About a third of the United States population experiences excessive daytime sleepiness (EDS), a complex sleep disorder that often occurs with metabolic diseases such as hypertension and diabetes.1,2
The association between EDS and metabolism motivated epidemiologist Tariq Faquih of Brigham and Women’s Hospital to identify metabolic biomarkers for EDS. Recently, Faquih’s team performed a large-scale bioinformatics analysis using metabolomics data obtained from thousands of individuals in the United States, United Kingdom, and Finland.3 They discovered that some lipid metabolites were negatively associated with EDS, cementing the relationship between metabolism and EDS and revealing metabolites that could potentially alleviate this condition.
First, the researchers performed untargeted metabolomics to profile the blood sera of participants of the Hispanic Community Health Study/Study of Latinos.4,5 They defined EDS based on an eight-item questionnaire called the Epworth Sleepiness Scale.
The researchers measured nearly 900 metabolites from over 6,000 individuals in the United States who self-identified as Hispanic/Latinx. After adjusting for age, sex, body mass index, and Hispanic background, the researchers identified seven metabolites—five of which were lipids—that were negatively associated with EDS. They found that these trends remained consistent when they further adjusted for diet, physical activity, smoking habits, and alcohol use.
Next, the researchers used informatics approaches such as pathway enrichment analysis to look for connections between the EDS-associated metabolites. They found that steroid hormone biosynthesis was at the heart of biological pathways linked to EDS. Faquih’s team noted that this was consistent with the known immunosuppressive effects of steroids as well as the link between inflammation and sleep disorders.6
To see if their findings would replicate in other populations, the team performed additional bioinformatics analyses using metabolomics data from the United Kingdom biobank and the Finnish Health 2000 study, which involved over 100,000 and 7,000 individuals, respectively.7,8 They found that the same classes of lipid metabolites, namely linoleic acid and sphingomyelins, were negatively associated with EDS.
The researchers’ findings demonstrate that EDS and metabolism are indeed intertwined. The team also identified metabolic pathways and compounds that could likely protect individuals against EDS. Future studies that directly investigate the roles of these metabolites in EDS may uncover novel therapeutic strategies—or perhaps more simply, dietary guidelines, considering some of the metabolites that the researchers identified can be found in food—that could help alleviate this complex sleep disorder.
- Pérez-Carbonell L, et al. Understanding and approaching excessive daytime sleepiness. Lancet. 2022;400(10357):1033-1046.
- Bock J, et al. Excessive daytime sleepiness: an emerging marker of cardiovascular risk. Heart. 2022;108(22):1761-1766.
- Faquih, et al. Steroid hormone biosynthesis and dietary related metabolites associated with excessive daytime sleepiness. Lancet eBioMedicine. 2025.
- Sorlie PD, et al. Design and implementation of the Hispanic Community Health Study/Study of Latinos. Ann Epidemiol. 2010;20(8):629-641.
- Lavange LM, et al. Sample design and cohort selection in the Hispanic Community Health Study/Study of Latinos. Ann Epidemiol. 2010;20(8):642-649.
- Li Y, et al. Objective, but not subjective, sleepiness is associated with inflammation in sleep apnea. Sleep. 2017;40(2):zsw033.
- Julkunen H, et al. Atlas of plasma NMR biomarkers for health and disease in 118,461 individuals from the UK Biobank. Nat Commun. 2023;14(1):604.
- Würtz P, et al. Quantitative serum nuclear magnetic resonance metabolomics in large-scale epidemiology: a primer on -omic technologies. Am J Epidemiol. 2017;186(9):1084-1096.
