Research Studies
Research Topics & Databases
Human studies on Fluoride’s Neurotoxicity

Fluoride Studies funded by the U.S. Government

The first U.S. government-funded Mother-Offspring study on fluoride's neurotoxic effects was published in 2017 - some 67 years since fluoridation of drinking water began. There are now more studies since 2017 that have revealed that in fluoridated communities the fetus and the formula-fed infant are the most vulnerable to fluoride’s neurotoxicity. These and other studies funded by the U.S. government on fluoride's toxicity are presented here.

Human studies on Fluoride’s Neurotoxicity

U.S. agencies funding the studies:

NIH (National Institute of Heath). The NIEHS and the NIDCR come under the aegis of the NIH.

NIEHS (National Institute of Environmental Health Sciences) has responsibility for the NTP (National Toxicology Program). The NIEHS is the research arm of U.S. regulatory agencies. The NTP is best known for its Reports on Carcinogens.

NIDCR (National Institute of Dental and Craniofacial Research) is a pro-fluoridation federal agency. It funds the majority of studies on dental research in the U.S. but avoids funding research on fluoride’s neurotoxicity.

EPA (Environmental Protection Agency) has responsibility for ensuring “safe” fluoride levels in drinking water. The EPA has never performed a risk assessment on pregnant women, the fetus, or the formula-fed infant living in fluoridated communities. According to the Mother-Offspring fluoride studies, these are the very populations most at risk to fluoride’s neurotoxicity.

CDC (Center for Disease Control and Prevention). The Division of Oral Health at the CDC are the nation’s promoters of fluoridation. They recently contracted to bring to market a system to fluoridate small communities using ‘sodium fluorosilicate tablets’ which they estimate will allow up to 19 million more Americans to drink fluoridated water.

NOTE: Not all studies funded by U.S. agencies are listed below, but we will attempt to identify all the studies as we find them. If you know of studies that should be included here, please email us

Year Published,

US funding agency

Author, Study, Journal

Finding
Jan 24, 2024

NIEHS

Hall et al.

Fluoride exposure and thyroid hormone levels in pregnancy: The MIREC cohort.

 

• Fluoride may disrupt thyroid function in pregnant women.

• Fluoride exposure was associated with alterations in maternal thyroid hormone levels.

• Urinary fluoride was associated with significantly higher TSH among those pregnant with females.

• Adjustment for maternal iodine status did not change the results.

Discussion: Fluoride exposure was associated with alterations in maternal thyroid hormone levels, the magnitude of which appeared to vary by fetal sex. Given the importance of maternal thyroid hormones for fetal neurodevelopment, replication of findings is warranted.
Nov 27, 2023

NIEHS

Krzeczkowski et al.

 

Prenatal fluoride exposure, offspring visual acuity and autonomic nervous system function in 6-month-old infants.

Journal:
Environment International

Conclusion: “Fluoride in drinking water was associated with reduced visual acuity and alterations in cardiac autonomic function in infancy, adding to the growing body of evidence suggesting fluoride’s developmental neurotoxicity.”

“… Visual acuity, which refers to the ability to detect small visual details with precision (Teller et al., 1986), can be reliably assessed within the first postnatal year and can be used to detect toxicity to the developing central nervous system (Brémond-Gignac et al., 2011). Indeed, prenatal exposure to various toxic chemicals, such as methylmercury (Murata et al., 2006, Yorifuji et al., 2013), chlorpyrifos (Silver et al., 2018), lead (Silver et al., 2016), molybdenum (Wang et al., 2023) and organic solvents (Till et al., 2005, Till et al., 2001) during gestation have been linked to poorer offspring visual acuity. Poorer visual acuity early in life has been associated with cognitive dysfunction and may be linked to further visual problems over the lifespan (Brémond-Gignac et al., 2011). To our knowledge, no studies have examined links between prenatal fluoride exposure and visual acuity in infancy.”
Nov-Dec 2023

NIEHS

Godebo et al.

Association between fluoride exposure in drinking water and cognitive deficits in children: A pilot study.

Journal:
Neurotoxicology and Teratology
  • Cognitive ability was assessed in children exposed to a range of fluoride levels in drinking water.
  • The study successfully implemented the CANTAB test to children residing in rural Ethiopia.
  • Water fluoride levels were negatively associated with children’s drawing skills, and CANTAB’s memory and learning tests.
  • Children exposed to high fluoride made more errors as CANTAB task difficulty increased.
  • The findings add urgency to further study the potential neurotoxicity of low and high fluoride in drinking water.
Oct 26, 2023

NIEHS,
NIH,
HHS,
EPA

Malin et al.

Urinary fluoride levels and metal co-exposures among pregnant women in Los Angeles, California.

Journal:
Environmental Health

 

Note: We’ve added this study on maternal urinary fluoride (MUF) levels as it’s only the second one published in the US (the first was published in 2020).  MUF levels are essential for understanding fluoride’s neurodevelopmental outcomes. (EC)

Conclusions

Maternal urinary fluoride levels observed were comparable to those found in pregnant women in Mexico and Canada that have been associated with poorer neurodevelopmental outcomes. Lower urinary fluoride levels among Hispanic and non-Hispanic Black participants in MADRES compared to non-Hispanic White participants may reflect lower tap water consumption or lower fluoride exposure from other sources. Additional research is needed to examine whether MUFsg levels observed among pregnant women in the US are associated with neurodevelopmental outcomes.

Oct 5, 2023

Correctd Proof

NIEHS
&
many European institutes

Grandjean et al.

Dose dependence of prenatal fluoride exposure associations with cognitive performance at school age in three prospective studies.

Journal:
European Journal of Public Health
The authors “merged new data from the prospective [Danish] Odense Child Cohort (OCC) with results from two previous birth cohort studies from Mexico and Canada to characterize the dose–effect relationship in greater detail.
“The joint analysis of all three cohorts showed a statistically significant association between urine-fluoride and IQ, with a BMC of 0.45 mg/l (BMCL, 0.28 mg/l), slightly higher than the BMC previously reported for the two North American cohorts alone.”
June 30, 2023

NIEHS NIH
HHS

Hefferon et al.

Regional and racial/ethnic inequalities in public drinking water fluoride concentrations across the US.

Journal:
Journal of Exposure Science & Environmental Epidemiology
… chronic exposure to population-relevant levels of fluoride may also be associated with adverse child neurodevelopmental outcomes. To our knowledge, a nationally representative database of CWS fluoride concentration estimates that can be readily linked to US epidemiologic cohorts for further study is not publicly available. Our objectives were to evaluate broad regional and sociodemographic inequalities in CWS fluoride concentrations across the US, and to determine if county-level racial/ethnic composition was associated with county-level CWS fluoride.
Feb 9, 2023
Online before print version (Dec 27, 2022)

NIEHS

Hall et al.

Fluoride exposure and hypothyroidism in a Canadian pregnancy cohort

Journal:
Science of the Total Environment

Highlights

• Fluoride may disrupt thyroid function.
• Thyroid dysfunction in pregnancy can adversely impact offspring development.
• Fluoride in water increased risk of hypothyroidism in pregnant women.
• Boys had lower IQ scores if their mothers were hypothyroid in pregnancy.
• Thyroid disruption may contribute to developmental neurotoxicity of fluoride.
2022
(July 16)

NIEHS

Goodman et al.

Iodine Status Modifies the Association between Fluoride Exposure in Pregnancy and Preschool Boys’ Intelligence

Journal:
Nuitrients

“We evaluated whether the maternal urinary iodine concentration (MUIC) modifies the association between maternal urinary fluoride (MUF) and boys’ and girls’ intelligence. We used data from 366 mother–child dyads in the Maternal–Infant Research on Environmental Chemicals Study….

“For boys whose mothers had low iodine, a 0.5 mg/g increase in MUFCRE was associated with a 4.65-point lower FSIQ score (95% CI: -7.67, -1.62). For boys whose mothers had adequate iodine, a 0.5 mg/g increase in MUFCRE was associated with a 2.95-point lower FSIQ score (95% CI: -4.77, -1.13). These results suggest adequate iodine intake during pregnancy may minimize fluoride’s neurotoxicity in boys.”
2022
(April)

NIEHS

Goodman et al.

Maternal fluoride exposure, fertility and birth outcomes: The MIREC cohort.

Journal: Environmental Advances

 Data on fertility, birth weight, gestational age, preterm birth, and small-for-gestational age (SGA) were assessed… fluoride exposure during pregnancy was not associated with these birth outcomes.
2022
(March)

NIH,

NIEHS,

EPA

Goodman et al.

Domain-specific effects of prenatal fluoride exposure on child IQ at 4, 5, and 6–12 years in the ELEMENT cohort.

Journal: Environmental Research

 “The negative association between prenatal fluoride exposure and longitudinal IQ was driven by decrements in non-verbal intelligence (i.e. PIQ [Performance IQ] ), suggesting that visual-spatial and perceptual reasoning abilities may be more impacted by prenatal fluoride exposure as compared to verbal abilities.”
2022
(Feb)

NIEHS

Spinu et al.

Probabilistic modelling of developmental neurotoxicity based on a simplified adverse outcome pathway network.

Journal: Computational Toxicology

 This paper is complex and contains many Figures and Tables.
Figure 4 ranks Sodium Fluoride (NaF) in the medium category for developmental neurotoxicity.
Figure 3 shows probability of NaF for impairment of learning, memory and cognitive function.
2021
(Dec)

NIEHS

Adkins & Brunst:

Impacts of Fluoride Neurotoxicity and Mitochondrial Dysfunction on Cognition and Mental Health: A Literature Review.

Journal:
International Journal of Environmental Research and Public Health

 “… there is no agreed-upon mechanism for the neurotoxic effects of fluoride; however, fluoride can induce mitochondrial damage, including decreasing circulating mitochondrial DNA content, dysregulating biogenesis, and circular structure loss. Additionally, many neurodevelopmental conditions have mitochondrial underpinnings. More work is needed to elucidate the impact and timing of fluoride exposure on mental health and the role of mitochondrial function as a biological mechanism.”
2021
(Oct)

NIEHS

Adkins et al.

Fluoride exposure during early adolescence and its association with internalizing symptoms.

Journal: Environmental Research

 

• Adolescents with elevated urinary fluoride concentrations exhibit more somatization symptoms.

• Males may represent an at-risk population for fluoride-related internalizing behaviors.

• While somatization is typically comorbid with anxiety and depression, fluoride concentrations were not associated with increased depressive or anxiety symptoms.

“This is the first study to link fluoride exposure and internalizing symptoms, specifically somatization. Somatization represents an interface of physical and psychological health. Continued follow-up will help shed light on the sex-specific relationship between fluoride and mental health and the role of somatization.”
2021
(Aug)

NIEHS

Cantoral et al.

Dietary fluoride intake during pregnancy and neurodevelopment in toddlers: A prospective study in the Progress Cohort.

Journal: NeuroToxicology

Lowered IQ

“In the mixed-effects longitudinal model, we observed a statistically significant negative association between dietary fluoride intake in pregnancy and cognitive score (averaged across both time points) in boys, but not girls (interaction p value = 0.07) (Table 4).

“These findings suggest that the development of nonverbal abilities in males may be more vulnerable to prenatal fluoride exposure than language or motor abilities, even at levels within the recommended intake range.”
2021
(June)

NIEHS

Grandjean et al.

A Benchmark Dose Analysis for Maternal Pregnancy Urine-Fluoride and IQ in Children.

Journal:
Risk Analysis

The analysis found that a maternal urine fluoride concentration of 0.2 mg/L was enough to lower IQ by 1 point.  This level is exceeded 4 to 5 times in pregnant women living in fluoridated communities.
2021
(June)

NIEHS,

EPA

Castiblanco-Rubio et al.

Dietary Influences on Urinary Fluoride over the Course of Pregnancy and at One-Year Postpartum.

Journal:
Biological Trace Element Research

 No significant observations made in this study.
2021
(June)

NIEHS

Ayele et al.

Neuro-medical manifestations of fluorosis in populations living in the Main Ethiopian Rift Valley.

Journal: Environmental Geochemistry and Health

 Headache and joint pain reported by 67.1% and 56.3% of the participants as the most common neurological manifestation.
2021
(Feb)

NIEHS

Cunningham et al.

Fluoride exposure and duration and quality of sleep in a Canadian population-based sample.

Journal: Environmental Health

Conclusion

Fluoride exposure may contribute to sleeping less than the recommended duration among older adolescents and adults in Canada.
2020

NIEHS

Till et al.

Fluoride exposure from infant formula and child IQ in a Canadian birth cohort.

Journal:
Environment International

Lowered IQ

“In summary, fluoride intake among infants younger than 6 months may exceed the tolerable upper limits if they are fed exclusively with formula reconstituted with fluoridated tap water. After adjusting for fetal exposure, we found that fluoride exposure during infancy predicts diminished non-verbal intelligence in children…”
2020
(Sept)

NIH

Farmus et al.

Critical Windows of Fluoride Neurotoxicity in Canadian Children.

Journal: Environmental Research

• The strongest association between fluoride and Performance IQ was during the prenatal window; the association was also significant during infancy.

• Within sex, the association between fluoride and PIQ significantly differed across the three exposure windows; among boys, the strongest association was during the prenatal window, whereas among girls, the strongest association was during infancy.

• The susceptibility of infants to fluoride from drinking water is further amplified by their higher level of water intake than adults on a per body-weight basis (Snodgrass, 1992) and lower ability to detoxify exogenous compounds than adults.

In particular, formula-fed infants, whose formula is made with fluoridated water, have an approximate 70-fold higher fluoride intake than exclusively breastfed infants

(Ekstrand, 1981; Zohoori et al., 2018; US EPA, 2010). Thus, level and timing of fluoride exposure are critical for determining the window of greatest vulnerability for neurodevelopmental outcomes.
2020

NIH,

EPA

Uyghurturk et al.

Maternal and fetal exposures to fluoride during mid-gestation among pregnant women in northern California.

Journal: Environmental Health

 The first U.S. study of urinary fluoride levels  in pregnant women as well as fluoride levels in serum and the amniotic fluid of pregnant women.
2020

NIEHS

Green et al.

Sex-Specific Neurotoxic Effects of Early-Life Exposure to Fluoride: a Review of the Epidemiologic and Animal Literature.

Journal:
Current Epidemiology Reports

 Compared with females, male offspring appear to be more sensitive to prenatal, but not postnatal, exposure to fluoride. We discuss several sex-specific mechanisms and emphasize the need for future research.
2020

EPA

Nilsen, Ruiz, Tulve.

A Meta-Analysis of Stressors from the Total Environment Associated with Children’s General Cognitive Ability.

Journal:
International Journal of Environmental Research and Public Health

Cognitive Ability

“Fluoride was observed to have the greatest increase in impacting cognitive ability (OR = 1.40, p ? 0.05) and it is often reported to affect memory and cause cognitive deficits [241].
2019

NIEHS

Green et al.

Association Between Maternal Fluoride Exposure During Pregnancy and IQ Scores in Offspring in Canada.

Journal:
JAMA Pediatrics

Lowered IQ

“In this study, maternal exposure to higher levels of fluoride during pregnancy was associated with lower IQ scores in children aged 3 to 4 years. These findings indicate the possible need to reduce fluoride intake during pregnancy.”
2019

NIEHS,

NIDCR,

NIH

Lu et al.

Fluoride related changes in behavioral outcomes may relate to increased serotonin.

Journal:
Physiology & Behavior

 This is both a human and animal study.
• Fluoride added to drinking water postnatally, resulted in reduced anxiety in mice.• Increased fluoride was associated with significantly increased serum serotonin in mice and in children.• Fluoride concentrations in brain increased with increased time of exposure.• Serotonin immunolocalization was increased in long term fluoride exposed brain.
2019

NIEHS

Grandjean P.

Developmental fluoride neurotoxicity: an updated review.

Journal: Environmental Health

 

 Conclusion: The recent epidemiological results support the notion that elevated fluoride intake during early development can result in IQ deficits that may be considerable. Recognition of neurotoxic risks is necessary when determining the safety of fluoride-contaminated drinking water and fluoride uses for preventive dentistry purposes.
2018

NIEHS

NIH

Bashash et al.

Prenatal fluoride exposure and attention deficit hyperactivity disorder (ADHD) symptoms in children at 6–12 years of age in Mexico City.

Journal:
Environment International

Higher concentration of maternal urinary fluoride was associated with more ADHD-like symptoms in school-age children.

Prenatal exposure to fluoride was most strongly associated with behavioral ratings of inattention
2018

NIEHS

NIH

Till et al.

Community Water Fluoridation and Urinary Fluoride Concentrations in a National Sample of Pregnant Women in Canada.

Journal: Environmental Health Perspectives

 The first national survey in Canada of urinary fluoride levels in pregnant women.
2017

NIEHS

NIH,

EPA

Bashash et al.

Prenatal Fluoride Exposure and Cognitive Outcomes in Children at 4 and 6–12 Years of Age in Mexico.

Journal: Environmental Health Perspectives

Lowered IQ

“In this study, higher prenatal fluoride exposure, in the general range of exposures reported for other general population samples of pregnant women and nonpregnant adults, was associated with lower scores on tests of cognitive function in the offspring at age 4 and 6–12 y.”
2017

NIEHS

Rango et al.

Biomarkers of chronic fluoride exposure in groundwater in a highly exposed population.

Journal:
Science of The Total Environment

 “The finding of exceptionally high F– concentrations in water, fingernail clippings and urine in this region should motivate further investigations of other potential health consequences such as bone disease and abnormalities in the function of the neurological and endocrine systems.”
2016

NIH

Thomas et al.

Urinary and plasma fluoride levels in pregnant women from Mexico City.

Journal: Environmental Research

 “To our understanding, this is the first large exposure assessment of fluoride during multiple time points of pregnancy using two different biomarkers (urine, plasma). Where other studies have provided exposure data for the last trimester and delivery, our work examined exposure trends from the first month of pregnancy through delivery and found that levels in urine and plasma are relatively stable. Specifically, the population-average pattern of fluoride levels over time were fairly stable.”
2015

NIH

González-Horta et al.

A Concurrent Exposure to Arsenic and Fluoride from Drinking Water in Chihuahua, Mexico.

Journal:
International Journal of Environmental Research and Public Health

 

“… significant differences were found in U-tAs and U-F– levels between males and females. Specifically, urine from women contained on average less tAs (41.5 vs 59.4 ng/mL) and F– (1.9 vs 2.4 µg/mL) than urine of men.

“Notably, both signs of dental fluorosis and skin lesions typical of the chronic iAs exposure (keratosis and changes in pigmentation) were observed in several participants during the introductory medical exam (unpublished data). Previously, dental fluorosis was reported for 80% of the population in this area as a consequence of the high F– levels in drinking water (0.7 to 8.6 mg/L) []. Although the adverse effects of the isolated exposures to iAs and F– have been widely studied and are relatively characterized, the potential effects associated with the simultaneous exposure have not been systematically examined.

“… immediate measures should be taken to reduce the exposure, particularly for vulnerable population, and specifically for pregnant women and children. The role of F– exposure in the health risks previously attributed to iAs exposure alone [,] should be systematically studied.”
2015

NIDCR

Broadbent et al.

Community Water Fluoridation and Intelligence: Prospective Study in New Zealand.

Journal:
American Journal of Public Health

 This is one of eight (8) fluoride IQ studies that found no association between exposure to fluoride and reduced IQ. [74 studies found the opposite effect.] The NTP rated this study as relatively low quality and high risk of bias. There are several glaring problems with this study including the fact that virtually all of the children in the “non-fluoridated” community used fluoride supplements (a prescription drug designed to deliver the same amount of fluoride a child would get from drinking fluoridated water). FAN discusses these problems here.
2015

EPA

Mundy WR, Padilla S, Breier JM, et al.

 

Expanding the test set: Chemicals with potential to disrupt mammalian brain development.

Journal: Neurotoxicology and Teratology

 “Out of 400 chemicals reviewed, approximately 100 had evidence of developmental neurotoxicity. Of these 100 chemicals, 21 had evidence in human studies.”[Fluoride was one of the 21 studies]
2014

NIEHS

NIH

Grandjean & Landrigan.

Neurobehavioural effects of developmental toxicity.

Journal: The Lancet Neurology

 “In 2006, we did a systematic review and identified five industrial chemicals as developmental neurotoxicants: lead, methylmercury, polychlorinated biphenyls, arsenic, and toluene. Since 2006, epidemiological studies have documented six additional developmental neurotoxicants—manganese, fluoride, chlorpyrifos, dichlorodiphenyltrichloroethane, tetrachloroethylene, and the polybrominated diphenyl ethers.”
Undated
(around 2013)

EPA

Mundy et al.

Building a Database of Developmental Neurotoxicants: Evidence from Human and Animal Studies.

Published as a poster

 Fluoride is listed under:

“Chemicals with Substantial Evidence of Developmental Neurotoxicity (n=100)”

 
2006

CDC

Macek et al.

Blood lead concentrations in children and method of water fluoridation in the United States, 1988-1994.

Journal: Environmental Health Perspectives

 

 “… Our analysis does not offer support for the hypothesis that silicofluorides in community water systems increase PbB [lead-blood] concentrations in children. On the other hand, given the limitations of our data, our analyses cannot refute a possible link between water fluoridation method and lead uptake in children, particularly among those who live in older dwellings [built before 1946] …”

 

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