{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T13:08:48Z","timestamp":1774616928490,"version":"3.50.1"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":35,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"This study was supported by the Kochi Medical School Hospital President\u2019s Discretionary Grant 2025 (SF)."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Med Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u00a0mg\/day for 12\u00a0weeks. 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\u2019 blood pressure and adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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 (\u2212\u20092.29) in the 5-ALA group and from 8.54 to 6.35 (\u2212\u20092.35) in the placebo group (both:\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.008). However, no significant difference was noted between the two groups at week 12 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.956). 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,\u2009\u2212\u20091.63 to 1.75;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.944).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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\u2019s efficacy in patients with OAB, this study holds important value as a pilot study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>This study was prospectively registered in the Japan Registry of Clinical Trials (jRCT); registration number: jRCTs061220050; registration date: [August 29, 2022].<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40001-026-04113-5","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T16:05:56Z","timestamp":1771603556000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oral 5\u2011aminolevulinic acid for overactive bladder: a double\u2011blind, randomized, placebo\u2011controlled pilot trial"],"prefix":"10.1186","volume":"31","author":[{"given":"Satoshi","family":"Fukata","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobutaka","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahira","family":"Kuno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rie","family":"Yoshimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Sugimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayano","family":"Kawaguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshitaka","family":"Kurano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daigo","family":"Takemori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinkuro","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taeko","family":"Nishioka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natsuko","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hajime","family":"Kuroiwa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroko","family":"Iijima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Karashima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiji","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"4113_CR1","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1111\/iju.15454","volume":"31","author":"T Mitsui","year":"2024","unstructured":"Mitsui T, Sekido N, Masumori N, Haga N, Omae K, Saito M, et al. Prevalence and impact on daily life of lower urinary tract symptoms in Japan: results of the 2023 Japan Community Health Survey (JaCS 2023). Int J Urol. 2024;31:747\u201354.","journal-title":"Int J Urol"},{"key":"4113_CR2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222111862","volume":"22","author":"JH Yang","year":"2021","unstructured":"Yang JH, Choi HP, Niu W, Azadzoi KM. Cellular stress and molecular responses in bladder ischemia. Int J Mol Sci. 2021;22:11862.","journal-title":"Int J Mol Sci"},{"key":"4113_CR3","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.812967","volume":"9","author":"Z Xu","year":"2022","unstructured":"Xu Z, Elrashidy RA, Li B, Liu G. Oxidative stress: a putative link between lower urinary tract symptoms and aging and major chronic diseases. Front Med. 2022;9:812967.","journal-title":"Front Med"},{"key":"4113_CR4","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22116014","volume":"22","author":"YH Wu","year":"2021","unstructured":"Wu YH, Chueh KS, Chuang SM, Long CY, Lu JH, Juan YS. Bladder hyperactivity induced by oxidative stress and bladder ischemia: a review of treatment strategies with antioxidants. Int J Mol Sci. 2021;22:6014.","journal-title":"Int J Mol Sci"},{"key":"4113_CR5","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-4-66","volume":"4","author":"S Ogura","year":"2011","unstructured":"Ogura S, Maruyama K, Hagiya Y, Sugiyama Y, Tsuchiya K, Takahashi K, et al. The effect of 5-aminolevulinic acid on cytochrome c oxidase activity in mouse liver. BMC Res Notes. 2011;4:66.","journal-title":"BMC Res Notes"},{"key":"4113_CR6","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s40360-016-0108-3","volume":"18","author":"U Ota","year":"2017","unstructured":"Ota U, Hara T, Nakagawa H, Tsuru E, Tsuda M, Kamiya A, et al. 5-aminolevulinic acid combined with ferrous ion reduces adiposity and improves glucose tolerance in diet-induced obese mice via enhancing mitochondrial function. BMC Pharmacol Toxicol. 2017;18:7.","journal-title":"BMC Pharmacol Toxicol"},{"key":"4113_CR7","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.ejphar.2018.05.009","volume":"833","author":"H Ito","year":"2018","unstructured":"Ito H, Nishio Y, Hara T, Sugihara H, Tanaka T, Li XK. Oral administration of 5-aminolevulinic acid induces heme oxygenase-1 expression in peripheral blood mononuclear cells of healthy human subjects in combination with ferrous iron. Eur J Pharmacol. 2018;833:25\u201333.","journal-title":"Eur J Pharmacol"},{"key":"4113_CR8","doi-asserted-by":"publisher","first-page":"1813","DOI":"10.1016\/j.bbagen.2017.03.018","volume":"1861","author":"TA Takeda","year":"2017","unstructured":"Takeda TA, Sasai M, Adachi Y, Ohnishi K, Fujisawa JI, Izawa S, et al. Potential role of heme metabolism in the inducible expression of heme oxygenase-1. Biochim Biophys Acta Gen Subj. 2017;1861:1813\u201322.","journal-title":"Biochim Biophys Acta Gen Subj"},{"key":"4113_CR9","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.urology.2006.02.042","volume":"68","author":"Y Homma","year":"2006","unstructured":"Homma Y, Yoshida M, Seki N, Yokoyama O, Kakizaki H, Gotoh M, et al. Symptom assessment tool for overactive bladder syndrome: overactive bladder symptom score. Urology. 2006;68:318\u201323.","journal-title":"Urology"},{"key":"4113_CR10","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1002\/nau.22559","volume":"34","author":"KS Coyne","year":"2015","unstructured":"Coyne KS, Thompson CL, Lai JS, Sexton CC. An overactive bladder symptom and health-related quality of life short form: validation of the OAB-q SF. Neurourol Urodyn. 2015;34:255\u201363.","journal-title":"Neurourol Urodyn"},{"key":"4113_CR11","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1111\/iju.14928","volume":"29","author":"T Kuno","year":"2022","unstructured":"Kuno T, Shimizu T, Kawada C, Kurabayashi A, Zou S, Mogawa H, et al. 5-aminolevulinic acid has the potential to prevent bladder dysfunction in cyclophosphamide-induced hemorrhagic cystitis. Int J Urol. 2022;29:897\u2013904.","journal-title":"Int J Urol"},{"key":"4113_CR12","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1111\/iju.15226","volume":"30","author":"T Hara","year":"2023","unstructured":"Hara T. Heterogeneity of placebo effects on urinary incontinence in overactive bladder syndrome: a meta-analysis of Japanese placebo-controlled clinical trials. Int J Urol. 2023;30:896\u2013905.","journal-title":"Int J Urol"},{"key":"4113_CR13","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1186\/s12885-021-08976-1","volume":"21","author":"H Fukuhara","year":"2021","unstructured":"Fukuhara H, Nohara T, Nishimoto K, Hatakeyama Y, Hyodo Y, Okuhara Y, et al. Identification of risk factors associated with oral 5-aminolevulinic acid\u2013induced hypotension in photodynamic diagnosis for non\u2013muscle-invasive bladder cancer: a multicenter retrospective study. BMC Cancer. 2021;21:1223.","journal-title":"BMC Cancer"},{"key":"4113_CR14","doi-asserted-by":"publisher","DOI":"10.1016\/j.pdpdt.2021.102342","volume":"34","author":"S Nakatani","year":"2021","unstructured":"Nakatani S, Ida M, Wang X, Naito Y, Kawaguchi M. Oral 5-aminolevulinic acid administration prior to transurethral resection of bladder tumor causes intraoperative hypotension: propensity score analysis. Photodiagnosis Photodyn Ther. 2021;34:102342.","journal-title":"Photodiagnosis Photodyn Ther"}],"container-title":["European Journal of Medical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40001-026-04113-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40001-026-04113-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40001-026-04113-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T12:23:50Z","timestamp":1774614230000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s40001-026-04113-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,20]]},"references-count":14,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4113"],"URL":"https:\/\/doi.org\/10.1186\/s40001-026-04113-5","relation":{},"ISSN":["2047-783X"],"issn-type":[{"value":"2047-783X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,20]]},"assertion":[{"value":"8 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was prospectively registered in the Japan Registry of Clinical Trials (jRCT; registration number: jRCTs061220050) and approved by the institutional review boards of all participating centers, including the ethics committee of Kochi Medical School. Written informed consent was obtained from all participants prior to enrollment. This study was conducted in accordance with the principles of the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent for publication was obtained from all participants.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interest"}}],"article-number":"453"}}