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

Abstract

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.

Keywords: childhood/adolescent environmental health; developmental neurotoxicity; longitudinal fluoride exposure; mitochondrial function; prenatal/perinatal fluoride exposure.

Figure 1

Potential mechanisms of fluoride-based mitochondrial damage. The proposed impact of fluoride exposure is detailed regarding the PGC-1α/NRF1/TFAM signaling pathway, p53 deactivation, alterations in neurotransmitter levels, and fission/fusion levels in mitochondria. Fluoride exposure is highlighted in blue; mechanisms of mitochondrial damage are highlighted in green, and outcomes are highlighted in yellow.