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Natural polyphenols have been widely used for inhibiting the formation of HAAs, whereas the effect of natural polyphenols on HAAs formation is complex and the mechanisms are far from being clearly elucidated. In order to clarify the comprehensive effect of polyphenols on HAAs, this review focused on the structure\u2013activity relationships and effect mechanisms of polyphenols on the formation of HAAs. In addition, the effects of polyphenols on HAAs toxicity were also first reviewed from cell, gene, protein, and animal aspects. An overview of the effect of polyphenol structures such as parent ring and exocyclic group on the mitigation of HAAs was emphasized, aiming to provide some valuable information for understanding their effect mechanism. The HAAs formation is inhibited by natural polyphenols in a dose\u2010dependent manner largely through eliminating free radicals and binding precursors and intermediates. The inhibitory effect was probably affected by the quantity and position of hydroxyl groups in the aromatic rings, and polyphenols with\n                    <jats:italic>m<\/jats:italic>\n                    \u2010hydroxyl group in the aromatic ring had the stronger inhibitory effect. However, the presence of other substituents and excessive hydroxyl groups in natural polyphenols might mitigate the inhibitory effect and even promote the formation of HAAs. This review can provide theoretical reference for effectively controlling the formation of HAAs in thermal\u2010processed food by natural polyphenols and reducing their harm to human health.\n                  <\/jats:p>","DOI":"10.1111\/1541-4337.70032","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T02:14:26Z","timestamp":1731291266000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["A comprehensive review of structure\u2013activity relationships and effect mechanisms of polyphenols on heterocyclic aromatic amines formation in thermal\u2010processed food"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7611-3341","authenticated-orcid":false,"given":"Hao","family":"Dong","sequence":"first","affiliation":[{"name":"College of Light Industry and Food Sciences Zhongkai University of Agriculture and Engineering  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Key Laboratory of Microbiomics and Precision Application, Ministry of Agriculture and Rural Affairs, Institute of Microbiology Guangdong Academy of Sciences  Guangzhou China"},{"name":"School of Biology and Biological Engineering South China University of Technology  Guangzhou China"},{"name":"Guangdong Huankai Microbiology Science &amp; Technology Co., Ltd.  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiping","family":"Ye","sequence":"additional","affiliation":[{"name":"College of Light Industry and Food Sciences Zhongkai University of Agriculture and Engineering  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Bai","sequence":"additional","affiliation":[{"name":"College of Light Industry and Food Sciences Zhongkai University of Agriculture and Engineering  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Zeng","sequence":"additional","affiliation":[{"name":"College of Light Industry and Food Sciences Zhongkai University of Agriculture and Engineering  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingping","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied 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