Federal science panel recommends revisions to fluoride-IQ report

Association leaders question methods, messaging, transparency

A federal science panel recommended May 4 that a National Toxicology Program draft report and meta-analysis examining potential associations between fluoride and IQ be revised to account for potential study biases and more recent literature.

The NTP Board of Scientific Counselors voted unanimously to adopt the findings and recommendations of a BSC Working Group, convened to determine whether NTP adequately addressed outside questions and criticisms of a systematic literature review examining fluoride exposure and children’s IQ.

The systematic review, which has been underway for several years, is intended to summarize the literature about a potential relationship between fluoride exposure and neurodevelopmental and cognitive health. The original report has been revised several times, a common practice for peer-reviewed papers.

NTP Director Rick Woychik convened the scientific review panel after questioning whether NTP had fully resolved the methodological concerns expressed by several federal agencies and others, including the report’s original peer reviewer, the National Academies of Sciences, Engineering and Medicine.

The BSC Working Group report rated nearly 13% of NTP’s responses to comments on the draft state of the science report and more than one third (35.5 percent) of NTP’s responses to comments on the meta-analysis to be inadequate. The panel recommended or suggested revisions to the meta-analysis, based on 57.4 percent of reviewer comments.

Howard Pollick, B.D.S., a fluoridation consultant for the California Department of Public Health, health sciences professor at the University of California San Francisco School of Dentistry and a member of the ADA’s National Fluoridation Advisory Committee, testified on the ADA’s behalf. Dr. Pollick questioned why NTP switched peer reviewers after the National Academies of Sciences, Engineering and Medicine reported in 2021 that neither of the first two drafts would survive scientific scrutiny without major revision.

“NTP abandoned that course of peer review and, instead, hand-picked its own panel to review the draft before you,” Dr. Pollick said. “That is not consistent with the spirit of a truly independent peer review.”

Dr. Pollick also told the panel, “Since there is no compelling scientific or public health reason for rushing this report to publication, we urge NTP not to publish this report until our concerns —identified both here and in our written comments — are resolved.”

ADA President George R. Shepley, D.D.S., and Executive Director Raymond A. Cohlmia, D.D.S., sent a letter April 28 to Kathleen M. Gray, Ph.D., chair of the BSC, urging the board of scientific counselors to adopt several recommendations to improve the agency’s research methods, clarity, and transparency.

The draft NTP state of the science report claims that its review of 19 studies found “with moderate confidence” that higher fluoride exposure is consistently associated lower IQ in children. At least nine more studies, including two meta-analyses, have been published since the study period ended in 2020.

One meta-analysis, co-authored by former NTP director, Dr. Linda Birnbaum and published in the March 15 edition of Environmental Research, found the methodologies used in most studies have been too flawed to conclude that potential links between fluoride exposure and IQ exist.

The authors reported, “The limitations of most studies … with particular reference to the risk of residual confounding, raise uncertainties about both the causal nature of such relation and the exact thresholds of exposure involved. Such key issues can only be confirmed by additional, high-quality longitudinal studies.”

Another meta-analysis, published in the April online edition of “Public Health,” reached the same conclusion.

“Uncritical acceptance of fluoride-IQ studies, including nonprobability sampling, inadequate attention to accurate measurement of exposure, covariates and outcomes, and inappropriate statistical procedures has hindered methodological progress. Therefore, the authors urge a more scientifically robust effort to develop valid prenatal and postnatal exposure measures and to use interventional studies to investigate the fluoride-IQ hypothesis in populations with high fluoride (endemic) exposure,” the authors wrote.

The BSC Working Group recommended that NTP include a statement acknowledging and describing the potential impact of publication bias on the study conclusions. The working group also recommended that NTP:

• Use more precise language throughout the report when referring to fluoride exposure levels.
• Stress that the report refers to total exposure to fluoride and not just exposure to fluoride from drinking water.
• Replace “exposure measures” with “exposure assessment measures” or “exposure biomarkers” because exposure is seldom, if ever, directly measured.
• Replace “effects” with “associations” to avoid implying causality, which generally cannot be established from single studies.
• Reframe or describe why the benchmark of 1.5 mg/L was used, as there are likely sources of fluoride exposure other than water.
• Clearly summarize the inconsistencies and consistencies among the studies reviewed.
• Expound on what evidence is and is not available regarding dose/exposure-response between fluoride and adverse neurodevelopmental outcomes, including the importance of both dose/exposure and timing of exposure.
• Seek to publish the state of the science report and meta-analysis as standalone documents, and not reference each other for information unless timing for publication can be coordinated.

The panel observed that a journal would likely ask the NTP authors to update its literature search before publishing the meta-analysis.

The BSC’s adopted recommendations will be forwarded to the NTP director, who will decide whether and how the publications should move forward.

Earlier drafts contained a hazard assessment stating fluoride is “presumed to be a cognitive neurodevelopmental hazard to humans,” regardless of exposure level. The hazard assessment was later removed after a second NASEM peer review found, “The monograph falls short of providing a clear and convincing argument that supports its assessment.”