Study uncovers biological clues about daytime sleepiness

Mass General Brigham researchers identified seven molecules in the blood linked to excessive daytime sleepiness, including factors related to diet and hormones.

Approximately one in three Americans reports experiencing overwhelming drowsiness during the day—a condition known as excessive daytime sleepiness (EDS). EDS is linked to an increased risk of serious conditions such as cardiovascular disease, obesity, and diabetes. A new study led by investigators from Mass General Brigham and Beth Israel Deaconess Medical Center identifies several molecules in the blood, known as metabolites, that are linked to EDS. Findings suggest that risk of the condition may be influenced by both internal body processes, such as hormone levels, and external factors such as diet. Results are published in Lancet eBioMedicine. 

“Our study suggests diet and genetics may play an important role in EDS,” said lead author Tariq Faquih, PhD, a  postdoctoral fellow in the Division of Sleep and Circadian Disorders at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system. “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.” 

Researchers collected data on 877 metabolites, naturally occurring molecules in the body influenced by diet and hormones. The team used blood samples from 6,000 participants in the Hispanic Community Health Study/Study of Latinos. The team also used data from a questionnaire that assesses how often a person dozes off during the day in various scenarios. The team replicated the findings in The Multi-Ethnic Study of Atherosclerosis (MESA) study and studies in the UK and Finland. 

They identified seven metabolites associated with EDS. An additional three metabolites were identified that varied by sex. The team found that omega-3 and omega-6 fatty acids, which are commonly found in foods that make up Mediterranean-like diets, were associated with lower risk of EDS. Other metabolites, such as tyramine, which is found in fermented and overripe foods, were associated with increased daytime sleepiness, particularly in men. Sex steroid metabolites, such as progesterone, were associated with sleep-related processes such as melatonin production. 

Researchers note that the results suggest potential treatment targets for EDS and that dietary changes or medications may lead to better treatment. They also note some limitations to the study, including difficulty in interpreting exact values of metabolites and using a sleep questionnaire instead of bringing participants into a sleep lab for tests. 

Future directions could include conducting a clinical trial to see if dietary changes or supplements can help reduce daytime sleepiness. Additionally, the authors identified some unknown metabolites that they plan to explore further. 

“Conducting a clinical trial would be a big next step and could help us understand if omega-3s and omega-6s obtained from diet could help lower risk of EDS,” said Faquih.   

Authorship: In addition to Faquih, MGB authors include Kaitlin S. Potts, Pavithra Nagarajan, Hanna M. Ollila, Tianyi Huang, Clary B. Clish, Susan Redline, Tamar Sofer, and Heming Wang. 

Disclosures: Redline discloses consulting relationships with Eli Lilly Inc., Jazz Pharma, and Apnimed Inc. Additionally, Redline serves as an unpaid board member for the Alliance for Sleep Apnoea Partners and has received loaned equipment for a multi-site study: oxygen concentrators from Philips Respironics and polysomnography equipment from Nox Medical. 
 
Funding: This study was funded by the National Institutes of Health (R01HL153814, R01HL161012 and 7R01HL161012) and the JLH Foundation.  

Paper cited: Faquih, T. et al “Steroid Hormone Biosynthesis and Dietary Related Metabolites Associated with Excessive Daytime Sleepiness.” Lancet eBioMedicine DOI: 10.1016/j.ebiom.2025.105881 

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