Exposure to Per- and Polyfluoroalkyl Substances and the Risk of Sarcopenia: The Mediating Role of Serum Albumin

Sun, Mingkun; Chu, Chu; Zhao, Kun; Qian, Zhengmin (Min); Schootman, Mario; McMillin, Stephen Edward; Dong, Jiaxiang; Bao, Wenwen; Amjad, Muhammad; Moryani, Haseeb Tufail; Zhou, Yang; Yang, Yan; Wang, Peipei

doi:10.3390/toxics14060478

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Exposure to Per- and Polyfluoroalkyl Substances and the Risk of Sarcopenia: The Mediating Role of Serum Albumin

by

Mingkun Sun

^1,†,

Chu Chu

^1,†,

Kun Zhao

¹,

Zhengmin (Min) Qian

²

,

Mario Schootman

³

,

Stephen Edward McMillin

⁴

,

Jiaxiang Dong

⁵,

Wenwen Bao

¹,

Muhammad Amjad

¹

,

Haseeb Tufail Moryani

¹,

Yang Zhou

¹,

Yan Yang

^6,* and

Peipei Wang

^7,*

¹

Joint International Research Laboratory of Environment and Health, Ministry of Education, Guangdong Provincial Engineering Technology Research Center of Environmental Pollution and Health Risk Assessment, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China

²

Department of Epidemiology and Biostatistics, College for Public Health & Social Justice, Saint Louis University, Saint Louis, MO 63104, USA

³

Department of Internal Medicine, College of Medicine, University of Arkansas for Medical Sciences, Springdale, AR 72762, USA

⁴

School of Social Work, Saint Louis University, Saint Louis, MO 63103, USA

⁵

Thornlea Secondary School, York Region District School Board, 8075 Bayview Avenue, Thornhill, ON L3T 4N4, Canada

⁶

Engineering Research Center of Small Molecule Drugs, Ministry of Education, College of Public Health, Guangdong Pharmaceutical University, Guangzhou 510310, China

⁷

Sleep Medicine Department, Sanya Central Hospital (The Third People’s Hospital of Hainan Province), Sanya 572029, China

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work and should be listed as first author.

Toxics 2026, 14(6), 478; https://doi.org/10.3390/toxics14060478 (registering DOI)

Submission received: 27 March 2026 / Revised: 19 May 2026 / Accepted: 27 May 2026 / Published: 29 May 2026

(This article belongs to the Special Issue Multi-Media Exposure to Emerging Contaminants and Health Effects Across Physiological Systems: Exposure Pathways, Risk Assessment and Public Health Implications)

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Abstract

Widespread exposure to per- and polyfluoroalkyl substances (PFAS) is a growing public health concern, but its link to muscle damage remains largely unexplored. As PFAS exposure is associated with liver dysfunction, which is an established risk factor for muscle damage, we examined their associations and potential mediating pathways. A total of 1261 participants were recruited from Guangdong province, China, from November 2018 to August 2019 and examined for muscle mass, strength, serum PFAS levels, and biomarkers of liver function. The key results demonstrated significant positive associations between serum PFAS exposure and sarcopenia risk. Specifically, a per ln ng/mL increase in linear perfluorooctane sulfonate (PFOS), branch PFOS, and perfluorooctanoic acid (PFOA) was associated with adjusted odds ratios of 2.32 (95% CI: 1.77 to 3.00), 2.18 (95% CI: 1.67 to 2.90) and 3.01 (95% CI: 1.96 to 4.70), respectively. Analysis of PFAS mixtures via the BKMR model revealed a linear dose–response relationship of sarcopenia, with PFOS and PFOA being the primary contributor. Importantly, mediation analyses showed that liver function biomarkers served as significant mediators of the PFAS–sarcopenia association. Notably, liver synthesis function markers (albumin and globin) mediated a substantial proportion of the association, ranging from 3.48% to 82.42%, whereas liver injury markers (aspartate aminotransferase and gamma-glutamyl transferase) accounted for only 1.93–15.44%. This study underscores the need to be aware of the increased risk of muscle damage associated with PFAS exposure, which may primarily operate through liver function abnormalities.

Keywords: PFAS isomer; muscle loss; skeletal muscle; bio-electrical impedance analysis; liver dysfunction

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MDPI and ACS Style

Sun, M.; Chu, C.; Zhao, K.; Qian, Z.; Schootman, M.; McMillin, S.E.; Dong, J.; Bao, W.; Amjad, M.; Moryani, H.T.; et al. Exposure to Per- and Polyfluoroalkyl Substances and the Risk of Sarcopenia: The Mediating Role of Serum Albumin. Toxics 2026, 14, 478. https://doi.org/10.3390/toxics14060478

AMA Style

Sun M, Chu C, Zhao K, Qian Z, Schootman M, McMillin SE, Dong J, Bao W, Amjad M, Moryani HT, et al. Exposure to Per- and Polyfluoroalkyl Substances and the Risk of Sarcopenia: The Mediating Role of Serum Albumin. Toxics. 2026; 14(6):478. https://doi.org/10.3390/toxics14060478

Chicago/Turabian Style

Sun, Mingkun, Chu Chu, Kun Zhao, Zhengmin (Min) Qian, Mario Schootman, Stephen Edward McMillin, Jiaxiang Dong, Wenwen Bao, Muhammad Amjad, Haseeb Tufail Moryani, and et al. 2026. "Exposure to Per- and Polyfluoroalkyl Substances and the Risk of Sarcopenia: The Mediating Role of Serum Albumin" Toxics 14, no. 6: 478. https://doi.org/10.3390/toxics14060478

APA Style

Sun, M., Chu, C., Zhao, K., Qian, Z., Schootman, M., McMillin, S. E., Dong, J., Bao, W., Amjad, M., Moryani, H. T., Zhou, Y., Yang, Y., & Wang, P. (2026). Exposure to Per- and Polyfluoroalkyl Substances and the Risk of Sarcopenia: The Mediating Role of Serum Albumin. Toxics, 14(6), 478. https://doi.org/10.3390/toxics14060478

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Exposure to Per- and Polyfluoroalkyl Substances and the Risk of Sarcopenia: The Mediating Role of Serum Albumin

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