1. Implications of the Xylitol for Adult Caries Trial (X-ACT) for Prevention Programs and Individuals NIDCR U01DE018038, U01DE018047, U01DE018048, U01DE018049, U01DE018050 JP Brown 1, BT Amaechi 1, JD Bader 2, GH Gilbert 3, DA Shugars 2, and WM Vollmer 4 1 UTHSC San Antonio TX 2 UNC Chapel Hill NC 3 UA Birmingham AL 4 Kaiser Permanente CHR Portland OR APHA MEETING San Francisco CA October 29, 2012

2. Trial Registration ClinicalTrials.Gov NCT00393055 Public Web Site www.kpchr.org/xact/public/index.aspx?pageid=1 Bader JD et al Design of the xylitol for adult caries trial (X-ACT) BMC Oral Health 2010 Sept 29;10:22. Banting DW etal Examiner training and reliability in two randomized clinical trials of adult dental caries J Pub Health Dent 2011;71:335-44.

3. X-ACT Xylitol Reviews: Hayes C, J Dent Educ, 2001SR+ Lingström P, Acta Odont Scand, 2003SR? Maguire A, Brit Dent J, 2003TR+ van Loveren C, Caries Res, 2004TR? Deshpande A, J Am Dent Assoc, 2008SR+ Antonio, A, J Pub Health Dent, 2011SR? Rethman M, J Am Dent Assoc, 2011SR? SR = Systematic Review TR = Traditional Review

4. Discussion of Principal Outcome X-ACT First large-scale, placebo-controlled, multi- site, randomized, double-blind study of xylitol Lozenges, not gum: possible mechanical plaque removal, chewing stimulates saliva Adults, not children Adequate fluoride exposure Regular dental attenders

5. X-ACT Discussion of Principal Outcome – cont’d Surfaces saved ~ 0.30/year (crude increment), NS Greater but NS effect in those with higher baseline D 2 FS, but not in those with higher D 2 S at baseline No indication of dose-response

6. Conclusion re Principal Outcome X-ACT Xylitol lozenges (≤ 5gm/day), used as a supplement, in caries active adults (av. ~ 3 D 2 FS/year), with adequate fluoride exposure, did not substantially reduce their caries experience.

7. Conclusions for this Secondary Analysis, assessing non-cavitated and cavitated lesions, over 12, 24, and 33 months 1.The xylitol effect for cavitated lesion (D 2 FS) declined over time, was significant only at 12 months, and was not of a clinically relevant size. 2.The xylitol effect for non-cavitated plus cavitated lesions (D 12 FS) declined over time, was not significant and was not of a clinically relevant size. 3.These results mirrored the principal trial outcome.

8. The Secondary Analysis of selected subjects with higher lifetime caries experience at baseline showed: 4. for cavitated lesions (D 2 FS) a somewhat greater xylitol effect, declining over time, but significant only at 12 and 24 months 5.for non-cavitated plus cavitated lesions (D 12 FS) a decline in xylitol effect over time, significant only at 12 and 33 months. These effects (4 and 5) were of larger magnitude, but then more total lesions were under consideration. If non-cavitated lesions retardation (remin or stasis) was occurring, even in periods shorter than one year, this could be expected to reveal differences over a longer time as fewer lesions progressed. This was not observed.

9. Implications of the X-ACT Xylitol Trial 1.Xylitol caries preventive effect in caries active adults with adequate fluoride exposure is small and not clinically relevant. 2.Even in subjects with higher baseline lifetime caries experience and presumably of even higher caries activity, the effect was marginal. 3.Using xylitol as a caries preventive agent in caries active adult patients is not well supported. (other reviews in children have been equivocal) 4.Using xylitol in organized public programs for caries prevention is not well supported. 5.Recommending xylitol as a caries preventive agent for populations has even less grounding.