Systematic evaluation and comparison of the

Kidney stone disease (KSD), particularly calcium oxalate (CaOx) type, remains a global health problem. Many efforts have been made to prevent KSD, including the use of some dietary supplements. However, mechanisms underlying their anti-KSD properties have remained poorly understood, and their relative anti-KSD properties have previously been unknown. Herein, we systematically evaluated and compared the inhibitory effects of five well-known dietary supplements on CaOx crystals. Caffeine (CAF), epigallocatechin-3-gallate (EGCG), N-acetylcysteine (NAC), resveratrol (RES) and trigonelline (TRIG) (at 1, 10 and 100 μM, which are within their physiologic levels in the urine) were subjected to CaOx crystallization, growth and aggregation assays. Degrees of their CaOx crystal-inhibitory activities were then compared. CAF inhibited crystal formation, EGCG inhibited crystal formation and growth, NAC inhibited crystal aggregation, RES inhibited crystal growth, and TRIG inhibited crystal formation and growth. However, RES promoted crystal aggregation and thus served as a dual modulator (acting as an inhibitor and promoter at different steps of stone formation). Almost all of these inhibitory effects were concentration-dependent. Comparing the CaOx-inhibitory activities of these compounds revealed that EGCG was the most potent inhibitor against CaOx crystal formation (with the crystal abundance-inhibitory activity of 85.61 ± 5.12 %), whereas RES was the most potent inhibitor against CaOx crystal growth (with the crystal growth-inhibitory activity of 92.99 ± 1.67 %). NAC was the only inhibitor against CaOx crystal aggregation (with the crystal aggregation-inhibitory activity of 22.97 ± 0.75 %). These data indicate the direct inhibitory effects of various dietary supplements against CaOx crystal formation, growth and aggregation, supporting their roles in KSD prevention.