Exposure to high levels of fluoride in drinking water may harm children's neurodevelopment, according to a systematic review and metaanalysis of published studies.
Philippe Grandjean, MD, PhD, of the Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, and colleagues found that children living in highly fluoridated areas had significantly lower IQ scores than their peers living in areas of low fluoridation.
"The results suggest that fluoride may be a developmental neurotoxicant that affects brain development at exposures much below those that can cause toxicity in adults," they write.
The study was published online July 20 in Environmental Health Perspectives.
A 2006 report from the US National Research Council (NRC) concluded that harmful effects of high fluoride concentrations in drinking water may be of concern and that additional research is warranted.
Acute fluoride poisoning is known to cause neurotoxicity in adults, and negative effects on memory and learning have been reported in rodent studies, but little is known about fluoride's effect on children's neurodevelopment.
Dr. Grandjean and colleagues at Harvard and China Medical University in Shenyang, China, combined 27 studies published over 22 years and found strong indications that fluoride can adversely affect cognitive development in children.
Most of the epidemiological studies available on this topic come from China, where fluoride generally occurs in drinking water as a natural contaminant. The concentration depends on local geological conditions.
"In many rural communities in China, populations with high exposure to fluoride in local drinking water sources live in close proximity to populations without high exposure," the authors note.
The studies they included in the metaanalysis had high exposures and reference exposures to fluoride in drinking water. Endpoints of the studies were IQ scores or related cognitive function measures, with means and variances for the 2 exposure groups.
In a random-effects model, the standardized weighted mean difference in IQ score between exposed and reference populations was -0.45 (95% confidence interval [CI], -0.56 to -0.35).
"Thus, children in high fluoride areas had significantly lower IQ scores than those who lived in low fluoride areas. Subgroup and sensitivity analyses also indicated inverse associations, although the substantial heterogeneity did not appear to decrease," the authors write.
The investigators acknowledge that the estimated decrease in average IQ associated with fluoride exposure seen in the analysis may seem small and may be within the measurement error of IQ testing. However, they note that "as research on other neurotoxicants has shown, a shift to the left of IQ distributions in a population will have substantial impacts, especially among those in the high and low ranges of the IQ distribution."
Cause for Concern
Commenting on the findings for Medscape Medical News, John R. Bucher, PhD, associate director of the National Toxicology Program, National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina, said the findings are "relatively consistent, to the extent that they can be compared, resulting in about a half of a point IQ decrease in fluoridated areas or what one would consider high fluoridated areas vs low to normal fluoridated areas."
"The fact that there are so many studies and they are all showing something that is pretty much in the same direction is a little concerning. The authors appropriately call for this to be looked at further. If there are ways to repeat this kind of analysis or other situations that can be studied that are analogous to this, that would be helpful," he added.
Dr. Bucher, who was not involved in the research, also praised the study's methodology, which he described as "very good."
The authors, he said, "have explained in fairly good detail in the manuscript that when you do a metaanalysis, you don't necessarily compensate for all of the deficiencies that the individual studies have."
He also noted that most of the studies were done in China "and reported in Chinese journals using the standards that were required at the time for reporting sufficiency and things of that nature, so there are some cautions that were appropriately put into the manuscript."
Nonetheless, Dr. Bucher said, "the data really sort of speak for themselves."
Call for More Research
Dr. Grandjean and colleagues believe the analysis is a good first step in evaluating the potential risk of fluoride on neurodevelopment.
"For the first time, we have been able to do a comprehensive metaanalysis that has the potential for helping us plan better studies," Anna L. Choi, research scientist in the Department of Environmental Health at Harvard School of Public Health and the study's first author, said in a statement.
In future studies, "we want to make sure that cognitive development is considered as a possible target for fluoride toxicity," she added.
The children included in the analyzed studies were up to 14 years of age, but the investigators speculate that any toxic effect on brain development may have happened earlier, and that the brain may not be fully capable of compensating for the toxicity.
"Fluoride seems to fit in with lead, mercury, and other poisons that cause chemical brain drain," Dr. Grandjean noted in the statement. "The effect of each toxicant may seem small, but the combined damage on a population scale can be serious, especially because the brain power of the next generation is crucial to all of us."
The authors note this analysis cannot be used to derive an exposure limit, because actual exposures of individual children are not known, and misclassification of children in both the high- and low-exposure groups may have occurred.
As reported previously by Medscape Medical News, the US Department of Health and Human Services announced in 2011 a proposal to lower fluoride in drinking water to 0.7 mg/L from the currently recommended range of 0.7 to 1.2 mg/L. The US Environmental Protection Agency will consider whether it should lower the maximum amount of fluoride allowed in drinking water, which currently is set at 4.0 mg/L.
Source: MedScape-Environ Health Perspect. Published online July 20, 2012.