Risk of Parkinson's Disease (PD) Associated with the Herbicide Paraquat Is Attenuated by High Dietary Intake of Polyunsaturated Fatty Acids (PUFAs) (S42.004)

Abstract

Objective: Evaluate associations of PD with paraquat exposure and dietary PUFA intake, separately and in combination. Background PD risk may be associated with exposure to the herbicide paraquat, possibly through a mechanism involving oxidative stress. Dietary intake of PUFAs may reduce oxidative stress, potentially modifying the association of PD risk with paraquat. Design/Methods: We recruited PD cases and controls from the Agricultural Health Study, a cohort including 84,739 private pesticide applicators and spouses. Diagnosis was confirmed by movement disorder specialists. Using a food frequency questionnaire, we collected information from 89 cases on diet before diagnosis and from 336 matched controls on diet before a corresponding date. We also collected information on lifetime use of paraquat in agriculture. Data were analyzed using logistic regression. Results: After adjusting for age, sex, state, smoking, and total energy intake, PD risk was inversely associated with intake of PUFAs (highest vs lowest tertile: OR 0.6, 95% CI 0.3-1.1), particularly the two essential fatty acids linoleic acid (0.6, 0.3-1.2) and alpha-linolenic acid (0.4, 0.2-0.8). Compared to individuals with high linoleic acid intake and no exposure, the increase in PD risk was modest in those with either low intake and no exposure (1.3, 0.7-2.5) or high intake and paraquat exposure (1.4, 0.5-3.9) but substantial in those with both low intake and paraquat exposure (4.5, 1.7-12). Similar results were observed with alpha-linolenic acid (ORs 1.2, 1.2, and 3.6 respectively). Conclusions: PD risk associated with paraquat was lower in individuals with high intake of PUFAs, consistent with the hypothesis that the mechanism of paraquat toxicity involves oxidative stress. These results may suggest approaches to preventing or modifying progression of PD. Supported by: NIEHS R01-ES10803, Intramural Research Program of the NIH (NIEHS Z01-ES044007 and Z01-ES049030, NCI Z01-CP010119), and James and Sharron Clark. Disclosure: Dr. Kamel has nothing to disclose. Dr. Richardson has nothing to disclose. Dr. Umbach has nothing to disclose. Dr. Richards has nothing to disclose. Dr. Bhudhikanok has nothing to disclose. Dr. Blair has nothing to disclose. Dr. Chade has nothing to disclose. Dr. Comyns has nothing to disclose. Dr. Goldman has nothing to disclose. Dr. Hoppin has nothing to disclose. Dr. Kasten has nothing to disclose. Dr. Korell has nothing to disclose. Dr. Marras has received personal compensation for activities with Solvay Pharmaeuticals as a consultant. Dr. Meng has nothing to disclose. Dr. Ross has nothing to disclose. Dr. Langston has nothing to disclose. Dr. Sandler has nothing to disclose. Dr. Tanner has received personal compensation for activities with Impax Pharmaceuticals, Allergan, Inc. & Genentech, Inc. as a consultant. Dr. Tanner has received research support from Michael J. Fox Foundation, Department of Defense, Parkinson9s Disease Foundation, Parkinson9s Institute, Unity Walk and Brin Foundation.