Li X, Yuan PC, Gao Q, Cao QQ, Ma Z, Chen X, Wang CJ, Mao ZX, Huo WQ. Dual effects of synthetic phenolic antioxidants in type 2 diabetes mellitus: Mechanisms and advances. World J Diabetes 2026; 17(5): 115619 [DOI: 10.4239/wjd.v17.i5.115619]
Corresponding Author of This Article
Wen-Qian Huo, PhD, Associate Professor, Department of Occupational and Environmental Health, College of Public Health, Zhengzhou University, No. 100 Kexue Avenue, Zhengzhou 450001, Henan Province, China. huowenqian@zzu.edu.cn
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May 15, 2026 (publication date) through May 14, 2026
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World Journal of Diabetes
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Li X, Yuan PC, Gao Q, Cao QQ, Ma Z, Chen X, Wang CJ, Mao ZX, Huo WQ. Dual effects of synthetic phenolic antioxidants in type 2 diabetes mellitus: Mechanisms and advances. World J Diabetes 2026; 17(5): 115619 [DOI: 10.4239/wjd.v17.i5.115619]
World J Diabetes. May 15, 2026; 17(5): 115619 Published online May 15, 2026. doi: 10.4239/wjd.v17.i5.115619
Dual effects of synthetic phenolic antioxidants in type 2 diabetes mellitus: Mechanisms and advances
Xin Li, Peng-Cheng Yuan, Qian Gao, Qing-Qing Cao, Zhen Ma, Xuan Chen, Chong-Jian Wang, Zhen-Xing Mao, Wen-Qian Huo
Xin Li, Peng-Cheng Yuan, Qian Gao, Qing-Qing Cao, Zhen Ma, Xuan Chen, Wen-Qian Huo, Department of Occupational and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
Chong-Jian Wang, Zhen-Xing Mao, Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
Author contributions: Li X contributed to conceptualization, literature search, and writing the original draft; Yuan PC, Gao Q, Cao QQ, Ma Z, Chen X contributed to writing and editing the review; Wang CJ and Mao ZX contributed to conceptualization, writing and editing, and supervision; Huo WQ contributed to conceptualization, writing and editing, supervision, and funding acquisition.
Supported by the National Natural Science Foundation of China, No. 21806146; and the Postdoctoral Science Foundation of China, No. 2021M702934.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Corresponding author: Wen-Qian Huo, PhD, Associate Professor, Department of Occupational and Environmental Health, College of Public Health, Zhengzhou University, No. 100 Kexue Avenue, Zhengzhou 450001, Henan Province, China. huowenqian@zzu.edu.cn
Received: October 24, 2025 Revised: December 17, 2025 Accepted: February 6, 2026 Published online: May 15, 2026 Processing time: 199 Days and 20.6 Hours
Abstract
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia, oxidative stress, and inflammation. Synthetic phenolic antioxidants (SPAs), primarily butylated hydroxyanisole, butylated hydroxytoluene, and tert-butylhydroquinone, have been widely detected in various environmental and consumer product matrices. Although they possess free radical scavenging ability, SPAs have dual effects on T2DM under different conditions. This review aims to outline the current research landscape in this field. We systematically analyze the literature and specifically note that the current understanding of the association between SPAs and T2DM is predominantly based on hypotheses from animal and cellular experiments, whereas direct human research data remain extremely scarce. This article elaborates on the paradoxical roles of SPAs, potentially increasing disease risk while alleviating complications, and analyzes the underlying regulatory mechanism centered on the balance of the nuclear factor erythroid 2-related factor 2/nuclear factor kappa-light-chain-enhancer of activated B cells pathway. Finally, we emphasize the urgent need for future well-designed, large-scale human studies to fill this critical evidence gap and clarify the precise role of SPAs in T2DM.
Core Tip: This review systematically elucidates the dual regulatory role of synthetic phenolic antioxidants in the development of type 2 diabetes mellitus, identifying the balance of the nuclear factor erythroid 2-related factor 2/nuclear factor kappa-light-chain-enhancer of activated B cells pathway as the core regulatory mechanism. However, current evidence predominantly comes from preclinical studies, making it difficult to extrapolate the findings to human populations.
