Combined exposure to alcohol and ‘forever chemicals’ increases liver damage

Have you ever wondered why some people who drink alcohol develop serious liver problems while others don’t? A study by University of Louisville researchers published in Toxicological Sciences suggests that the answer might be hidden in everyday sources such as drinking water, food packaging or even non-stick cookware.

Scientists at UofL, along with colleagues from Boston University and the University of Massachusetts Lowell, have identified perfluorooctane sulfonate (PFOS) as a potential environmental factor that worsens alcohol-associated liver disease.

PFOS is a man-made chemical belonging to the group known as per- and polyfluoroalkyl substances (PFAS), often referred to as “forever chemicals” because they do not readily break down in the environment or the human body. These substances have been used for decades in products such as non-stick cookware, water-resistant clothing, fast-food packaging, stain-resistant carpets and upholstery, and firefighting foams. Their extensive use has led to widespread contamination in the environment.

Recent data from the National Health and Nutrition Examination Survey show that PFAS can be detected in approximately 95% of Americans, sparking increasing concern about their long-term health effects.

At the same time, alcohol consumption remains a significant global health issue. According to the World Health Organization, alcohol contributes to nearly 3 million deaths worldwide each year, and its consumption continues to rise globally. In the U.S. alone, excessive alcohol use is responsible for approximately 95,000 deaths annually, making it one of the leading causes of preventable death and a major contributor to liver disease.

“Given the increasing prevalence of alcohol consumption and the widespread presence of PFAS in the environment, many individuals who drink alcohol may be inevitably exposed to these persistent pollutants. This makes it critically important to study how combined exposures to alcohol and environmental chemicals like PFOS might influence liver health,” said Matthew Cave, UofL professor of medicine and publication co-author.

Although it is well known that both alcohol and PFOS cause liver damage individually, little has been understood about their combined effects until now. Recent studies have shown that only about 35% of heavy drinkers develop severe forms of liver disease, indicating that additional factors such as genetics, sex, microbiome and environmental exposures may contribute to individual susceptibility.

“This work helps explain why two people with similar alcohol consumption may experience very different liver outcomes,” said Frederick Ekuban, assistant professor of medicine at UofL and first author of the study. “Environmental exposures like PFOS may be the missing link.”

Using animal models, the researchers simulated real-world exposures to both alcohol and PFOS. The study showed that co-exposure to alcohol and PFOS significantly increased fat accumulation and markers of liver damage, as well as clear signs of disrupted metabolism and activation of genes and pathways predicted to be associated with oxidative stress and cancer development.

In short, the study demonstrates that PFOS exposure can significantly worsen liver damage when combined with alcohol consumption. While this research used high levels of alcohol to understand the underlying mechanisms, the findings reveal important biological pathways that warrant further investigation across different drinking patterns.

The research team also found that PFOS interferes with the liver’s ability to manage fats, disrupts its natural protective and repair systems and activates pathways that promote liver injury.

“While the liver typically has a remarkable capacity to recover from alcohol-induced stress, PFOS appears to push that resilience beyond its limits, resulting in compounded and more severe damage,” said Jennifer Schlezinger, professor of environmental health at Boston University and co-author of the publication.

Perhaps most concerning, the team discovered that 60% of all PFOS exposure ended up concentrated in the liver, exactly where alcohol damage occurs.

Ongoing research at UofL is examining how other PFAS compounds may interact with alcohol, whether males and females respond differently to these exposures and what the long-term consequences of combined exposures might be. The team is also exploring whether targeted therapies can be developed to prevent or mitigate this type of liver damage.

Although more studies are needed, people can take practical steps now to limit their exposure to PFAS. These include:

• Choose stainless steel or cast-iron cookware instead of nonstick pans
• Use water filters, especially in areas near industrial zones
• Avoid stain-resistant treatments on furniture and carpets
• Reduce consumption of packaged fast foods and microwave popcorn.
• Select household products with PFAS-free labels

Given that liver disease affects millions of Americans and is becoming more prevalent worldwide, the findings of this research support growing calls for stronger regulation and oversight of persistent chemical contaminants. By better understanding the hidden interactions between environmental toxicants and lifestyle behaviors, scientists and policymakers may be better equipped to prevent and treat liver disease.

Have you ever wondered why some people who drink alcohol develop serious liver problems while others don’t? A study by University of Louisville researchers published in Toxicological Sciences suggests that the answer might be hidden in everyday sources such as drinking water, food packaging or even non-stick cookware.

Scientists at UofL, along with colleagues from Boston University and the University of Massachusetts Lowell, have identified perfluorooctane sulfonate (PFOS) as a potential environmental factor that worsens alcohol-associated liver disease.

PFOS is a man-made chemical belonging to the group known as per- and polyfluoroalkyl substances (PFAS), often referred to as “forever chemicals” because they do not readily break down in the environment or the human body. These substances have been used for decades in products such as non-stick cookware, water-resistant clothing, fast-food packaging, stain-resistant carpets and upholstery, and firefighting foams. Their extensive use has led to widespread contamination in the environment.

Recent data from the National Health and Nutrition Examination Survey show that PFAS can be detected in approximately 95% of Americans, sparking increasing concern about their long-term health effects.

At the same time, alcohol consumption remains a significant global health issue. According to the World Health Organization, alcohol contributes to nearly 3 million deaths worldwide each year, and its consumption continues to rise globally. In the U.S. alone, excessive alcohol use is responsible for approximately 95,000 deaths annually, making it one of the leading causes of preventable death and a major contributor to liver disease.

“Given the increasing prevalence of alcohol consumption and the widespread presence of PFAS in the environment, many individuals who drink alcohol may be inevitably exposed to these persistent pollutants. This makes it critically important to study how combined exposures to alcohol and environmental chemicals like PFOS might influence liver health,” said Matthew Cave, UofL professor of medicine and publication co-author.

Although it is well known that both alcohol and PFOS cause liver damage individually, little has been understood about their combined effects until now. Recent studies have shown that only about 35% of heavy drinkers develop severe forms of liver disease, indicating that additional factors such as genetics, sex, microbiome and environmental exposures may contribute to individual susceptibility.

“This work helps explain why two people with similar alcohol consumption may experience very different liver outcomes,” said Frederick Ekuban, assistant professor of medicine at UofL and first author of the study. “Environmental exposures like PFOS may be the missing link.”

Using animal models, the researchers simulated real-world exposures to both alcohol and PFOS. The study showed that co-exposure to alcohol and PFOS significantly increased fat accumulation and markers of liver damage, as well as clear signs of disrupted metabolism and activation of genes and pathways predicted to be associated with oxidative stress and cancer development.

In short, the study demonstrates that PFOS exposure can significantly worsen liver damage when combined with alcohol consumption. While this research used high levels of alcohol to understand the underlying mechanisms, the findings reveal important biological pathways that warrant further investigation across different drinking patterns.

The research team also found that PFOS interferes with the liver’s ability to manage fats, disrupts its natural protective and repair systems and activates pathways that promote liver injury.

“While the liver typically has a remarkable capacity to recover from alcohol-induced stress, PFOS appears to push that resilience beyond its limits, resulting in compounded and more severe damage,” said Jennifer Schlezinger, professor of environmental health at Boston University and co-author of the publication.

Perhaps most concerning, the team discovered that 60% of all PFOS exposure ended up concentrated in the liver, exactly where alcohol damage occurs.

Ongoing research at UofL is examining how other PFAS compounds may interact with alcohol, whether males and females respond differently to these exposures and what the long-term consequences of combined exposures might be. The team is also exploring whether targeted therapies can be developed to prevent or mitigate this type of liver damage.

Although more studies are needed, people can take practical steps now to limit their exposure to PFAS. These include:

• Choose stainless steel or cast-iron cookware instead of nonstick pans
• Use water filters, especially in areas near industrial zones
• Avoid stain-resistant treatments on furniture and carpets
• Reduce consumption of packaged fast foods and microwave popcorn.
• Select household products with PFAS-free labels

Given that liver disease affects millions of Americans and is becoming more prevalent worldwide, the findings of this research support growing calls for stronger regulation and oversight of persistent chemical contaminants. By better understanding the hidden interactions between environmental toxicants and lifestyle behaviors, scientists and policymakers may be better equipped to prevent and treat liver disease.