Michael Connett had been preparing for this moment for four years. The California-based attorney was headed to court, where he would be suing the US Environmental Protection Agency (EPA). Connett was slated to appear at the San Francisco federal courthouse on behalf of several individuals and advocacy groups. His contention: that supplemental water fluoridation is unsafe and should be halted. Immediately.

On the first day of the hearing, Connett woke up at 3.30 a.m. to put the finishing touches to his opening presentation. He downed a cup of coffee and an energy bar, then walked the two blocks from the hotel to his office, where he sat down, signed into Zoom and prepared to give his opening statement. The date was 8 June 2020, and the court had been closed to in-person business since March because of the COVID-19 pandemic. There was no bailiff, no audience sitting in the gallery. Instead of 50 onlookers in a physical courtroom, more than 500 people had signed in to view the virtual proceedings. They watched as Connett enumerated issues that have been bubbling up in the world of fluoride research.

The bulk of public opinion, based on decades of dental-health research, is against him — at least in the United States, where more than 63% of people have access to fluoridated water. One study after another, from the 1940s through to the 1970s, has pointed to fluoride as an important factor in preventing tooth decay, also known as caries. The mineral has become part of public-health lore, and has been hailed by the US Centers for Disease Control and Prevention as one of the ten greatest public-health achievements of the twentieth century. Most people who live in areas with fluoridated water on tap take the benefits for granted and view with suspicion those who question the supplementation.

Yet research over the past 50 years has sown a seed of doubt. Rates of tooth decay in some high-income countries with no fluoridation have declined at a pace similar to that seen in fluoridated US communities. And an increasing number of studies are indicating that fluoride — which occurs naturally in soil and therefore also in groundwater — might be a developmental neurotoxin, even at the level that the US Public Health Service has declared optimal for fluoridation.

Some toxicologists and epidemiologists are now questioning whether even low doses of fluoride can have systemic effects, including causing a dip in IQ in children who were exposed to it in utero. The first indications of this came from studies that compared unfluoridated villages and communities with fluoridated ones (where fluoride is either naturally occurring or added to water), followed by better-controlled studies that measured fluoride in individuals. In the United States, each new study was met with extreme criticism, ridicule and anger that, at times, threatened the careers of those involved.

Many dentists, having seen what life was like before fluoridation, have no interest in returning to the pre-fluoridation era of widespread cavities, abscesses, dentures and people in pain. But toxicologists worry that dental-health gains have come at a cost. Today, despite a shared goal of protecting public health, researchers on opposing sides of the fluoridation debate have trouble finding common ground.

Landmark in oral health

Fluoride has, without doubt, improved oral health and decreased rates of dental caries. Community water fluoridation has its roots in the 1940s, when a handful of trials were conducted after it was noticed that some communities with naturally fluoridated groundwater had a lower-than-average incidence of tooth decay. The first of these trials began in Michigan, New York state and Ontario, Canada, in 1945. In Michigan, researchers compared rates of tooth decay in Grand Rapids, where fluoride was added to the community water supply, and in Muskegon, where it was not¹. When the five-year data were analysed and formally reviewed, the results were so striking that Muskegon abandoned the trial and began adding the mineral to its water, too. Over the following five decades, fluoridation was introduced in communities around the United States.

The practice remains common not only in the United States but elsewhere, including Australia (where 90% of municipal water supplies are fluoridated), New Zealand (47%), and Canada (39%), and has strong proponents in the United Kingdom (10%), where many dentists and public-health officials have been exerting pressure to start fluoridating the water in more communities.

Dental practitioners who remember the time before fluoridation know well what impact it has had. “My first practice was on the border of Birmingham, which was fluoridated, and Sandwell, which wasn’t,” says Nigel Carter, a paediatric dentist and chief executive of the Oral Health Foundation in Rugby, UK. It was clear from their charts, he says, that children with extensive tooth decay were almost always from Sandwell. In 1987, Sandwell began fluoridating its water, making it one of the most recent UK communities to do so. “Within five years, it went from the bottom ten, in terms of oral health, to the top five, purely due to fluoride being introduced in the water,” Carter says.

Yet as research pushed forward in the late 1970s and 1980s, it became clear that the common understanding of how fluoride works was wrong. For decades, it was thought that fluoride was most effective at strengthening teeth when it was consumed, and that this would benefit a fetus exposed to fluoride during gestation. But it turns out although fluoride is incorporated into developing teeth in utero, it is protective against dental caries only after the teeth have emerged from the gums².

In the mouth, fluoride ions incorporate themselves into plaque, a biofilm on teeth. When the environment becomes too acidic, the ions are released from the plaque and help pull minerals from the saliva to remineralize enamel surfaces and slow down tooth decay³. Fluoride ions can get into the mouth either by applying them directly to the teeth — with topical products such as toothpaste and varnish — or by ingesting fluoridated water and foods. The latter results in a tiny amount being constantly secreted in saliva. About 50% of ingested fluoride is absorbed and retained in bones and teeth, and the rest is excreted in urine; ingesting too much causes weakened bones and joints, in a condition known as skeletal fluorosis.

As research showing that topical fluoride was at least as effective as systemic doses piled up⁴, fluoridated toothpastes flooded the market. Children in primary schools were given fluoride tablets and told to swish and spit. Dentists incorporated fluoride varnishes and lacquers into their patients’ twice-yearly cleanings. And the incidence of dental caries in the United States and around the world continued to fall⁵.

Despite widespread adoption of topical fluoride, tap-water fluoridation continued. If topical fluoride has proven so effective, and rates of dental caries around the world have dropped without water fluoridation, then why is fluoride still being added to water supplies, opponents ask. Connett thinks it shouldn’t be. Others say that the answer is not so simple, and point to knottier issues of health inequities and environmental justice.

First, do no harm

Most of the research into water fluoridation’s protective effects was done before 1975, meaning that few studies directly address whether the widespread use of fluoridated rinses and toothpastes has made systemic fluoride unnecessary. But there are some clues that suggest this might be the case. Even in countries with no water fluoridation, such as Denmark, tooth decay has declined at rates comparable to those seen in US communities with fluoridation. That alone is enough to convince some researchers that adding fluoride to water is not necessary for cavity prevention, at least in societies with comprehensive public-health measures in place.

“We’re talking about a simple, highly electronegative anion. That’s it. That’s all fluoride is,” says Pamela Den Besten, a paediatric dentist who studies fluorosis and enamel formation at the University of California, San Francisco.

Den Besten has spent her career trying to work out the systemic effects of swallowing this anion. The fact that fluoride can affect ameloblasts, the cells that produce and deposit tooth enamel, suggests that it could affect other cells of the body. In fact, she notes, studies in animals and humans show that, in addition to fluorosis, cellular effects of fluoride also include inflammation and altered neurodevelopment. That, in turn, suggests that it could make its way into the brain. Den Besten says that means researchers should be looking into whether fluoride has potential effects on the central nervous system. “It should be a high priority to answer these questions. And yet, it’s not.” These potential effects of fluoride are important for individuals at all ages, she says.

The possibility of neurological effects is part of what Connett is trying to draw attention to in his lawsuit against the EPA. The finding that has garnered the most attention is a 2019 study in JAMA Pediatrics⁶, in which researchers compared the IQ of children who were born to women living in fluoridated areas and non-fluoridated areas. The data, which came from 512 mother–child pairs in 6 cities in Canada, indicated that, depending on how fluoride intake was assessed, exposure during fetal development was associated with as much as a five-point drop in IQ. A second study, led by public-health physician and epidemiologist Howard Hu at the Keck School of Medicine at the University of Southern California in Los Angeles, found a correlation between increased maternal urinary fluoride and decreased IQ in children born in Mexico City⁷.

“It’s not disputed that fluoride is toxic at high levels,” says Christine Till, a neuropsychologist at York University in Toronto, Canada, and lead researcher of the JAMA Pediatrics study. But what happens at lower levels, such as the 0.7 milligrams of fluoride per litre recommended in US fluoridation, is contested. That’s what Till and her colleagues have been working to tease out. “You have some weaker studies saying there’s no effect. And then you have our study, and the Mexico study, that are high quality, saying there is an effect,” she says.

On the basis of these two studies, Philippe Grandjean, a physician and environmental medicine researcher at the University of Southern Denmark in Odense, put together a benchmark-dose study on fluoride to document concentrations at which fluoride begins to have detectable adverse effects on IQ. According to the report, published in June⁸, that level is 0.2 milligrams per litre. That’s less than one-third of the recommended level for US water supplementation and one-twentieth of the US maximum allowable level of 4?mg l^?1 (a level originally intended to prevent skeletal fluorosis). These numbers are just the beginning. More cohort studies are under way, and toxicologists and epidemiologists hope they’ll help to bring clarity to the fraught debate.

Earlier in his career, Grandjean had worked to prove the dangers of mercury exposure, and of lead exposure before that. Bruce Lanphear, an environmental neurotoxicologist at Simon Fraser University in Burnaby, Canada, was also involved in the lead toxicity studies and worked with Till on the Canadian fluoridation study. Both Lanphear and Grandjean testified during Connett’s lawsuit, noting that the data from their fluoride analyses are comparable to those used to limit the use of mercury and lead.

Over the past 30 years, researchers have shown that the developing brain is uniquely vulnerable to lead, mercury and other neurotoxins. “Low-level lead was contentious, but it doesn’t match up to fluoride,” Lanphear says. “I don’t think people have been sceptical enough about the benefits or the safety of [systemic] fluoride.”

Hard benefits

Some public-health dentists think the issue isn’t quite so clear cut. E. Angeles Martinez Mier, who studies dental public health at Indiana University’s School of Dentistry in Indianapolis, agrees that fluoride safety is worth investigating but says there’s not yet enough evidence to convince her that the risks outweigh the benefits. “Fluoridated water works for caries prevention,” says Martinez Mier, whose laboratory did the fluoride analysis on both the Canadian and Mexico cohorts, and who is an author of both papers.

But the magnitude of this benefit could be modest. Comparing fluoridated and non-fluoridated US communities, dentists see about one fewer cavity in baby teeth in fluoridated areas, and about 0.3 fewer cavities on average in adults⁹. “The size of the effect is not as much as people might think,” Till says.

Still, that benefit means something to those who can not afford dental care or to miss school or work because of poor oral health. “It’s not realistic, given the system that we have, that we’ll be able to reach every child with topical fluoride,” Martinez Mier says. “A lot of public-health dentists are adamant that fluoridated water is the only thing we have that reaches the public, regardless of access to care, regardless of public health.” If fluoridated water can help prevent so much hardship, public-health dentists argue, why wouldn’t people want it?

They also point out that although rates of tooth decay have gone down across the world, many of the countries studied have government-funded universal health-care programmes that educate citizens on the proper care of teeth and gums. The United States does not. “We are not Scandinavia. We are not Canada. Our public-health system, our infrastructure, is very different than those countries,” Martinez Mier says. “In Scandinavia, many countries have nurses who visit you at home, teach you how to brush, and you have access to fluoride through universal health care.” In the United States, she says, “it’s not realistic that we’ll be able to reach every child with topical fluoride.” Fluoridated water, however, reaches anyone who drinks or cooks with treated tap water. That’s insurance Martinez Mier is not yet willing to give up.

Hard questions

“If we’re looking at a practice that affects so many people, we want it to be scrutinized. We need transparency in the science,” says Brittany Seymour, a dentist who studies oral-health policy and epidemiology at the Harvard School of Dental Medicine in Cambridge, Massachusetts. She thinks there are some who are so fixed in their views of fluoridation that they will not reassess their stance no matter what the latest research might show. But she also thinks that the questions Till, Lanphear and others are asking are important.

Seymour, who is also a spokesperson for the American Dental Association, studies online health misinformation and has seen all the ways in which fluoride has been demonized. For now, at least, she thinks it’s too early to consider revising a programme that has clearly made a difference to children’s oral health, especially when the data are limited to just a few cohorts. And while tooth decay might be down globally, she doesn’t think it’s because of fluoridated toothpaste alone. She points to two cities — Juneau in Alaska¹⁰, and Calgary in Canada¹¹ — where the ending of water fluoridation seems to be directly correlated with a rise in dental caries. “If we remove something that we know has a protective benefit, we’re trading that for another problem,” she says.

Martinez Mier agrees. “It’s too early to be reactive and to cease water fluoridation without understanding the full scope of what that would mean for a community,” she says. If something designed to protect people’s oral health is removed, then new protective measures need to be put in place, she says.

It is difficult to ignore the importance of equity in these arguments. On the one hand, dentists think that fluoridated water most benefits those who lack access to dental services, oral-health education, or a steady supply of fluoridated toothpaste — the very people who are most susceptible to poor oral health and who experience the greatest financial hardship when dental problems strike. On the other hand, toxicologists worry about any impact of fluoridated water on IQ, especially in populations that are already vulnerable because of exposure to high rates of air pollution and elevated poverty rates, for example. And even if such populations are aware of the potential risks of fluoridation, they are least likely to be able to afford bottled water to use when formula-feeding infants, for instance.

“A couple of cavities and a couple of IQ points are both serious when you think about a population. If you’re in a place of privilege, and luck and environment is with you, and you have a child testing in the high percentile, a few IQ points may not be of great impact. But for others, in different conditions, it can be.” And, she says, “At a population level, it’s a big shift. Being in a disadvantaged position cuts across domains — health, economics, education, exposure. The most vulnerable populations are most vulnerable to a lot of things, not just dental caries and neurotoxicants.”

Back in the Zoom federal court, Connett closed his case. One scientist after another, specializing in epidemiology, toxicology and risk assessment, took to the virtual stand and testified that there was consistent evidence pointing to fluoride being a developmental neurotoxin. And Connett informed the judge of a draft report from the US National Toxicology Program (NTP), which reached the same conclusion in early 2019. Although the report wasn’t entered as evidence, Connett says, “its presence loomed large.” Today, the case is still open. Before the judge commits to a ruling, he wants to know the NTP’s conclusion — the third and final draft of the report is expected early in 2022.

Till is not holding her breath. “I don’t think they’ll ever come up with a consensus,” she says, noting that she doesn’t anticipate a scenario that will please dentists and toxicologists alike, at least not without the courts being involved. It has become a circular argument: The two groups can’t convince each other because they’re having different conversations, each siloed in their respective fields of study. “We’re in this odd situation where dental public health is in tension with environmental public health, and it’s really a dispute within the family,” Hu says.

Hu sees two big problems with how the dental public-health community has reacted. The first, he says, is that most of those in the dental community who are critiquing his and Till’s conclusions are doing so without a deep understanding of how they got them. “From the environmental epidemiology perspective, the methods employed in the most recent studies of prenatal fluoride exposure and neurodevelopment are exceptionally rigorous,” he says, and were put through stringent peer review. The second problem is a misplaced idea that decades of research on fluoride prove it is safe. “They are ignoring the fact that almost none of these ‘decades’ of research have focused on the very specific issue of prenatal fluoride exposure and neurodevelopment. The unfortunate result is that the two sides — environmental health and dental public health — keep talking past each other.” What they need, he says, is a neutral forum in which experts can dispassionately discuss and debate the evidence.

The other thing they need is more data. “There hasn’t been a single US study of fluoridation, prenatal exposure and natal development,” Hu says. He and his collaborators are starting one now, using data from past studies, and they aim to have answers in the next two years. Whether that study, or the anticipated revision of the NTP report, end up casting fluoride in a positive or negative light, their very existence will at least push the conversation forwards.

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