at risk of heart or bone diseases.

In addition to studying the normal and irradiated probiotics on mice, the researchers also tested a synthetic form of bacterial DNA called immunostimulatory (ISS) oligonucleotide (ODN), a short segment of synthetic DNA with immunostimulatory properties, which mimics bacterial DNA. In a previously published paper in Gastroenterology, ISS-ODN had been found to reduce the harmful effects of experimental colitis in mice, indicating that it worked in a manner similar to probiotics.

Evaluation of the immunostimulatory activities of probiotics may also provide an easy screening system for the selection of probiotic bacteria prior to their clinical use, noted the study’s first author, Daniel Rachmilewitz, from the Shaare Zedek Medical Center.

http://www.nutraingredients.com/news/news.asp?id=8601

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Probiotic Improves Postinfective Gut Dysfunction in Animal Model new
      #112122 - 10/11/04 04:30 PM

Probiotic Improves Postinfective Gut Dysfunction in Animal Model

NEW YORK (Reuters Health) Sept 22 - Treatment with the probiotic Lactobacillus paracasei reduces the muscle hypercontractility seen in an animal model of postinfective gut dysfunction, suggesting a possible benefit for patients with postinfective irritable bowel syndrome (IBS), new research shows.

The findings, which appear in the September issue of Gastroenterology, are based on a study of mice that developed gut dysfunction after being infection with Trichinella spiralis. The animals were then treated with various active or heat-inactivated probiotics.

Treatment with L. paracasei several days after infection attenuated the muscle hypercontractility normally seen, lead author Dr. Elena F. Verdu, from McMaster University in Hamilton, Canada, and colleagues note. In contrast, other probiotics, such as L. johnsonii, Bifidobacterium lactis, and B. longum, had no effect.

Further analysis revealed that L. paracasei's effect was associated with a drop in the T. spiralis-related T-helper 2 response and with a reduction in muscle levels of TGF-beta1, cyclooxygenase-2, and prostaglandin E2.

"To our knowledge, no studies have been performed on the effect of probiotics in patients with postinfective IBS," the authors state. "Our results raise the possibility that L. paracasei could be useful in attenuating postinfective gut dysfunction in humans and in treating postinfective IBS."

Gastroenterology 2004;127:826-837.

http://www.medscape.com/viewarticle/489848

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Probiotic VSL#3 Could Relieve Some Irritable Bowel Abdominal Bloating new
      #120087 - 11/08/04 04:04 PM

Probiotic VSL#3 Could Relieve Some Irritable Bowel Abdominal Bloating

A DGReview of :"A randomized controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhoea-predominant irritable bowel syndrome"

Alimentary Pharmacology & Therapeutics

04/01/2003
By Elda Hauschildt


Probiotic formulation VSL#3 appears promising in relieving abdominal bloating in patients with diarrhoea-predominant irritable bowel syndrome (IBS).

Researchers from the Mayo Clinic and Mayo Foundation in Rochester, Minnesota, United States, found that the action was unrelated to alteration in gastrointestinal (GI) or colonic transit in a randomised, controlled trial with 25 diarrhoea-predominant IBS patients.

Following a 2-week run-in period, participants were randomly assigned to either VSL#3 or placebo twice daily for eight weeks. Patients underwent pre- and post-treatment measurement of GI transit. They also recorded bowel function and symptoms daily during the 10-week study.

No significant differences were observed between treatment groups pre- or post-therapy on measurements of GI transit, bowel function or satisfactory global symptoms.

The investigators say that further analysis indicated abdominal bloating was reduced in patients receiving VSL#3. This effect was not seen in patients receiving placebo.

"With the exception of changes in abdominal bloating, VSL#3 had no effect on other individual symptoms: abdominal pain, gas and urgency," they report.

All patients were able to tolerate the probiotic.
Alimentary Pharmacology 2003;17:7:895-904. "A randomized controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhoea-predominant irritable bowel syndrome"









All contents Copyright (c) 1995-2004 Doctor's Guide Publishing Limited. All rights reserved.

http://www.docguide.com/news/content.nsf/news/8525697700573E1885256CF70032C574

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Effectiveness of a symbiotic preparation in irritable bowel syndrome new
      #120107 - 11/08/04 04:44 PM

Chinese Journal of Digestive Diseases

Official Journal of the Chinese Society of Gastroenterology and the Chinese Medical Association Shanghai Branch

Edited by:
Xiao Shudong

Print ISSN: 1443-9611
Online ISSN: 1443-9573
Frequency: Quarterly
Current Volume: 5



---------------------------------------------------------------------------


Volume 5: Issue 4

Single-blind follow-up study on the effectiveness of a symbiotic preparation in irritable bowel syndrome

J TSUCHIYA
R BARRETO
R OKURA
S KAWAKITA
E FESCE
F MAROTTA




Abstract

OBJECTIVE:

Experimental and clinical studies have shown that a novel symbiotic (known as SCM-III) exerts a beneficial effect on gut translocation and local and systemic inflammatory and microbial metabolic parameters. The present investigation was a preliminary trial on the effectiveness of SCM-III for irritable bowel syndrome (IBS).

METHODS:

Sixty-eight consecutive adult patients with IBS who were free from lactose malabsorption, abdominal surgery, overt psychiatric disorders and ongoing psychotropic drug therapy or ethanol abuse were studied prospectively and divided into 2 groups that were comparable for age, gender, body size, education and pattern of presenting symptoms. The 2 groups were blindly given for 12 weeks either SCM-III 10 mL t.i.d or the same dosage of heat-inactivated symbiotic.

RESULTS:

Treatment with SCM-III was ‘effective’ or ‘very effective’ in more than 80% of the patients (P < 0.01 vs baseline values and control). Less than 5% reported ‘not effective’ as the final evaluation compared with over 40% of patients in the control group. After 6 weeks of treatment, a significant improvement of pain and bloating was reported in the treatment group compared with control and baseline values. There was also a benefit for bowel habits, mostly for patients with constipation or alternating bowel habits. No overt clinical or biochemical adverse side-effects were recorded.

CONCLUSION:

Compared with baseline values and the control group, SCM-III resulted in a significant increase in lactobacilla, eubacteria and bifidobacteria, which suggests that some selected IBS patients could benefit substantially from symbiotics, but the treatment may need to be given on a cyclic schedule because of the temporary modification of the fecal flora.

http://www.blackwellpublishing.com/abstract.asp?ref=1443-9611&vid=5&iid=4&aid=6&s=&site=1

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New evidence supports camomile tea's health benefits new
      #136197 - 01/07/05 05:02 PM

New evidence supports camomile tea's health benefits


05/01/2005 - The popular herbal tea camomile may help relieve a wide range of health ailments, finds new research.

The study lends some scientific support to use of the tea as an ancient remedy for numerous conditions.
Elaine Holmes, a chemist at Imperial College London, recruited 14 volunteers (seven women and seven men) who each drank five cups of the herbal tea daily for two consecutive weeks. The tea was made with the flowers and leaves of German camomile (Matricaria recutita), also known as manzanilla.

Daily urine samples were taken and tested throughout the study, both before and after drinking camomile tea.

The researchers found that drinking the tea was associated with a significant increase in urinary levels of hippurate, a breakdown product of certain plant-based compounds known as phenolics, some of which have been associated with increased antibacterial activity.

This could help explain why the tea appears to boost the immune system and fight infections associated with colds, say the researchers in the 26 January issue of the Journal of Agricultural and Food Chemistry.

Drinking the tea also was associated with an increase in urinary levels of glycine, an amino acid that has been shown to relieve muscle spasms. This could be responsible for its benefit in relieving menstrual cramps in women, probably by relaxing the uterus, noted the researchers.

Glycine also is known to act as a nerve relaxant, which may explain the mildly sedative effect of the tea.

Levels of both hippurate and glycine remained elevated for up to two weeks after the study participants stopped drinking the tea, indicating that the compounds may remain active for quite some time.

Additional studies are needed before a more definitive link between the tea and its alleged health benefits can be established.

Holmes commented: “This is one of a growing number of studies that provide evidence that commonly used natural products really do contain chemicals that may be of medicinal value.”

Funding for the study was provided by UK-based Oxford Natural Products.

The online version of study was initially published on the journal's website on 21 December.



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