Summary: A new study has identified seven blood metabolites linked to excessive daytime sleepiness (EDS), a common condition affecting roughly one in three Americans. The research points to both dietary and hormonal influences: certain omega-3 and omega-6 fatty acids were associated with lower risk of EDS, while compounds such as tyramine and some hormone-related metabolites were linked to higher risk.
Hormonal metabolites that affect melatonin production and other sleep-related pathways were also implicated. The investigators suggest that targeted dietary changes, supplements, or medications might become promising strategies to treat or reduce excessive daytime sleepiness.
Key Facts
- Seven Metabolites Identified: Researchers found seven primary blood metabolites associated with EDS, with three additional sex-specific metabolites identified in men.
- Protective Role: Long-chain omega-3 and omega-6 fatty acids—nutrients common in Mediterranean-style diets—were associated with reduced daytime sleepiness.
- Increased Risk: Tyramine, a compound found in fermented or overripe foods, and certain steroid hormone metabolites were linked to greater EDS risk, particularly among men.
Source: Mass General
Overview
Excessive daytime sleepiness (EDS) is a widespread and disruptive condition, reported by about one-third of U.S. adults. EDS is associated with higher risks for cardiovascular disease, obesity, and diabetes, and it often co-occurs with inadequate sleep and other sleep disorders. To better understand biological contributors to EDS, researchers from Mass General Brigham and Beth Israel Deaconess Medical Center analyzed blood metabolites—small molecules shaped by both diet and internal physiology—for links to daytime sleepiness.
Their results, published in Lancet eBioMedicine, indicate that both endogenous processes (including steroid hormone biosynthesis) and dietary components influence risk of EDS. Lead author Tariq Faquih, PhD, a postdoctoral fellow in the Division of Sleep and Circadian Disorders at Brigham and Women’s Hospital, emphasizes that aligning metabolic insights with clinical tools could improve detection and treatment of EDS.
The study assessed 877 metabolites measured in blood samples from 6,071 participants enrolled in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS), a questionnaire that measures how likely a person is to doze off in everyday situations. The researchers adjusted their analyses for demographic, lifestyle, and physiological factors and performed both overall and sex-specific analyses.
Findings were replicated in independent cohorts, including The Multi-Ethnic Study of Atherosclerosis (MESA) and other studies from the UK and Finland, strengthening the evidence that specific metabolites are consistently associated with EDS across populations.
In the primary analysis, seven metabolites clustered within steroid hormones, sphingomyelin species, and long-chain fatty acid sub-pathways were associated with ESS scores. An additional three metabolites emerged in male-specific analyses. Notably, omega-3 and omega-6 fatty acids—commonly consumed in diets rich in fish, nuts, and olive oil—were associated with lower EDS risk, while tyramine and certain steroid hormone metabolites showed positive associations with greater daytime sleepiness.
The involvement of steroid hormone pathways suggests links between sex steroids, melatonin regulation, and sleepiness. Some metabolites likely reflect dietary intake, indicating that nutrition may play a modifiable role in EDS risk. The study also identified several unknown metabolites that warrant further investigation.
Researchers acknowledge limitations: metabolite measurements vary by method and interpretation, and the study relied on a validated sleep questionnaire rather than laboratory-based sleep studies for assessing EDS. Despite these constraints, the metabolomic patterns identified highlight potential biological pathways and therapeutic targets for future research.
Future steps include clinical trials to test whether dietary interventions, omega-3/omega-6 supplementation, or pharmacologic approaches can reduce excessive daytime sleepiness. Such trials would help determine whether the metabolite associations represent causal pathways suitable for intervention.
“A randomized clinical trial would be an important next step to determine if increasing omega-3 and omega-6 intake through diet or supplements could lower the risk or severity of EDS,” said Faquih.
Authorship: In addition to Tariq Faquih, Mass General Brigham authors include Kaitlin S. Potts, Pavithra Nagarajan, Hanna M. Ollila, Tianyi Huang, Clary B. Clish, Susan Redline, Tamar Sofer, and Heming Wang.
Disclosures: Susan Redline reports consulting relationships with Eli Lilly Inc., Jazz Pharma, and Apnimed Inc., and serves as an unpaid board member for the Alliance for Sleep Apnoea Partners. Redline has also received loaned equipment for a multi-site study: oxygen concentrators from Philips Respironics and polysomnography equipment from Nox Medical.
Funding: This research was supported by the National Institutes of Health (R01HL153814, R01HL161012 and 7R01HL161012) and the JLH Foundation.
About this metabolism and sleep research news
Author: Cassandra Falone
Source: Mass General
Contact: Cassandra Falone – Mass General
Image: The image is credited to Neuroscience News
Original Research: Open access. “Steroid Hormone Biosynthesis and Dietary Related Metabolites Associated with Excessive Daytime Sleepiness” by Tariq Faquih et al., eBioMedicine (DOI: 10.1016/j.ebiom.2025.105881)
Abstract
Steroid Hormone Biosynthesis and Dietary Related Metabolites Associated with Excessive Daytime Sleepiness
Background
Excessive daytime sleepiness (EDS) affects roughly 33% of the U.S. population. While EDS often coincides with insufficient sleep and circadian disorders, genetic and metabolic pathways unique to EDS have emerged from recent research. This study aims to clarify the metabolic profile of EDS using large-scale metabolomics at both single-metabolite and pathway levels.
Methods
Metabolomics data for 877 metabolites were analyzed in 6,071 participants from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). EDS was measured with the Epworth Sleepiness Scale (ESS). Linear regression models assessed associations between each metabolite and continuous ESS scores, adjusting for demographic, lifestyle, and physiological confounders, including analyses stratified by sex. Gaussian graphical modeling, pathway, and enrichment analyses were performed to construct an integrated metabolomic network related to EDS.
Findings
Seven metabolites from steroid, sphingomyelin, and long-chain fatty acid sub-pathways were associated with EDS in the main analysis, with three additional metabolites identified in men. Several identified metabolites relate to diet (including omega fatty acids) and steroid hormone biosynthesis.
Interpretation
The metabolomic profile of EDS appears to include both endogenous and diet-derived metabolites, especially within steroid hormone biosynthesis pathways, with some sex-specific differences. These metabolic pathways may offer insight into the biological causes or consequences of EDS and point to potential targets for future prevention or treatment strategies.
Funding
Funding details and acknowledgements for this work and participating studies are provided in the original publication.