Since its introduction in 1945, fluoride has played a critical role in reducing cavities and improving oral health. However, growing concerns about overexposure, particularly in vulnerable populations such as pregnant women and children, prompted the U.S. Department of Health and Human Services' National Toxicology Program to conduct a systematic review on the potential neurodevelopmental effects of fluoride.

Key Findings

The National Toxicology Program (NTP) conducted a systematic review evaluating the association between fluoride exposure and neurodevelopmental and cognitive outcomes. The review focused on human studies and found consistent evidence that higher fluoride exposure is associated with lower intelligence quotient (IQ) scores in children. The NTP review was designed to evaluate total fluoride exposure from all sources, including drinking water, foods, beverages, and dental products, rather than focusing solely on fluoridated drinking water.

Human Studies

• Children’s IQ and Fluoride Exposure: Seventy-two studies examined the relationship between fluoride exposure and IQ in children. Of these, 19 were classified as high-quality, with 18 showing an inverse association between fluoride exposure and IQ. In high-fluoride areas, mean IQ scores were generally lower; for example, one study found that children exposed to fluoride levels exceeding 1.5 mg/L in drinking water had a higher odds of having an IQ below 80 for each 1-mg increase in daily fluoride intake.
• Sex-Specific Effects: Although some studies analyzed data by sex, the results did not consistently indicate differential susceptibility between boys and girls. Five low risk-of-bias studies evaluated sex differences, but no consistent trends emerged to suggest one sex was more affected by fluoride exposure than the other.
• Geographic Spread: Studies were conducted across various countries, including China, India, Mexico, and Canada. For example, in a Chinese study, children living in areas with high fluoride levels in water (2.20 mg/L) showed significant deficits in motor and sensory function compared to those living in areas with lower fluoride levels.
• Adult Cognitive Function and Fluoride Exposure: Two low risk-of-bias studies focused on cognitive effects of fluoride exposure in adults. These studies, conducted in France and China, found no significant association between fluoride exposure and cognitive impairment in adults. However, the evidence was limited, and the studies did not provide conclusive results on the impact of fluoride on adult cognition.

Data and Results

• Robustness of Findings: Across the 19 high-quality studies, consistent evidence showed an inverse relationship between estimated fluoride exposure and IQ scores, regardless of study design or population. For example, one study showed a significant linear trend of decreasing IQ with increasing serum fluoride levels.
• Covariate Consideration: These studies accounted for various potential confounders, such as age, sex, socioeconomic status, and parental education. The consistency of the findings across different studies and covariate adjustments suggests that confounding factors are unlikely to explain the observed associations.
• Dose-Response Relationship: Evidence from multiple studies suggested a dose-response relationship, where higher fluoride exposure was associated with greater reductions in IQ scores. This relationship was observed across different fluoride exposure assessment methods, including drinking water levels and urinary fluoride concentrations.

Mechanistic Studies

Mechanistic data explored potential biological processes, such as thyroid hormone disruption and oxidative stress, that might link fluoride to neurodevelopmental outcomes. However, the studies were too heterogeneous to allow for definitive conclusions.

Conclusions

The NTP concluded with moderate confidence that higher levels of fluoride exposure, particularly above 1.5 mg/L, are associated with lower IQ scores in children. The review highlighted the need for further studies to better understand the potential health risks associated with fluoride exposure at levels currently recommended for U.S. community water supplies.

Reference:

National Toxicology Program (NTP). 2024. NTP monograph on the state of the science concerning fluoride exposure and neurodevelopment and cognition: a systematic review. Research Triangle Park, NC: National Toxicology Program. NTP Monograph 08.