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Since the Industrial Revolution, increasing levels of chemical pollution have been altering the Earth’s system-processes, on which human life depends, and degrading the vitality of human health.¹ The high rate of change in the production and variety of synthetic chemicals over the last four decades alone outpaces many other drivers of environmental change.¹ Some scientists warn that chemical pollution is one of the planetary boundaries that ought not to be crossed to safeguard humanity.^1,2 In August 2022, the US Environmental Protection Agency (EPA) issued a new advisory warning that even small amounts of two of the most widely used per-and polyfluoroalkyl substances (PFAS) found in drinking water pose health risks and labeled them as hazardous.³ Human biomonitoring studies report widespread exposure to PFAS, with detection rates of over 98% in the blood of US adults.⁴

Recently termed “forever chemicals,” PFAS are a class of over 4,700 heterogenous manmade compounds that persist in the environment.⁵ Humans have exploited PFAS for close to 60 years due to their chemical stability and resistance to thermal degradation, as well as their wide applicability in the industrial sector and in consumer products.⁵ Increasing evidence suggests that these compounds represent a serious concern for human health due to their ubiquitous distribution, extreme persistence in the environment, and potential to bioaccumulate and biomagnify in biota through contamination of food chains.⁵ Some PFAS have been reported in the blood, milk, urine, tissues, and organs of different human populations living in developed countries⁵ and have been associated with a number of adverse health effects, including liver disease and cancer, thyroid disease, diabetes, adverse reproductive outcomes, and more.^4-14 What do the most recent scientific studies tell us about the toxic health effects of PFAS? How can practitioners assess for PFAS exposure and educate patients about the importance of toxicity testing and behavior change for reducing encounters?

Transmission & Human Health Effects of PFAS

Major sources of PFAS pollution are derived from industrial and municipal treatment plants, which release these chemicals into the atmosphere and water systems.⁵ In the European Union alone, recent reports estimate that over 100,000 potential sites emit PFAS in some quantity.⁵ When released, these pervasive pollutants contaminate the natural world by entering the atmosphere, the water (ground water, fresh water, marine water, and drinking water), and the soil, contaminating food sources.⁵ A recent study found that even rainwater in Europe and the US has been tainted with PFAS at dangerously high levels.¹⁴

In addition to being released into water and the atmosphere, PFAS are commonly used in pesticide formulation, firefighting foams, cosmetics, textiles coating, oil production, medical products, food processing, building and construction, paper and packaging, cables and wiring, and electronics and semiconductors.⁵ However, dietary intake and the consumption of drinking water represent major pathways for exposure to PFAS in the general population. Specifically, perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are two of the PFAS species that, among others, contribute most to human exposure. It is important to note that the potential of PFAS to negatively impact health is multifactorial and includes considerations around conditions of exposure (dose/concentration, duration, route of exposure, etc.) and characteristics associated with the exposed patient (age, sex, ethnicity, health status, and genetic predisposition).⁵ That said, the human health effects of PFAS include, but are not limited to:

• Liver Disease & Cancer: Population and longitudinal studies demonstrate significant associations of long-chain PFAS (>6 fluorinated carbons) exposure to elevated liver enzymes, such as alanine aminotransferase in adults and adolescents.^6,9 These associations may be more evident in obese patients.⁶

A 2022 first-of-its-kind nested case-control study published in the Journal of Hepatology found that high PFOS levels (one form of PFAS) were associated with a 4.5-fold increased risk of non-viral hepatocellular carcinoma (HCC) in humans.⁴ HCC is the most common form of liver cancer, accounting for 85% of cases, and is one of the most lethal cancers, with a five-year survival rate of less than 20%.⁴

Recent evidence also suggests that PFAS are associated with increased risk of non-alcoholic fatty liver disease (NAFLD), diagnosed using liver MRI or liver biopsy, in both children and adults.^4,9 In a clinic-based study, mostly obese (85%) children, 7 to 19?years old with biopsy-proven NAFLD, had more advanced disease associated with PFAS exposure, as well as associations with lipid and amino acid pathways linked to NAFLD pathogenesis.⁶

• Thyroid Disease: Studies suggest that PFAS may alter thyroid hormones and potentially contribute to thyroid disease and dysfunction.⁷ A 2018 meta-analysis suggests that PFAS are negatively associated with total thyroxine (T4) in adults, and their effect can be different depending on the PFAS concentration.⁷ Pregnancy can affect the influence of PFAS on thyroid function. Maternal PFAS can be transferred to fetuses, and the PFAS concentration in cord sera is positively correlated with PFAS in maternal serum.⁸

• Diabetes: Studies suggest that PFAS exposure may increase the risk of incident type 2 diabetes, and that PFOAs (a type of PFAS), specifically, may exert non-monotonic dose-response effect on type 2 diabetes risk.^10,14 A 2023 systematic review and meta-analysis of 22 studies suggests that exposure to PFAS may increase type 2 diabetes risk among the general population.¹⁴ Statistically significant PFAS-T2DM associations were consistent in cohort studies, while the association were almost non-significant in case-control and cross-sectional studies. As well, the direction and magnitude of these associations varied across individual PFAS. Dose-response meta-analysis showed a “parabolic-shaped” association between perfluorooctanoate acid (PFOA) exposure and T2DM risk.¹⁴

An interesting prospective cohort study in Diabetologia (the journal of the European Association for the Study of Diabetes) suggests that exposure to PFAS may be associated with an increased risk of developing diabetes in middle-aged women.¹¹ The authors observed that higher serum concentrations of certain PFAS were associated with higher risk of incident diabetes in the study group, and women in the high tertile for all seven PFAS found in the environment were 2.62 times more likely to develop diabetes than those in the low category. This increased risk is roughly equivalent to having overweight or obesity compared with having normal weight. Increased risk associated with each individual PFAS ranged from 36% to 85%, suggesting a potential additive or synergistic effect of multiple PFAS on diabetes risk.¹¹

• Reproductive Outcomes: Pregnant women and their developing children may be vulnerable to PFAS due to associations between maternal PFAS exposure and adverse pregnancy outcomes, including low birth weight, increased gestational weight gain, preeclampsia, gestational hypertension, and gestational diabetes.¹² PFAS pass from the mother to the fetus through the placenta, and PFAS have been shown to increase risk for placenta-mediated pregnancy complications.^6,12 A 2021 systematic review and meta-analysis suggests that PFAS exposure during pregnancy may be associated with increased preterm birth risk, the risk of miscarriage, and preeclampsia.¹³

Interventions

Humans may be exposed to PFAS in myriad ways, most commonly through drinking water, through contaminated food sources, and in household products.^15,16 Understanding human exposure is important in mitigating health effects. Outlined below are some of the most important steps patients can take in reducing exposures, as well as links to critical resources.

• Filtering Drinking Water: Drinking water is identified by the NIH as a substantial source of PFAS exposure for many populations; a variety of water filtration systems have demonstrated effectiveness at reducing levels of certain PFAS.^15,16 There are several steps, outlined by the EPA, that US residents can take to find out if PFAS are in their drinking water—whether they are on well water or public water.¹⁷

Options for filtering PFAS from drinking water include whole-house, under-sink, and filtering-pitcher devices.¹⁶ Reverse osmosis and dual-stage filters were found consistently to remove most measured compounds at an average of greater than 90% efficiency; some short-chain replacement PFAS are difficult to remove with carbon filtration. Bottled water can also be a way to reduce PFAS exposure from drinking water, although some bottled waters contain detectable levels of C-3–C-10 perfluorocarboxylic acids (PFCAs) and C-3–C-6 and C-8 perfluorosulfonic acids.¹⁶

• Changing Diet: Changes in diet may potentially reduce PFAS exposure, given that PFAS can be present in a number of food products, including wild-caught fish and game, livestock, and produce, as well as prepared foods.¹⁶ Fish and seafood have been identified as sources of PFAS, but the levels of PFAS vary by fish type and water body.¹⁶ Patients residing in the US can determine which waterways are of concern by contacting their state or tribal fish advisory programs using EPA’s list of state, territory, and tribal fish advisory contacts.¹⁶

• Lifestyle Modifications: The NIH recommends that patients be educated to avoid stain-resistant carpets and upholstery, as well as stain-resistant treatments and waterproofing sprays; avoid products with the ingredient PTFE or other “fluoro” ingredients listed on the label; choose cookware made of cast iron, stainless steel, glass, or enamel instead of Teflon; eat more fresh foods to avoid take-out containers and other food packaging; avoid microwave popcorn and greasy foods wrapped in plastic; look for nylon or silk dental floss that is uncoated or coated in natural wax.¹⁵

The Green Science Policy Institute has put together a list of product brands that are PFAS-free, including apparel, cosmetics, baby products, furniture, and more.

Functional Medicine Considerations

Functional medicine individual intake assessments are integral at helping to identify and evaluate patterns of potential toxic exposures throughout the lifespan. These assessments help the clinician develop and personalize strategies to reduce the exposure, enhance detoxification through appropriate avenues, and promote the body’s natural ability to heal. Personalized treatments may include lifestyle modifications and other techniques to increase toxicant elimination. Examples include:

• Therapeutic diets, like IFM’s Detox Food Plan, with increased fiber and specific nutrients.
• Promotion of glutathione production in the body.
• Use of saunas to increase elimination of certain toxicants through sweat and urine.

Many toxic chemicals are ubiquitous and difficult to avoid completely; however, helping a patient reduce contact with potential sources is an important goal. Identifying those contaminants specific to a patient’s daily life is a first step, followed by a clinical evaluation to assess the total toxic load or body burden. Interventions include ways to improve biotransformation and elimination. Training in functional medicine teaches clinicians how to develop personalized dietary treatments using the IFM Elimination Diet and Detox Food Plan suites, as well as how to apply various nutraceuticals, botanicals, pharmaceuticals, and lifestyle interventions to increase the mobilization, biotransformation, and elimination of toxic compounds in the body. Learn more about the health impact of pollutant exposures and treatment strategies at IFM’s Environmental Health Advanced Practice Module (APM).

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References

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2. Naidu R, Biswas B, Willett IR, et al. Chemical pollution: a growing peril and potential catastrophic risk to humanity. Environ Int. 2021;156:106616. doi:1016/j.envint.2021.106616
3. Environmental Protection Agency. EPA proposes designating certain PFAS chemicals as hazardous substances under Superfund to protect people’s health. Updated August 10, 2023. Accessed September 20, 2023. https://www.epa.gov/newsreleases/epa-proposes-designating-certain-pfas-chemicals-hazardous-substances-under-superfund
4. Goodrich JA, Walker D, Lin X, et al. Exposure to perfluoroalkyl substances and risk of hepatocellular carcinoma in a multiethnic cohort. JHEP Rep. 2022;4(10):100550. doi:1016/j.jhepr.2022.100550
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7. Kim MJ, Moon S, Oh BC, et al. Association between perfluoroalkyl substances exposure and thyroid function in adults: a meta-analysis. PLoS One. 2018;13(5):e0197244. doi:1371/journal.pone.0197244
8. Yang L, Li J, Lai J, et al. Placental transfer of perfluoroalkyl substances and associations with thyroid hormones: Beijing prenatal exposure study. Sci Rep. 2016;6:21699. doi:1038/srep21699
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10.  Gui SY, Qiao JC, Xu KX, et al. Association between per- and polyfluoroalkyl substances exposure and risk of diabetes: a systematic review and meta-analysis. J Expo Sci Environ Epidemiol. 2023;33(1):40-55. doi:1038/s41370-022-00464-3
11.  Park SK, Wang X, Ding N, et al. Per- and polyfluoroalkyl substances and incident diabetes in midlife women: the Study of Women’s Health Across the Nation (SWAN). Diabetologia. 2022;65(7):1157-1168. doi:1007/s00125-022-05695-5
12.  Blake BE, Rickard BP, Fenton SE. A high-throughput toxicity screen of 42 per- and polyfluoroalkyl substances (PFAS) and functional assessment of migration and gene expression in human placental trophoblast cells. Front Toxicol. 2022;4:881347. doi:3389/ftox.2022.881347
13.  Gao X, Ni W, Zhu S, et al. Per- and polyfluoroalkyl substances exposure during pregnancy and adverse pregnancy and birth outcomes: a systematic review and meta-analysis. Environ Res. 2021;201:111632. doi:1016/j.envres.2021.111632
14.  Gui SY, Qiao JC, Xu KX, et al. Association between per- and polyfluoroalkyl substances exposure and risk of diabetes: a systematic review and meta-analysis. J Expo Sci Environ Epidemiol. 2023;33(1):40-55. doi:1038/s41370-022-00464-3
15.  Cousins IT, Johansson JH, Salter ME, Sha B, Scheringer M. Outside the safe operating space of a new planetary boundary for per- and polyfluoroalkyl substances (PFAS). Environ Sci Technol. 2022;56(16):11172-11179. doi:1021/acs.est.2c02765
16.  National Academies of Sciences, Engineering, and Medicine. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. National Academies Press; 2022. Accessed September 14, 2023. doi:17226/26156
17.  Environmental Protection Agency. PFOA, PFOS, and other PFAS: meaningful and achievable steps you can take to reduce your risk. Updated August 8, 2023. Accessed September 15, 2023. https://www.epa.gov/pfas/meaningful-and-achievable-steps-you-can-take-reduce-your-risk
18.  Waterfield G, Rogers M, Grandjean P, Auffhammer M, Sunding D. Reducing exposure to high levels of perfluorinated compounds in drinking water improves reproductive outcomes: evidence from an intervention in Minnesota. Environ Health. 2020;19(1):42. doi:1186/s12940-020-00591-0