A new study sheds light on the biological underpinnings of excessive daytime sleepiness, a persistent and inappropriate urge to fall asleep during the day — during work, at meals, even mid-conversation — that interferes with daily functioning.

The findings, published in The Lancet eMedicine, open the door to exploring how nutrition, lifestyle, and environmental exposures interact with genetic and biological processes to affect alertness.

“Recent studies identified genetic variants associated with excessive daytime sleepiness, but genetics explains only a small part of the story,” said co-corresponding author Tamar Sofer, director of Biostatistics and Bioinformatics at the Cardiovascular Institute at Beth Israel Deaconess Medical Center, and an associate professor at Harvard T.H. Chan School of Public Health and Harvard Medical School. “We wanted to identify biomarkers that can give stronger insights into the mechanisms of excessive daytime sleepiness and help explain why some people experience persistent sleepiness even when their sleep habits seem healthy.”

Investigators from Harvard-affiliated BIDMC and Brigham and Women’s Hospital turned to metabolite analysis to better understand the biology behind excessive daytime sleepiness. Metabolites are small molecules produced as the body carries out its normal functions, from synthesizing hormones, to metabolizing nutrients to clearing environmental toxins. By measuring these metabolites researchers created a profile of excessive daytime sleepiness.

The scientists analyzed blood levels of 877 metabolites in samples taken from more than 6,000 individuals in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a long-running study sponsored by the National Institutes of Health since 2006. When they cross-referenced these data with participants’ self-reported measures of sleepiness on an official survey, investigators identified seven metabolites that were significantly linked with higher levels of excessive daytime sleepiness.

The seven metabolites turned out to be involved in the production of steroids and other biological processes already implicated in excessive daytime sleepiness. When the investigators looked only at data from male participants, an additional three metabolites were identified, suggesting there might be sex-based biological differences in how excessive daytime sleepiness manifests.

The findings add weight to the idea that excessive daytime sleepiness isn’t just the result of too little sleep but can reflect physiological circumstances that might someday be diagnosed through blood tests or treated through targeted interventions.

“As we learn what’s happening biologically, we are beginning to understand how and why EDS occurs, the early signs that someone might have it, and what we can do to help patients,” said lead author Tariq Faquih, a postdoctoral research fellow in Sofer’s lab, the lab of Heming Wang at BWH, and a fellow in medicine at HMS. “These insights could eventually lead to new strategies for preventing or managing sleep disorders that include daytime sleepiness as a major symptom.”

This research was supported in part by the National Institutes of Health and the National Institute on Aging.