Impact of sugar substitute consumption on the development of diabetes and obesity

Abstract

The consumption of sugar substitutes, particularly non-nutritive sweeteners, has increased significantly as a strategy for body weight management and glycemic regulation. Despite being promoted as safe, some studies suggest that these substitutes may disrupt glycemic homeostasis and insulin sensitivity, negatively impacting glucose regulation; consequently, concerns have been raised regarding their health benefits and risks. This article presents a literature review aimed at identifying molecular and pathophysiological mechanisms. A total of 61 publications were selected, including systematic reviews, primary studies (preclinical in vitro and in vivo, and human trials), and technical reports from the World Health Organization (WHO), the Pan American Health Organization (PAHO), and the American Diabetes Association (ADA). The findings demonstrate heterogeneous effects on glycemic regulation depending on the specific type of substitute evaluated. Compounds such as stevia, neotame, and erythritol showed benefits in reducing glucose and insulin levels. In contrast, others—including acesulfame-K, aspartame, and sorbitol—were associated with metabolic alterations, intestinal dysbiosis, and an increased risk of type 2 diabetes and obesity. Specifically, acesulfame-K and aspartame are linked to a higher risk of type 2 diabetes, while acesulfame-K and saccharin promote weight gain through metabolic shifts and gut microbiota alterations. Although these effects depend on their chemical nature and metabolism, most available trials are short-term, and long-term evidence in humans remains insufficient. This underscores the need for further research to evaluate their sustained impact on metabolic regulation and the intestinal microbiota