Fluoride exposure and metabolic alterations: a scoping review of metabolomic studies

BACKGROUND: Evidence from in-vitro and animal studies suggests that fluoride exposure may alter key metabolic pathways such as amino acid, fatty acid and energy metabolism in different tissues, requiring an understanding of its impact at the molecular level, especially in human populations. AIM OF REVIEW: This scoping review aims to systematically map and synthesize the available evidence on metabolic alterations associated with fluoride exposure, specifically focusing on studies employing metabolomic analysis techniques to identify altered metabolites and metabolic pathways at the cellular, tissue, and organ levels. KEY SCIENTIFIC CONCEPTS OF REVIEW: Fluoride exposure has been found to alter a broad range of metabolic pathways, including those involved in energy metabolism (glycolysis, TCA cycle, mitochondrial activity), macromolecule metabolism (purine and fatty acid metabolism, amino acid pathways), and cellular stress responses (oxidative stress and glutathione metabolism). However, there is limited evidence in humans and potential mechanistic studies. While supportive, the reliance on animal models and in-vitro studies points to the need for human studies to compare metabolic alterations at different levels of fluoride exposure to aid in understanding the systemic effects of fluoride on human health.