Food sweeteners: Angels or clowns for human health?

With the global prevalence of obesity and diabetes continuing to rise, metabolic diseases caused by excessive sugar intake have become a significant public health issue. In this context, various sweeteners as sugar substitutes have been widely used in the food industry. Sweeteners are highly favored for their good safety profile, cost-effectiveness, low-calorie properties, and potential blood sugar regulation effects, and their applications have extended to fields such as pharmaceuticals and daily chemicals. However, recent studies indicate that the impact mechanisms of sweeteners on human health are more complex than previously understood, and the long-term safety of their use has sparked widespread concern in both academia and the public. This review systematically examines relevant literature from the past three decades, employing evidence-based medicine methods for screening and meta-analysis, aiming to comprehensively assess the potential effects of sweeteners on human metabolic indicators (including blood glucose homeostasis and body fat composition) and cancer risk. The discussion will unfold in the following four sections: (1) Definition and classification of sweeteners; (2) Application areas of various sweeteners; (3) Beneficial effects of sweetener use on human health; (4) Adverse effects of sweetener use on health issues in different population groups. Current evidence suggests that the rational use of specific types of sweeteners within recommended dosage ranges can effectively improve blood glucose control, promote weight management, and play a positive role in maintaining oral health. However, excessive or long-term use of certain sweeteners may disrupt gut microbiota balance, affect glucose and lipid metabolism homeostasis, increase cardiovascular disease risk, and potentially be associated with the occurrence of certain malignant tumors. Notably, sweetener exposure during pregnancy may affect the fetus through mechanisms such as epigenetic modifications, necessitating special caution in sweetener selection for pregnant women. This review aims to provide clinicians, nutritionists, and food science professionals with the latest evidence-based medical evidence, guiding consumers to make informed sweetener choices by weighing health benefits against potential risks. It also offers scientific basis for formula optimization and product development in the food industry, thereby promoting public health.