Flavonoids for gastrointestinal tract local and associated systemic effects: A review of clinical trials and future perspectives

Xiaopeng Li; Enjun Xie; Shumin Sun; Jie Shen; Yujin Ding; Jiaqi Wang; Xiaoyu Peng; Ruting Zheng; Mohamed A Farag; Jianbo Xiao

doi:10.1016/j.jare.2025.01.014

Flavonoids for gastrointestinal tract local and associated systemic effects: A review of clinical trials and future perspectives

J Adv Res. 2025 Jan 9:S2090-1232(25)00033-5. doi: 10.1016/j.jare.2025.01.014. Online ahead of print.

Authors

Xiaopeng Li¹, Enjun Xie², Shumin Sun², Jie Shen², Yujin Ding³, Jiaqi Wang⁴, Xiaoyu Peng⁴, Ruting Zheng⁴, Mohamed A Farag⁵, Jianbo Xiao⁶

Affiliations

¹ Center of Nutrition and Food Sciences Hunan Agricultural Products Processing Institute Hunan Academy of Agricultural Sciences Changsha China. Electronic address: xiaopengli@hunaas.cn.
² School of Public Health Zhejiang University School of Medicine Hangzhou China.
³ National Clinical Research Center for Metabolic Diseases Metabolic Syndrome Research Center Department of Metabolism and Endocrinology The Second Xiangya Hospital of Central South University Changsha China.
⁴ Ausnutria Dairy Co., Ltd., Changsha 410200 China.
⁵ Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo 11562 Egypt.
⁶ Universidade de Vigo, Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Instituto de Agroecoloxía e Alimentación (IAA) - CITEXVI 36310 Vigo, Spain; Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Isabel Torres 21 39011 Santander, Spain. Electronic address: jianboxiao@uvigo.gal.

PMID: 39798849
DOI: 10.1016/j.jare.2025.01.014

Abstract

Background: Flavonoids are naturally occurring dietary phytochemicals with significant antioxidant effects aside from several health benefits. People often consume them in combination with other food components. Compiling data establishes a link between bioactive flavonoids and prevention of several diseases in animal models, including cardiovascular diseases, diabetes, gut dysbiosis, and metabolic dysfunction-associated steatotic liver disease (MASLD). However, numerous clinical studies have demonstrated the ineffectiveness of flavonoids contradicting rodent models, thereby challenging the validity of using flavonoids as dietary supplements.

Aim of review: This review provides a clinical perspective to emphasize the effective roles of dietary flavonoids as well as to summarize their specific mechanisms in animals briefly.

Key scientific concepts of review: First, this review offers an in-depth elucidation of the metabolic processes of flavonoids within human, encompassing the small, large intestine, and the liver. Furthermore, the review provides a comprehensive overview of the various functions of flavonoids in the gastrointestinal tract, including hindering the breakdown and assimilation of macronutrients, such as polysaccharides and lipids, regulating gut hormone secretion as well as inhibition of mineral iron absorption. In the large intestine, an unabsorbed major portion of flavonoids interact with the gut flora leading to their biotransformation. Once absorbed and circulated in the bloodstream, bioactive flavonoids or their metabolites exert numerous beneficial systemic effects. Lastly, we examine the protective effects of flavonoids in several metabolic disorders, including endothelial dysfunction, MASLD, cardiovascular disease, obesity, hyperlipidemia, and insulin resistance. In conclusion, this review outlines the safety and future prospects of flavonoids in the field of health, especially in the prevention of metabolic syndrome (MetS).

Keywords: Clinical evidence; Dietary flavonoids; Health benefits; Metabolic disorder; Metabolism.

Publication types

Review