What it is:
In the natural world, everything is temporary. Life is born or blossoms and eventually returns to the earth where it decomposes and serves as the raw materials from which new organisms can emerge. This circle of life existed for millennia until humans developed synthetic compounds so resistant to degradation that we now refer to them as “forever chemicals.”
Perfluoroalkyl and polyfluoroalkyl substances, or “PFAS” for short, are a large group of manufactured chemicals consisting of a long chain of carbon atoms with at least one bound fluoride atom. This carbon-fluoride bond is extremely strong, making the compounds incredibly resistant. Hence, the “forever” part.
As of 2022, more than 4,700 PFAS have been intentionally developed and distributed worldwide. These compounds are found in non-stick cookware, waterproof coatings, firefighting foams, carpets, floor and ski wax, construction materials, clothing, pesticides, and personal care products, to name but a few. Once touted as a modern marvel during their proliferation in the mid-twentieth century, we have now come to understand the profound adverse health effects of PFAS. Data from the CDC’s National Health and Nutritional Examination Survey (NHANES) have shown that nearly 100% of American adults are exposed to PFAS through various routes, including drinking water, air, dust, food, and consumer products. This widespread exposure underscores the urgent need to address the issue of PFAS contamination.
The purported claims:
Thousands of unregulated compounds that may contribute to human disease are used in manufacturing.
There is a probable link between PFAS and cancer, ulcerative colitis, thyroid dysfunction, high cholesterol, pre-eclampsia, immune dysfunction, dyslipidemia, decreased fetal/infant growth, mood disorders, and changes in liver enzymes.
These compounds cannot easily be detoxified, so the best strategy is to minimize exposure through specific diet and lifestyle measures.
What the science says:
In a famous 2010 Science paper, Drs. Stephen Rappaport and Martyn Smith boldly stated that 70-90% of diseases are probably due to environmental factors rather than genetics. As more and more data emerge linking chemical pollutants with cellular dysfunction, this argument only gains traction, and for good reason. PFAS and other poorly regulated alternatives are an important part of this story.
It Started with Teflon
Public concern about PFAS began in the late 1990s when contaminated water was identified in Parkersburg, West Virginia. This came 45 years after the chemical giant DuPont first purchased these chemicals from 3M for Teflon production. Despite guidance from 3M on how to properly dispose of these compounds and DuPont’s own internal instructions, which stipulated that manufacturing waste was not to be flushed into surface waters or sewers, DuPont pumped hundreds of thousands of pounds of PFAS into the Ohio River, polluting the local water supply for decades to come.
Fast-forward to the 1990s when local farmer Wilbur Tennant reported that more than 150 of his cows had died after suffering from what appeared to be poisoning. Lesions, receding eyes, incurable diarrhea, hair loss, skin discoloration, and an inability to walk straight were just some of the signs that piqued the interest of environmental attorney Robert Bilott, who was brought to the case. This eventually led to a class action lawsuit (The Lawyer Who Became Dupont’s Worst Nightmare) and 20+ year battle against DuPont that has garnered much media attention but has not resulted in nearly enough restriction on further PFAS pollution.
How PFAS Impact Health
Contact with PFAS occurs primarily by ingesting contaminated water, seafood harvested from contaminated water, or other contaminated foods. Processed foods, or foods prepared and served in certain kinds of plastic, can also be a source of PFAS. Occupational exposure is particularly relevant for firefighters who work with PFAS-containing foams. Individuals who live near PFAS plants or incinerators are also at risk of PFAS contamination via inhalation of airborne particles. Lastly, commercial airports, military bases, wastewater treatment plants, farms, and landfill sites are all considered high-risk areas for these chemicals.
PFAS are implicated in many different kinds of disorders and diseases. The first of these is the endocrine system. Impaired cell signaling between the pituitary gland and sex organs impacts both men and women alike.
Among women, PFAS can alter the time that girls experience their first period. PFAS can also lead to irregular monthly periods thereafter and an advance in the timing of menopause. PFAS can change the number of receptors found on the ovaries for important hormones, such as follicular stimulating hormone and luteinizing hormone. These compounds can also decrease progesterone levels, which may affect fertility. Alarmingly, PFAS have also been linked to an increase in oocyte apoptosis or the death of egg cells.
Among men, PFAS can decrease the production of testosterone and have been shown to decrease sperm and semen quality and increase the risk of testicular cancer. Interestingly, there is also evidence from animal research to suggest that PFAS may synergize with a high-fat diet to activate signaling pathways, which increase the risk of tumorigenesis in prostate cancer.
One of the ways that PFAS might increase the risk of cancer is due to their structural similarity to fatty acids. In a form of “biomimicry”, these compounds can bind to certain transcription factors, such as peroxisome proliferator-activated receptors (PPARs), which subsequently alter glucose and lipid metabolism. This can lead to dyslipidemia, insulin resistance, liver disorders, and several cancers.
For a long time, cancer was thought to be primarily a genetic disease: an accumulation of mutations that lead to an inability of cells to regulate growth. This leads to cell proliferation and the eventual development of a tumor. However, there is now a shift in thinking, which reframes cancer as a metabolic disorder. Scientists have teased this apart by performing experiments in which they transfer the cell nucleus (which contains a cell’s genetic material) from a cancer cell into an otherwise healthy cell. The result? No tumor growth. And this is thought to be because of evidence indicating that dysfunctional mitochondria are what drive tumor growth in cancer instead.
As tumors grow, the surrounding cellular environment becomes hypoxic. This triggers the release of specific transcription factors which reprogram aspects of the glucose metabolic pathway. There’s also an increased demand for glutamine in cancer cells and altered expression of glutaminases in cancer, along with fatty acid reprogramming. PFAS bind to the phospholipid membranes of our cells and change PPAR signaling and downstream lipid metabolism.
Some research has identified altered liver function in animals exposed to PFAS, including upregulation of bile acids, ceramics, and triacylglycerols. This is thought to contribute to metabolic-dysfunction-associated steatotic liver disease (MASLD, formerly called non-alcoholic fatty liver disease; NAFLD). Some evidence suggests that females may be particularly vulnerable to this.
Other research has investigated the role of PFAS and their alternatives, such as GenX, 6:2 Cl-PFESA, and OBS, on cardiovascular health. Several studies have shown that mothers exposed to PFAS give birth to children with an elevated risk of cardiovascular disease. Changes in heart rate and suppressed cardiac output have been observed in early-life exposure to PFAS among chickens and zebrafish. PFAS exposure increases oxidative stress and myocardial apoptosis, along with reduced ATP production, the vital energy source used by our cells.
In guinea pig cells isolated in a petri dish, PFAS changed the activity of calcium signaling in heart cells, resulting in subsequent changes in contractility. Other research has shown that disrupted blood vessel endothelial cells combine with increased aggregation of platelets to elevate the risk of atherosclerosis.
PFAS are also associated with an increased risk of hypertension. Some studies have shown that the risk is higher in men, while others suggest that women may be at greater risk. Either way, this is mediated by a disruption to the mechanism that dilates blood vessels.
There’s some evidence to show that the blood-brain barrier can become more permeable during long-term PFAS exposure. This is particularly concerning given the innate vulnerability of the brain to chemical pollutants. Data from 12,000 adults between 2005 to 2018 showed that PFAS were associated with greater depressive symptoms. Some evidence suggests that elevated PFAS in breast milk may increase childhood neurodivergence and attention disorders. PFAS may also disrupt memory and impair the brain’s ability to make new connections (neuroplasticity). Lastly, PFAS may contribute to Alzheimer’s disease, given what we know about their role in vascular impairment and plaque aggregation - hallmarks of this disease and other dementias.
There are mixed findings on thyroid function during PFAS exposure, but good evidence in animal models shows that PFAS can alter thyroid hormones during pregnancy, which may alter fetal development. Hypothyroidism may be associated with PFAS exposure among human populations.
PFAS can disrupt the gut barrier and gut microbiome diversity. Given the importance of microbiome-derived metabolites in overall health, this may be one way that PFAS increases the risk of insulin resistance and obesity. PFAS may induce both immunosuppression and chronic inflammation, contributing to conditions such as ulcerative colitis and irritable bowel syndrome.
Synergism with Microplastics
As if this wasn’t concerning enough, it appears that PFAS can synergize with microplastics in the environment by adsorbing onto their surfaces. This makes them more potent as they bioaccumulate up the food chain. When items such as GoreTex jackets, carpets, or other items with a waterproof coating are washed, PFAS and microplastics can be shed concurrently into the waterways. This is particularly problematic for industrial runoff.
A recent study involving patients undergoing carotid endarterectomy, a surgery to remove arterial plaques, revealed a startling connection. Microplastics were found in these plaques, and patients with such plaques were at a significantly higher risk of heart attack, stroke, or death from any cause 34 months later. This underscores the potential health risks associated with micro- and nanoplastics, which can be easily ingested through water and seafood, and are equally threatening to apex marine predators like dolphins, seals, and polar bears.
Researchers have shown that PFAS aggregate most densely in the benthic (seafloor) environment rather than in the pelagic zone, affecting bottom dwellers and their predators. In a Spanish study, anchovies, sole, and sardines had the highest PFAS levels, while Spanish adults were found to be ingesting the greatest levels of PFAS from consumption of crustaceans and octopus. In a US study, the highest concentration of PFAS was found in clams and crabs, followed by cod, tuna, pollock, tilapia, salmon, and shrimp.
What Does the Law Say?
In 2015, 200 scientists signed The Madrid Statement, expressing concern about the impact of PFAS on health. However, production of PFAS continues to grow because of demand from the electronics, transportation, and materials processing industries. The excess and harm from these compounds will not cease until global leaders take action to ban PFAS.
The most effective way to curb the spread of PFAS in the environment is to adsorb them onto a suitable binding surface before they can escape into the waterways. In an ideal scenario, this responsibility should lie with the manufacturers in PFAS processing facilities. This highlights the need for collective action and stricter regulations to mitigate the environmental and health risks posed by PFAS and microplastics.
The Environmental Protection Agency (EPA) has taken steps in recent years to protect the public from the risks associated with PFAS, but the process is incremental and truly cannot keep up with the rate at which new PFAS and their alternatives are being developed and released into the environment. Bans require evidence to demonstrate deleterious health effects, and those experiments - often conducted in animal models - take time, money, and effort. That said, in April 2024, the Biden-Harris Administration issued a national drinking water standard to reduce PFAS contamination for 100 million Americans. It’s crucial to consider that PFAS contamination disproportionately affects low-income populations, as well as Black, Hispanic, and Indigenous peoples within the United States.
Safety Levels
As of 2022, guidelines from the National Academies on safety levels in human plasma or serum are as follows:
risk not expected if blood concentration is less than 2 ng/mL
there may be risks if blood concentration is between 2-20 ng/mL
there is probably risk at levels exceeding 20 ng/mL
If levels are between 2-20ng/mL, physicians are advised to test patients for dyslipidemia, thyroid function, hypertension, and breast cancer, where appropriate.
If levels exceed 20 ng/mL, patients should be screened for the above, along with signs of kidney cancer, testicular cancer, and ulcerative colitis.
Our take:
Given that PFAS are fat soluble and bioaccumulate up the food chain, it is difficult to excrete them once ingested. Instead, take measures to prevent that initial ingestion and clear your system. Test your tap water and use a water filter.
If you consume seafood, try your best to determine the source of the ingredients to rule out contamination. This is particularly challenging if you are not buying directly from the source. Eating seafood has many health benefits, so cutting it out altogether is not advised. Some evidence suggests that freshwater fish can have much higher PFAS levels than saltwater fish, particularly in certain states, including Alabama, Maryland, Michigan, New Jersey, Indiana, New York, Minnesota, Pennsylvania, Wisconsin, Massachusetts, and Connecticut, as of 2023.
When it comes to food packaging, including takeout orders, support retailers who provide sustainable, non-toxic packaging options. Importantly, beware of “greenwashing,” a form of advertising that makes false claims about how “clean” or sustainable products actually are. For example, food can be organic but still contaminated with PFAS via plastic packaging.
If you buy prepackaged ingredients or cooked meals, transfer the food into glass or ceramic before reheating. Do not microwave in coated plastic packaging. Also, replace nonstick cookware with cast iron, stainless steel, or aluminum.
There is some evidence to suggest that a high-fiber diet might help the body cope with PFAS contamination. When exposed to these forever chemicals, mice given soluble fiber (inulin) had fewer negative changes in liver gene expression and gut microbiome composition. Fiber is vital for multiple dimensions of health, so it is an easy addition to a healthy eating plan for protection against chemical contaminants.
Will this benefit me?
It’s easy to read this long list of health concerns, consider how ubiquitous PFAS are in our environment, and feel hopeless. Before settling on despair, however, bear in mind that there are many things in your environment that you can indeed control. Eating a nutritious diet, moving your body regularly, prioritizing sleep, and practicing mindfulness can all build resilience, reduce inflammation, and help you function at peak performance.
Still curious to try it? If you do, here’s what to keep an eye on:
Chemicals can only be banned when sufficient investigation has shown them to be harmful. As mentioned earlier, this takes time and money. It is virtually impossible for testing to ever keep up with the rate at which these compounds are created, nor is it practical to expect that they can be avoided entirely. Instead of fearing these compounds, be discerning of your choices and advocate for alternatives in your local community. A cleaner environment benefits everyone for generations to come.
References and additional materials
National Academies Guidance - https://pubmed.ncbi.nlm.nih.gov/35939564/
The Lawyer Who Became Dupont’s Worst Nightmare - https://www.nytimes.com/2016/01/10/magazine/the-lawyer-who-became-duponts-worst-nightmare.html
The Madrid Statement - https://ehp.niehs.nih.gov/doi/10.1289/ehp.1509934
Movie: Dark Waters (based on a true story) - Available on Netflix and Amazon Prime
Interactive Map of PFAS contamination in the US - https://www.ewg.org/interactive-maps/pfas_contamination/map
Health disparities and contamination - http://www.scientificamerican.com/article /pollution-poverty-people-color-living-industry
Consumer Reports Food Packaging - https://www.consumerreports.org/health/food-contaminants/dangerous-pfas-chemicals-are-in-your-food-packaging-a3786252074/
Consumer Reports - How to test your tap water - https://www.consumerreports.org/water-quality/how-to-test-your-tap-water-a1537953804/
PFAS and the ovary - https://pubmed.ncbi.nlm.nih.gov/32476019/
Cancer as a metabolic disorder - https://pubmed.ncbi.nlm.nih.gov/35163079/
PFAS and cancer mechanisms - https://pubmed.ncbi.nlm.nih.gov/35740585/
PFAS and thyroid function - https://pubmed.ncbi.nlm.nih.gov/33542707/
PFAS and cardiovascular disease - https://pubmed.ncbi.nlm.nih.gov/36947184/
PFAS alternatives and circadian rhythms - https://pubmed.ncbi.nlm.nih.gov/36860044/
PFAS and NAFLD - https://pubmed.ncbi.nlm.nih.gov/34627976/
PFAS and mental health - https://pubmed.ncbi.nlm.nih.gov/37775007/
PFAS and neurological health - https://pubmed.ncbi.nlm.nih.gov/31962063/
Innovating beyond PFAS - https://pubmed.ncbi.nlm.nih.gov/37471534/
Plastic in arteries - https://pubmed.ncbi.nlm.nih.gov/38551597/
Microplastics and the marine environment - https://ui.adsabs.harvard.edu/abs/2022FrESE..16..136D/abstract
PFAS and the marine environment - https://pubmed.ncbi.nlm.nih.gov/37591052/
EPA Drinking Water Standard Press Release - https://www.epa.gov/newsreleases/biden-harris-administration-finalizes-first-ever-national-drinking-water-standard
PFAS in Spanish seafood - https://pubmed.ncbi.nlm.nih.gov/37652217/
PFAS in US seafood - https://pubmed.ncbi.nlm.nih.gov/36251396/
PFAS and inflammation - https://pubmed.ncbi.nlm.nih.gov/36592815/
PFAS and ulcerative colitis - https://pubmed.ncbi.nlm.nih.gov/29777922/
PFAS and gut microbiome in turtles - https://pubmed.ncbi.nlm.nih.gov/36005619/
PFAS and gut microbiome in humans - https://pubmed.ncbi.nlm.nih.gov/38522229/
Is fiber protective? https://pubmed.ncbi.nlm.nih.gov/36331819/
Freshwater fish and PFAS - https://www.scientificamerican.com/article/pfas-forever-chemicals-found-in-freshwater-fish-yet-most-states-dont-warn-residents/
FDA testing of PFAS in seafood - https://www.fda.gov/food/cfsan-constituent-updates/fda-shares-results-pfas-testing-seafood
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