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Fluoride, Teeth, and Developing Brains: Dental Health in Tension With Environmental Health, Millions Affected.Abstract
The recent transition in US presidential administrations may precipitate changes to the nation’s policies on the fluoridation of water. Touted as a great public health achievement that dramatically reduced dental caries, water fluoridation has become the subject of intensifying environmental health research and a target for action as a threat to health by Robert F. Kennedy Jr, who was recently confirmed as the new Secretary of the Department of Health and Human Services. Fluoride was also the focus of a lawsuit by consumer groups against the US Environmental Protection Agency (EPA) that led a US District Court to conclude in September of 2024 that
“Plaintiffs have proven, by a preponderance of the evidence, that water fluoridation at the level of 0.7 mg/L—the prescribed optimal level of fluoridation in the United States—presents an unreasonable risk of injury to health or the environment, without consideration of costs or other non-risk factors, including an unreasonable risk to a potentially exposed or susceptible subpopulation under the conditions of use.” 15 USC §2620(b)(4)(B)(ii)1
The ruling was based on five years of deliberations, testimony from dozens of scientists, and the release by the US National Toxicology Program (NTP) in August 2024 of a systematic review of the literature contained in a State of the Science report2 on fluoride. By contrast, the American Dental Association (ADA) subsequently issued an announcement stating that the court ruling provides no scientific basis for the ADA to change its endorsement of community water fluoridation,3 a position also taken by the American Academy of Pediatrics.4
Unsurprisingly, this leaves the public health, medical, and dental communities, as well as the general public, confused. Policies regarding fluoridation have enormous implications for the 209 million Americans whose drinking water undergoes community fluoridation, as well as the many people whose tap water is naturally fluoridated (11 million whose fluoride concentration exceeds the current public health service recommendation of 0.7 milligrams per liter [mg/L]).
So, what are the facts and implications for science and policy?
In the 1930s and 1940s, the prevalence of dental caries (i.e., tooth decay) in the United States increased markedly following a general increase in sugar consumption.5 This led to prospective field studies in selected US cities in the 1940s that showed that community water fluoridation was associated with a 50% to 70% reduction in caries.6 Fluoride has been shown to prevent decay by slowing demineralization, promoting remineralization of enamel by enhancing the precipitation of hydroxyfluorapatite, and inhibiting bacterial metabolism and acid production.7 In 1950, the ADA and the American Medical Association endorsed the widespread fluoridation of community water to a target level of 0.7 to 1.2 parts per million (mg/L). By 1969, 43.7% of the US population lived in communities supplied by fluoridated water.8
At the same time, however, many fluoride-containing consumer products had become available and were being used. A systematic review and meta-analysis published in 2003 found that the use of toothpastes, gels, and mouth rinses was associated with a 26% reduction in the number of decayed, missing, and filled tooth surfaces.9 A subsequent Cochrane Collaboration systematic review and meta-analysis of 21 studies initiated after 1975 concluded that community water fluoridation led to a reduction in cavities, but with a much smaller effect size (equivalent to the prevention of one quarter of a cavity per individual) than had been seen in pre-1975 studies.10 Research has also shown that, mechanistically, fluoride’s beneficial effect predominantly occurs after tooth eruption and is a topical phenomenon (i.e., from contact of tooth surfaces with oral solutions of fluoride or fluoride that has been ingested, absorbed, and excreted into saliva).11,12 An exception may be the pits and fissures of permanent molars, which are difficult for topical fluorides to reach and may benefit from pre-eruptive fluoride exposure.13 On the other hand, a Cochrane Collaboration systematic review showed that fluoride supplements taken by pregnant women do not benefit the dental health of their offspring.14
In 2006, an expert panel convened by the US National Academies concluded that there was growing evidence that fluoride at levels of 2 to 4 mg/L in drinking water may increase the risk of skeletal fluorosis, bone fractures, IQ deficits, and assorted endocrine and other effects, and that more research was needed.15 Such research has since accelerated, particularly with respect to epidemiology and toxicology studies relevant to neurodevelopment. In its August 2024 report, based on a detailed systematic review, the NTP concluded that fluoride exposures associated with drinking water levels exceeding 1.5 mg/L of fluoride, the limit recommended by the World Health Organization, are consistently associated with lower IQ in children.2 Although 1.5 mg/L of fluoride is higher than the US Public Health Service’s optimal water fluoride level since 2015 of 0.7 mg/L, in a meta-analysis NTP subsequently conducted of pooled data from the 13 best studies relevant to drinking water fluoride levels of less than 1.5 mg/L,16 an increase in maternal or child urinary fluoride (a validated biomarker of fluoride exposure) of 1 mg/L was associated with a significant decrease in child IQ of 1.63 points (95% confidence interval [CI]?=??2.33, ?0.93). When confined to the three best studies that were prospective, rated as high quality and having a low risk of bias, and that focused on prenatal fluoride exposure, the estimated decrease in offspring IQ points associated with an increase in maternal urinary fluoride during pregnancy (MUF) was 1.70 points.
In a separate dose-response analysis by Grandjean et al. that focused on the previously mentioned three studies, an increase in maternal pregnancy urinary fluoride of 1 mg/L was associated with a decrease in IQ of 2.06 points.17 Although the studies of fluoride and IQ lack data on US women, a recent prospective study of prenatal fluoride exposure among 490 pregnant US women living in Los Angeles, California, examined offspring behavioral outcomes and found that MUF was associated with significantly increased measures of anxiety and other internalizing behaviors.18 The median MUF level among these US women of 0.76 mg/L is very close to 0.87 mg/L, the mean MUF level seen in both of the high-quality and low-risk-of-bias prospective studies included in the NTP and Grandjean et al. publications that found a significant negative association between prenatal fluoride exposure and offspring IQ.
In terms of biological plausibility, recent toxicological research indicates that the mechanism of fluoride’s neurotoxicity may be exerted through impacts on oxidative stress, synaptic and neurotransmission dysfunction, disruption of mitochondrial and energy metabolism, and calcium channel dysregulation.19 Another mechanism that may be at play relates to observations made in epidemiological studies that fluoride exposure is associated with reductions in maternal thyroid hormone levels20 as well as clinical hypothyroidism,21 which, in turn, are well-known risk factors for adverse neurodevelopmental outcomes.
Clearly, more research is needed. We need to increase the base of evidence on the impacts on intelligence and behavior of prenatal and postnatal fluoride exposure at the levels seen in most communities. Research is needed on potential susceptibility factors, because from a policy perspective regarding risk, EPA is required to consider setting standards that provide a margin of safety, currently dramatically exceeded by EPA’s regulatory limit of 4 mg/L, to protect potentially susceptible individuals. This includes pregnant women and children and, arguably, individuals who may be genetically susceptible (such as those recently found to have variants related to dopamine metabolism that are associated with amplified fluoride neurotoxicity effects22). Research is also needed that, apart from water fluoridation, compares the benefits in terms of caries prevention and risk of systemic ingestion of fluoride via various modes of fluoride application (e.g., the use of toothpastes, gels, and mouth rinses). New methods of fluoride application could potentially be developed that further minimize the risk of ingesting fluoride, especially in young children, while maximizing the benefit of fluoride for caries prevention.
In the meantime, however, we believe that the time has come for dental, medical, public health, environmental health, health policy, epidemiology, and risk assessment professionals to come together, weigh the evidence, and arrive at a consensus on policy recommendations and steps. As a first step, given that neither prenatal nor infant exposures to fluoride contributes toward the reduction of cavities in permanent teeth, whereas the major anticaries benefits of fluoride are from topical contact with posterupted teeth, it may be prudent to consider recommendations that minimize prenatal and infant fluoride exposure. We owe our young ones and future generations nothing less.
ACKNOWLEDGMENTS
This work was supported by US National Institutes of Health grant R01ES021446.
Note. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Institute of Environmental Health Sciences or National Institutes of Health.
CONFLICTS OF INTEREST
The authors are not aware of any affiliations, memberships, funding, or financial holdings that might be perceived as affecting the objectivity of this commentary. H. Hu served as a nonretained scientific expert witness for the recent federal trial on water fluoridation (Food & Water Watch et al. v US Environmental Protection Agency, US District Court for the Northern District of California at San Francisco).