Abstract Background 5-Aminolevulinic acid (5-ALA) reportedly improves overactive bladder (OAB) symptoms by reducing reactive oxygen species derived from vascular endothelial cells to protect vascular function and enhance bladder blood flow and by inhibiting bladder C-fiber activity. This double-blind, randomized controlled trial aimed to evaluate the efficacy and safety of 5-ALA in participants with OAB. Methods This randomized, prospective study classified the participants into the 5-ALA and placebo groups. The 5-ALA group received oral 5-ALA phosphate at 150 mg/day for 12 weeks. The efficacy of 5-ALA was determined by assessing the changes in the Overactive Bladder Symptom Score (OABSS) and the Overactive Bladder Questionnaire Short Form from baseline to weeks 4 and 12 after treatment initiation, as well as the post-void residual urine volume. Regarding safety, we evaluated participants’ blood pressure and adverse events. Results This study enrolled and randomized 49 participants, with 23 in the 5-ALA group and 26 in the placebo group. Ultimately, 47 participants completed the study (21 and 26 in the 5-ALA and placebo groups, respectively). From baseline to week 12, OABSS significantly decreased from 8.81 to 6.52 (− 2.29) in the 5-ALA group and from 8.54 to 6.35 (− 2.35) in the placebo group (both: p = 0.008). However, no significant difference was noted between the two groups at week 12 ( p = 0.956). Using a mixed model for repeated measures with a random intercept, the model-adjusted between-group difference in the change from baseline to week 12 in the OABSS between the 5-ALA and placebo groups was 0.06 points (95% confidence interval, − 1.63 to 1.75; p = 0.944). Conclusions This study found no significant improvement in OAB symptoms with 5-ALA administration. Nevertheless, given that no previous double-blind, randomized controlled trial has assessed 5-ALA’s efficacy in patients with OAB, this study holds important value as a pilot study. Trial registration This study was prospectively registered in the Japan Registry of Clinical Trials (jRCT); registration number: jRCTs061220050; registration date: August 29, 2022.
Fukata et al. (2026) studied this question.