Xylitol Field Trials

The field trials
an excerpt from:      XYLITOL - SWEETEN YOUR SMILE by John Peldyak, DMD

Five trials demonstrated that xylitol was well-tolerated at levels of at least 90 grams per day (more than 3 ounces or 22 teaspoons) with no adverse effects, except for a transient laxative effect in a few unadapted individuals.

By the early 1970's evidence was mounting that xylitol was a particularly safe sweetener for teeth.

In Finland an ambitious study (later known as "Turku Sugar Studies") was proposed to test the hypothesis that
replacing dietary sucrose with another sweetener could reduce the incidence of tooth decay. Fructose (fruit
sugar) and xylitol were selected for testing.

Young adult volunteers were divided into sucrose, fructose, and xylitol groups. They were issued the special
food during the next two years and told to maintain their usual dietary and oral hygiene habits.

Before the end of the first year it was becoming obvious that the xylitol group had less decay, along with less
plaque and lower ms (strep-mutan) counts. Some in the fructose group reduced their sweet snacking.

Sensing astonishing success with full xylitol substitution, the researchers quickly organized a new trial just
using the chewing gum. It was designed to run concurrently with the substitution experiment, but the total
xylitol amount consumed would be only one-tenth as much.

During and after the study volunteers were given complete physical exams. In the first six months the xylitol
substitution group reported more episodes of flatulence and diarrhea. About 30% of the volunteers reported
these symptoms, usually after consuming large amounts of xylitol in soft drinks. By the end of the study there
were no differences between the three groups on any of the physical parameters, including blood chemistries.

In the dental results the fructose group did a little better than sucrose, while the xylitol substitution group had
an astounding caries reduction of at least 85%! Remarkably, the xylitol chewing gum group also had nearly an
85% reduction, so just a small dietary addition worked as well as the full substitution, implying a real-world
practical application of major importance.

By the end of the trial both xylitol groups had a declining caries rate, suggesting that small caries had
remineralized. At the time of the report it was considered pretty audacious to flatly state that teeth can heal!

          Summary of Field Trials Using Xylitol

year                place         form of         grams       caries
Duration(mo)       (notes)          xylitol         /day      reduced

1972 (24)        Turku (1)      substitution       67          85%
1973 (12)        Turku (2)          gum             6.7        82%
1975 (24)         USSR (3)         candy           30          73%
1981 (32)       Polynesia (4)    candy & gum       20          39%
1982 (36)        Hungary (5)       candy         14-20         45%
1982 (24)      Ylivieska (6)    gum 1x / day       <5           0
                                  gum 2x / day        7          33%
                                  gum 3x / day       10          60%
1983 (36)    Ylivieska II (7)   gum 1x / day       <5           0
                                  gum 2x / day        7          50%
                                  gum 3x / day       10          80%
1984 (12)      Montreal (8)     gum 15% xyl        <1          47%
                                  gum 65% xyl         3.5        60%
1988 (40)       Belize (9)         gum             10         >80%
1989 (18)        Mich (10)         gum             10          30%
1989 (36)      Dayton (11)      gum & mints        10          80%
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NOTES:
1. Xylitol or fructose replaced sucrose in products where practicable. The fructose group
had about 30% fewer cavities than the sucrose group.
2. Control group used sucrose gum.
3. Xylitol only replaced about half of the usual candy.
4. Both groups used fluoride.
5. Xylitol also reduced caries about 25% compared to a fluoride group.
6. Gum used in addition to "state of the art" prevention program
7. Population considered at "moderate risk" for caries
8. Xylitol was mixed with sorbitol
9. Remineralization was also best with xylitol
10. Sorbitol gum as control. Xylitol group had significantly lower ms counts
11. GERIATIC GROUP - Root surface caries; periodontal condition also improved

Brief history leading to the field trials by John Peldyak, DMD

Xylitol was synthesized through the hydrogenation of wood sugar (xylose) by German chemist Emil Fischer in 1891. It did not receive much attention until after World War II, when chronic sugar shortages prompted a search for other sweeteners using locally available materials. For instance, in Finland, xylose (and xylitol) could be readily obtained from birch trees and wood scraps produced by furniture manufacturing.

By the late 1950's xylitol had been identified as a normal intermediate in human metabolism, with a turnover capacity of about 15 grams (about half an ounce) per day in the flucuronic acid pathway. Another cycle termed the hexose monophosphate shunt or pentose shunt was found to process much larger amounts of xylitol for a total metabolic capacity of nearly 600 grams per day - more than one pound, administered via infusion. That's a lot of xylitol!

The potential of xylitol as a major energy source was now readily apparent, especially in light of its largely insulin-independent metabolism. By the 1960's xylitol was being used (mostly in Germany, Switzerland, the Soviet Union, and Japan) as a preferred sweetener in diabetic diets and as an energy source for infusion therapy in patients with impaired glucose tolerance (diabetic, burn, severe trauma) and insulin resistance. Xylitol was approved for special dietary purposes in 1963 by the United State Food and Drug Administration (FDA).

In early 1969 xylitol was introduced to Australia for use as an intravenous nutrient. Ten reports of adverse reactions prompted withdrawal of xylitol from clinical use in Australia by 1970. Abnormalities were also reported from Chicago. These reports negatively influenced attitudes toward xylitol worldwide, with particular persistence in the United States.

Review of the cases revealed possible contamination of the Australian preparation. Otherwise the toxicity could be attributed to overwhelming the metabolic capacity and hyperosmolarity (administering too much, too quickly.)

Further research helped to define safe levels and rates of xylitol administration to prevent side effects from unutilized accumulations. Xylitol continues to be used intravenously within these guidelines.

The Turku results were so spectacular that the participating manufacturers quickly made xylitol products available to the public. In Scandinavia xylitol became immediately popular.

A xylitol study conducted in the Soviet Union used a partial substitution approach. Xylitol confections replaced half of the children's usual sucrose sweets. After two years the xylitol group had a dramatic 73% decreased caries incidence. Equally impressive, most of the xylitol decay was confined to small shallow spots, whereas most of the control group's lesions were large and severe.

The World Health Organization (WHO) had been paying close attention to the promise of xylitol dampening the surge of dental disease in developing countries and was planning trials to assess xylitol in widely diverse conditions.
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By 1978, just when xylitol seemed poised and ready for widespread professional and popular acceptance, enthusiasm was cooled by preliminary reports from England about possible health risks. More time and tests were needed. Meanwhile xylitol was put on hold in the U.S. The National Institute of Dental Research canceled an important xylitol trial just three days old, and turned its attention away from diet to vaccines and sealants. To top it off, the artificial intense sweetener aspartame was approved to replace cyclamate and quickly dominated the rapidly expanding sugarfree market of the beverage and food industry.

The health status of the Turku subjects was re-examined later in 1978. One subgroup had continued to use large amounts of xylitol since 1972. Again, aside from the dental aspect, no differences could be found between the xylitol and control groups. These re-examinations confirmed observations from other investigators with long-term xylitol experience.

When the safety data was thoroughly reviewed and xylitol got a clean bill of health, WHO proceeded with its trials in Thailand and French Polynesia. Although these could not be completed because of the difficult field conditions-supply delays, high dropout rates, poor compliance with fluoride, etc.-preliminary results looked good. A microhardness test showed a decreasing trend with sucrose, but an increase of enamel hardness with xylitol.

French Polynesia II was eventually completed. Both groups used fluoride toothpaste but the group enjoying xylitol sweets did 40% better than fluoride only.

WHO then compared xylitol with fluoride in Hungary. The fluoride group used fluoride toothpaste and systemic fluoride in water and milk. The xylitol group had 45% fewer cavities than the controls (no fluoride) and 35% fewer cavities than the fluoride group!

By the mid-1980�s a surprising result came in from Montreal where small amounts of xylitol in chewing gum having xylitol/sorbitol mixtures produced large decreases in caries incidence.

From 1982 the Finnish government sponsored an effort to see if existing "maximum" caries prevention programs could be improved. The control group in a small rural town, Ylivieska, received fluoride toothpaste, topical fluoride and fluoride tablets, along with hygiene instruction and monitoring. The caries rate was already low. In addition to this existing program, the test groups used xylitol gum one, two, or three times each day. After two years, "one gum" was the same as the controls, "two gums" resulted in a 30% caries reduction, and "three gums" yielded an impressive 60% reduction. A parallel program for "high risk" children with higher caries rates produced similar results in three years with decreased caries of "one gum" 0%, "two gums" 50%, and "three gums" 80%! Ylivieska clearly showed that the frequency of xylitol use is a crucial factor in its effectiveness.

The amazing results from Ylivieska demonstrated that "state of the art" caries prevention programs for both low risk and high-risk populations are now obsolete without the addition of xylitol.

Follow-up examinations in Ylivieska revealed another exciting xylitol advantage. Even five years after the discontinuation of the program, the xylitol groups did not backslide, but maintained extremely low caries rates. The powerful protective effect of xylitol was most evident with teeth which had erupted during regular xylitol use, which seem almost impervious to decay.

Long-term and perhaps permanent xylitol protective effect can be explained by optimal mineralization and/or the shift in bacterial populations with the disappearance of harmful germs.

Belize trials (begun in 1988) clearly show that the concentration of xylitol is a crucial factor. The best gum contains 100% xylitol, while xylitol/sorbitol mixtures are very good. Sugarfree gum without xylitol provides some benefit but gum with sugar is worse than no gum at all.

Notice that all of these large trials have been conducted with children or young adults. An encouraging preliminary report from a study in Dayton Ohio with a geriatric population indicates a positive xylitol effect on root caries and gum disease.

Follow up notes
by John Peldyak, DMD

Despite overwhelming evidence in support of superior dental benefits, commercial success of xylitol has developed sporadically. It has been a big hit in Scandinavia, where xylitol chewing gum is the number one sweet product in the marketplace. These countries have nationally-supported prevention programs. Xylitol has the official endorsement of national dental organizations, and label statements that highlight the benefits of xylitol boost consumer awareness.

Commercialization efforts in the US have not yet received that kind of official backing. There is a nagging perception the Food and Drug Administrations is an inflexible bureaucracy that is only slowly recognizing the importance of "nutraceuticals", food ingredients that have been shown to promote health. Examples include calcium to prevent osteoporosis, antioxidants to prevent cancer, and dietary fiber to reduce heart disease. Food items that contain nutraceuticals could be referred to as "functional foods". For instance, a sugarfree confection sweetened with xylitol could be considered a "functional candy" which helps to protect teeth. Understandably, deciding on a clear label statement for these products can be complicated because xylitol is optimally effective only when formulated and used properly.

Large manufacturers are understandably reluctant to encourage widespread xylitol use. Launching a new xylitol product line is costly, risky, and could only send conflicting messages about the company�s existing profitable items. Xylitol itself is still in short supply and relatively expensive. The first big players would bear the brunt of costly informational advertising. If successful, they would automatically trigger competition which could squeeze supplies and raise prices or cut profit margins.

Label statements can be confusing and contentious. How can xylitol be classified? Is it just another carbohydrate? Manufacturers tend to prefer the term "polyol" (just means "many �alcohol� �or �OH� chemical groups", which also could be applied to sugars). The FDA wants to use the term "sugar alcohols". This guarantees more confusion of sugarfree products: 78% of those recently surveyed believe that products labeled "sugar alcohols" contain sugar, and 69% think they contain alcohol! The apparent contradiction of the simultaneous (justifiable) declaration of "no sugar" & "no alcohol" creates an information gap with enough suspicion for at least an image problem if not a public relations nightmare.

How about calories? Can everyone agree that xylitol provides 4 calories per gram, the same as any carbohydrate? Not so easy; because of incomplete absorption, the actual calorie yield is smaller. Tiny amounts that are more completely utilized yield close to 4, while larger servings only yield about 2 calories per gram. Since an honest label statement as "Calories�it depends" is unsatisfying, a compromise reduced calorie calism of 2.4 calories per gram is allowed, at least temporarily. That�s 40% fewer calories than other carbohydrates, something to
remember when replacing fat with carbs, or just adding on a few xylitol goodies.

A diabetic claim? The FDA now permits the statement "Diabetics: this product may be useful in your diet on the advice of a physician? For sugarfree products, including xylitol. Because the American Diabetes Association has now taken the official position that sugar is no worse than other isocaloric food items, this "diabetic statement" is expected to be deleted eventually. Diabetics who us large amounts of xylitol should consult their physicians and closely monitor their blood sugar.

Reasonably daily servings of foods that supply 20 grams of mannitol or 50 grams of sorbitol are required to carry a warning statement: "excess consumption may have a laxative effect". Expect professional consumer advocated to be miffed when they discover that no such warning is mandatory with xylitol. Most xylitol users can self-adjust their intake and do not concern themselves with these squabbles.

If all that was confusing, we are still left with the dental health claim for xylitol products. Simple, right? How about "fights cavities" or "remineralizes teeth" or "helps beginning cavities heal"? Slow down�until recently the FDA only allowed weakling statements for sugarfree products claiming special dietary usefulness�"does not promote tooth decay" or "useful in not promoting tooth decay" or "expressly for not promoting tooth decay." Not very impressive, and nothing that distinguishes xylitol form any other ingredient used in sugarless items. In 1993 the FDA even considered revoking these weak statements as unauthorized health claims, subject to further review. There are some legitimate fears that unscrupulous manufactures would make unsubstantiated claims for all products containing insignificant amounts of xylitol. In the US, regulators tend to believe that "anticariogenic" claims are "therapeutic" claims and belong in the realm of prescription drugs. It would not be in the public�s best interest to have a non-patentable, nonproprietary, safe, and readily available food ingredient like xylitol reclassified as a drug.

Other countries seem to find less-adversarial solutions. The Swiss test individual products for change in pH ( xylitol and lactitol are two sweeteners with the best profile when tested this way). Items that do not cause a drop in pH below 5.7 earn a "Safe for teeth" label approval. In Canada, a type of xylitol gum tested there can claim: "Clinically proven to reduce cavities by up to 62% when used in conjunction with a proper oral hygiene program (based on a 2 year study)", and xylitol is referred to as a "medicinal ingredient. Some countries allow statements of their national dental associations on the label for sugarfree products with xylitol as the principal sweetener. These official endorsements for xylitol include: UK, (xylitol gum) "helps to reduce plaque acid�helps to reduce buildup of harmful plaque�helps to prevent cavities�helps to promote remineralization in the early stages of dental decay" �Finland and Iceland.