insights

Learn proven functional medicine strategies for treating toxic exposures at the upcoming Environmental Health Advanced Practice Module. SEE FULL PROGRAM DETAILS

Read Time: 5 Minutes

Endocrine-disrupting chemicals (EDCs) are substances (natural or manufactured) that alter endocrine function. EDCs are so prevalent in air, water, soil, and everyday products that they affect the majority of the world’s population. Bisphenol A (BPA), a commonly found EDC, has been detected in 96% of the general population in the US,¹ and recently, the European Food Safety Authority recommended to substantially lower the BPA daily exposure threshold deemed safe to humans.² Chronic, long-term exposure to EDCs has been shown to have widespread physical effects, including negative health impacts beyond the reproductive system.³

Epidemiological studies and expert opinions worldwide continue to describe chronic EDC exposure as a risk factor for obesity, insulin resistance, and diabetes,^4-9 and associated healthcare costs due to EDC exposures are estimated to be well into the billions.^10,11 Understanding the epigenetic mechanisms of EDCs may inform lifestyle and other interventions that could reduce the risk of type 2 diabetes mellitus (T2DM).

Endocrine-Disrupting Chemicals: Mechanisms

EDCs can act as hormone agonists, antagonists, or modulators, triggering transgenerational reproductive dysfunctions by epigenetic mechanisms.⁹ Specific to T2DM, EDCs have been found to directly alter functional beta cell mass and decrease insulin secretion and indirectly act as obesogens, increasing insulin resistance.⁸ EDCs may affect DNA methylation and histone modifications, impacting gene expression, and increase expression of inflammatory genes.^5,8

Some EDCs, known as metabolism-disrupting chemicals (MDCs), act on cells involved in metabolic control, on gene expression, and on enzyme, hormone, and adipokine biosynthesis.¹² MDC exposure creates mitochondrial dysfunction, laying the path to insulin resistance and T2DM.¹³

spotlight on bpa

The National Institute of Environmental Health Sciences states that EDCs, including bisphenol A (BPA), are inhaled, ingested, or absorbed by the skin through contact with everyday products (plastic bottles, metal food cans, detergents, food, toys, cosmetics), flame retardants, and pesticides.¹⁴ Findings from US National Health and Nutrition Examination Surveys (NHANES) have associated higher BPA exposure with an increased risk of cardiovascular diseases, hyperlipidemia, and all-cause mortality in adults with hyperlipidemia.^15,16 BPA and its analogues, bisphenol S (BPS) and bisphenol F (BPF), have also been associated with lipid metabolism disorders and obesity in adults.¹⁷

A 2018 meta-analysis concluded that in humans, BPA exposure is positively associated with type 2 diabetes risk.¹⁸ A 2019 French prospective case cohort study followed 755 participants over nine years and found significant positive associations between urinary BPA and BPS exposure and type 2 diabetes, independent of any other diabetes risk factors.¹⁹

BPA acts on pancreatic β-cells, increasing glucose-induced insulin biosynthesis as well as release of insulin.⁸ In healthy, non-obese adults, oral administration of BPA has been shown to rapidly result in dysregulated glucose responses.^20,21 Importantly, BPA substitutes (plastics often labeled “BPA-free”) show similar endocrine-disrupting effects—sometimes at even lower doses.²²

OTHER EDCS

Serum and urinary concentrations of polychlorinated biphenyls (PCBs), per- and polyfluoroalkyl substances (PFAS), chlorinated pesticides, phthalates, and dioxin have also been significantly associated with T2DM risk, impaired fasting glucose, and insulin resistance.^23,24 For example:

• A 2022 case-control study of 100 participants found that T2DM diagnosis was positively associated with dioxin blood concentrations.²³
• Data from a 2022 meta-analysis (n=7 observational studies with 12,139 participants) found that urinary concentrations of phthalates were positively associated with risk of diabetes mellitus development and elevated markers of insulin resistance.²⁵
• A 2022 observational study (n=1,237 diabetes-free women aged 45-56 years) reported an increased risk of T2DM for those with higher serum concentrations of PFAS compared to lower concentrations.²⁶

Population-Specific Differential Effects

Endocrine-disrupting chemicals often have sexually dimorphic effects, so it’s important to consider how EDCs may affect various populations.

EDCs can cause congenital malformations of the male reproductive system and decrease fertility.²⁷ International studies increasingly show a positive association between environmental pollutants and declining male fertility.³ EDCs in the female body are associated with increased risk of breast cancer, endometriosis, decreased serum levels of sex hormones, and irregular menstrual periods.^28,29 BPA exposure has also been associated with polycystic ovary syndrome³⁰ and altered bone metabolism.³¹ Recent studies of women have also found higher levels of urinary free bisphenol A in self-reported diabetics³² and associated with higher fasting glucose levels in non-diabetics.³³

Clinical Applications: Functional Medicine Approach

Humans may be exposed to EDCs in myriad ways. Many of these chemicals are ubiquitous and difficult to avoid completely; however, helping a patient reduce contact with potential sources is an important goal. Functional medicine individual intake assessments are integral for helping identify and evaluate patterns of potential toxic exposures throughout the lifespan. These assessments help the clinician develop and personalize strategies to reduce 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. Optimizing a patient’s nutritional status, ensuring adequate fiber and water intake, eating more phytonutrient-dense and diverse foods, and supporting liver function through targeted, nutrient-dense diets are all dietary treatment approaches within the functional medicine model that may be implemented to help support the elimination of toxic compounds and alleviate toxic burden.

As previously shared, EDC research has emphasized the significant impact of EDCs on human health, yet further research is needed to clarify associations and causation. Mechanisms of EDC-T2DM associations are just beginning to be understood; however, study results indicate that there is sufficient evidence to drive national policies to reduce EDC exposure. In addition, chemicals are often used in combination rather than singly; therefore, exposure to EDCs may be compounded. As research continues, this is an important consideration because the synergism effect may not only confound study results but also influence patient exposures and outcomes.

Learn more about the health impact of endocrine disruptors and effective treatment strategies at IFM’s Environmental Health Advanced Practice Module (APM).

Related Articles

Common Endocrine-Disrupting Chemicals and Women’s Health

Pollutants and the Healthy Child

Detoxification: Supporting Liver Function With Nutrition

References

1. Lehmler HJ, Liu B, Gadogbe M, Bao W. Exposure to bisphenol A, bisphenol F, and bisphenol S in U.S. adults and children: the National Health and Nutrition Examination Survey 2013-2014. ACS Omega. 2018;3(6):6523-6532. doi:1021/acsomega.8b00824
2. Vom Saal FS, Antoniou M, Belcher SM, et al. The conflict between regulatory agencies over the 20,000-fold lowering of the tolerable daily intake (TDI) for bisphenol A (BPA) by the European Food Safety Authority (EFSA). Environ Health Perspect. 2024;132(4):45001. doi:1289/EHP13812
3. Brehm E, Flaws JA. Transgenerational effects of endocrine-disrupting chemicals on male and female reproduction. 2019;160(6):1421-1435. doi:10.1210/en.2019-00034
4. Fine AM, Patrick L. Environmental medicine: exploring the pollutome for solutions to chronic diseases. Phys Med Rehabil Clin N Am. 2022;33(3):719-732. doi:1016/j.pmr.2022.04.010
5. Barbieri M, Prattichizzo F, La Grotta R, et al. Is it time to revise the fighting strategy toward type 2 diabetes? Sex and pollution as new risk factors. Ageing Res Rev. 2024;99:102405. doi:1016/j.arr.2024.102405
6. Dagar M, Kumari P, Mirza AMW, et al. The hidden threat: endocrine disruptors and their impact on insulin resistance. Cureus. 2023;15(10):e47282. doi:7759/cureus.47282
7. Kim B, Park B, Kim CH, Kim S, Park B. Association between endocrine-disrupting chemical mixture and metabolic indices among children, adolescents, and adults: a population-based study in Korea. Environ Pollut. 2022;315:120399. doi:1016/j.envpol.2022.120399
8. Martínez-Pinna J, Sempere-Navarro R, Medina-Gali RM, et al. Endocrine disruptors in plastics alter β-cell physiology and increase the risk of diabetes mellitus. Am J Physiol Endocrinol Metab. 2023;324(6):E488-E505. doi:1152/ajpendo.00068.2023
9. Ahn C, Jeung EB. Endocrine-disrupting chemicals and disease endpoints. Int J Mol Sci. 2023;24(6):5342. doi:3390/ijms24065342
10.  Attina TM, Malits J, Naidu M, Trasande L. Racial/ethnic disparities in disease burden and costs related to exposure to endocrine-disrupting chemicals in the United States: an exploratory analysis. J Clin Epidemiol. 2019;108:34-43. doi:1016/j.jclinepi.2018.11.024
11.  Kassotis CD, Vandenberg LN, Demeneix BA, Porta M, Slama R, Trasande L. Endocrine-disrupting chemicals: economic, regulatory, and policy implications. Lancet Diabetes Endocrinol. 2020;8(8):719-730. doi:1016/S2213-8587(20)30128-5
12.  Nadal A, Quesada I, Tudurí E, Nogueiras R, Alonso-Magdalena P. Endocrine-disrupting chemicals and the regulation of energy balance. Nat Rev Endocrinol. 2017;13(9):536-546. doi:1038/nrendo.2017.51
13.  Marroqui L, Tudurí E, Alonso-Magdalena P, Quesada I, Nadal Á, Dos Santos RS. Mitochondria as target of endocrine-disrupting chemicals: implications for type 2 diabetes. J Endocrinol. 2018;239(2):R27-R45. doi:1530/joe-18-0362
14.  National Institute of Environmental Health Sciences. Endocrine disruptors. National Institutes of Health. Reviewed July 22, 2024. Accessed July 25, 2024. https://www.niehs.nih.gov/health/topics/agents/endocrine/index.cfm
15.  Chen Z, He J, Shi W. Association between urinary environmental phenols and the prevalence of cardiovascular diseases in US adults. Environ Sci Pollut Res Int. 2022;29(28):42947-42954. doi:1007/s11356-021-18323-3
16.  Guo L, Zhao P, Xue S, Zhu Z. Association of urinary bisphenol A with hyperlipidemia and all-cause mortality: NHANES 2003-2016. PLoS One. 2024;19(7):e0304516. doi:1371/journal.pone.0304516
17.  Choi JY, Lee J, Huh DA, Moon KW. Urinary bisphenol concentrations and its association with metabolic disorders in the US and Korean populations. Environ Pollut. 2022;295:118679. doi:1016/j.envpol.2021.118679
18.  Hwang S, Lim JE, Choi Y, Jee SH. Bisphenol A exposure and type 2 diabetes mellitus risk: a meta-analysis. BMC Endocr Disord. 2018;18(1):81. doi:1186/s12902-018-0310-y
19.  Rancière F, Botton J, Slama R, et al. Exposure to bisphenol A and bisphenol S and incident type 2 diabetes: a case-cohort study in the French cohort D.E.S.I.R. Environ Health Perspect. 2019;127(10):107013. doi:1289/EHP5159
20.  Hagobian TA, Bird A, Stanelle S, Williams D, Schaffner A, Phelan S. Pilot study on the effect of orally administered bisphenol A on glucose and insulin response in nonobese adults. J Endocr Soc. 2019;3(3):643-654. doi:1210/js.2018-00322
21.  Stahlhut RW, Myers JP, Taylor JA, Nadal A, Dyer JA, Vom Saal FS. Experimental BPA exposure and glucose-stimulated insulin response in adult men and women. J Endocr Soc. 2018;2(10):1173-1187. doi:1210/js.2018-00151
22.  Pelch K, Wignall JA, Goldstone AE, et al. A scoping review of the health and toxicological activity of bisphenol A (BPA) structural analogues and functional alternatives. 2019;424:152235. doi:10.1016/j.tox.2019.06.006
23.  Lee S, Lim Y, Kang Y, Jung K, Jee S. The association between blood concentrations of PCDD/DFs, DL-PCBs and the risk of type 2 diabetes mellitus and thyroid cancer in South Korea. Int J Environ Res Public Health. 2022;19(14):8745. doi:3390/ijerph19148745
24.  Song Y, Chou EL, Baecker A, et al. Endocrine-disrupting chemicals, risk of type 2 diabetes, and diabetes-related metabolic traits: a systematic review and meta-analysis. J Diabetes. 2016;8(4):516-532. doi:1111/1753-0407.12325
25.  Zhang H, Ben Y, Han Y, Zhang Y, Li Y, Chen X. Phthalate exposure and risk of diabetes mellitus: implications from a systematic review and meta-analysis. Environ Res. 2022;204(Pt B):112109. doi:1016/j.envres.2021.112109
26.  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
27.  Di Nisio A, Foresta C. Water and soil pollution as determinant of water and food quality/contamination and its impact on male fertility. Reprod Biol Endocrinol. 2019;17(1):4. doi:1186/s12958-018-0449-4
28.  Gonsioroski A, Mourikes VE, Flaws JA. Endocrine disruptors in water and their effects on the reproductive system. Int J Mol Sci. 2020;21(6):1929. doi:3390/ijms21061929
29.  Wan MLY, Co VA, El-Nezami H. Endocrine disrupting chemicals and breast cancer: a systematic review of epidemiological studies. Crit Rev Food Sci Nutr. 2022;62(24):6549-6576. doi:1080/10408398.2021.1903382
30.  Zhan W, Tang W, Shen X, Xu H, Zhang J. Exposure to bisphenol A and its analogs and polycystic ovarian syndrome in women of childbearing age: a multicenter case-control study. Chemosphere. 2023;313:137463. doi:1016/j.chemosphere.2022.137463
31.  Reeves KW, Vieyra G, Grimes NP, et al. Urinary phthalate biomarkers and bone mineral density in postmenopausal women. J Clin Endocrinol Metab. 2021;106(7):e2567-e2579. doi:1210/clinem/dgab189
32.  Murphy L, Mérida-Ortega Á, Cebrián ME, et al. Exposure to bisphenol A and diabetes risk in Mexican women. Environ Sci Pollut Res Int. 2019;26(25):26332-26338. doi:1007/s11356-019-05731-9
33.  Wang B, Li M, Zhao Z, et al. Urinary bisphenol A concentration and glucose homeostasis in non-diabetic adults: a repeated-measures, longitudinal study. 2019;62(9):1591-1600. doi:10.1007/s00125-019-4898-x