Beyond Sweetness: Evaluating the Bioactivity and Safety of Chemical Sugar Substitutes and Natural Functional Polysaccharides

With the global pandemic of obesity, type 2 diabetes mellitus (T2DM), and other metabolic syndromes, excessive sucrose intake has been widely recognized as a core modifiable risk factor for chronic non-communicable diseases. Driven by rising global health awareness, the market demand for sugar substitutes has undergone a fundamental transformation: from the initial goal of simple calorie reduction and sucrose replacement to the pursuit of additional functional health benefits while reducing sugar intake. Against this background, this paper systematically evaluates the performance, advantages, and limitations of two major categories of sugar substitutes: chemical synthetic sweeteners (CSS) and natural functional polysaccharides (NPs), with a specific focus on polysaccharides extracted from white hyacinth beans (Lablab purpureus (L.) Sweet), a classic medicinal and edible homologous plant in China. For CSS represented by aspartame, sucralose, and acesulfame potassium, their core advantages lie in ultra-high sweetness intensity (up to 600 times that of sucrose), zero or near-zero caloric value, and low production cost, which have made them dominate the global sugar substitute market for decades. However, emerging toxicological studies, clinical trials, and cohort studies in recent 5 years have gradually revealed the potential long-term risks of CSS intake, including disruption of gut microbiota homeostasis, impairment of intestinal barrier integrity, induction of glucose intolerance and insulin resistance, and even increased risk of metabolic syndrome. In contrast, NPs derived from medicinal and edible plants, especially the white hyacinth bean polysaccharides (WHBP) and white hyacinth flower polysaccharides (WHFP) focused on in this study, exhibit multiple biological activities and health benefits beyond simple sucrose replacement. In this study, we adopted a green extraction strategy combining composite enzymatic hydrolysis and low-temperature ultrasound, which achieved a polysaccharide purity of ≥65% and a biological activity retention rate of ≥90%, avoiding the activity loss caused by traditional high-temperature extraction. Furthermore, microbial fermentation modification with Bacillus subtilis or Lactobacillus casei significantly reduced the molecular weight of WHBP (from 87.7 kDa to 45.8 kDa) and WHFP (from 106.387 kDa to 36.364 kDa), exposing more active hydroxyl and carboxyl groups, thus further enhancing their biological activities. A series of in vitro and in vivo experiments confirmed that the fermented WHBP and WHFP have strong free radical scavenging capacity, significant inhibitory effect on α-amylase activity to reduce postprandial blood glucose, excellent bile salt binding capacity to regulate cholesterol metabolism, and prebiotic effects to modulate gut microbiota. This study not only systematically compares the safety and functionality of CSS and NPs through multi-dimensional evidence, but also provides theoretical support and technical reference for the development of new-generation functional sugar substitutes based on medicinal and edible plant polysaccharides, as well as the high-value utilization of white hyacinth bean resources.