Lime-based supplement reduces calcium oxalate stone recurrence: A multicenter randomized controlled trial

Background Recurrent urolithiasis is a major clinical challenge, with more than 50% of patients experiencing recurrence within 5 years. While potassium citrate effectively reduces recurrence, poor adherence due to cost and gastrointestinal side effects limits its long-term use. Citrus-based interventions, such as lime juice, have shown potential in enhancing urinary citrate and alkalinity but require further validation. This study evaluated the efficacy of a lime-based phytochemical-rich regimen (LPR) in preventing stone recurrence and reducing urinary inflammation in post-operative urolithiasis patients. Objective This multicenter, double-blind, randomized controlled trial aimed to evaluate the efficacy and safety of a novel lime-based preparation called LPR in preventing kidney stone recurrence over 24 months. Methods In a double-blind, randomized, placebo-controlled, multicenter trial, 173 patients with calcium oxalate urolithiasis who had undergone successful stone removal were enrolled from six hospitals in Thailand. Participants were randomized to receive either LPR or placebo for 24 months. The primary outcome was the incidence of stone recurrence confirmed by computerized topography (CT). Secondary outcomes included changes in urinary protein excretion and urinary interleukin-8 (IL-8) level, a pro-inflammatory cytokine implicated in renal inflammation and stone formation. Kaplan–Meier survival analysis and multivariate Cox regression were used to assess recurrence risk. Results Of 173 enrolled participants, 151 completed the study. The recurrence rate at 2 years was significantly lower in the LPR group (14%) compared to placebo (45%) (p < 0.001). Kaplan–Meier analysis demonstrated a hazard ratio (HR) of 0.24 (95% CI: 0.13–0.44; log-rank p < 0.0001) favoring LPR. Among completers, LPR significantly reduced urinary IL-8 level (p = 0.017) and 24-hour urinary protein excretion (p = 0.032) compared to baseline and placebo. No serious adverse events were reported, and adherence was high in both groups. Conclusion LPR, a lime-based supplement rich in citrate and flavonoids, significantly reduced the 2-year recurrence rate of calcium oxalate stones by approximately 76%. This effect may be mediated by increased urinary citrate excretion, alkalinization, and attenuation of renal inflammation, as evidenced by reduced urinary IL-8 and proteinuria. LPR was well tolerated, with minimal adverse effects, and may serve as a safe, cost-effective adjunct for secondary prevention in patients intolerant to conventional alkali therapy.