How a "Forever Chemical" PFOA Confounded Scientists
For the communities near Parkersburg, West Virginia, the tap water held a secret ingredient with a lasting effect on their health.
Imagine a chemical so persistent that it earns the name "forever chemical," one that doesn't break down in the environment or the human body. This is the reality of perfluorooctanoic acid (PFOA), a man-made substance used for decades in manufacturing non-stick cookware, waterproof fabrics, and fire-fighting foams. When a class-action lawsuit in West Virginia forced a scientific investigation into its health effects, one finding emerged with particular strength: a "probable link" between PFOA exposure and high cholesterol. This article explores the scientific journey to unravel this connection, a discovery that challenged long-held assumptions and revealed a complex threat to public health.
Perfluorooctanoic acid (C8HF15O2) is a synthetic fluorinated compound with a carbon-fluorine bond that is one of the strongest in organic chemistry, making it extremely resistant to degradation.
Non-stick coatings, waterproof fabrics, fire-fighting foam
Does not break down in environment or human body
Found in blood of nearly all Americans tested
The story begins in Parkersburg, West Virginia, where a DuPont plant had released PFOA (also known as C8) into the environment for decades, contaminating the drinking water of nearby communities1 5 . In 2005, as part of a major class-action lawsuit settlement, a landmark scientific effort was launched: The C8 Science Panel.
This panel, composed of independent epidemiologists, was tasked with determining whether there was a "probable link" between PFOA exposure and any human diseases within the affected community1 . From 2005 to 2013, the panel conducted extensive research, enrolling over 69,000 participants1 . In 2012, they published their conclusions, identifying six diseases for which a "probable link" existed. Among them, alongside thyroid disease and kidney cancer, was diagnosed high cholesterol1 5 .
The C8 Science Panel enrolled over 69,000 participants from affected communities, making it one of the largest epidemiological studies on PFOA exposure.
The panel identified six diseases with a "probable link" to PFOA exposure, including high cholesterol, thyroid disease, and kidney cancer.
Class-action lawsuit filed on behalf of Parkersburg, WV residents
Settlement establishes the C8 Science Panel to investigate health effects
Panel collects health data from 69,000+ participants
Panel concludes probable link between PFOA and six diseases, including high cholesterol
Final reports published, completing the panel's work
For years, the PFOA-cholesterol connection was plagued by a baffling contradiction. Human studies consistently showed a hypercholesterolemic effect (elevated cholesterol), while studies in laboratory rodents consistently showed the opposite—a hypocholesterolemic effect (reduced cholesterol)2 . This discrepancy made it difficult to study the underlying mechanisms and cast doubt on the human findings.
A crucial 2015 mouse experiment sought to resolve this paradox by investigating a critical variable: diet2 .
The researchers designed an experiment to test the hypothesis that a standard rodent diet, which is low in fat and cholesterol, was masking PFOA's true effect.
Male and female mice from two different genetic strains (C57BL/6 and BALB/c) were used to see if the effects were universal or strain-specific2 .
One group was fed a standard rodent chow. The test groups were fed a high-fat diet containing 0.25% cholesterol and 32% fat, designed to more closely mimic a typical human diet2 .
The experimental group's high-fat diet was laced with 3.5 mg of PFOA per kg of diet. This was calculated to deliver a daily dose of approximately 0.5 mg of PFOA per kg of body weight2 .
The results were striking. When fed the high-fat, high-cholesterol diet, the mice—particularly female C57BL/6 mice—developed marked hypercholesterolemia after PFOA exposure2 . This was the complete opposite of what was seen in rodents on a standard diet.
The experiment revealed that PFOA ingestion led to:
| Measurement | Standard Diet + PFOA | High-Fat Diet + PFOA | Interpretation |
|---|---|---|---|
| Plasma Cholesterol | Decreased (Hypocholesterolemia) | Increased (Hypercholesterolemia) | Dietary fat and cholesterol are key to triggering the human-like response. |
| Liver Mass | Increased | Increased | PFOA causes enlarged livers regardless of diet. |
| Gene Expression | Altered PPARα pathways | Altered sterol/bile acid genes | The metabolic pathway triggered by PFOA depends on dietary context. |
With a reliable animal model established, scientists could dig deeper into the "how." While the exact mechanisms are still being uncovered, research points to PFOA's disruptive effect on the liver, the body's primary cholesterol-processing center.
Recent and sophisticated human studies have added another layer of clarity. A 2023 study used proton nuclear magnetic resonance (¹H-NMR) spectroscopy to perform a detailed analysis of lipid profiles in 50-year-old men and women. The researchers found that PFOA, PFOS, and PFDA were specifically and consistently associated with increased cholesterol concentrations in all low-density lipoprotein (LDL) subfractions (often called "bad cholesterol") and small high-density lipoprotein (HDL) particles3 . This suggests PFOA's influence is nuanced, altering the very quality and type of cholesterol particles in your bloodstream.
| Lipoprotein Fraction | Particle Size (nm) | Association with PFOA/PFOS |
|---|---|---|
| Intermediate-Density Lipoprotein (IDL) | ~28.6 nm | Positive Association |
| LDL - Large | ~25.5 nm | Positive Association |
| LDL - Medium | ~23.0 nm | Positive Association |
| LDL - Small | ~18.7 nm | Positive Association |
| HDL - Small | ~8.7 nm | Positive Association |
| Most Triglyceride subfractions | Various | Weak to No Association |
Laboratory studies show that PFOA and PFOS activate the PPARγ (Peroxisome Proliferator-Activated Receptor Gamma) pathway, a key regulator of lipid metabolism and inflammation7 .
PFOA and PFOS directly enhance cholesterol accumulation in human-derived macrophages, which can turn into "foam cells" and drive atherosclerosis7 .
The finding of a "probable link" between PFOA and high cholesterol by the C8 Science Panel was more than a legal determination—it was a catalyst for scientific discovery. It prompted research that resolved fundamental contradictions, advanced our understanding of how persistent chemicals can disrupt our metabolism, and provided tangible evidence for public health action.
Although PFOA production has been largely phased out in the US, its legacy as a "forever chemical" means it remains in the environment and in us5 . The research into its effects on cholesterol has underscored the vulnerability of our metabolic health to industrial chemicals and has set a precedent for how to investigate the thousands of other PFAS compounds that still surround us. The journey from contaminated water in West Virginia to a clarified mechanism in the laboratory stands as a powerful example of science in service of public health.
PFOA remains in water systems and the environment for decades, continuing to pose health risks long after its use has ended.
Findings from the C8 Science Panel contributed to regulatory actions and phase-outs of PFOA in the United States and globally.
The investigation established a framework for studying other PFAS compounds and their potential health effects.
This article was based on scientific studies and reviews published in peer-reviewed journals.