Association Between ω‐3, ω‐6 Polyunsaturated Fatty Acid and Sleep Disorders: From Cross‐Sectional to Mendelian Randomization Studies

Sleep disorders are a common health problem affecting a significant proportion of the adult population. Emerging evidence suggests that dietary factors, particularly polyunsaturated fatty acid (PUFA) intake, may play a role in modulating sleep quality. This study aims to investigate the association between omega-3 (ω-3) and omega-6 (ω-6) PUFA and sleep disorders using cross-sectional survey data and data from genome-wide association studies (GWAS). Using data from the National Health and Nutrition Examination Survey (NHANES, 2005-2018), we analyzed a cohort of 31,920 participants, with the primary independent variables being intake of ω-3 and ω-6 PUFAs. Multivariate regression was used to assess associations, and restricted cubic spline analysis was used to explore potential non-linear dose-response relationships. Two-sample Mendelian randomization (MR) analyses were performed to evaluate the causal effects of levels of multiple fatty acids on the risk of sleep disorders. For analysis on NHANES data, the participants with sleep disorders had significantly lower ω-3 PUFA intake (1.71 ± 1.11 g) compared to those without sleep disorders (1.78 ± 1.14 g, <i>p</i> < 0.001). Regression analysis revealed that higher ω-3 PUFA intake was associated with a reduced risk of sleep disorders, while the MR analyses showed that a higher ratio of ω-6 to total fatty acid levels was causally associated with a lower risk of sleep disorders (IVW OR = 0.930, 95% CI: 0.880-0.983, <i>p</i> = 0.011). Our findings suggest that increased ω-3 FA intake and increased ratio of ω-6 to total fatty acid level may be associated with a lower risk of sleep disorders, highlighting the potential benefits of dietary modification for sleep health. Future research should further explore these associations and consider intervention studies to establish causality and optimal dietary recommendations to prevent sleep disorders.