Ergothioneine Supplementation and Patient-Reported Urological Symptoms in Adults with Mildly Reduced or Borderline Renal Function: An Exploratory Open-Label Trial
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Background
Early renal function decline is often accompanied by bothersome urological symptoms, yet effective early-stage nutritional interventions remain limited. L-Ergothioneine (EGT), a diet-derived antioxidant concentrated in renal tissue via the OCTN1 transporter, has shown renoprotective potential preclinically, but human interventional data are sparse.
Methods
In this single-center, open-label, self-controlled trial, 31 adults (aged 45–70 years) with early renal function decline and persistent urological symptoms (≥3 months) received oral EGT (120 mg/day) for 90 days; 27 completed the study. Participants served as their own controls. The primary outcome was the within-subject change in eGFR (CKD-EPI 2021 creatinine); secondary outcomes included cystatin C-based eGFR, serum creatinine, UACR, a 10-item voiding diary, and a low-back-pain visual analogue scale (VAS). Within-subject changes were assessed by paired t-test or Wilcoxon signed-rank test.
Results
Creatinine-based eGFR increased from 86.04 ± 17.89 to 93.25 ± 19.00 mL/min/1.73 m² (+8.4%; p = 0.0016) and serum creatinine fell by 7.0% (p = 0.015). However, cystatin C-based eGFR and serum cystatin C were unchanged (p = 0.31 and p = 0.99), so the filtration signal was not corroborated by an independent, muscle-mass-independent marker. UACR showed a non-significant downward trend. Patient-reported outcomes improved most robustly: the total voiding diary score decreased by 57.2% (p < 0.0001) and low-back-pain VAS by 67.2% (p = 0.0002), with significant relief of urgency, frequency, and voiding difficulty. No product-related adverse events occurred.
Conclusions
In this uncontrolled study, 90-day EGT supplementation was associated with marked improvement in urological symptoms and in creatinine-based eGFR, although the latter was not confirmed by cystatin C. These changes cannot be attributed to EGT alone and may substantially reflect placebo and natural-history effects. The findings are hypothesis-generating and warrant confirmation in a randomized, placebo-controlled trial using validated symptom instruments.
Trial Registration
ChiCTR2500108897; Prospectively registered on 2025-09-08.