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The interference between effects of PFAS exposure on thyroid hormone disorders and cholesterol levels: an NHANES analysis

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Abstract

Studies have documented that per- and polyfluoroalkyl substance (PFAS) exposures are associated with thyroid hormones (TH) and lipid levels. This study investigates whether these effects interfere with each other. We analyzed data on 3954 adults in the US National Health and Nutrition Examination Survey (NHANES; 2007–2012). TH disorder was defined using thyroid hormones. Serum high-density lipoprotein (HDL) cholesterol, total cholesterol, and six types of PFAS were included. Weighted quantile sum (WQS) regression was used to estimate the overall effect of PFAS mixture on TH disorder and cholesterols, respectively. Potential confounders, including age, race, gender, education, household poverty, smoking, and alcohol drinking, were adjusted. PFAS mixture was associated increased risk for TH disorder (odds ratio = 1.21, 95% confidence interval (CI): 1.02, 1.43), higher HDL cholesterol (linear coefficient = 1.31, 95% CI: 0.50, 2.11), and higher total cholesterol (linear coefficient = 5.30, 95% CI: 3.40, 7.21). TH disorder was associated with higher HDL cholesterol (linear coefficient = 2.30, 95% CI: 0.50, 2.11), but not total cholesterol. When adjusted for TH disorder, the effect estimates of PFAS mixture remain roughly unchanged on HDL cholesterol (linear coefficient = 1.13, 95% CI: 0.28, 1.98) and total cholesterol (linear coefficient = 5.61, 95% CI: 3.58, 7.63). Sex modified the effect of PFAS mixture on HDL cholesterol (P for interaction: 0.04) but did not change the interaction between PFAS and TH disorder on cholesterols. We corroborated the adverse health effects of PFAS exposure on TH and lipids; however, these two effects appear to be independent of and not interfere with each other.

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Data availability

The data are available from the US National Health and Nutrition Examination Survey (NHANES) 2007–2012.

References

  • Andersen ME, Hagenbuch B, Apte U, Corton JC, Fletcher T, Lau C, Longnecker MP (2021) Why is elevation of serum cholesterol associated with exposure to perfluoroalkyl substances (PFAS) in humans? A workshop report on potential mechanisms. Toxicology 459:152845. https://doi.org/10.1016/j.tox.2021.152845

    Article  CAS  Google Scholar 

  • Beggs KM, McGreal SR, McCarthy A, Gunewardena S, Lampe JN, Lau C, Apte U (2016) The role of hepatocyte nuclear factor 4-alpha in perfluorooctanoic acid- and perfluorooctanesulfonic acid-induced hepatocellular dysfunction. Toxicol Appl Pharmacol 304:18–29. https://doi.org/10.1016/j.taap.2016.05.001

    Article  CAS  Google Scholar 

  • Behr A-C, Plinsch C, Braeuning A, Buhrke T (2020) Activation of human nuclear receptors by perfluoroalkylated substances (PFAS). Toxicol in Vitro 62:104700

    Article  Google Scholar 

  • Boas M, Main KM, Feldt-Rasmussen U (2009) Environmental chemicals and thyroid function: an update. Curr Opin Endocrinol Diabetes Obes 16(5):385–391. https://doi.org/10.1097/MED.0b013e3283305af7

    Article  CAS  Google Scholar 

  • Bobb JF, Valeri L, Claus Henn B, Christiani DC, Wright RO, Mazumdar M, Coull BA (2015) Bayesian kernel machine regression for estimating the health effects of multi-pollutant mixtures. Biostatistics 16(3):493–508

    Article  Google Scholar 

  • Calafat AM, Kuklenyik Z, Reidy JA, Caudill SP, Tully JS, Needham LL (2007) Serum concentrations of 11 polyfluoroalkyl compounds in the U.S. population: data from the national health and nutrition examination survey (NHANES). Environmen Sci Technol 41(7):2237–2242. https://doi.org/10.1021/es062686m

    Article  CAS  Google Scholar 

  • Caporale N, Leemans M, Birgersson L, Germain P-L, Cheroni C, Borbély G, Cavallo F (2022) From cohorts to molecules: adverse impacts of endocrine disrupting mixtures. Science 375(6582):eabe8244

    Article  CAS  Google Scholar 

  • Carrico C, Gennings C, Wheeler DC, Factor-Litvak P (2015) Characterization of weighted quantile sum regression for highly correlated data in a risk analysis setting. J Agric Biol Environ Stat 20(1):100–120. https://doi.org/10.1007/s13253-014-0180-3

    Article  Google Scholar 

  • Chang SC, Thibodeaux JR, Eastvold ML, Ehresman DJ, Bjork JA, Froehlich JW, Butenhoff JL (2008) Thyroid hormone status and pituitary function in adult rats given oral doses of perfluorooctanesulfonate (PFOS). Toxicology 243(3):330–339. https://doi.org/10.1016/j.tox.2007.10.014

    Article  CAS  Google Scholar 

  • Cleeman JI, Grundy SM, Becker D, Clark LT, Cooper RS, Denke MA, Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001) Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). Jama-J Am Med Assoc 285(19):2486–2497. https://doi.org/10.1001/jama.285.19.2486

    Article  Google Scholar 

  • Das KP, Wood CR, Lin MT, Starkov AA, Lau C, Wallace KB, Abbott BD (2017) Perfluoroalkyl acids-induced liver steatosis: effects on genes controlling lipid homeostasis. Toxicology 378:37–52. https://doi.org/10.1016/j.tox.2016.12.007

    Article  CAS  Google Scholar 

  • Dunder L, Lind PM, Salihovic S, Stubleski J, Karrman A, Lind L (2022) Changes in plasma levels of per- and polyfluoroalkyl substances (PFAS) are associated with changes in plasma lipids-a longitudinal study over 10 years. Environmental Research 211:112903. https://doi.org/10.1016/j.envres.2022.112903

  • Duntas LH, Brenta G (2018) A renewed focus on the association between thyroid hormones and lipid metabolism. Front Endocrino 9:511. https://doi.org/10.3389/fendo.2018.00511

  • Fletcher T, Galloway TS, Melzer D, Holcroft P, Cipelli R, Pilling LC, Harries LW (2013) Associations between PFOA, PFOS and changes in the expression of genes involved in cholesterol metabolism in humans. Environ Int 57:2–10

    Article  Google Scholar 

  • Fragki S, Dirven H, Fletcher T, Grasl-Kraupp B, BjerveGutzkow K, Hoogenboom R, Luijten M (2021) Systemic PFOS and PFOA exposure and disturbed lipid homeostasis in humans: what do we know and what not? Critical Rev Toxicol 51(2):141–164. https://doi.org/10.1080/10408444.2021.1888073

    Article  CAS  Google Scholar 

  • Franco M, Chávez E, Pérez-Méndez O (2011) Pleiotropic effects of thyroid hormones: learning from hypothyroidism. J Thyroid Res. 321030. https://doi.org/10.4061/2011/321030

  • Gao CX, Yang B, Guo Q, Wei LH, Tian LM (2015) High thyroid-stimulating hormone level is associated with the risk of develo** atherosclerosis in subclinical hypothyroidism. Horm Metab Res 47(3):220–224. https://doi.org/10.1055/s-0034-1394370

    Article  CAS  Google Scholar 

  • Jones PD, Hu WY, De Coen W, Newsted JL, Giesy JP (2003) Binding of perfluorinated fatty acids to serum proteins. Environ Toxicol Chem 22(11):2639–2649. https://doi.org/10.1897/02-553

    Article  CAS  Google Scholar 

  • Kato K, Wong LY, Jia LT, Kuklenyik Z, Calafat AM (2011) Trends in exposure to polyfluoroalkyl chemicals in the U.S. Population: 1999–2008. Environ Sci Technol 45(19):8037–8045. https://doi.org/10.1021/es1043613

    Article  CAS  Google Scholar 

  • Keil AP, Buckley JP, O’Brien KM, Ferguson KK, Zhao S, White AJ (2020) A quantile-based g-computation approach to addressing the effects of exposure mixtures. Environ Health Perspect 128(4):047004

    Article  Google Scholar 

  • Kim KI, Kim MA, Kim MK, Kim SH, Kim HS, Moon MK, Manage CKG (2016) 2015 Korean guidelines for the management of dyslipidemia: executive summary (english translation). Korean Circulation J 46(3):275–306. https://doi.org/10.4070/kcj.2016.46.3.275

    Article  CAS  Google Scholar 

  • Kim MJ, Moon S, Oh BC, Jung D, Ji K, Choi K, Park YJ (2018) Association between perfluoroalkyl substances exposure and thyroid function in adults: a meta-analysis. PloS One, 13(5):e0197244. https://doi.org/10.1371/journal.pone.0197244

  • Li CH, Ren XM, Ruan T, Cao LY, **n Y, Guo LH, Jiang G (2018) Chlorinated polyfluorinated ether sulfonates exhibit higher activity toward peroxisome proliferator-activated receptors signaling pathways than perfluorooctanesulfonate. Environ Sci Technol 52(5):3232–3239. https://doi.org/10.1021/acs.est.7b06327

    Article  CAS  Google Scholar 

  • Lin CY, Chen PC, Lin YC, Lin LY (2009) Association among serum perfluoroalkyl chemicals, glucose homeostasis, and metabolic syndrome in adolescents and adults. Diabetes Care 32(4):702–707. https://doi.org/10.2337/dc08-1816

    Article  CAS  Google Scholar 

  • Liu FH, Hwang JS, Kuo CF, Ko YS, Chen ST, Lin JD (2018) Subclinical hypothyroidism and metabolic risk factors association: a health examination-based study in northern Taiwan. Biomed J 41(1):52–58. https://doi.org/10.1016/j.bj.2018.02.002

    Article  Google Scholar 

  • Long M, Ghisari M, Bonefeld-Jorgensen EC (2013) Effects of perfluoroalkyl acids on the function of the thyroid hormone and the aryl hydrocarbon receptor. Environ Sci Pollut Res Int 20(11):8045–8056. https://doi.org/10.1007/s11356-013-1628-7

    Article  CAS  Google Scholar 

  • Lopez-Espinosa MJ, Mondal D, Armstrong B, Bloom MS, Fletcher T (2012) Thyroid function and perfluoroalkyl acids in children living near a chemical plant. Environ Health Perspect 120(7):1036–1041. https://doi.org/10.1289/ehp.1104370

    Article  CAS  Google Scholar 

  • Luxia L, **gfang L, Songbo F, Xulei T, Lihua M, Weiming S, Pei S (2021) Correlation between serum TSH levels within normal range and serum lipid profile. Hormone Metabol Res 53(1):32–40. https://doi.org/10.1055/a-1191-7953

    Article  CAS  Google Scholar 

  • Ma Y, Yang J, Wan Y, Peng Y, Ding S, Li Y, Xu S (2018) Low-level perfluorooctanoic acid enhances 3 T3–L1 preadipocyte differentiation via altering peroxisome proliferator activated receptor gamma expression and its promoter DNA methylation. J Appl Toxicol 38(3):398–407. https://doi.org/10.1002/jat.3549

    Article  CAS  Google Scholar 

  • Malin AJ, Lesseur C, Busgang SA, Curtin P, Wright RO, Sanders AP (2019) Fluoride exposure and kidney and liver function among adolescents in the United States: NHANES, 2013–2016. Environ Int 132:105012

    Article  CAS  Google Scholar 

  • Melzer D, Rice N, Depledge MH, Henley WE, Galloway TS (2010) Association between serum perfluorooctanoic acid (PFOA) and thyroid disease in the U.S. National Health and Nutrition Examination Survey. Environ Health Perspect 118(5):686–692. https://doi.org/10.1289/ehp.0901584

    Article  CAS  Google Scholar 

  • Olsen GW, Burris JM, Ehresman DJ, Froehlich JW, Seacat AM, Butenhoff JL, Zobel LR (2007) Half-life of serum elimination of perfluorooctanesulfonate, perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers. Environ Health Perspect 115(9):1298–1305. https://doi.org/10.1289/ehp.10009

    Article  CAS  Google Scholar 

  • Peppa M, Betsi G, Dimitriadis G (2011) Lipid abnormalities and cardiometabolic risk in patients with overt and subclinical thyroid disease. J Lipids 575840. https://doi.org/10.1155/2011/575840

  • Porterfield SP (1994) Vulnerability of the develo** brain to thyroid abnormalities: environmental insults to the thyroid system. Environ Health Perspect 102 Suppl 2(Suppl 2), 125–130. https://doi.org/10.1289/ehp.94102125

  • Reinehr T (2010) Obesity and thyroid function. Mol Cell Endocrinol 316(2):165–171. https://doi.org/10.1016/j.mce.2009.06.005

    Article  CAS  Google Scholar 

  • Rigamonti E, Chinetti-Gbaguidi G, Staels B (2008) Regulation of macrophage functions by PPAR-α, PPAR-γ, and LXRs in mice and men. Arterioscler Thromb Vasc Biol 28(6):1050–1059

    Article  CAS  Google Scholar 

  • Shah AD, Bartlett JW, Carpenter J, Nicholas O, Hemingway H (2014) Comparison of random forest and parametric imputation models for imputing missing data using MICE: a CALIBER study. Am J Epidemiol 179(6):764–774

    Article  Google Scholar 

  • Steenland K, Tinker S, Frisbee S, Ducatman A, Vaccarino V (2009) Association of perfluorooctanoic acid and perfluorooctane sulfonate with serum lipids among adults living near a chemical plant. Am J Epidemiol 170(10):1268–1278. https://doi.org/10.1093/aje/kwp279

    Article  Google Scholar 

  • Unal E, Akin A, Yildirim R, Demir V, Yildiz I, Haspolat YK (2017) Association of subclinical hypothyroidism with dyslipidemia and increased carotid intima-media thickness in children. J Clin Res Pediatr Endocrinol 9(2):144–149. https://doi.org/10.4274/jcrpe.3719

    Article  Google Scholar 

  • US Department of Health Human Services Centers for Disease Control Prevention (2005) Laboratory Procedure Manual. https://wwwn.cdc.gov/nchs/data/nhanes/2009-2010/labmethods/PFC_F_Polyfluorinated_Compounds_met.pdf. Accessed 18 July 2023

  • Vanden Heuvel JP, Thompson JT, Frame SR, Gillies PJ (2006) Differential activation of nuclear receptors by perfluorinated fatty acid analogs and natural fatty acids: a comparison of human, mouse, and rat peroxisome proliferator-activated receptor-alpha, -beta, and -gamma, liver X receptor-beta, and retinoid X receptor-alpha. Toxicol Sci 92(2):476–489. https://doi.org/10.1093/toxsci/kfl014

    Article  CAS  Google Scholar 

  • Wan HT, Zhao YG, Wei X, Hui KY, Giesy JP, Wong CK (2012) PFOS-induced hepatic steatosis, the mechanistic actions on beta-oxidation and lipid transport. Biochim Biophys Acta 1820(7):1092–1101. https://doi.org/10.1016/j.bbagen.2012.03.010

    Article  CAS  Google Scholar 

  • Webster GM, Rauch SA, Marie NS, Mattman A, Lanphear BP, Venners SA (2016) Cross-sectional associations of serum perfluoroalkyl acids and thyroid hormones in US adults: variation according to TPOAb and iodine status (NHANES 2007–2008). Environ Health Perspect 124(7):935–942

    Article  CAS  Google Scholar 

  • Weiss JM, Andersson PL, Lamoree MH, Leonards PEG, van Leeuwen SPJ, Hamers T (2009) Competitive binding of poly- and perfluorinated compounds to the thyroid hormone transport protein transthyretin. Toxicol Sci 109(2):206–216. https://doi.org/10.1093/toxsci/kfp055

    Article  CAS  Google Scholar 

  • White SS, Fenton SE, Hines EP (2011) Endocrine disrupting properties of perfluorooctanoic acid. J Steroid Biochem Mol Biol 127(1–2):16–26. https://doi.org/10.1016/j.jsbmb.2011.03.011

    Article  CAS  Google Scholar 

  • Wolf CJ, Takacs ML, Schmid JE, Lau C, Abbott BD (2008) Activation of mouse and human peroxisome proliferator-activated receptor alpha by perfluoroalkyl acids of different functional groups and chain lengths. Toxicol Sci 106(1):162–171. https://doi.org/10.1093/toxsci/kfn166

    Article  CAS  Google Scholar 

  • Wolf CJ, Schmid JE, Lau C, Abbott BD (2012) Activation of mouse and human peroxisome proliferator-activated receptor-alpha (PPARalpha) by perfluoroalkyl acids (PFAAs): further investigation of C4–C12 compounds. Reprod Toxicol 33(4):546–551. https://doi.org/10.1016/j.reprotox.2011.09.009

    Article  CAS  Google Scholar 

  • Xu J, Shimpi P, Armstrong L, Salter D, Slitt AL (2016) PFOS induces adipogenesis and glucose uptake in association with activation of Nrf2 signaling pathway. Toxicol Appl Pharmacol 290:21–30. https://doi.org/10.1016/j.taap.2015.11.002

    Article  CAS  Google Scholar 

  • Yamamoto J, Yamane T, Oishi Y, Kobayashi-Hattori K (2015) Perfluorooctanoic acid binds to peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation in 3T3-L1 adipocytes. Biosci Biotechnol Biochem 79(4):636–639. https://doi.org/10.1080/09168451.2014.991683

    Article  CAS  Google Scholar 

  • Yuan Y (2011) Multiple imputation using SAS software. J Stat Softw 45:1–25

    Article  Google Scholar 

  • Zhao M, Liu L, Wang F, Yuan Z, Zhang X, Xu C, Zhao J (2016) A worthy finding: decrease in total cholesterol and low-density lipoprotein cholesterol in treated mild subclinical hypothyroidism. Thyroid 26(8):1019–1029. https://doi.org/10.1089/thy.2016.0010

    Article  CAS  Google Scholar 

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Funding

This study was supported by the National Natural Science Foundation of China (Grant No. 82203292, 82203461), the Medical Science and Technology Research Foundation of Guangdong Province (Grant No. 2019111811570248), and the Guangzhou Science and Technology Planning Project (Grant No. 202201011314).

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Author notes

  1. Liang Zheng, Zhecun Wang, and Rui Yang contributed equally to this work.

Authors and Affiliations

  1. Department of Thyroid Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, Guangdong, China

    Liang Zheng, Wanna Chen, **g Zhang, Ruixia Li, Weiming Lv & Bo Lin

  2. Department of Vascular Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, Guangdong, China

    Zhecun Wang

  3. Department of Urology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, Guangdong, China

    Rui Yang

  4. Institute for Population and Precision Health, The University of Chicago, Chicago, IL, USA

    Jiajun Luo

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  1. Liang Zheng
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Contributions

LZ and ZCW conceived the study design and drafted the manuscript. RY and BL collected the data. WNC and JZ performed statistical analyses. RXL and WML critically revised the manuscript. All authors approved the version for publication. JJL supervised the whole manuscript. All authors read and approved the final manuscript.

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Correspondence to Jiajun Luo.

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Zheng, L., Wang, Z., Yang, R. et al. The interference between effects of PFAS exposure on thyroid hormone disorders and cholesterol levels: an NHANES analysis. Environ Sci Pollut Res 30, 90949–90959 (2023). https://doi.org/10.1007/s11356-023-28739-8

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