Effect of High‑Dose Oral Vitamin C on 24‑Hour Urinary Oxalate Excretion: A Systematic Review and Meta‑analysis of Intervention Trials

Abstract

Background: High-dose oral vitamin C (≥ 1,000 mg/day) is widely consumed, yet its impact on 24-hour urinary oxalate—a primary driver of calcium oxalate supersaturation—remains a critical clinical concern, particularly for patients with nephrolithiasis. This study evaluated the effect of high-dose vitamin C on changes in 24-hour urinary oxalate concentration, with specific subgroup analyses comparing stone formers (SF) to non-stone formers (NSF).
Methods: We conducted a systematic review and random-effects meta-analysis of human intervention trials published between January 2000 and December 2025. Eligible studies included adults receiving oral vitamin C (≥1,000 mg/day) for >2 days, with documented 24-hour urinary oxalate measurements.
Results: Three short-term trials (n=141$; SF=59, NSF=82) were included. In the primary analysis (r=0.50), high-dose vitamin C significantly increased 24-hour urinary oxalate concentration by a pooled mean difference (MD) of 9.57 mg/day (95% CI: 0.56 to 18.57; I2=96.4 %). Subgroup analysis revealed a significantly larger increase in SF (MD 15.86 mg/day; 95% CI: 5.01 to 26.70) compared to NSF (MD 6.76 mg/day; 95% CI: 0.28 to 13.24; p < 0.001). While the magnitude of statistical significance for the overall and NSF effects was sensitive to the correlation coefficient, the direction of the effect remained consistently positive. 
Conclusion: High-dose oral vitamin C is associated with increased 24-hour urinary oxalate excretion, with a more pronounced effect observed in the SF group. Given the high heterogeneity and the sensitivity of the results, supplementation in high-risk individuals should be managed with caution.