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A large study that looked at data from nearly every general medical practice in England suggests that water fluoridation may increase the risk of developing hypothyroidism, or underactive thyroid. This condition, in which the thyroid gland doesn’t produce enough hormones, is associated with symptoms such as fatigue, obesity and depression.

The study found that locations with fluoridated water supplies were more than 30 percent more likely to have high levels of hypothyroidism, compared to areas with low levels of the chemical in the water. Overall, there were 9 percent more cases of underactive thyroid in fluoridated places.

Fluoride is added to the water of about 10 percent of England’s population—and to the taps of about two-thirds of Americans—for the purpose of preventing cavities. It has proved controversial ever since being adopted by American public health authorities in the 1950s, and then spreading to some other countries; supporters say it is a boon for dental health, while critics say it may lead to a variety of health problems.

The paper, published today in the Journal of Epidemiology & Community Health, also directly compared the fluoridated city of Birmingham with the city of Manchester, which doesn’t add the substance to the water. After controlling for factors such as sex and age (women are more likely than men to have the condition, and the elderly more likely than the young), the researchers concluded that doctor’s offices in Birmingham were nearly twice as likely to report high levels hypothyroidism, says study co-author Stephen Peckham, a researcher at the University of Kent.

“It raises a red flag,” says Dr. Philippe Grandjean, an environmental health researcher and physician at Harvard University, “that possible interference with thyroid function needs serious consideration when regulating fluoride levels in drinking water.”

The findings are all the more important since this is the “largest population ever studied in regard to adverse effects of elevated fluoride exposure,” says Grandjean, who wasn’t involved in the study. Data was collected from 99 percent of England’s 8,020 general medical practices, and the study found that a total of 3.2 percent of the population had hypothyroidism, a 14 percent increase from 2008.

“The study is an important one because it is large enough to detect differences of potential significance to the health of the population,” says Trevor Sheldon, a medical researcher and dean of the Hull York Medical School. Sheldon, who has authored numerous studies in this field, no longer thinks (as he once did) that the “case for general water fluoridation” is clear.

Considering the comprehensiveness of this study—it covered nearly the whole of England—regional differences in fluoride intake or other confounding factors are unlikely to have played a role in the striking results, says Kathleen Thiessen, a senior scientist at the Oak Ridge Center for Risk Analysis, a company that does human health risk assessments for a variety of environmental contaminants.

But John Warren, a professor and researcher in the department of dentistry at the University of Iowa, disagrees. He points out that the study merely shows correlation, not causation. It also “assumes that since one group lives in a fluoridated community, they have higher exposure to [the substance] than those in the non-fluoridated area,” he says. This is significant flaw, he says—to draw a valid connection between fluoride and hypothyroidism, you’d have to measure individual exposure to the chemical and show that those with the condition had higher levels of exposure.

But other researchers interviewed for this story disagreed with this point, saying that such group studies are a valid way to begin to assess health effects of chemical exposure and make up the bulk of the scientific basis for fluoridation; this paper uses a much larger sample size than the vast majority of studies showing positive effects of fluoride, Thiessen says. Collecting individual data from tens of thousands of people is also not very feasible, they say.

“It’s unlikely that other sources of fluoride exposure—from tea, swallowed toothpaste, a few types of foods—would be distributed amongst the population of England in a way that would bias the results in one direction or another,” says Chris Neurath, senior scientist with the Fluoride Action Network, which opposes adding the substance to water.

Moreover, several other studies have suggested that fluoride in water accounts for a majority of an individual’s exposure to the chemical in the United States, and Peckham says this is also probably true in the United Kingdom. Thus it stands to reason that people in areas with higher levels in the water are generally exposed to more of it, Peckham says.

The connection between fluoridation and thyroid problems has not been widely studied, says Thiessen, who wasn’t involved in the paper. But the research that does exist shows that at a certain dose fluoride does indeed impair the activity of the thyroid gland, through an as-yet-unclear mechanism, she says.

In fact, fluoride was used to treat hyperthyroidism (or an overactive thyroid) in the 1950s. It may put a damper on the gland’s activities by suppressing the activity of various enzymes, causing physical damage or interfering with the absorption and use of iodine, a substance that is critical for thyroid health, Thiessen says.

In 2006, the U.S. Environmental Protection Agency convened a panel that recommended lowering the maximum allowable level of fluoride in water; Thiessen was amongst that group and helped write sections of the report regarding health effects on the thyroid. Nine years later, the EPA is still considering whether or not to revise its fluoride standards.

Grandjean’s work has shown that high levels of fluoride—above the concentrations found in most fluoridated water—are associated with reduced IQ measures in children in China and India. Based on that work, he and a co-author listed fluoride as a developmental neurotoxin in a 2014 study in The Lancet.

“We don’t know how fluoride may cause the decreases in IQs in children, but this new study suggests that thyroid toxicity could be a very relevant mechanism,” Grandjean says. The thyroid produces hormones that are vital for proper metabolism, growth and brain function, and children of mothers with thyroid problems can suffer deficits in these areas, he adds.

The Centers for Disease Control and Prevention, which lists fluoridation as one of the top 10 public health initiatives of the 20th century, declined to comment on the study. The Food and Drug Administration referred questions about the study to the EPA, which didn’t respond by publication time. Public Health England maintains that fluoridation is “ a safe and effective public health measure.”

But some researchers aren’t so sure. “This study illustrates that there are potential harms [with fluoridation] that need large scale studies to explore; at the same time it is not a reason for panic,” Sheldon says.

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