Exposure to so called “forever chemicals” may cause sleep disturbances and reduced quality of sleep, new research suggests.

Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic chemicals used in various consumer products and industries across the world. Since the 1950s, these chemicals have been exploited for their resistance to water, heat, grease, and stains. Because of this, they are found in most households: in nonstick pots and pans, food packaging, waterproof clothing, furniture, and so on.

In recent years, PFAS have become notorious for their longevity, taking extremely long periods of time to break down in the environment, as well as their ability to accumulate in human bodies. Although the research is still emerging, PFAS have already been linked to various adverse health conditions, including liver damage, thyroid disease, fertility issues, increased risk of cancer, and impaired immune systems.

At the same time, evidence suggests PFAS may also impact sleep. It is hypothesized that these chemicals can cross the blood-brain barrier and disrupt the levels of neurotransmitters and calcium that are important for sleep. It is also possible that PFAS’s influence on the immune system and metabolic functions could indirectly affect sleep. However, this research is far from conclusive.

“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,” Shiwen (Sherlock) Li, PhD, a postdoctoral researcher in the Department of Population and Public Health Sciences at the Keck School of Medicine, said in a statement.

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

Li and colleagues have now conducted the first ever study that examines the relationship between exposure to specific types of PFAS and sleep in young adults. The team are the first to analyze the underlying molecular mechanisms, the body’s natural defences, and a hormone that regulates sleep.

The researchers collected blood samples and self-reported information about sleep from 144 participants aged between 19 and 24, who were part of the USC Children’s Health Study. Two sets of measurements were taken several years apart, for which about half of the participants contributed to both.

In total, the research examined seven types of PFAS, but it found that four – PFDA, PFHxS, PFOA, and PFOS – were significantly associated with less sleep or poor-quality sleep.

For the first three types of PFAS, young adults with blood levels in the highest third of the group slept around 80 minutes less per night on average than those in the lowest third. High combined levels of PFAS were also linked with shorter sleep. In particular, those with high concentrations of PFOS in their blood tended to self-report problems falling asleep, staying asleep, waking up, or feeling tired during waking hours. 

All four of these chemicals are now considered “legacy PFAS”. They were widely used from the 1950s to the early 2000s, but have now been phased out and replaced by similar compounds with unknown safety implications.

“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.”

The four types of PFAS were analyzed using two large databases, The Comparative Toxicogenomics Database and Toxicology in the 21st Century. These databases compile research connecting chemicals with diseases and changes in gene expression.

The team also profiled a panel of proteins from participant’s blood samples. They found that, out of over 600 candidate genes, seven activated by PFAS seemed to affect sleep. One important factor was the immune-oriented gene, HSD11B1, which plays a valuable role in regulating sleep and wakefulness as it produces the hormone cortisol.

“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.”

Cathepsin B, which is related to memory and cognitive function, was also found to be linked to PFAS’s impact on sleep. The enzyme produced by this gene is a precursor to amyloid beta proteins, which form plaques in the brains of Alzheimer’s patients. Higher levels of this enzyme have been associated with cognitive decline in Alzheimer’s, which has its own link to sleep deficits.

Further research will now explore PFAS and sleep patterns in children as part of the National Institutes of Health’s Multi-Omics for Health and Disease Consortium. The team are also pursuing laboratory studies into the genes identified so far, as well as the association between PFOS and brain development.

The study is published in Environmental Advances.