ORIGINAL ABSTRACT

BACKGROUND: Glyphosate, the active ingredient in many widely used herbicides, is a pervasive environmental contaminant due to extensive agricultural and residential use. Initially deemed safe, emerging evidence suggests chronic glyphosate exposure may impair metabolic health. This scoping review maps the evidence linking glyphosate exposure with metabolic syndrome (MetS), type 2 diabetes (T2DM), and related outcomes, integrating findings from human, animal, and cellular studies. METHODS: We reviewed studies published from 2004 in PubMed and Google Scholar that examined glyphosate exposure in relation to metabolic outcomes. Thirteen epidemiological (cross-sectional and cohort) and 25 experimental (animal or in vitro) studies were included. Key data were extracted and synthesized narratively. RESULTS: Most human studies, primarily cross-sectional analyses of U.S. NHANES data, reported positive associations between glyphosate biomarkers and metabolic risk factors. Higher exposure was consistently linked to elevated liver enzymes, insulin resistance, hyperglycemia, and increased odds of MetS. Two longitudinal studies supported these associations, while one occupational cohort found an inverse association with T2DM. Experimental models demonstrated that glyphosate induces hepatic steatosis, inflammation, oxidative stress, and mitochondrial dysfunction, disrupts glucose metabolism and insulin signaling, alters the gut microbiome, and modulates endocrine and epigenetic pathways, supporting its role as a metabolic disruptor. CONCLUSION: While predominantly cross-sectional human data limit causal inference, the convergence of epidemiological associations and mechanistic findings indicate that glyphosate may be an environmental risk factor for metabolic syndrome and related conditions. Given its widespread use, even modest metabolic effects warrant further investigation through longitudinal studies with robust exposure assessment.