The FDA announced on October 31, 2025, that it has issued enforcement notices to four companies marketing unapproved ingestible fluoride prescription drugs for children, marking a significant regulatory shift based on emerging safety concerns about gut microbiome disruption and systemic health risks. The action targets products labeled for use in children younger than 3 years or older children at low to moderate risk for dental caries.
Safety Concerns Drive Regulatory Action
FDA Commissioner Marty Makary, MD, MPH, emphasized the agency's precautionary approach, stating: "The best way to prevent cavities in children is by avoiding excessive sugar intake and good dental hygiene, not by altering a child's microbiome. For the same reason that fluoride may kill bacteria on teeth, it may also kill intestinal bacteria important for a child's health."
The decision follows the Make Our Children Healthy Again Strategy, issued by President Trump's Make American Healthy Again Commission on September 9, 2025, which specifically directed the FDA to reevaluate pediatric fluoride products. HHS Secretary Robert F. Kennedy Jr. characterized the move as "driving a stake through the heart of outdated science and protecting our kids from the risks associated with ingestible fluoride."
Scientific Evidence Supporting Microbiome Concerns
A systematic review published March 10, 2025, in Nutrition Reviews provided crucial evidence supporting the FDA's concerns. The review examined 49 studies exploring systemic fluoride's effects on gut microbiota composition, gene expression, and metabolic function. Among the human studies, which included participants with dental fluorosis and breast cancer patients, researchers observed significant shifts in microbial composition.
The studies documented increased relative abundance of Acidobacteria and Proteobacteria, alongside decreased Firmicutes and Bacteroidetes. Particularly concerning, an ex vivo study of human feces indicated that concentrations of 10 mg L⁻¹ NaF or higher could increase the ratio of unhealthy microbes after 24 hours, while lower concentrations (≤ 2 mg L⁻¹ NaF) might boost health-associated taxa.
Lack of Regulatory Oversight Since 1940s
The FDA's latest scientific evaluation revealed that ingestible fluoride drugs have operated without agency review for safety, effectiveness, or quality since their introduction in the 1940s. This regulatory gap contrasts sharply with topical fluoride products like toothpaste and mouth rinses, which fall under FDA oversight and have proven effectiveness.
The agency cited newer data suggesting potential neurologic and endocrine implications, including a meta-analysis linking higher fluoride exposure to lower IQ scores in children and observed associations with thyroid dysfunction. Additionally, a Cochrane review of multiple studies found no evidence that fluoride supplementation prevents dental caries in primary teeth.
Enforcement Strategy and Timeline
While topical fluoride use remains regulated and supported by the FDA, the agency concluded that ingestible fluoride products should not be used in children younger than 3 years and should be limited to those at high risk for caries. The FDA has begun drafting a Dear Healthcare Provider letter advising clinicians to avoid prescribing these products for children at low or moderate risk for caries.
Although a formal market withdrawal process may take years, the FDA will initially request voluntary removal from manufacturers. The agency is collaborating with the National Institutes of Health and HHS to establish a national fluoride research agenda and develop the first US oral health strategy aimed at closing data gaps and developing safer preventive measures.
Professional Guidance and Future Directions
The HHS announced plans to publish guidance on best practices for pediatric dental hygiene that are "feasible, effective, and do not alter gut health." The American Dental Association continues to support community water fluoridation and topical fluoride use as effective caries-prevention strategies, while acknowledging that fluoride supplements may be appropriate for high-risk children aged 6 months to 16 years whose drinking water contains low fluoride concentrations.
Commissioner Makary's directive to the Center for Drug Evaluation and Research emphasizes the need to "evaluate the evidence regarding the risks of systemic fluoride exposure from FDA-regulated pediatric ingestible fluoride prescription drug products to better inform parents and the medical community on this emerging area."
