Research led by the Keck School of Medicine of USC has shown that levels of “forever chemicals” in the blood are linked with disruptions to a fundamental pillar of health—sleep.

In the first study to examine that relationship in young adults, participants with higher levels of four specific types of per- and polyfluoroalkyl substances (PFAS) in their blood experienced worse sleep. The scientists are the first to delve into underlying molecular mechanisms, identifying genes involved with the body’s natural defenses and a hormone that regulates sleep.

PFAS enter the body through contact with consumer items and are even ingested with food and water. They don’t break down easily and can persist in the environment for decades. The vast majority of Americans have detectable levels of PFAS in their blood.

In recent years, forever chemicals have been associated with health harms from cancer and neurological disease to deficits in hormone and immune function. The study, supported by the National Institutes of Health (NIH) and published in the journal Environmental Advances, is among a small body of research concerning PFAS and sleep.

“Because the body needs sleep every day, if PFAS might be interfering with your sleep, that may affect you more immediately than other chronic health issues,” said first and corresponding author Shiwen (Sherlock) Li, Ph.D., a postdoctoral researcher in the Department of Population and Public Health Sciences at the Keck School of Medicine.

“Long term, poor sleep has been connected to outcomes including neurological and behavioral problems, type 2 diabetes and Alzheimer’s disease.”

In addition to providing insight into the biology of PFAS’ influence on sleep, the study may add to evidence suggesting a rationale for closer regulation of forever chemicals.

“Sleep quality is an issue that affects almost everybody, so the impact of PFAS on sleep may have policy implications,” said Li, who is advised by study co-authors Lida Chatzi, MD, Ph.D., director of the USC Center for Translational Research on Environmental Health and professor of population and public health sciences and of pediatrics, and Max Aung, Ph.D., MPH, associate director of community engagement for the center, and assistant professor of population and public health sciences.

Identifying forever chemicals potentially detrimental to good sleep

The researchers collected blood samples and information about sleep from 144 participants, ages 19 to 24, who were part of the USC Children’s Health Study. Two sets of measurements were taken years apart, with about half of the participants contributing to both.

Out of seven types of PFAS examined, four were significantly associated with less sleep or worse quality of sleep—PFDA, PFHxS, PFOA and PFOS.

For the first three of those, young adults with blood levels in the highest one-third slept an average of about 80 fewer minutes nightly than those in the lowest third. High combined levels of PFAS also correlated with shorter sleep. For PFOS, high blood concentrations were significantly linked to self-reported problems falling asleep, staying asleep, waking up or feeling tired during waking hours.

All four forever chemicals—some of which are associated with cancer and neurological disorders from ADHD to Alzheimer’s disease—are considered “legacy PFAS.” Though widely used from the 1950s to the early 2000s, they have since been largely phased out in favor of similar compounds with unknown safety profiles.

“It could be a matter of cumulative exposure over time,” Li said. “What we measured in the blood is likely driven by exposure since birth, or even prenatal exposures.”

Biological clues emerge about PFAS and sleep disruptions

The team analyzed the four types of PFAS using toxicology databases that compile research connecting chemicals, diseases and changes in gene expression. Because no previous research drew together PFAS, sleep and gene expression, the team looked at the overlap between genes affected by the four forever chemicals and genes related to sleep disorders.

The investigators then profiled a panel of proteins—the products of the blueprints inscribed in genes—from participants’ blood samples. Out of 600-plus candidate genes, seven activated by PFAS seemed to influence sleep.

An important factor was an immune-oriented gene called HSD11B1. It helps produce the hormone cortisol, which plays an important role in regulating the rhythm of sleep and wakefulness.

“If the expression of the protein encoded by HSD11B1 is disrupted, that means that cortisol levels could also be disrupted,” Li said. “That, in turn, affects sleep.”

Another gene seemingly prominent in PFAS’ impact on sleep, cathepsin B, is related to cognitive function and memory. The resulting enzyme is a precursor of amyloid beta proteins, which are found in plaques in the brains of Alzheimer’s patients. High levels of the enzyme have been linked to cognitive decline in Alzheimer’s—which has its own connections to sleep deficits.

The investigators will continue to explore forever chemicals and sleep patterns in children as part of the NIH’s Multi-Omics for Health and Disease Consortium. They are also pursuing lab studies into the genes identified in the study and into associations between PFOS and brain development.