PFAS, Your Genes, and Your Health: From Mitochondrial Function to Immune Response

Key takeaways:
~ PFAS are persistent “forever chemicals” found in everyday products that are used to make products water-resistant, stain-resistant, and non-stick.
~ Research shows PFAS are associated with reproductive issues, immune suppression, thyroid dysfunction, fatty liver disease, asthma, high blood pressure, ADHD, and increased risk of certain cancers.
~At a cell level, PFAS causes oxidative stress, disrupts mitochondrial function, alters gene expression, interferes with hormones (acting as endocrine disruptors), and affects lipid metabolism.
~ Genetic variants can impact your risk of specific harms from PFAS and your ability to eliminate them from the body.

What are perfluorinated substances?

PFAS stands for per- and polyfluoroalkyl substances (PFAS), which are a general class of commonly used industrial chemicals. The carbon-fluorine (C-F) bonds cause PFAS to be water and fat-repellent as well as thermally resistant.[ref]

PFAS is incorporated into materials to make them:

• Stain and water-resistant: Used in clothing, carpeting, furniture, and automotive interiors
• Non-stick: Used in food wrappers and cookware, dental floss, and personal care products
• Resistant to fats: Used in food packaging
• Film forming: Firefighting foam that forms a film of water to smother the fire

PFAS is an umbrella term that includes PFOA (perfluorooctanoic acid), perfluorooctanesulfonic acid (PFOS), perfluorohexane sulfonate (PFHxS), and other per- and polyfluoroalkyl substances.

Well-known uses of PFOA and PFOS were Teflon non-stick coatings and  Scotchguard to make carpet and clothes stain-resistant. They were also widely used on food wrappers to make them resistant to water and oils. For the most part, PFOA and PFOS production has been phased out in the US due to the negative health effects seen in studies published in the early 2000s – 2010s.[ref]

The legacy PFOA, PFOS, and PFHxS compounds were replaced with shorter-chain or modified PFAS chemicals. Many products have changed to newer or different fluorinated substances over the past 15 years, but they are now being discovered to have many of the same negative health effects. A 2023 study showed that almost all of the replacement compounds directly affect the same biochemical pathways that were a concern with the legacy compounds.[ref]

GenX: One replacement for PFOA that you’ll often see is called GenX. About 15 years ago, in response to concerns about PFOA, DuPont introduced a PFOA-free Teflon coating, which they called GenX (not to be confused with kids in Generation X). A 2019 study from the Netherlands, where PFOA was phased out in 2012, showed that the newer GenX was ubiquitous in the environment (plants, animals, water) in areas near or downstream of a fluoropolymer plant.[ref]

In this article, I’ll refer to PFAS as a general term most of the time, but will get specific with the detoxification and excretion information. I’ll also point out whether a research study was funded by industry (when it is disclosed). Industry-funded studies aren’t necessarily always bad science, but you may want to take a closer look at how the study results are obtained.

What’s the problem with PFAS?

PFAS are usually referred to in news stories as “the forever chemical” because these substances don’t break down easily and persist in the environment. The perfluoroalkyl moiety (C_nF_2n+1−) is a carbon-fluorine bond in PFAS that makes them very chemically stable and resistant to degradation. The properties that make them very useful as chemicals – water and fat repellent, thermal resistance – also make them hang around for a long time.[ref] While PFOA and PFAS production have been mostly phased out in the US, the persistence in the environment means that in many areas, they are still found in the soil, drinking water, and game animals.[ref]

In addition to persisting in the environment, PFAS has a long half-life in the body. This is a problem because PFAS are linked to a number of potential health effects.

Let’s hit the highlights here. Click on the references to dive deeper into any of these health effects.

Reproductive issues:
A hundred or more studies show that PFOA, PFOS, and other PFAS cause problems with fertility and birth outcomes, increase the risk of PCOS, and premature ovarian failure.[ref] Animal studies that differentiate between the original PFOA and PFOS compared to the newer, shorter-chain PFAS indicate that the older PFAS types were likely more of a problem for ovarian follicle cells.[ref]

Lung function:
Epidemiological studies show increased lung problems with higher PFAS levels. A recent study explains why: PFOS and PFOA exposure significantly downregulated surfactant protein B, causing impaired lung function. Specifically, PFOA caused hypermethylation of HSD17B1 (hydroxysteroid 17-beta dehydrogenase 1), which in turn caused a decrease in surfactant protein B, which is a substance that lines the alveoli (tiny air sacs) in the lungs and prevents them from collapsing when you exhale.[ref]

Immune suppression:
A number of studies show that higher levels of PFAS correlate with a reduced immune response to vaccinations, which is a direct way to measure suppressed immune response.[ref]

Thyroid:
Higher levels of PFAS are associated with increased TSH and hypothyroidism.[ref]

Fatty liver (NAFLD, MAFLD):
Studies show that PFAS exposure increases lipids in the liver, leading to fatty liver in some individuals. A recent metabolomics study showed that PFAS downregulated the gene expression of NUDT7, which is a key for lipid regulation in the liver. This gene expression change was found at levels that humans are regularly exposed to.[ref]

Hormones and obesity:
PFAS act as an endocrine disruptor, altering hormone secretions and menstrual cycles in women.[ref] Higher levels are associated with volume of uterine fibroids.[ref]

Asthma:
Studies show that certain types of PFAS are associated with an increased risk of asthma in children. Higher PFAS levels correlate to more asthma attacks as well.[ref][ref]

Gut barrier, fat accumulation:
Another connection between higher PFAS levels, obesity, and insulin resistance is seen in the gut. A 2024 study looked at how PFAS and PFAS in combination with BPA and other common environmental toxins affected the gut microbiome. The researchers found that higher PFAS plus other environmental toxicants cause a shift in the composition of the microbiome in ways that alter secondary bile acids and promote obesity and insulin resistance.[ref]

Neurodegeneration:
PFAS accumulates in the brain, but the newer, shorter-chain versions don’t cross into the brain as effectively as the older PFOA and PFOS types.[ref]

High blood pressure:
A meta-analysis of 14 human studies showed that exposure to general PFAS or PFOS increased the risk of hypertension. [ref]

Neurodevelopmental problems:
PFAS can cross the blood-brain barrier, and animal studies show that it accumulates in the brain at higher levels. Some studies show that higher levels of PFAS are associated with increased risk of ADHD.[ref] However, not all studies agree. A meta-analysis conducted by Chinese researchers found that maternal PFAS exposure was unlikely to cause ADHD in their children.[ref]

A 2025 study looked at PFAS exposure in utero in the first and second trimester. The results showed that higher PFAS exposure doubled the risk of developmental delays at 6 and 12 months of age. However, the risk was mitigated by increased DHA consumption during breastfeeding.[ref]

Animal studies show that certain types of PFAS interact with FOLR2 (folate receptor beta) and cause social deficits.[ref] A 2024 study in Shanghai found that prenatal PFOA exposure increased autistic traits in children at the age of 4 in those with genetic risk factors. The risk was mitigated by higher folate intake.[ref]

Related article: FOLR1 and FOLR2

Mast cell activation:
Animal studies and cell studies show that PFOS, a type of PFAS, causes mast cell activation.[ref] This is likely one of several mechanisms connecting higher PFAS levels and increased asthma risk.

Carcinogenic (Cancer-causing):
Perfluorooctanoic acid (PFOA) was recently classified by the IARC as a Class 1 carcinogen. PFOS is classified as a Class 2B possible carcinogen.[ref]

How big a worry is PFAS for cancer? A large 2025 study in the US looked at levels of PFAS in public water systems compared to county-level cancer incidence. After adjusting for other covariates that also cause cancer, researchers found that higher PFAS levels are associated with an increased relative risk of thyroid cancer, bladder cancer, brain cancer, and leukemia. The researchers estimated up to ~6800 cases of cancer per year were caused by PFAS (not a large number, in the context of the million or so cases of cancer each year in the US).[ref]

Mechanisms of action: Why is PFAS harmful to health?

While PFAS exposure is linked to numerous health changes, the association studies don’t really explain why it’s a problem. So let’s take a look at the studies on what is going on biochemically from PFAS.

Here are some of the actions that go on at a cellular level:

Oxidative stress:
Recent studies show that PFAS induces oxidative stress by increasing ROS levels, leading to mitochondrial dysfunction. PFOA alters the KEAP-NFE2L2 signaling pathways (Nrf2 pathway). A study in mesenchymal stem cells showed that PFOA accelerates aging and impairs regeneration.[ref] Animal studies show that PFAS downregulates gene expression of antioxidant defense, such as superoxide dismutase, CAT, and glutathione-related detoxification genes. These experiments were done with the newer alternative PFAS substances that replaced the legacy PFOA and PFAS.[ref]

Lipid perturbations:
In mice, PFAS alters fatty acid oxidation genes, lipid transport genes, and bile acid synthesis.[ref] Studies also show that PFAS alters gene expression for PPAR and other lipid-related genes.[ref]

Changes to gene transcription, hormones:
A study using ovarian cells exposed to realistic levels of PFAS found changes to gene expression that caused altered steroid hormone synthesis, including increased FSH and progesterone.[ref]

Specifically, exposure to PFAS causes hypermethylation of 17β-HSD1, which is the enzyme that converts estrone (E1) to estradiol (E2). This is one way that PFAS exposure causes changes to reproduction for women. Hypermethylation causes decreased expression of the 17β-HSD1, which is also involved in testosterone conversion, to a lesser extent than the effect on estrogen in humans. A complete deficiency in 17β-HSD1 during development causes XY (male) individuals to have more female-appearing genitalia at birth, which can change then during puberty. (To be clear – I’m not saying that PFAS hypermethylation of 17β-HSD1 causes males to appear as females at birth. That is just an example of what severe deficiency from genetic mutations in the gene can cause, given here as a way to explain the role of the enzyme in male development.)[ref][ref]

In addition to the methylation changes to hormone-related genes, PFAS exposure has a broader effect on methylation of other genes, including genes related to cardiovascular health, cognitive function, and kidney function. [ref][ref] Changes to gene expression are a more subtle way that an environmental exposure can change susceptibility to health outcomes. Researchers have found that prenatal exposure to PFAS causes increased 5-methylcytosine methylation, which is a type of methylation that decreases gene expression more permanently than other methylation sites. These methylation changes in utero can persist throughout life.[ref]

Active Vitamin A synthesis:
Vitamin A in the active retinol form is important for gene expression during development, immune function, and overall health. Multiple animal studies show that PFAS can interfere with retinol synthesis, transport, and metabolism.[ref]

Genotoxicity:
The epidemiological studies do show that PFAS exposure likely increases the relative risk of certain types of cancers. Genotoxicity studies show that PFOS increases micronuclei formation, which is a marker of errors in cell division.[ref]

Cell proliferation:
PFAS has also been shown to cause gene expression changes that promote cell proliferation and migration.[ref]

Inflammasome (NLRP3) activation:
Studies show that PFOA and PFOS alone or in a mixture will prime and activate the NLRP3 inflammasome. It is thought that this is one factor that increases lung problems from PFAS.[ref]

Related article: NLRP3 inflammasome and genetic susceptibility

Changes to circadian rhythm: 
Animal studies also show that PFAS exposure changes gene expression for circadian rhythm genes.[ref]

Exposure routes:

There are multiple ways that we get PFAS into the body, including oral, transdermal, and inhalation.

Oral exposure routes include drinking water containing PFAS as well as eating foods or consuming drinks with PFAS. PFAS can also be inhaled (e.g. dust) or absorbed transdermally through your skin.

A 2024 study in children found that PFAS levels were higher in those who drank tea, ate hot dogs, or ate other processed meats. Another 2023 study in children found that those eating more whole foods, fiber, fruits, and vegetables had lower levels.[ref][ref] Of note, all the participants had detectable PFAS. This is generally true for most studies — pretty much everyone has a little PFAS in them.

One problem is that conventional water treatment methods don’t remove PFAS, and they get recycled into the biosludge.[ref] In the US and a few other countries, biosludge from wastewater treatment plants gets spread on fields. This then contaminates groundwater, plants, livestock, and rivers.

Drinking water limits:
In 2022, the US EPA recommended stricter standards for PFAS with limits of 0.004 ng/L for PFOA and 0.02 ng/L for PFOS. Prior to this, there was a 70 ng/L lifetime drinking water health advisory level set in 2016.[ref]

Elimination of PFAS:

OK – so we have looked at the long-term health effects of PFAS, as well as the mechanisms and pathways affected. Now let’s take a look at how the body gets rid of the forever chemical.

Half-life:
Researchers looked at blood samples from 2010 and 2016 from people living in a city in Alabama near a plant that produced PFOA, PFOS, and PFHxS (perfluorohexane sulfonic acid) with discharge into the area until 2008. Levels of PFAS were much higher than the national average in 2010, and the longitudinal nature of the study allowed researchers to estimate the half-life of PFAS in the body. Also included were prior study estimates on half-life. The results showed that PFOA had a half-life in the body of 3.5-4.1 years, while PFHxS has a half-life of 13.4-17.6 years.[ref] Other studies show a slightly shorter 2.4 years for the half-life of PFOA in the body.[ref]

Circulation in the body:
A 2020 study showed that PFAS binds to and is carried by albumin in the blood. The tested PFAS types had little affinity for binding to lipoproteins such as LDL cholesterol. Albumin is a protein produced in the liver that normally carries free fatty acids and other nutrients throughout the body in the blood. PFAS mimic fatty acids structurally and functionally.[ref]

A 2024 study went a step further and showed how electrostatic interaction and van der Waals forces are involved in how albumin complexes with PFAS.[ref]

Elimination through urine and feces:
These are the main pathways for PFAS excretion. The kidneys filter PFAS from the blood and excrete them in urine. However, the way that PFAS is bound to albumin means that most of it ends up getting reabsorbed and put back into circulation. Similarly, excretion through bile into the intestines often ends up reabsorbed back into the body.[ref]

Stored in organs:
A 2013 study in Spain investigated the concentration of PFOA and PFOS in different organs and body tissues. The results showed that the lungs had the highest concentration, followed by the kidneys. Smokers actually had less accumulation of PFAS in the lungs, compared to non-smokers. However, some amount of PFAS was found in all sampled organs.[ref]

Animal studies on the newer PFAS alternatives also show that they accumulate in the body. For example, perfluorobutane sulfonate (PFBS) bioaccumulates in the brain.[ref]

Lifehacks: Getting rid of PFAS

Is it a problem? 
A 2025 study in Canada showed that 100% of the tested population (samples taken mainly in 2020) had four types of long-chain PFAS and two types of shorter-chain PFAS. About 70% also had GenX in the blood samples. These were ordinary people who weren’t involved in industrial exposure.[ref]

Sources of PFAS in everyday life:

PFAS can be found in lots of products, including:

• Cleaning products, including some glass cleaners and granite cleaner or sealant.[ref]
• Water-resistant and stain-resistant fabrics
• Grease-resistant paper, such as food wrappers or microwave popcorn bags
• Nonstick cookware that has a coating on it
• Personal care products, including some dental floss, nail polish, shampoo, and eye makeup
• Stain-resistant carpets, upholstery, and other fabrics, which can break down and incorporate into your dust

Check with the manufacturer of your cleaning products. For example, Sprayway glass cleaner announces they are phasing out PFAS from their products by Winter 2025.[ref]

For personal care products and cookware, check out the Mamavation lab testing of products for PFAS.

A ConsumerLab.com report on dental floss showed that most of the glide-type dental flosses contain PFAS. For example, Oral-B Glide floss contains PFAS according to the manufacturer.  Alternatives are floss made from silk or bamboo that isn’t coated. [ref]

Microwave popcorn bags are usually coated with PFAS to prevent the oil from coming through the bag. If you like to microwave popcorn, an alternative is to put a quarter cup of popcorn into a brown paper lunch bag, fold the top down twice, and put it in the microwave.

If you are buying new carpet or new furniture, look for options that don’t have stain-resistant coatings.

Alternatives to non-stick coated pans include using carbon steel pans or cast iron (check your HFE gene before cooking with cast iron).

Where is PFAS in the water?

In areas around PFAS manufacturing facilities or near where firefighting foam was used, there can be high levels of PFAS in the water supply. Here’s a PFAS contamination map marking some spots in the US.

Testing for PFAS:

If you’ve had occupational exposure or live in an area with contaminated water, you could consider getting your PFAS levels tested. In the US, you can order the test yourself through Quest.

Getting rid of PFAS from your body:

The problem with PFAS is that it circulates attached to albumin, gets recycled back into the body in the kidneys, and gets reabsorbed, at least partly, when excreted in bile.

On the plus side, there have been several recent studies that show positive results from decreasing PFAS levels.

Gut microbes that detox PFAS:

The gut microbiome may be the key to removing PFAS that comes in through food and drinks. Researchers have found that certain gut microbiomes increase PFAS levels, but others can help with removal from the body. They are currently working on specific probiotics to help with detoxification. [ref][ref]

A cross-sectional, nationally representative study in the US found that either taking probiotics or regularly consuming yogurt correlates with lower levels of many types of PFAS in the body.[ref] A preprint study in animals specifically found that Lactobacillus rhamnosus, which is commonly found in yogurt and probiotics, is beneficial for reducing PFAS levels.[ref] However, studies in humans are definitely needed to determine the most effective species and strains.

Fiber and PFAS:

A study in Canadian adults looked at the effect of increasing dietary fiber. The results showed that increased dietary fiber (a supplemental fiber drink containing 1 g β-glucan, 1.9 g fiber) reduced long-chain PFAS concentrations a little bit after 4 weeks.[ref]

A 2025 study in mice looked at different types of fiber and the blood concentrations of PFAS when exposed to realistic levels in their drinking water. The researchers found that beta-glucans from oats were more effective at reducing PFAS concentrations than inulin.[ref]

Bringing this back around to the gut microbiome playing a role in detoxifying PFAS from the body, the oat beta-glucans act as a prebiotic to encourage the growth of beneficial gut microbes.

Mitigating risk during infancy with DHA:

A Sept. 2025 study involving ~2,500 mother-child pairs showed that higher PFAS levels significantly increased the risk of delays in reaching developmental milestones. Importantly, the risk was mitigated by supplemental DHA for the infants.[ref]

Clay binders:

One problem with PFAS is that when it is excreted in bile, it can be reabsorbed into the body in the colon. Edible clays can bind and help to remove PFAS in theory. Research shows that edible binding clays enhanced with choline, carnitine, caffeine, or riboflavin have advantages for increased binding of different forms of PFAS.[ref]

Reducing ROS from PFAS:

A 2025 study showed that PFAS increases ROS in cells, and that quercetin or a mitochondrial antioxidant called mito-tempo could mitigate the increased ROS.[ref] While mito-tempo is not available other than as a research chemical, the point of the study is that targeting excess mitochondrial ROS can help to reduce the negative effects of PFAS. Other options here may include mitoQ or urolithin A.

Genetic Connections with PFAS:

In addition to the genes that have been directly identified in the genotype report above, the following topics also connect to PFAS.

Mast cell and histamine connection: 
PFOA and PFAS exposure cause mast cell degranulation and histamine release. Multiple studies show that PFAS and PFOAs (Perfluorooctanoic acid) directly release histamine and cause mast cell degranulation.[ref] [ref][ref]

Related articles: Mast cell activation syndrome and Histamine intolerance genes

BH4 (Tetrahydrobiopterin) connection:
Perfluorinated substances (PFAS, PFOAs) cause oxidative stress that has research directly linked to increased nitric oxide and decreased BH4. [ref]

Related articles: BH4 synthesis and genetic interactions

Asthma connection:
Inhalation of PFOS or PFAS has been shown in animal studies and epidemiological studies to cause inflammation and trigger IL-1β in the lungs. Animal studies also show that PFOS exposure leads to impaired epithelial barrier function.[ref][ref] This is a timely topic when coupled with the research showing that most face masks (surgical, some N95, KN95) contain PFAS and that the main route of exposure is via inhalation.[ref][ref][ref][ref] A meta-analysis found PFOA exposure decreases lung function and increases the risk of asthma in children. [ref]

Related article: Asthma genes

Gilbert’s syndrome:
Gilbert’s syndrome causes increased bilirubin due to genetic impairment of UGT1A1.  PFOA and PFOS also inhibit UGT1A1, which could exacerbate problems with Gilbert’s syndrome.[ref]

Related article: Gilbert’s syndrome and UGT variants

ADHD connection:
Prenatal exposure to PFOA at a higher level was linked to a 3-fold increase in the relative risk of ADHD in children.[ref] Multiple studies show this, and a 2023 meta-analysis found that prenatal PFOA and PFOS exposure are associated with a higher risk of ADHD. [ref]

Related article: ADHD genes

Estrogen detoxification connection:
Recent research points to perfluorinated compounds, such as PFOA and PFOS, acting as endocrine disruptors by activating estrogen receptor alpha.[ref][ref]

Related article: Estrogen metabolism and detoxification

PPARG connection:
PFAS (or PFOA) exposure also interacts with the PPARG gene. In placental cells, PPAR-gamma signaling is inhibited by PFOS.[ref] In animal studies, PFOAs have been shown to upregulate PPARG.[ref]

Related article: PPARG genetic variants

Vitamin A connection:
Animal studies clearly show that PFAS exposure interacts with vitamin A and decreases conversion to the active, retinol form.[ref] If you think you could be low on vitamin A due to diet, consider supplementing with retinyl palmitate periodically. Vitamin A is a fat-soluble vitamin and will build up, so you may not need to continually supplement with it.

Related article: BCO1, beta-carotene conversion to active vitamin A

Related articles and topics:

BPA and BPS: How Your Genes Influence Bisphenol Detoxification

Microplastics Research Roundup