Sleep deprivation and sleep disorders can negatively affect daily activities, mood, and health, with long-term consequences for organs like the heart, liver, and brain. Per- and poly-fluoroalkyl substances (PFAS), a group of chemicals used for their water—and stain-resistant properties, are widely present in consumer products and the human population.
They have a long half-life in the body and have been linked to sleep disturbances, as shown by three studies conducted in China. These studies found that both individual PFAS chemicals and PFAS mixtures are associated with poorer sleep quality.
Now, a new study led by the Keck School of Medicine of USC has shown that blood levels of “forever chemicals” 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.
First and corresponding author Shiwen (Sherlock) Li, PhD, a postdoctoral researcher in the Department of Population and Public Health Sciences at the Keck School of Medicine, said, “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. Long-term, poor sleep has been connected to outcomes including neurological and behavioral problems, type 2 diabetes, and Alzheimer’s disease.”
“Sleep quality is an issue that affects almost everybody, so the impact of PFAS on sleep may have policy implications.”
The study involved 144 participants, ages 19 to 24, from the USC Children’s Health Study. Blood samples and sleep data were collected in two phases, years apart, with about half of the participants contributing to both. The researchers examined seven types of PFAS and found that four—PFDA, PFHxS, PFOA, and PFOS—were significantly associated with poorer sleep quality or shorter sleep duration.
For PFDA, PFHxS, and PFOA, individuals with blood levels in the highest third slept, on average, 80 fewer minutes per night than those in the lowest third. High combined levels of PFAS were also linked to shorter sleep. PFOS, in particular, was associated with self-reported difficulties in falling asleep, staying asleep, waking up, and feeling tired during the day.
These four chemicals, known as “legacy PFAS,” have been linked to various health issues, including cancer and neurological disorders like ADHD and Alzheimer’s disease. Though they were widely used from the 1950s to the early 2000s, they have since been phased out in favor of similar compounds, whose safety profiles remain largely unknown.
Li said, “It could be a matter of cumulative exposure over time. What we measured in the blood is likely driven by exposure since birth or even prenatal exposures.”
The research team used toxicology databases to analyze the connection between the four PFAS types, sleep disturbances, and changes in gene expression. Since no previous studies had explored the overlap between PFAS, sleep, and gene expression, the researchers focused on identifying genes affected by these chemicals that might also be linked to sleep disorders.
They profiled a panel of proteins from participants’ blood samples, looking at over 600 candidate genes. Seven genes activated by PFAS appeared to influence sleep. One key gene identified was *HSD11B1*, which produces cortisol, a hormone critical for regulating the sleep-wake cycle. This finding suggests that PFAS may disrupt sleep through immune system-related changes, specifically by altering cortisol levels.
Li said, “If the expression of the protein encoded by HSD11B1 is disrupted, cortisol levels could also be disrupted. That, in turn, affects sleep.”
Another gene identified in the study, *cathepsin B*, is associated with cognitive function and memory. The enzyme produced by this gene is a precursor to amyloid beta proteins, which form plaques in the brains of Alzheimer’s patients. High levels of this enzyme have been linked to cognitive decline. Since Alzheimer’s is often associated with sleep disturbances, this suggests that PFAS exposure could also hurt brain function and sleep.
The researchers plan to continue investigating the effects of PFAS on sleep patterns in children as part of the NIH’s Multi-Omics for Health and Disease Consortium. Additionally, they are conducting lab studies to explore the role of the identified genes further and examine the potential effects of PFOS on brain development.
Journal Reference:
- Shiwen Li, Jessse A. Goodric et al. Per-and polyfluoroalkyl substances and disrupted sleep: mediating roles of proteins. Environmental Advances. DOI: 10.1016/j.envadv.2024.100585
