Sugar reduction in complex food systems: linking metabolic mechanisms, matrix engineering, and safety evaluation

Excessive intake of rapidly absorbable sugars challenges metabolic regulation beyond caloric imbalance. Glucose and fructose differ in absorption kinetics and hepatic metabolic pathways, leading to distinct effects on glycemic dynamics, de novo lipogenesis, insulin signaling, and microbiota-host interactions. Emerging evidence further indicates that sugar bioavailability and metabolic outcomes are strongly influenced by food matrix structure, physicochemical interactions, and processing-induced microstructural changes. This review synthesizes recent advances in understanding these metabolic distinctions and examines how matrix-level reformulation strategies can modulate metabolic responses while preserving functional and sensory performance. Contemporary technological approaches-including non-sugar sweeteners, structural and bulking redesign, multisensory sweetness modulation, and digital formulation tools-are evaluated with attention to ingredient interactions, product stability, and safety profiles. Regulatory and risk-assessment frameworks are discussed in relation to ingredient deployment and translational feasibility. By integrating molecular metabolism with food engineering and safety evaluation, this review proposes a mechanistically grounded framework for the rational design of reduced-sugar foods within complex food systems.