Fluoride — can it lower children's intelligence?

Aim of the study: To perform a systematic review and meta-analysis of epidemiological studies investigating children's IQ scores and prenatal or postnatal fluoride exposure.

Results: Of 74 studies included (64 cross-sectional and 10 cohort studies), most were conducted in China (n = 45); other locations included Canada (n = 3), Denmark (n = 1), India (n = 12), Iran (n = 4), Mexico (n = 4), New Zealand (n = 1), Pakistan (n = 2), Spain (n = 1), and Taiwan (n = 1). Fifty-two studies were rated high risk of bias and 22 were rated low risk of bias. Sixty-four studies reported inverse associations between fluoride exposure measures and children's IQ. Analysis of 59 studies with group-level measures of fluoride in drinking water, dental fluorosis, or other measures of fluoride exposure (47 high risk of bias, 12 low risk of bias; n = 20 932 children) showed an inverse association between fluoride exposure and IQ (pooled SMD, -0.45; 95% CI, -0.57 to -0.33; P < .001).

Aim of the study: Many uncertainties still surround the possible harmful effect of fluoride exposure on cognitive neurodevelopment in children.

Results: A weaker and substantially linear decrease of -2.15 (95% CI -4.48; 0.18) IQ points with increasing urinary fluoride emerged above 0.28 mg/L (approximately reflecting a water fluoride content of 0.7 mg/L). The inverse association between fluoride exposure and IQ was particularly strong in the studies at high risk of bias, while no adverse effect emerged in the only study judged at low risk of bias. Overall, most studies suggested an adverse effect of fluoride exposure on children's IQ, starting at low levels of exposure. However, a major role of residual confounding could not be ruled out, thus indicating the need of additional prospective studies at low risk of bias to conclusively assess the relation between fluoride exposure and cognitive neurodevelopment.

Aim of the study: Different studies have suggested that fluoride is related to neurological disorders in children and adolescents, but clinical evidences of which neurological parameters associated to fluoride exposure are, in fact, still controversial. In this way, this systematic review and meta-analysis aimed to show if there is an association between fluoride exposure from different sources, doses and neurological disorders.

Results: Ten studies were included on the meta-analysis, which showed IQ impairment only for individuals under high fluoride exposure considering the World Health Organization criteria, without evidences of association between low levels and any neurological disorder. However, the high heterogeneity observed compromise the final conclusions obtained by the quantitative analyses regarding such high levels. Furthermore, this association was classified as very low-level evidence. At this time, the current evidence does not allow us to state that fluoride is associated with neurological damage, indicating the need for new epidemiological studies that could provide further evidences regarding this possible association.

Aim of the study: Higher fluoride concentrations in water have inconsistently been associated with the levels of intelligence in children. The following study summarizes the available evidence regarding the strength of association between fluoridated water and children's intelligence.

Results: Twenty-six studies reporting data on 7258 children were included. The summary results indicated that high water fluoride exposure was associated with lower intelligence levels (standardized mean difference : -0.52; 95% CI: -0.62 to -0.42; P < 0.001). The findings from subgroup analyses were consistent with those from overall analysis. The dose-response meta-analysis suggested a significant association between water fluoride dosage and intelligence (P < 0.001), while increased water fluoride exposure was associated with reduced intelligence levels. Greater exposure to high levels of fluoride in water was significantly associated with reduced levels of intelligence in children. Therefore, water quality and exposure to fluoride in water should be controlled in areas with high fluoride levels in water.

Aim of the study: This paper presents a systematic review of the literature concerning fluoride that was carried out to investigate whether fluoride exposure increases the risk of low intelligence quotient (IQ) in China over the past 20 years. MEDLINE, SCI, and CNKI search were organized for all documents published, in English and Chinese, between 1988 and 2008 using the following keywords: fluorosis, fluoride, intelligence, and IQ.

Results: Sixteen case-control studies that assessed the development of low IQ in children who had been exposed to fluoride earlier in their life were included in this review. A qualitative review of the studies found a consistent and strong association between the exposure to fluoride and low IQ. The meta-analyses of the case-control studies estimated that the odds ratio of IQ in endemic fluoride areas compared with nonfluoride areas or slight fluoride areas. The summarized weighted mean difference is -4.97 (95%confidence interval [CI] = -5.58 to -4.36; p < 0.01) using a fixed-effect model and -5.03 (95%CI = -6.51 to 3.55; p < 0.01) using a random-effect model, which means that children who live in a fluorosis area have five times higher odds of developing low IQ than those who live in a nonfluorosis area or a slight fluorosis area.

Aim of the study: Thyroid hormones (THs) are critical for brain development. Whether low-moderate fluoride exposure affects thyroid function and what the impact is on children's intelligence remain elusive. We conducted a cross-sectional study to examine the associations between low-moderate fluoride exposure and thyroid function in relation to children's intelligence.

Results: In adjusted models, every 1 mg/L increment of water fluoride was associated with 0.13 uIU/mL increase in TSH. Every 1 mg/L increment of urinary fluoride was associated with 0.09 ug/dL decrease in TT4, 0.009 ng/dL decrease in FT4 and 0.11 uIU/mL increase in TSH. Fluoride exposure was inversely related to IQ scores (B = -1.587; 95% CI: -2.607, -0.568 for water fluoride and B = -1.214; 95% CI: -1.987, -0.442 for urinary fluoride). Higher TT3, FT3 were related to the increased odds of children having high normal intelligence (OR = 3.407, 95% CI: 1.044, 11.120 for TT3; OR = 3.277, 95% CI: 1.621, 6.623 for FT3). We detected a significant modification effect by TSH on the association between urinary fluoride and IQ scores, without mediation by THs. Our study suggests low-moderate fluoride exposure is associated with alterations in childhood thyroid function that may modify the association between fluoride and intelligence.

Aim of the study: Infant consumption of formula reconstituted with fluoridated water can lead to excessive fluoride intake. We examined the association between fluoride exposure in infancy and intellectual ability in children who lived in fluoridated or non-fluoridated cities in Canada.

Results: Thirty-eight percent of mother-child dyads lived in fluoridated communities. An increase of 0.5 mg/L in water fluoride concentration (approximately equaling the difference between fluoridated and non-fluoridated regions) corresponded to a 9.3- and 6.2-point decrement in Performance IQ among formula-fed (95% CI: -13.77, -4.76) and breast-fed children (95% CI: -10.45, -1.94). The association between water fluoride concentration and Performance IQ remained significant after controlling for fetal fluoride exposure among formula-fed (B = -7.93, 95% CI: -12.84, -3.01) and breastfed children (B = -6.30, 95% CI: -10.92, -1.68). A 0.5 mg increase in fluoride intake from infant formula corresponded to an 8.8-point decrement in Performance IQ (95% CI: -14.18, -3.34) and this association remained significant after controlling for fetal fluoride exposure (B = -7.62, 95% CI: -13.64, -1.60).

Aim of the study: Excessive fluoride exposure is related to adverse health outcomes, but whether dopamine (DA) relative genes are involved in the health effect of low-moderate fluoride exposure on children's intelligence remain unclear. We conducted a cross-sectional study to explore the role of DA relative genes in the health effect of low-moderate fluoride exposure in drinking water.

Results: In adjusted model, fluoride exposure was inversely associated with IQ scores (β = -5.957, 95% CI: -9.712, -2.202). The mean IQ scores of children with high-activity MAOA genotype was significantly lower than IQ scores of those with low-activity (P = 0.006) or female heterozygote (P = 0.016) genotype. We detected effect modification by four DA relative genes (ANKK1, COMT, DAT1 and MAOA) on the association between UF and IQ scores. We also found a high-dimensional gene-environment interaction among UF, ANKK1, COMT and MAOA on the effect of IQ (testing balanced accuracy = 0.5302, CV consistency: 10/10, P = 0.0107). Our study suggests DA relative genes may modify the association between fluoride and intelligence, and a potential interaction among fluoride exposure and DA relative genes on IQ.

Aim of the study: In animal studies, the combination of in utero fluoride exposure and low iodine has greater negative effects on offspring learning and memory than either alone, but this has not been studied in children. We evaluated whether the maternal urinary iodine concentration (MUIC) modifies the association between maternal urinary fluoride (MUF) and boys' and girls' intelligence.

Results: The MUICCRE by MUFCRE interaction was significant for boys (p = 0.042), but not girls (p = 0.190). 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.

Aim of the study: Tea consumption can substantially contribute to fluoride intake. We examined the association between child intelligence and prenatal fluoride exposure from mother's tea consumption.

Results: Most participants (61%) reported consuming either green or black tea during pregnancy, with daily consumption reported by 2.3% and 8.4%, respectively. Women who consumed tea during pregnancy had higher mean total fluoride intake levels (0.76 mg/day) than those who did not (0.41 mg/day). Each 0.5 mg/day increase in fluoride intake was associated with a 2.24-point decrease in FSIQ (95%CI: -3.93,-0.55) when estimated from tea alone and a 1.67-point decrease (95%CI: -3.10,-0.24) when estimated from all beverages combined. The association between total fluoride intake and child IQ did not differ between tea consumers and non-tea consumers (p-interaction = 0.58). Maternal fluoride exposure from tea consumption is associated with reduced child FSIQ independent of other beverages. As tea can be a major source of exposure, pregnant women may consider limiting intake. Clearer labeling of fluoride content could support informed choices.