ORCID

https://orcid.org','0000-0001-9533-2582

Date of Award

Fall 2025

Language

English

Embargo Period

12-1-2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Environmental Health Sciences

Program

Environmental Health Sciences

First Advisor

David O. Carpenter

Second Advisor

David A. Lawrence

Committee Members

David O. Carpenter; David A. Lawrence; Erin M. Bell; Lawrence Lessner; Michael Weitzman

Keywords

Glyphosate, herbicides, Pesticides, Metabolic Syndrome, Metabolic Health, Mixture Effects

Subject Categories

Environmental Public Health | Public Health

Abstract

Glyphosate, the most extensively used herbicide worldwide, has become a ubiquitous environmental contaminant. Although initially considered safe due to its specific biochemical target in plants, emerging evidence suggests that chronic, low-level human exposure may disrupt metabolic processes. Simultaneously, the global rise in metabolic disorders such as metabolic syndrome (MetS), obesity, and type 2 diabetes, has created a pressing need to identify novel, potentially modifiable environmental contributors. This dissertation investigates the relationship between glyphosate and metabolic health through a triangulated framework that integrates individual-level epidemiological analysis, systematic synthesis of mechanistic evidence, and ecological evaluation of pesticide mixtures.

The first study employed U.S. National Health and Nutrition Examination Survey (NHANES, 2013–2018) data to examine associations between urinary glyphosate concentrations and a continuous MetS score derived via exploratory factor analysis. Findings revealed a significant, non-linear (inverted U-shaped) association, with the strongest effects at moderate exposure levels. Stratified analyses demonstrated that older adults and racial/ethnic minorities like non-Hispanic Black and Hispanic participants, exhibited the greatest susceptibility, suggesting population disparities in exposure response.

The second component systematically reviewed 38 studies (13 human and 25 mechanistic), integrating epidemiological and experimental evidence. Human studies consistently linked glyphosate biomarkers to metabolic outcomes, including hepatic injury, hyperglycemia, insulin resistance, and MetS. Mechanistic studies across diverse species elucidated convergent biological pathways such as oxidative stress, mitochondrial dysfunction, endocrine disruption, gut–liver axis impairment, and transgenerational epigenetic effects, providing strong biological plausibility for the observed associations. Despite heterogeneity in exposure levels and study designs, the weight of evidence indicates that glyphosate acts as a potential metabolic toxicant.

The third study adopted an ecological perspective, analyzing U.S. county-level data (2013–2018) on herbicide applications and obesity prevalence. Using single pollutant mixed-effects regression and quantile g-computation models, significant positive associations were observed between obesity rates, individual herbicides, and the herbicide mixture, with glyphosate, 2,4-D, and metolachlor contributing most strongly to mixture effects. Models stratified on rurality demonstrated that mixture–outcome relationships were particularly pronounced in rural counties, underscoring both cumulative environmental risk and social vulnerability in agricultural regions.

Taken together, these three studies provide a coherent, multi-scalar view of how glyphosate and related pesticide mixtures may influence metabolic health. While causality cannot be definitively established, the consistent directionality, biological plausibility, and population-level coherence of findings strengthen the inference that chronic glyphosate exposure contributes to metabolic dysfunction. This research highlights the importance of integrating multiple methodological approaches to address complex environmental health questions and calls for improved biomonitoring, regulatory evaluation of metabolic endpoints, and targeted interventions for vulnerable populations.

License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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