Overview

• In eBioMedicine, researchers from Mass General Brigham and Beth Israel Deaconess report seven blood metabolites associated with excessive daytime sleepiness after profiling 877 compounds in about 6,000 HCHS/SOL participants using the Epworth Sleepiness Scale.
• Five of the seven metabolites were lipids and showed negative associations with sleepiness that persisted after adjusting for lifestyle factors.
• Findings were replicated across external datasets, including the UK Biobank, the Finnish Health 2000 study, and MESA, with consistent links for classes such as linoleic acid and sphingomyelins.
• Diet-related omega-3 and omega-6 fatty acids were associated with lower risk, while tyramine correlated with higher sleepiness, particularly in men, and three additional metabolites showed sex-specific patterns.
• Pathway analyses implicated steroid hormone biosynthesis, but the authors note limitations from observational design and questionnaire-based sleepiness measures and call for clinical trials to test dietary changes or supplements.