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PFAS “Forever Chemicals” Linked to Sleep Disturbances

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Exposure to certain per- and poly-fluoroalkyl substances (PFAS) chemicals is linked to sleep disturbances, according to researchers from the Keck School of Medicine of the University of Southern California. Published in Environmental Advances, their study identified four types of PFAS significantly associated with reduced sleep quality.

Sleep disorders are linked to various health conditions

PFAS are a group of man-made chemicals used in various industrial and consumer products for their water- and stain-resistant properties. They are commonly found in items like non-stick cookware, waterproof clothing, food packaging and firefighting foams. PFAS, often referred to as "forever chemicals", break down very slowly in the environment and can accumulate in human bodies over time.


Exposure to PFAS has been linked to health issues such as hormonal disruption, weakened immune systems and increased risk of certain cancers. Emerging research has also associated PFAS exposure with increased sleep disturbances, although studies using data from the US National Health and Nutrition Examination Surveys showed mixed results.

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Sleep disorders encompass a range of conditions that impact normal sleep patterns. The most common sleep disorder, insomnia, affects around one-third of adults, potentially impacting their physical, mental and emotional wellbeing. Long-term sleep disturbances are associated with negative impacts on various parts of the body, including the heart, liver and brain.


“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,” said first author Dr. Shiwen Li, a postdoctoral researcher in the department of population and public health sciences at the Keck School of Medicine.

 

Understanding how PFAS exposure may potentially impact sleep health is vital for developing strategies to reduce risks and protect overall public health.

Certain PFAS types are linked with sleep disturbances

Blood samples were collected from 144 participants who were part of the USC Children’s Health Study, along with data on their sleep patterns using self-reported forms. Two sets of measurements were taken several years apart, with around half of the participants contributing to both. Plasma PFAS levels were calculated using liquid-chromatography high-resolution mass spectrometry.


To explore how PFAS chemicals might affect sleep, researchers used two large databases, The Comparative Toxicogenomics Database and Toxicology in the 21st Century, to look for possible genetic connections. They then ran a mediation analysis using protein data to confirm the results from the earlier computer analysis.


Out of the seven types of PFAS measured, four were significantly associated with reduced sleep or a worse quality of sleep: PFDA, PFHxS, PFOA and PFOS.

 

For the first 3 types of PFAS, participants with blood levels in the highest third of the group slept around 80 minutes less per night on average compared to those in the lowest third. High combined PFAS levels were also associated with shorter sleep duration. Elevated PFOS concentrations were linked to self-reported difficulties falling asleep, staying asleep, waking frequently or feeling tired during the day.


“What we measured in the blood is likely driven by exposure since birth, or even prenatal exposures,” said Li.


All four "forever chemicals" are classified as legacy PFAS. These have been largely phased out in favor of similar compounds with unknown safety profiles, although they were widely used from the 1950s to the early 2000s.

The biological mechanism behind PFAS and sleep disruptions

Li and the team identified over 600 genes that were affected by PFAS and were also implicated in sleep disorders. Using the participant's blood samples, they then profiled a panel of proteins to confirm which genes may contribute to the pathogenesis of PFAS-related sleep concerns.

 

Of the 600 identified genes, 7 were found to be activated by PFAS. One important factor that appeared to play a critical role was an immune-orientated gene called HSD11B1.This gene helps to produce the hormone cortisol, important for 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. That, in turn, affects sleep,” said Li.

 

Cathepsin B was also highlighted as playing a role in PFAS's effects on sleep. The enzyme produced by this gene is a precursor to amyloid beta proteins, known to form plaques in the brains of Alzheimer’s patients. Elevated levels of this enzyme have been linked to cognitive decline in Alzheimer’s disease, which is similarly connected to sleep disturbances.

Impacting closer regulations of “forever chemicals”

Sleep is crucial for brain health and understanding factors that may affect it is vital for reducing the risk of several health concerns. These results may contribute to the closer regulation of these “forever chemicals” in the environment.


“Sleep quality is an issue that affects almost everybody, so the impact of PFAS on sleep may have policy implications,” said Li.

 

Future large-scale epidemiologic studies are needed to confirm the team's results. Li and colleagues are planning to pursue further investigations into the genes identified in the study and the associations between PFOS and brain development.


Reference: Li S, Goodrich JA, Chen JC, et al. Per-and polyfluoroalkyl substances and disrupted sleep: mediating roles of proteins. Environ Adv. 2024;17:100585. doi: 10.1016/j.envadv.2024.100585


This article is a rework of a press release issued by the Keck School of Medicine of USC. Material has been edited for length and content.