Cross-sectional analysis of NHANES data (1999–2018) found that higher intake of monounsaturated and polyunsaturated fatty acids—especially docosahexaenoic acid (DHA, C22:6)—was associated with lower odds of prevalent Parkinson's disease, while several medium-chain saturated fatty acids (C6:0–C14:0)…

The study highlights dietary fatty acid composition, particularly DHA, as a potentially modifiable factor and prioritizes specific lipids for mechanistic, prospective, or interventional PD research, though causality remains unproven due to the cross-sectional design.

BACKGROUND: The association between dietary fatty acid intake and Parkinson's disease (PD) remains uncertain, particularly regarding the relative contributions of individual fatty acids under combined exposure. METHODS: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Multivariable-adjusted logistic regression was used to examine associations between dietary fatty acid intake and PD, with restricted cubic splines (RCS) applied to evaluate dose-response relationships. Stratified and interaction analyses assessed the consistency of associations across population subgroups. Variance inflation factors (VIF) were calculated to detect multicollinearity. Weighted quantile sum (WQS) regression was used to assess the joint effect of 19 fatty acids and identify major contributors. RESULTS: Among 19,271 U S. adults, including 427 with PD, higher intakes of monounsaturated and polyunsaturated fatty acids, including ω-3 and ω-6 fatty acids, were linearly associated with lower odds of PD. These inverse associations were more evident among participants without hypertension. In contrast, several medium-chain saturated fatty acids (C6:0-C14:0) were positively associated with PD. Individual fatty acid and weighted quantile sum analyses identified docosahexaenoic acid (C22:6) as the main contributor to the inverse mixture association, whereas medium-chain SFAs contributed most to the positive mixture association. CONCLUSIONS: Dietary fatty acid composition, rather than total fat intake, was associated with PD prevalence in U.S. adults. At the individual fatty acid level, inverse associations were most evident for docosahexaenoic acid (C22:6), whereas several medium-chain saturated fatty acids showed positive associations. These exploratory findings support evaluating fatty acids as mixtures and warrant confirmation in prospective studies.