Fluoride has been shown to have developmental neurotoxic effects [18,19] and to be associated with impaired cognitive functioning in infants and children. This is the first study to examine the relationship between exposure to fluoridated water and ADHD prevalence, and did so using population-based data collected by the CDC. It is also unique in that it examined ADHD prevalence within the U.S., decreasing the likelihood that differences in ADHD prevalence between states reflect differing diagnostic criteria (DSM criteria is most commonly applied in the U.S. to diagnose ADHD). Furthermore, ADHD state prevalence was determined using identical methodology, eliminating the common problem of differing methodologies when comparing ADHD prevalence between countries [1].

As hypothesized, water fluoridation prevalence was positively associated with parent-reported health care provider-diagnosed ADHD prevalence. Geographic regions and states in which a greater proportion of people received fluoridated water from public water systems tended to have a greater proportion of children and adolescents diagnosed with ADHD. This suggests that living in an “optimally” fluoridated community increases a child or adolescent’s risk of developing the disorder. Moreover, results did not appear to be confounded by socioeconomic status because they remained consistent after controlling for this variable. Our findings are consistent with prior epidemiological studies that have associated high and low fluoride concentration exposure [49,58] with neurodevelopmental effects in children.

Artificial water fluoridation prevalence was significantly positively associated with ADHD prevalence, while natural water fluoridation prevalence was either negatively or not significantly associated with it. Although this could imply that the relationship between exposure to fluoridated water and increased ADHD prevalence is specific to fluoridation chemicals, the high variability in naturally occurring fluoride concentrations (0.1 mg/L - 15.9 mg/L) [21] within states prevents this conclusion from being made. Specifically, natural fluoride concentration could potentially be confounding the relationship between natural fluoridation prevalence and ADHD prevalence leading to a misleading result. For example, counties with low natural fluoridation prevalence could have high concentrations of naturally occurring fluoride that pose a greater neurodevelopmental risk than high prevalence of low concentrations of naturally occurring fluoride. This could contribute to increased ADHD prevalence within states that have low natural fluoridation prevalence. Thus, future research controlling for the high variability in natural fluoride concentration is necessary to more validly examine this relationship. Additionally, unlike artificially fluoridated water, U.S. citizens can be exposed to naturally fluoridated water from sources other than public water systems (e.g. wells and springs). Therefore, the state prevalence of natural fluoridation from public water systems may not reflect the true state-based proportion of people exposed to naturally fluoridated water.

Since states of lower SES tended to have higher artificial water fluoridation prevalence and ADHD prevalence, another important area of investigation was whether artificial water fluoridation prevalence in 1992 still predicted ADHD prevalence after SES was considered. That is, did children and adolescents in states with higher artificial water fluoridation prevalence merely have higher rates of ADHD because they tended to be of lower socioeconomic status and therefore more likely to have additional ADHD risk factors? Results showed that this was not the case and prevalence of artificial water fluoridation in 1992 did indeed predict ADHD prevalence independent of SES. Moreover, artificial water fluoridation prevalence even appeared to be the more robust predictor.

Although more research is needed to investigate the relationship between exposure to fluoridated water and increased ADHD prevalence, there are two main pathways by which exposure to fluoridated water could theoretically contribute to the disorder. First, silicofluoride-treated water has been shown to corrode lead-bearing plumbing, increasing the leaching of lead in the water [66]. Silicofluorides appear to react synergistically with lead, which in turn, increases its uptake into the body [27]. Consequently, children living in communities with silicofluoride-treated water tend to have increased lead venous blood levels (VBLs) (above 5 μg/dL), and those with additional risk factors for lead exposure (e.g. living in a house built before 1939 or living in poverty during the ages of 0-5) appear most vulnerable [67-70]. Lead VBLs equal to and lower than those more commonly found among children living in silicofluoride-treated communities have repeatedly been associated with a significantly increased risk of developing ADHD [15,71]. In fact, it has been suggested that 25.4% (598 000) of ADHD cases among 8-15 year olds in the U.S. could be attributed to lead exposure greater than 1.3 μg/dL [72].

Second, exposure to fluoridated water may contribute to ADHD via suppression of the thyroid gland. Fluoride reduces thyroid gland activity [73-75] and thyroid hormones are particularly important for cholinergic activity in the basal forebrain and hippocampus [76]. Moreover, hypothyroxemia has been associated with ADHD and is considered a potential cause of the disorder [77]. In fact, thyroid gland suppression is the mechanism by which PCB exposure contributes to it [78]. Additional studies are necessary to investigate the interaction among fluoride exposure, thyroid function and ADHD symptoms and to clarify whether exposure to fluoridated water contributes to ADHD via suppression of the thyroid gland.

Even though current findings indicate a relationship between ADHD prevalence and fluoride exposure that occurs through the optimal fluoridation of public water systems, there are several study design limitations that should be considered. First, this study is an ecological design that broadly categorized fluoride exposure as exposed versus non-exposed rather than collecting information related to concentration of fluoride and patterns and frequency of exposure or outcome at the individual level. Future research could explore the relationship between exposure to fluoridated water and the occurrence of ADHD at the individual level. Further clarification of a potential dose–response relationship between fluoride exposure and ADHD symptoms would also be important for determining causality. Second, given that fluoridation prevalence in neighboring years was highly correlated from 2000 onward and unavailable for the mid to late 90s, it could not be determined whether exposure to fluoridated water at a particular period of development was most associated with increased ADHD prevalence. Nevertheless, given that other research has demonstrated the developing brain’s particular sensitivity to the neurotoxic effects of fluoride, it is likely that prenatal and early postnatal development presents a window of vulnerability. Third, fluoridation prevalence data was analyzed with ADHD prevalence data from different years, and therefore, it cannot be confirmed that those surveyed in a given year were living in the same region as when the fluoridation data were derived. Fourth, we were unable to obtain reliable population-based data on blood lead levels among 4-17 year old children and adolescents, and therefore could not determine whether lead was mediating the relationship between exposure to fluoridated water and ADHD. Lastly, parent-reported health-care provider-diagnosed ADHD prevalence was used in this study which is not as precise a measure as others (e.g. conducting formal ADHD assessments) or may be subject to potential parent biases regarding seeking or accepting an ADHD diagnosis for their child. Therefore, the survey method used in the current study may not completely capture ‘true’ ADHD prevalence. Despite these limitations, an association between exposure to fluoridated water and ADHD prevalence was still found, even after considering the increased tendency for children in low SES states to receive an ADHD diagnosis.