Hydroxycitric acid in functional foods: A multitargeted approach to preventing calcium oxalate nephrolithiasis

This review evaluates hydroxycitric acid (HCA), a compound derived from Garcinia cambogia, for its potential in preventing calcium oxalate nephrolithiasis, a common kidney stone disorder. This review aims to clarify HCA's multifaceted mechanisms and its applications in functional foods. HCA inhibits calcium oxalate crystallization by binding calcium ions and reducing crystal adhesion to renal tubular epithelial cells. HCA mitigates oxidative stress and inhibits ferroptosis, a lipid peroxidation-driven cell death, through the nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPX4) pathways, thereby protecting kidney tissue. Incorporating HCA into functional foods, combined with probiotics and dietary fiber, may reduce intestinal oxalate absorption, thereby lowering the risk of stone formation. Preclinical studies demonstrate HCA's potential to inhibit calcium oxalate crystal formation and mitigate oxidative stress, providing novel insights into its synergistic Nrf2/GPX4-mediated ferroptosis inhibition and its potential in functional foods combined with probiotics and dietary fiber. However, the limited number of human clinical trials hinders its translational application, requiring rigorous clinical validation of its efficacy, optimal dosing, and long-term safety to establish HCA as a viable dietary strategy for kidney stone prevention.