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

This review focuses on the synthesis of current experimental and observational data regarding the effect of fluoride exposure on childhood mental health and the role of mitochondrial function as a mechanism of action. We aggregated data on the relationships between fluoride neurotoxicity, mitochondrial function, and cognitive and mental health using PubMed. Current animal and human research suggest that prenatal and perinatal fluoride exposure might have neurotoxic effects. These studies observed physical changes (fur loss and delayed reflex development in animals), intelligence loss, increased hyperactivity, and irregular moods associated with fluoride exposure. Two gaps in the literature were identified: (1) there is limited research on the mental and emotional impacts of fluoride exposure compared to research on cognitive outcomes, and (2) human studies primarily focus on prenatal and perinatal exposure, with little research conducted at other time points (e.g., adolescence). Furthermore, 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

Fluoride Exposure and Age of Menarche: Potential Differences Among Adolescent Girls and Women in the United States

Fluoride exposure is associated with later pubertal development and decreased testosterone production in adolescent and adult males. However, its effects on female reproductive health and pubertal development are unclear. Therefore, we examined associations of fluoride exposure with reproductive health outcomes among adolescent girls and women in the United States. Participants were from The National Health and Nutrition Examination Surveys (2013 to 2016), aged 16–19 and identified as female. There were 524 and 460 participants with measures of plasma fluoride and household tap water fluoride respectively, who had at least one reproductive health outcome examined, and complete covariate data. We applied covariate adjusted survey-weighted linear or logistic regression to examine associations of fluoride exposure with age of menarche, menstrual cycle regularity, or serum sex steroid hormone levels. Median interquartile range (IQR) water and plasma fluoride concentrations were 0.48 (0.53) mg/L and 0.34 (0.30) µmol/L respectively. An IQR increase in water fluoride was associated with a 3.3 month earlier first menstrual period (B = − 0.28, 95%CI − 0.54, − 0.02, p = 0.05). Additionally, we observed a significant interaction between plasma fluoride and race/ethnicity in association with age of menarche (p = 0.01). Among Non-Hispanic Black adolescents, each IQR increase in plasma fluoride was associated with a 5-month earlier age of menarche (B = − 0.42, 95%CI − 0.61, − 0.23, p < 0.001). Potential impacts of chronic low-level fluoride exposure on reproductive health outcomes are an important area of study. Current study findings, as well as potential health disparities due to disproportionate fluoride exposure should be examined in prospective studies.

A systematic review and meta-analysis of the association between fluoride exposure and neurological disorders

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. Terms related to “Humans”; “Central nervous system”; “Fluorides”; and “Neurologic manifestations” were searched in a systematic way on PubMed, Scopus, Web of Science, Lilacs, Cochrane and Google Scholar. All studies performed on humans exposed to fluoride were included on the final assessment. A meta-analysis was then performed and the quality level of evidence was performed using the GRADE approach. Our search retrieved 4,024 studies, among which 27 fulfilled the eligibility criteria. The main source of fluoride was naturally fluoridated water. Twenty-six studies showed alterations related to Intelligence Quotient (IQ) while only one has evaluated headache, insomnia, lethargy, polydipsia and polyuria. 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.