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A Review of the Role of Fructose in the Development of Metabolic Diseases: From Diabetes to Cancer

Articles in Press

Document Type : Review Article

Authors

1 Division of Hematology and Blood Bank, Department of Medical Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

2 Diagnostic Laboratory Science and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

10.30476/smsj.2025.106508.1621

Abstract

Excessive dietary fructose intake is strongly associated with an increased prevalence of metabolic disorders, including obesity, type 2 diabetes, cardiovascular diseases, autoimmune conditions, and various cancers. The global rise in metabolic disorders, notably in Iran, underscores the growing burden of these diseases. This review was conducted through an extensive search in databases and motor search engines, such as Google Scholar, PubMed, Science Direct, and Research Gate, using keywords pertinent to the subject, including fructose, metabolic diseases, high-fructose corn syrup, zonulin, and microbiome, from 1979 to 2025. Recent studies indicated that low-dose fructose is primarily metabolized in the small intestine, whereas excessive consumption leads to the overflow of fructose into the liver for metabolism. A high-fructose diet can increase intestinal permeability and circulating endotoxins by elevating zonulin levels, which disrupts tight junction proteins in the intestinal epithelium and alters gut microbiota composition. These alterations, driven by increased bacterial endotoxins and subsequent inflammation in the liver and peripheral tissues, can suppress insulin signaling, leading to insulin resistance and the development of diverse metabolic disorders. Elevated levels of zonulin is also significantly correlated with metabolic disease pathogenesis. Therefore, minimizing the consumption of fructose-sweetened beverages and foods is a crucial lifestyle factor for the prevention of metabolic diseases.

Keywords

References
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