Big Xylitol Trial Finds Scant Benefits in Adult Caries

Laird Harrison

January 16, 2013

The first big randomized controlled trial of xylitol for caries has found no statistically significant benefits in a population of adults at high risk for the disease.

Published in the January issue of the Journal of the American Dental Association, the Xylitol for Adult Caries Trial (X-ACT) showed a 10% reduction in caries in a high-risk population who sucked xylitol lozenges compared with a matched population who sucked sucralose lozenges.

This effect fell below statistical significance (P = .06). "What this says is xylitol is not going to be a frontline defense for those at high risk," lead author James Bader, DDS, MPH, a research professor at the University of North Carolina at Chapel Hill, told Medscape Medical News. "Use it, but don't rely on it."

Aside from fluoride, only a handful of compounds have showed promise in changing the biochemistry that produces caries, and xylitol, a sugar substitute, has attracted as much interest as any. Previous research has suggested that it reduces the population of Streptococcus mutans.

Most previous studies have focused on children and have produced mixed results. Still, many clinicians already prescribe xylitol candies on the basis of favorable findings in some of this research.

In the X-ACT trial, 691 participants aged 21 through 80 years consumed five 1-g xylitol or placebo lozenges a day for 33 months. Researchers counted the decayed and filled surfaces of their teeth, where decay penetrated the enamel (D<2FS), at baseline and at 12, 24, and 33 months.

To be included, participants had to have at least a single coronal or root-surface cavitated caries lesion.

The trial took place in the dental schools of the University of North Carolina at Chapel Hill, the University of Alabama–Birmingham, and the University of Texas Health Science Center at San Antonio (UTHSCSA). The Kaiser Permanente Center for Health Research in Portland, Oregon, served as the data coordinating center.

The researchers checked how many lozenges the patients were consuming by noting how many replacement containers they requested.

Late in the study, monitors discovered that the adherence data at the UTHSCSA were unreliable. In addition, 10 participants who were household members of existing participants had been randomly assigned in violation of the protocol. Therefore, the researchers excluded those 10 participants and 17 others for whom data was missing. They also broke out the remaining data from that site for separate analysis.

However, they found no important differences when the UTHSCSA data were excluded and determined that the remaining sample size gave them adequate power to detect statistical significance even without those data.

Subgroup Analysis

They analyzed subgroups of the participants according to baseline caries scores, adherence to the study protocol, sex, and race or ethnicity.

Among participants from the University of North Carolina at Chapel Hill and University of Alabama–Birmingham sites, the crude annualized D<2FS increment in the xylitol group was 2.69 compared with 2.98 in the placebo group, a 10% lower increment. However, this difference did not reach statistical significance (relative risk [RR], 0.90; 95% confidence interval [CI], 0.78 - 1.03).

Analyzing covariates, the researchers found that annualized caries increments increased significantly with increasing baseline D<2FS score but did not differ according to site, age, routine dental visit history, use of over-the-counter fluoride, or frequency of oral hygiene.

Because the subgroup with high baseline D<2FS scores had greater caries increments, the researchers conducted a secondary analysis to assess treatment effects separately for those with baseline D<2FS scores of 20 or lower and those with scores of 21 or higher.

They saw no evidence of a treatment effect in the low baseline D<2FS group (RR, 1.00) but saw a significant effect in the higher D<2FS group (RR, 0.80; P = .03). However, when they included the UTHSCSA data, the treatment effect was reduced in the high D<2FS group to just below statistical significance (RR, 0.83; P = .05).

The researchers found no differences between men and women in either the 2-site or the 3-site analyses. They found a statistically significant treatment effect for non-Hispanic whites in the 2-site, but not in the 3-site, analysis. In addition, they found no evidence of a dose response.

The participants reported 46 severe adverse reactions, 22 in the xylitol group and 24 in the placebo group. They considered one, longstanding gastroparesis, to be possibly study related; they could not reach a conclusion about 3 others.

The rate of gastrointestinal adverse events ranged from 3.3% to 11.4% from one reporting interval to another. Severe oral adverse events ranged from 3.2% to 8.4%.

The study is "obviously important," said Donald Chi, DDS, PhD, assistant professor of oral health sciences at the University of Washington, Seattle.

However, he added, other research has led him to believe a larger dose (6 - 10 g/day, in 2 - 3 applications) is more efficacious, at least in children. "I consider xylitol to be part of a tool kit of preventive strategies that, when combined, lead to therapeutic effects," Dr. Chi told Medscape Medical News. He has conducted research on xylitol but was not involved in the current study.

Dr. Bader did not disagree. "This should not discourage public health groups that use xylitol for caries, because they use it primarily for children," he said. "Xylitol is not a magic bullet, but that doesn't mean it doesn't work at all."

In addition, xylitol chewing gum may have a mechanical effect of scrubbing plaque from teeth or might stimulate saliva flow more that lozenges, he said. One reason the researchers chose lozenges in their adult population is that chewing gum is less socially acceptable among adults.

Even in adults, xylitol may still have a role, said Dr. Bader. "A few patients seem to get caries no matter what you do," he said. "You have to throw everything you have at them."

This research was supported by the National Institute of Dental and Craniofacial Research. The authors and Dr. Chi have disclosed no relevant financial relationships.

JADA. 2013;144:21-30. Full text