Effects of artificial and natural sweeteners on host metabolic health: A double-edged sword

Humans have an innate preference for sweetness, with dietary sugar consumption patterns established early in life. While moderate intake of naturally occurring sugars from whole foods supports metabolic and physiological functions, excessive consumption of free sugars, particularly those added during processing, such as in sugar-sweetened beverages (SSB), is a major contributor to obesity and metabolic syndrome. As a result, non-sugar sweeteners (NSS) have been widely adopted as sugar substitutes to reduce caloric intake. However, emerging evidence suggests that NSS consumption may be associated with metabolic disturbances. This review provides a critical and comprehensive evaluation of recent findings on the effects of artificial sweeteners (AS) and natural sweeteners (NS) on weight management, appetite regulation, glucose and lipid homeostasis, cardiovascular health, liver function, and intestinal equilibrium. We summarize the dual nature of AS and NS in regulating host metabolism through receptor signaling, hormonal modulation, neural regulation, and generational inheritance, highlighting their potential benefits while also revealing adverse metabolic consequences under certain conditions. We elucidate the specific molecular pathways involved and the complex interactions between NSS and host metabolism, addressing the potential reasons for inconsistencies in current research findings and suggesting future research directions. This review emphasizes the necessity of personalized dietary strategies and balanced NSS consumption to provide evidence-based dietary recommendations for both healthy individuals and those with metabolic disorders, ultimately aiming to mitigate the risk of metabolic syndrome.