A structurally engineered β-alanine complex with enhanced multi-matrix stability, improved oral bioavailability, and reduced sensory side effects

Abstract

β-Alanine supplementation enhances skeletal muscle carnosine synthesis but is commonly associated with concentration-dependent paresthesia that may compromise user acceptability. This study aimed to develop a structurally engineered β-alanine complex (TriBsyn) with improved physicochemical stability and compatibility across diverse liquid and semi-solid matrices, and to evaluate its oral bioavailability and sensory tolerability compared with a conventional β-alanine formulation in healthy aged participants. Solid-state characterization was performed using FT-IR, XRD, particle size distribution, zeta potential analysis, FE-SEM, and TGA–DTA. In vitro release was assessed under simulated physiological conditions. Stability and compatibility were evaluated across aqueous, saline, protein-based, acidic carbonated, and dairy matrices under real-time and accelerated conditions. The engineered formulation exhibited favorable multi-matrix stability (>98% active retention) without physical instability and demonstrated a moderated release profile compared with conventional β-alanine. Thermal analysis supported structural modification with altered decomposition behavior. In a randomized, double-blind, crossover clinical study (n = 12), the β-alanine complex showed significantly higher systemic exposure (approximately 4-fold higher AUC and nearly 3-fold higher C_max; p < 0.001). Despite enhanced exposure, paresthesia intensity and sensory burden were reduced, with improvements in mood, anxiety-related descriptors, and pain perception measures (p < 0.001). These findings suggest that structural engineering of β-alanine may improve oral bioavailability while modulating release characteristics and reducing sensory side effects, providing preliminary support for advanced amino acid delivery systems in functional food applications.