Update on Sugar Alcohols and Their Role in Caries Prevention

Although largely preventable, dental caries remains the most common chronic disease in children.¹ Caries prevention is challenging due to the disease’s multifactorial etiology and risk factors. The three primary factors attributed to the etiology of dental caries are the host (teeth), cariogenic microflora and diet.^2,3 Specific to diet, early milestone research, such as the Vipeholm study,⁴ Hopewood House study⁵ and Turku sugar studies,6 found a direct association between the consumption of dietary sugars and dental caries. Since then, voluminous research has been published on the role of dietary sugars in caries development.⁷ Without the presence of sugars, the chain of causation is incomplete and decay does not occur, demonstrating that dental caries is a diet-mediated disease.⁷

Upon ingestion of fermentable sugars such as sucrose, glucose and fructose, acidogenic bacteria produce acid that can lower the pH of dental biofilm to levels that cause demineralization.⁸ Among the various dietary sugars, sucrose is thought to be the most cariogenic. Sucrose is readily fermented by cariogenic bacteria and serves as a substrate for synthesis of extracellular and intracellular polysaccharides that play roles in bacterial adhesion to enamel.⁹ The extracellular polysaccharides also may increase the porosity of the biofilm, thereby facilitating the diffusion of sugars to the microbiota in the deepest parts of the biofilm.¹⁰ High-sucrose biofilms also have notably lower concentrations of calcium, phosphate and fluoride, thus limiting tooth remineralization.¹¹

There has been ongoing interest in the use of sugar alcohols to replace traditional sugars in light of potential health benefits, such as reduced cariogenicity and fewer calories, as well as decreased glycemia and insulinaemia.¹² This is because sugar alcohols are hydrogenated carbohydrates that are not readily metabolized by bacteria, making them less cariogenic when used as alternatives to dietary sugars, especially sucrose.¹³ The defining characteristic of sugar alcohols is the presence of an alcohol group in place of carbonyl group in the aldose and ketose moieties of mono-, di-, oligo- and polysaccharides.¹² They also are referred to as polyol/polyhydric alcohol (compounds containing three or more hydroxyl groups). Polyols can be acyclic compounds, such xylitol, erythritol and sorbitol, or cyclic polyols, such as myo-inositol.¹⁴

As noted, noncariogenicity is common to all sugar alcohols because they are scarcely metabolized by microorganisms in the dental plaque.¹⁵ Thus, sugar alcohols can be classified as hypo- or nonacidogenic, with reduced or virtually no extracellular polysaccharide production.¹⁶ The fact that sugar alcohols do not produce extracellular polysaccharides is believed to be one of the reasons for their proven noncariogenicity. Another beneficial effect of sugar alcohol-based chewing gum is that chewing stimulates salivary secretion.¹⁷ Saliva can reduce caries due to its mechanical cleansing/flushing action, its ability to deliver ions for remineralization and buffer plaque acids, and its own antibacterial properties.¹⁸

In 2010, Makinen¹⁴ suggested that the efficacy of sugar alcohols for caries prevention can be determined by each molecule’s number of hydroxyl groups, with erythritol ≥ xylitol > sorbitol. Yet the effect on caries rates between erythritol and xylitol is not fully established.¹⁴ In 1989, Grenby and Mistry¹⁹ reported that the amount of polysaccharide matrices synthesized by incubated microorganisms varied between sugar alcohols, with sorbitol > mannitol > lactitol > xylitol.

Because sugar alcohols are poorly metabolized, they are only partially digested. As such, they may contribute to more frequent bowel movements, increased flatulence and diarrhea. Tolerance to sugar alcohols may vary from person to person, but most adapt to polyols within a few days.²⁰

Based on the evidence indicating that replacing sugars with sugar alcohols reduces the risk of dental caries, the U.S. Food and Drug Administration (FDA) approved a “do not promote dental caries” claim for various sugar alcohols such as xylitol, sorbitol, erythritol, mannitol, maltitol, hydrogenated starch hydrolysate (HSH), and lactilol.²¹ The FDA recently added isomalt to this list.²² The purpose of this paper is to provide an evidence-based update on the commonly used sugar alcohols and their role in caries prevention.

XYLITOL

The sugar alcohol Xylitol (C₅H₁₂O₅) is a five-carbon sugar. It naturally occurs in many fruits and vegetables, and is produced commercially from plants, such as birch and other hardwood trees.²³ Xylitol is the most studied sugar alcohol and thought to be most effective in reducing caries. There are conflicting results from research, however, regarding the role of xylitol in caries prevention.

Twetman²⁴ reported that xylitol reduced dental caries when given in doses of at least 5 g three to four times per day. The paper suggested that xylitol is nonfermentable, reduces the volume of dental plaque, prevents decreases in plaque pH, exerts a stimulating effect on saliva, and promotes selection of less virulent, xylitol-resistant mutans streptococci (MS).²⁴

A systematic review was conducted in 2008 on the use of xylitol as part of an oral hygiene regimen to prevent caries. This review included two randomized clinical trials and four controlled clinical trials that compared xylitol chewing gum with no chewing gum. In their conclusions, the authors noted that research gaps existed around the dose-response relationship, and relative efficacy of different sugar alcohols.²⁵ Another systematic review by Antonio et al²⁶ concluded that xylitol-based candies and lozenges may help reduce the risk of noninterproximal caries, but the level of evidence was noted as inconsistent and of limited quality.

Major health organizations have expressed limited recommendations regarding the use of xylitol for preventing caries. A systematic review sponsored by the American Dental Association Council on Scientific Affairs recommended that xylitol chewing gum marginally reduces the incidence of caries.²⁷ The 2014 U.S. Preventive Services Task Force reported insufficient evidence to formally recommend xylitol’s routine use for caries prevention.²⁸ A Cochrane review found low-quality evidence to support the use of fluoride toothpaste containing xylitol over fluoride-only toothpaste for preventing dental caries in children’s permanent teeth, as well as insufficient evidence to support the role of other xylitol interventions in caries prevention.¹⁸ In addition, the American Academy of Pediatric Dentistry (AAPD) revised their policy on xylitol use in 2015, stating that the results from trials of xylitol aimed at reducing dental caries, transmission of MS from mothers to children, and reduction of MS levels in children varied and were inconclusive. The AAPD policy emphasized that most studies used very large doses and frequencies, which may be unrealistic in clinical practice.²⁹

In summary, the three possible ways in which xylitol may reduce caries are by substitution of cariogenic free sugars, saliva stimulation, and a possible antibacterial effect. The literature suggests that xylitol may be effective against Streptococcus mutans when given above the daily dose threshold of 5 g to 6 g per day in three or more divided doses. It is difficult to conclude, however, if this anticaries effect is over and above sugar substitution and salivary stimulation.¹⁸ Therefore, there is low-quality evidence that supports the inclusion of xylitol in a caries prevention regimen.

SORBITOL

The sugar alcohol sorbitol (C₆H₁₄O₆) is a bulk sweetener naturally found in some fruits and manufactured commercially from dextrose produced from cornstarch.^23,30 Though the mechanism of anticariogenic action is the same for sorbitol as for other sugar alcohols, Ikeda31 reported that MS can metabolize sorbitol and produce acid. The amount of acid, however, was far smaller than that produced from sucrose.

Van Loveren¹⁶ concluded that most clinical trials with sorbitol-sweetened gum have a caries preventive effect in comparison with no gum use. Due to the limited number of studies included in this review, the caries preventive effect was difficult to quantify.¹⁶ Deshpande and Jadad²⁵ concluded from a systematic review that sorbitol (alone) chewing gum reduced dental caries, but there is a research gap regarding the dose-response relationship. Conflicting evidence regarding the efficacy of sorbitol was reported by Splieth et al,³² who found that the consumption of five xylitol lozenges per day for four weeks reduced acidogenicity of plaque. Such effects were not seen with sorbitol.

Makinen³³ reported that plaque can become adapted to sorbitol and its efficacy may be weaker than xylitol. Mickenautsch and Yengopal³⁴ concluded from a systematic review that the evidence to support the use of xylitol over sorbitol is contradictory, with studies having high risk for bias and other confounders. They called for more high-quality, randomized clinical trials to provide conclusive evidence regarding the efficacy of sorbitol.

ERYTHRITOL

Erythritol (C₄H₁₀O₄) is a natural tetritol sugar alcohol with four hydroxyl groups. It is a zero calorie sweetener and the newest sugar alcohol to be manufactured from cornstarch via a fermentation process. It occurs naturally in fruits, mushrooms and fermentation-derived foods, such as wine and cheese. Erythritol is rapidly absorbed in the small intestine, reducing the likelihood of laxative effects and increased flatulence.^23,30

In 2013, Runnel et al³⁵ studied the effects of three years of erythritol candy consumption in schoolchildren. They found lower levels of acetic acid and propionic acid in dental plaque, as well as a reduction in oral counts of MS when compared with the xylitol and sorbitol groups.³⁵ Honakala et al36 conducted a randomized clinical trial on schoolchildren that compared caries variables in long-term users of erythritol or xylitol candy, as compared with a control (sorbitol candy) on dental caries. The children consumed four erythritol, sorbitol or xylitol candies three to four times a day in school for three years. Daily intake of these polyols was about 7.5 g, and caries data were collected at 12 months, 24 months and 36 months using the International Caries Detection and Assessment System. The fewest le­sions and the longest time to develop caries were found in the erythritol group.36 In summary, erythritol is thought to be comparable to xylitol in caries prevention — however, more research is needed to support this claim.

MANNITOL

Mannitol (C₆H₁₄O₆) is a sugar alcohol similar to sorbitol. It is found in fruits, leaves and other parts of plants and mushrooms. For commercial purposes, it is manufactured from fructose, which is derived from cornstarch. Deshpande and Jadad²⁵ published a systematic review that reported that a combination of sorbitol and mannitol did not affect dental caries with statistical significance. In summary, there is inadequate evidence to support the use of mannitol alone for caries prevention.

MALTITOL

Maltitol (C₁₂H₂₄O₁₁) is a sugar alcohol that is a reduced calorie bulk sweetener manufactured by hydrogenating maltose, which is derived from cornstarch.^23,30 Birkhed et al³⁷ evaluated the effect of maltitol lozenges over three months and observed no statistical significant difference in relative numbers of facultative anaerobic bacteria. Edgar and Dodds¹⁷ reported that maltitol affects plaque by increasing salivary flow. Holgerson et al³⁸ conducted a randomized clinical trial among schoolchildren and reported that xylitol or sorbitol/maltitol reduced the amount of acid production in saliva and dental plaque, but only xylitol interfered with microbial composition.

In another randomized clinical trial, Lenkkeri et al³⁹ studied caries preventive effects of xylitol/maltitol and erythritol/malti­tol lo­zenges in children. These interventions did not provide additional preventive benefits when compared with comprehensive prevention. Thabuis et al⁴⁰ conducted a randomized clinical trial on maltitol and xylitol chewing gum. The maltitol group showed higher plaque pH and reduction in cariogenic bacteria in the four-week evaluation. They concluded that sugar-free chewing gum with either maltitol or xylitol could reduce plaque acidogenicity by decreasing the level of oral bacteria.⁴⁰ In summary, there is some evidence to support that maltitol affects bacterial acidogenicity, but evidence is lacking on whether it prevents caries.

ISOMALT

Isomalt (C₁₂H₂₄O₁₁), a sugar alcohol of hexopyranosyl-hexitol type, is similar to maltitol. It is derived from sucrose with the original glucose-fructose bond remaining intact. The glucose portion is unchanged, but the fructose portion is converted into equal amounts of sorbitol and mannitol. As such, isomalt is a mixture of two disaccharide alcohols: gluco-mannitol and gluco-sorbitol.^23,30

Out of the four papers identified that explored isomalt for caries prevention, only one was found to be somewhat relevant, with the effect of isomalt on de- and remineralization of bovine enamel lesions in vitro and in situ.⁴¹ The authors reported that isomalt facilitated tooth remineralization. In summary, there is inadequate evidence to support the use of isomalt for caries prevention.

HYDROGENATED STARCH HYDROLYSATE

Hydrogenated starch hydrolysate (HSH) is a bulk sweetener produced by partial hydrolysis of corn, wheat or potato starch, with subsequent hydrogenation of various starch fragments. This group includes hydrogenated glucose syrups, maltitol syrups and sorbitol syrups.^23,30 There is little evidence to support the efficacy of HSH in caries prevention. In 1979, Birkhed et al³⁷ evaluated the effect of HSH lozenges over three months and observed no statistical significant difference in relative numbers of facultative anaerobes. Thus, there is inadequate evidence to support the use of HSH for caries prevention.

CONCLUSION

The use of sugar alcohols, especially xylitol, remains popular. This has resulted in numerous products containing xylitol, such as candies, lozenges, syrups, chewing gum, toothpaste and wipes being marketed for caries prevention. It seems prudent that dental teams be well-versed in the evidence supporting/refuting the use of such products. Some basic information found in the literature^{23,30,31,42,43} on sugar alcohols has been summarized in Table 1.

If sugar alcohols are used to replace sugars in between-meal snacks, a reduction in caries may occur. There is inconclusive evidence, however, to support the therapeutic effect of commercially available products containing sugar alcohols in various forms and dosages.²⁹

Based on the literature, here are pertinent observations regarding sugar alcohols. They do not promote dental caries, and are considered passively noncariogenic. The beneficial effects of sugar alcohols may be attributed to the fact they are nonfermentable and/or promote salivary production, yet their abilities as cariostatic agents are not fully established. Currently, xylitol is the most promising sugar alcohol for caries prevention, but effective doses appear high and remain somewhat unclear. Furthermore, the high dosages used in most studies may be impractical for everyday use. Considering the inadequate evidence of efficacy and possible gastric side effects, it may be premature to support the routine use of any sugar alcohols in a caries prevention regimen.

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From Decisions in Dentistry. July 2016;2(07):44–47.