Randomized controlled trial on the regulation of MMP-9-NGAL ratio in diabetic patients with early renal dysfunction by Piper crocatum Ruiz & Pav. functional foods

Context: Diabetic nephropathy (DN) remains a leading cause of end-stage renal disease, largely driven by inflammation and oxidative stress. Piper crocatum is rich in bioactive compounds with antioxidant and anti-inflammatory effects. Aims: To evaluate the effects of P. crocatum-enriched functional foods on renal biomarkers in diabetic patients with early renal dysfunction. Methods: A 12-week double-blind, randomized, placebo-controlled trial was conducted among 387 diabetic adults with mild renal impairment. Participants consumed either P. crocatum-enriched cookies or placebo cookies. Serum matrix metalloproteinase-9 (MMP-9), neutrophil gelatinase-associated lipocalin (NGAL), and the MMP-9-NGAL ratio were measured pre- and post-intervention. Results: Compared with placebo, P. crocatum significantly reduced MMP-9 (518.45 to 350.34 ng/mL, false discovery rate (FDR)-adjusted p=0.0003), NGAL (195.67 to 174.31 ng/mL, FDR-adjusted p=0.0016), and the MMP-9-NGAL ratio (2.65 to 1.99, FDR-adjusted p=0.0011). Effect sizes were large. The placebo showed minimal changes. Conclusions: P. crocatum supplementation improved renal inflammation and oxidative stress markers, suggesting its potential as an adjunct therapy for DN.