Fluoride-Free Toothpastes for Caries Prevention: A Systematic Review of Clinical Evidence on Active Ingredients

Objective: To systematically identify and evaluate clinical trials assessing the caries-preventive efficacy of fluoride-free active ingredients in toothpaste formulations. Data: Randomized clinical trials analyzing the caries preventive effect of fluoride-free active ingredients in toothpastes. Sources: A PRISMA-related systematic review of MEDLINE and Embase was conducted. Inclusion criteria were human in vivo clinical trials on toothpastes, fluoride-free interventions, and caries-focused outcomes; exclusion criteria were in vitro or animal studies, non-toothpaste products, fluoride-only products, and non-English publications. The review followed the PICO framework: Population - participants of all ages with primary, mixed, or permanent dentition; Intervention - use of a toothpaste with a non-fluoride active ingredient; Comparison - a fluoride-containing toothpaste as control; Outcome - a measurable oral health effect based on in vivo caries estimation. Study Selection: Fifteen clinical trials met the inclusion criteria. Eleven used fluoride-free, non-therapeutic abrasive toothpastes as placebo controls. Three trials evaluated the caries-preventing efficacy of fluoride-free hydroxyapatite toothpastes across children, adolescents, and adults; one trial evaluated the caries-preventive efficacy of fluoride-free arginine toothpaste in children. Conclusion: Caries prevention relies on reducing sugar intake and thorough daily oral care, with toothpaste, containing evolving combinations of remineralizing agents, antibacterials, and abrasives, playing a central role. With growing global interest in fluoride-free options, this literature review shows that clinically proven fluoride alternatives are already in use. Clinical Significance: This review provides evidence-based guidance for dentists when recommending fluoride-free toothpastes to patients. Keywords: fluoride-free toothpaste, caries prevention, randomized clinical trials