Letter to editor regarding “Understanding the variation in salivary fluoride levels: A secondary trajectory‐based analysis of trial data”

Dear Editor, I read with great interest the article by Staun Larsen et al. [1], “Understanding the variation in salivary fluoride levels: A secondary trajectory-based analysis of trial data.” The authors provide valuable insights into the considerable interindividual variability in background salivary fluoride levels following the use of both 1450- and 5000-ppm fluoride toothpastes. Their trajectory-based modeling represents an innovative analytical approach that meaningfully extends the findings of the parent randomized controlled trial. The observation that participants using 5000-ppm toothpaste exhibited markedly greater variability, particularly toward the end of the trial phase, is noteworthy. The identification of three distinct salivary fluoride trajectories—low, middle, and high—highlights the complexity of fluoride retention and clearance in naturalistic conditions. Importantly, the finding that some individuals assigned to the high-fluoride regimen still demonstrated low salivary fluoride responses underscores the need to account for behavioral, biological, and methodological factors that may confound fluoride exposure assessments. I commend the authors for discussing potential contributors to this variability, including brushing habits, fluoride reservoir dynamics, dietary influences, and salivary flow characteristics. Their call for repeated cross-over designs to improve the understanding of treatment-effect heterogeneity is both timely and scientifically sound. Such designs would indeed help clarify whether individual “response profiles” are stable over time or context-dependent. Nevertheless, the study also emphasizes the practical challenges inherent in long-term fluoride exposure trials. Future work may benefit from more stringent protocol standardization—particularly regarding toothpaste quantity, brushing supervision, and dietary control—alongside objective compliance monitoring tools. These refinements could help reduce noise and improve the precision of estimates for both clinical and research purposes. Overall, this study makes a valuable contribution by advancing methodological considerations for fluoride research and by raising important questions about personalized responses to high-fluoride toothpaste. None.