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University of IowaI Health Care News

Week of October 16, 2000
UI researchers find that a simple sugar may
prevent lung infections in CF patients

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The lungs contain substances that kill inhaled and aspirated bacteria, thereby preventing lung infections. This system may be disrupted in people with cystic fibrosis (CF). University of Iowa researchers have discovered that a simple sugar may enhance the natural defense system and potentially help delay or prevent the onset of deadly bacterial infections in CF lungs. CF is the most common fatal inherited disease in Caucasians of Northern European descent and has no cure.

The UI team, led by Joseph Zabner, M.D., associate professor of internal medicine, reports in the October 10 issue of the journal Proceedings of the National Academy of Sciences, that a sugar, xylitol, lowers the salt concentration of the liquid that covers cells lining the inside of the lungs, thereby enhancing the bacteria-killing activity of the body's natural antibiotics.

Normal lungs have an effective innate defense system to counteract the small numbers of airborne bacteria we constantly inhale. These organisms land in the thin layer of liquid, called airway surface liquid, that overlays the cells lining the inside of the lungs. The airway cells produce a host of natural antibiotic substances and secrete them into the airway surface liquid where they kill the invading bacteria. However, in the lungs of people with CF the system breaks down, allowing the bacteria to get a foothold and eventually develop into the chronic infections that are the leading cause of death in CF patients.

UI scientists have suggested that the natural defense system in CF patients is disrupted because a genetic defect results in an increase in the salt concentration of the airway surface liquid.

"We have previously shown that the natural antibiotics work best in low salt and that the salt concentration in the airway surface liquid in cell models of CF lungs is high," Zabner said. "We thought that if we could lower the salt concentration in the liquid, it might be a way to prevent the onset of infection in the lungs of people with CF."

Zabner and his colleagues knew that they needed a substance called an osmolyte that would not be easily absorbed by the cells and would lower the salt concentration to favor the antimicrobial agents. Simple sugars fit the bill. However, airway bacteria can use many sugars as an energy source to aid their growth.

"As we were testing the sugars I read about some research showing that chewing gum containing a sugar called xylitol seemed to prevent inner ear infections," Zabner said. "This information and the fact that xylitol has been used for years in Europe as a safe sugar substitute, made me think that xylitol might be a good choice for our studies."

The UI team used a series of experiments to prove that xylitol was not used by airway bacteria to grow, and that the sugar did lower the salt concentration of the airway surface liquid, thereby enhancing the bacteria-killing activity of the natural antibiotics.

The UI team then used human volunteers to test the principle that xylitol helps the body to fight against airborne bacteria.

The amount of a particular bacterium, commonly found in nasal passages, was assessed for 21 healthy volunteers. In a blinded, randomized test, the volunteers then sprayed either a xylitol or a salt solution into their nostrils four times a day for four days. After that time, the nose-bacteria level was retested. The volunteers then waited a week to allow their nose bacteria levels to get back to normal and repeated the spraying experiment with the other solution.

Cells lining the nasal passages are almost identical to cells that line passages in the lungs, although the environment is very different. Normal subjects have fairly constant levels of bacteria in their nostrils. These factors, and the ease of testing changes in bacterial levels in nostrils, made the nose a good place to show that the sugar could do something in the body.

The results showed that the sugar spray significantly reduced the number of the nasal bacteria. The saline solution did not significantly alter the amounts of bacteria.

Zabner said the UI researchers plan to test whether the sugar can be effective in preventing bacterial infection in the lungs of people who are prone to infections such as pneumonia.

"The hope is that this could help prevent, or at least delay, the onset of infection in lungs of people with CF and people who don't have CF but are also prone to lung infections," said Michael J. Welsh, M.D., a Howard Hughes Medical Institute (HHMI) investigator and Roy J. Carver Professor of Internal Medicine and Physiology and Biophysics at the UI, who worked with Zabner on this study.

In addition to Zabner and Welsh, the other UI investigators on the study included Michael P. Seiler, research assistant in internal medicine, Janice L. Launspach, R.N., HHMI research associate in internal medicine, Philip H. Karp, HHMI research associate in internal medicine, William R. Kearney, Ph.D., associate research scientist and director of the Nuclear Magnetic Resonance Facility, and Jeffrey J. Smith, M.D., associate professor (clinical) of pediatrics. Dwight C. Look, M.D., assistant professor of medicine at Washington University in St. Louis was also part of the research team.

The research was funded in part by grants from the National Institutes of Health and the Cystic Fibrosis Foundation.

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...From the pages of Agricultural Research magazine

Making Xylitol Sweetener From Corn

A low-calorie sweetener called xylitol may someday be made from corn.

Makers of some specialty brand sugarless chewing gums now pay about $3 per pound for xylitol, which gives their product a minty-cool taste.

"New technologies may drive production costs down and the volume up," says Timothy D. Leathers, an Agricultural Research Service geneticist at the National Center for Agricultural Utilization Research (NCAUR), Peoria, Illinois. He's researching a way to derive the sweetener from corn fiber leftovers of U.S. ethanol production. Currently, industry sells corn fiber and fermentation coproducts together as cattle feed for a few pennies per pound.

Xylitol, a white crystalline powder termed a sugar alcohol or polyol, is made in Finland from acid-treated fibers of birch wood by a chemical process. The process requires high pressure and temperature, an expensive catalyst, and extensive steps to remove byproducts. A biotechnological approach involving corn fiber should require less energy, says Leathers.

Expecting that beet and cane sugar will remain much cheaper
than xylitol made from the xylose in corn fiber, Leathers
envisions that the future of the alternative sweetener lies in
niche markets. Already xylitol commands a $28 million
market in foods for special dietary uses, mouthwashes and
toothpastes, as well as chewing gums.

Xylitol has one-third fewer calories than conventional sugar but
about the same sweetening power. Diabetics process it
through the gut without involving insulin.

Researchers in the United States and abroad showed
children's dental health improved if their chewing gum
included xylitol. The sweetener allows harmless bacteria
to crowd out common mouth microbes that digest normal
sugars�the ones associated with tooth decay.

Leathers began to brighten the prospects for making xylitol in the United States from corn nearly 10 years ago. He found that one strain of Aureobasidium yeast, in a process called hydrolysis, released up to 20 percent of the xylose from corn fiber that was treated with alkaline hydrogen peroxide. Since then, he's found a mixture of Aureobasidium enzymes that releases up to 70 percent.

He and his colleagues also developed a process using a strain of another yeast, Pichia guilliermondii, to convert the xylose into xylitol. To overcome a distracting problem called glucose repression (in which glucose slows or shuts down some microbial metabolism), the scientists used two teams of P. guilliermondii. The first team gobbled up all the glucose�its first choice in food�in the fermentation vat. Then the next team focused on consuming xylose to produce xylitol.

NCAUR chemist Badal Saha identified another promising strain of xylitol-producing yeast, Candida peltata. In spite of glucose repression, he achieved a 56-percent yield of xylitol from xylose in the mixture.

Saha and Leathers found that a xylose-related sugar, arabinose, induced no repression of xylitol production. The scientists envision genetic engineering that might enable the yeasts to produce xylitol from arabinose as well as from xylose.� By Ben Hardin, Agricultural Research Service Information Staff.

The research is part of New Uses, Quality, and Marketability of Plant and Animal Products, an ARS National Program (#306) described on the World Wide Web at http://www.nps.ars.usda.gov/programs/cppvs.htm.

Timothy D. Leathers and Badal C. Saha are at the USDA-ARS National Center for Agricultural Utilization Research, 1815 N. University St., Peoria, IL 61604; phone (309) 681-6377 [Leathers], (309) 681-6276 [Saha], fax (309) 681-6686.
"Making Xylitol Sweetener From Corn" was published in the July 2000 issue of Agricultural Research magazine.

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A New Sweetener from Ethanol Waste
By Ben Hardin
July 3, 2000

Corn fiber that�s left over from ethanol production could be turned into a high-value, low- calorie sweetener for niche markets, based on a process being developed by Agricultural Research Service scientists.

The sweetener is a white crystalline powder called xylitol. Makers of some specialty brand sugarless chewing gums now pay about $3 per pound for xylitol, which gives their product a minty-cool taste. By comparison, industry now sells the ethanol leftovers as cattle feed for only a few pennies per pound.

The scientists found that certain strains of the yeast Pichia guilliermondii can excel at making xylitol, but that process can be hindered by glucose, another of the leftover sugars from fermented corn fiber. The problem: When P. guilliermondii comes in contact with both glucose and xylose in fermenting corn fiber, it �prefers� the glucose and--like a child who would rather gorge on ice cream than spinach--it spends its energy on gobbling the glucose, which leaves the yeast relatively ineffective for carrying out the xylose-to-xylitol transformation. The solution devised by ARS scientists: Send in the �B� team. The scientists add an initial batch of P. guilliermondii to the fermenting fibers to devour the glucose. Then they mix in more P. guilliermondii to tackle the task of transforming the xylose into xylitol.

Xylitol has one-third fewer calories than sugar and about the same sweetening power. It�s currently made in Finland in a chemical process by treating acid-treated fibers of birch wood. It�s now a $28 million market in foods for special dietary uses, mouthwashes, toothpastes and chewing gums.

Biological conversion of xylose should help make xylitol more economic to produce, according to the researchers, because it requires less energy than chemical conversion. This could drive production costs down and the market volume up.

An article about the research appears in the July issue of Agricultural Research magazine and online at:

http://www.ars.usda.gov/is/AR/archive/jul00/xylit0700.htm

Scientific contact: Timothy D. Leathers and Badal C. Saha, ARS National Center for Agricultural Utilization Research, Peoria, Ill., phone (309) 681-6377 (Leathers), (309) 681-6276 (Saha); fax (309) 681-6686, leathetd@mail.ncaur.usda.gov and sahabc@mail.ncaur.usda.gov.

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The Optimisation of Sweet Taste Quality (TOSTQ)

Abstracts of the Meeting 1999

September 27� 28, Viareggio, Italy.

Taste Acceptance in Pigs in Comparison with Primates

Dieter Glaser
Anthropological Institute and Museum, University of Z�rich-Irchel,
Winterthurerstrasse 190, 8057 Z�rich, (SWITZERLAND)

The aim of the present study was to investigate how the pig (Sus scrofa domesticus) responds to various compounds known to be sweet in man.

The gustatory preferences in pigs towards 33 compounds were evaluated through a specific two-choice preference method. A total number of 75 pigs (39 males and 36 females, 2-4 month old) were used for this study.

Experiments were carried out over a period of two years with eight different groups. During the test periods, pigs were housed in individual cages (2 m x 3 m), each of them being equipped with an automatic water supply freely accessible.

All the 14 carbohydrates tested are preferred over water, sucrose being the most effective. Sucrose and fructose response intensities are identical in pigs and humans but lactose, maltose, D-glucose and D-galactose are two times less efficient in pigs. The molar order of effectiveness is sucrose > D-fructose > maltose = lactose > D-glucose > D-galactose, roughly similar to humans. As in humans, D-glucose, L-glucose and methyl a-D-glucopyranoside display equal potency, while methyl b-D-glucopyranoside is ineffective. The 7 polyols tested are attractive; xylitol is the preferred one, being as effective as sucrose.

Out of 12 intense sweeteners experimented, 7 are ineffective (aspartame, cyclamate, monellin, NHDC, P-4000, perillartine, thaumatin), 5 are attractive (acesulfame, saccharin, alitame, dulcin, sucralose), but with a much weaker efficiency (acesulfame, 18 x less; saccharin, 65 x less).

We hope that we were able to go deeper into our understanding of the responses of pigs by analysing the gustatory behaviour of pigs towards the compounds mentioned.
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So... in this study, pigs prefer sucrose and fructose in the caubohydrates, Xylitol in the polyols, and acesulfame, saccharin, alitame, dulcin, & sucralose in the intense sweeteners. What does all this mean to you, the knowledgeable Xylitol consumer?
Beats us, we just thouht it was a interesting.. XN.
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Wellness Letter Advises
Sugarless Gum With Xylitol

The UC Berklely Wellness Letter in its "Wellness Tips" section, January 2001, advises sugarless gum containing Xylitol to help fight tooth decay. "A new study has confirmed that Xylitol gum partially suppresses the growth of cavity-promoting bacteria in the mouth" states the newsletter.
That's not New News to us! XN
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New study indicates improved bone properties in Xylitol fed rats

A new study by from From the University of Oulu, Oulu, Finland suggests that xylitol added to the diet of rats may increased the strength and size of bones. To view the abstract go to :
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11782878&dopt=Abstract

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                                                                               The Pharmaceutical Journal Vol 265 No 7118 p543
                                                                               October 14, 2000 Clinical

Xylitol may prevent lung infections, researchers suggest

Xylitol may provide a new approach in cystic fibrosis (CF) therapy by preventing the onset of bacterial infections. Researchers from the University of Iowa, US, have found that xylitol, a sugar which is used in chewing gum, lozenges and syrups, may enhance the innate antibacterial defence system at the airway surface. Other research from the same university explains the mechanism of bacterial biofilm formation in CF.
Dr Jospeh Zabner (associate professor of internal medicine) and colleagues explain that there is a thin layer of airway surface liquid in the airways that contains endogenous antimicrobial substances. An increase in salt concentration in this liquid inhibits the activity of antimicrobial factors and some studies have suggested that this increase in salt concentration may partially explain the pathogenesis of CF.
The researchers tested the effect of xylitol on salt concentration in airway surface liquid in in vitro experiments on human airway epithelia. The salt concentration fell in both CF epithelium and non-CF epithelium. The initial salt concentration in CF epithelium was approximately double that of non-CF epithelium but, following xylitol application, the values fell to approximately normal levels. The researchers examined the effect of xylitol on bacteria and found that it did not inhibit endogenous antibiotics, have an antibiotic effect or serve as a carbon source for bacterial growth. They suggest that, since xylitol had no antimicrobial effect of its own and because it decreases salt concentrations in airway surface liquid, its mechanism of action was to increase the activity of endogenous antimicrobial factors.
They also conducted a randomised, double-blind, crossover study of 21 patients, which showed that compared with saline, xylitol significantly reduced the number of Staphylococcus on the nasal surface. The researchers comment that while xylitol may be of value in preventing airway infection, it was unlikely that it would have any use once an infection was established (Proceedings of the National Academy of Sciences 2000;97:11614).

Bacterial biofilms
The reason that Pseudomonas aeruginosa infection cannot be eradicated once it has colonised the lungs in CF patients may be because it exists in biofilms, say Dr Pradeep Singh (department of internal medicine) and colleagues.
They examined sputum from CF patients with P aeruginosa infection and found that the bacterium was present in clusters encased in a densely stained matrix. This was consistent with the appearance of biofilms where bacterial cells were encased in an extracellular polysaccharide matrix. In order to form biofilms, bacteria secreted �quorum-sensing� agents above a certain threshold which turned a disorganised colony into a more organised biofilm. The abundance of two such agents differed in P aeruginosa in CF sputum compared with normal. Quorum-sensing signals could be used to identify agents that interfere with biofilm development, they suggest (Nature 2000;407:762).
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Ingredient in Sugarless Gums May Prevent Ear Infections

By: Sara Rea
Kids-MD Producer

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�There are some additional studies that need to be done to
determine the efficacy of using xylitol as a preventive measure.�
                                       - Dr. James Fortman -
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Two-year old Samira is a gum-chewer. She prefers gum to
candy and gum is her favorite treat in her Easter basket and
Christmas stocking. Her older brother and sister, Sachin and Selena, have also been chewing gum since they were two.

�They absolutely love gum. They would do anything for gum,� says their mother, Fiona.

After several episodes of gum getting stuck on the phone and in their hair, it is now reserved as a special treat for Fiona's kids. But there is one time that they always get gum.

�On the plane�because that time it hurts my ears,� says five-year-old Sachin.

Gum may help the ears in another way, too. A recent study of three hundred and six children shows that sugarless gums containing a substance called xylitol may be effective in preventing ear infections. The study was published in Pediatrics, a publication of the American Academy of Pediatrics, and in the British Medical Journal.

�They saw anywhere from a twenty-percent to a forty-percent decrease in the incidence of ear infections in that group of kids,� says Dr. James Fortman,

It did work on one group of kids. But experts say more research is needed to confirm that xylitol prevents the growth of bacteria that causes ear infections.

Dr. Fortman says, �There are some additional studies that need to be done to determine the efficacy of using xylitol as a preventive measure.�

Although Dr. Fortman wants more research on the xylitol-ear infection correlation, he is optimistic. It does kill cavity-causing bacteria and has no measurable side effects.

Fiona agrees, �It would be worth a shot. I mean, you have nothing to lose. It�s preventive, so I think I would try it.�

And Fiona says she won�t have any trouble convincing her kids.

What is Xylitol
Xylitol is a polyol sugar alcohol and is referred to as birch sugar because it can be produced from birch trees. Natural sources of xylitol include plums, strawberries, raspberries, and rowan berries. Xylitol has the same relative sweetness as sucrose, and it has been used as a sugar substitute for dietary and medical purposes. Xylitol reduces the growth and acid production of Streptococcus mutans, which is the most important bacterium in the pathomechanism of dental caries.

Source: British Medical Journal

Benefits of Xylitol
        � Good taste with no unpleasant aftertaste
        � Helps Reduce the development of dental caries
        � Reduces plaque formation
        � Increases salivary flow to aid in the repair of damaged tooth enamel
        � Provides one-third fewer calories than sugar � about 2.4 calories per gram
        � May be useful as an alternative to sugar for people with diabetes on the advice of their health care providers
Source: Calorie Control Council

How Do Ear Infections Develop?
The ear has three main parts: the outer ear, middle ear, and inner ear. A tiny tube, called the eustachian tube, connects the middle ear to the back of the throat and nose. When a child has a cold, nose or throat infection, or allergy, the eustachian tube can become blocked, causing a buildup of fluid in the middle ear. If this fluid becomes infected by bacteria or a virus, it can cause swelling of the eardrum and pain in the ear. This type of ear infection is called acute otitis media.

Often after the symptoms of acute otitis media clear up, fluid remains in the ear. Acute otitis media then develops onto another kind of ear problem called otitis media with effusion. This condition is harder to detect than acute otitis media because, except for the fluid and some hearing loss that is usually mild, there are often no other noticeable symptoms. This fluid often lasts for up to 3 months and, in most cases, disappears on its own. The child�s hearing then returns to normal.

Source: American Academy of Pediatrics

What Are The Symptoms?
Younger children with otitis media are usually fussy and irritable. They may also have trouble sleeping, feeding, or hearing. Older children often complain about ear pain, a feeling of fullness or pressure in the ear, and hearing loss. A child of any age with otitis media may also have a fever or show symptoms of an upper respiratory track infection (cold), including a stuffy or runny nose and mild cough.

Sometimes, in severe cases of acute otitis media, the pressure of the infection may actually cause the eardrum to rupture. Once this happens, the fever usually drops, ear pain suddenly stops, and pus begins to drain into the ear canal.

Source: American Medical Association and the Nemours

Resources
American Academy of Pediatrics � http://www.aap.org
Pediatrics � http://www.pediatrics.org
British Medical Journal � http://bmj.com/cgi/content/full/313/7066/1180
American Medical Association and the Nemours Foundation � http://www.ama-assn.org/insight/h_focus/nemours/infectio/childhd/ear.htm
Calorie Control Council � http://www.caloriecontrol.org/xylitol.html
Book: The Parents Complete Guide to Ear Infections, Author � Alan R. Greene MD

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Published by CWK Network, Inc.
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May 2001

Xylitol�s Role in Preventing Cavities
Acknowledged by Dental Experts

The important role that xylitol can play in the prevention of dental caries was recognised by a panel of dental experts at a recent consensus conference held in Washington, in the USA. The conference was organised by the National Institute of Health (a division of the US Department of Health and Human Services) in order to develop a consensus on the future direction in the diagnosis and management of dental caries.

The three-day event reviewed an extraordinary amount of scientific data, which was collated and presented by a number of leading experts in the field of dental health and dental caries research. The expert panel was then required to prepare a consensus statement.

Whilst the conference covered a diverse range of diagnostic, treatment and disease management techniques associated with dental caries, the potential importance of xylitol in further reducing dental caries, particularly when administered in the form of chewing gum, was clearly stated. The panel reported that there was strong evidence to support the use of chewing gum containing xylitol as an aid to dental health, and that this evidence was stronger than that for chewing gums containing sorbitol.

Catherine Hayes, D.M.D, D.M.Sc., of the Harvard School of Dental Medicine, presented the review of the scientific evidence supporting the use of non-cariogenic sweeteners in the prevention of dental caries. This extensive review demonstrated that xylitol was effective in reducing the occurrence of dental caries in both adults and children, and highlighted the fact that xylitol is clearly superior in this effect compared to other non-cariogenic sweeteners.

Several American news agencies reporting on the conference made positive references to xylitol, and highlighted the value of consuming chewing gum containing xylitol in the fight against dental caries.

A full report of the NIH Consensus Conference, entitled �Diagnosis and Management of Dental Caries Throughout Life� together with the full consensus statement, is available by visiting the NIH Consensus Development Program website at http://consensus.nih.gov. The panel�s press release is also available on the website at http://www.nih.gov/news/pr/mar2001/od-28a.htm

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New study shows 70% reduction in tooth decay among children whose mothers chew Xylitol sweetened gum. May 21, 2001 - Los Angeles Times by Amanda Ursell

Something for Cavity-Fighters to Chew On

    "The concept of dental decay as an infectious disease can be difficult to grasp. That a substance derived from a birch tree and found in chewing gum might reduce the chances of moms passing this infectious tooth destroyer to preschoolers may sound even more bizarre.

     Yet that was the finding of a Finnish study published earlier this year in the Journal of Dental Research that found that 5-year-olds of gum-chewing mothers had 70% less tooth decay than non-chewing mums.

     How is this so? The explanation involves the bacteria S. mutans, a ubiquitous resident of the mouth that, when combined with sugar and bits of stray food, produces the sticky, acid-producing plaque that clings to and erodes the tooth's enamel coating, creating cavities and decay.

     When mothers chewed gum, it stopped S. mutans in its tracks. The levels of the bacteria in their mouths declined, making them less likely to pass it on to their children through usual parental contact--kissing, food-sharing and using their mouths to clean pacifiers before popping them back in their babies' mouths.

     But it was not just any chewing gum that was working its magic in these moms, nor were the benefits restricted to young children, according to the study led by Eva Soderling, a researcher at Turku University in Finland. The specific gum ingredient responsible for reducing transmission of S. mutans is called xylitol, a sweet-tasting compound present in yellow plums, cherries and strawberries. Industrial sources of this bulk sweetener come from birch trees grown in the United States and Europe, where scientists at the World Health Organization have long appreciated its decay-fighting benefits."

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August 28, 2001 - London Times by Suzannah Olivier

Have a Nice Mouth

A look at new treatments and products that aim to keep teeth and gums in peak condition
"Periodontal, or gum, disease affects 95 per cent of people, making it the most common of all diseases... Plaque builds up as a mixture of mouth bacteria and food particles in a solution of mucus. A sweetener, Xylitol, which is finding its way into many chewing gums, mouth rinses and toothpastes, is being hailed as the latest effective anti-plaque weapon.

"Xylitol is possibly the most promising development since the introduction of fluoride.�

     Dr Ronnie Levine, author of the Scientific Basis of Dental Health Education for the Health Development Agency (formerly the Health Education Authority), says: �As an anti-plaque and anti-caries (tooth decay) agent, Xylitol is possibly the most promising development since the introduction of fluoride.�

     Xylitol is a bulk sweetener (as opposed to an artificial sweetener) related to sugar and extracted from birch wood. Unlike most other sugars, Xylitol cannot be converted to acid in the mouth by bacteria. It suppresses unfavourable mouth bacteria, especially Mutans streptococci, and inhibits plaque formation.

     A study published in the Journal of Dental Research showed that the children of mothers who regularly chewed Xylitol-sweetened gum had about a 70 per cent reduction in tooth decay..."

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