Nobiletin and tangeretin (NoT) are flavonoids derived from the peel of Citrus depressa, and they have been found to modulate circadian rhythms. Because nocturia can be considered a circadian rhythm disorder, we investigated the efficacy of NoT for treating nocturia. A randomized, placebo-controlled, double-blind, crossover study was conducted. The trial was registered with the Japan Registry of Clinical Trials (jRCTs051180071). Nocturia patients aged ≥50 years who presented nocturia more than 2 times on a frequency-volume chart were recruited. Participants received NoT or a placebo (50 mg once daily for 6 weeks), followed by a washout period of ≥2 weeks. The placebo and NoT conditions were then switched. Changes in nocturnal bladder capacity (NBC) were the primary endpoint, and changes in nighttime frequency and nocturnal polyuria index (NPi) were secondary endpoints. Forty patients (13 women) with an average age of 73.5 years were recruited for the study. Thirty-six completed the study, while four withdrew. No adverse events directly related to NoT were observed. NoT had little effect on NBC compared with the placebo. In contrast, NoT significantly changed nighttime frequency by -0.5 voids compared with the placebo (p = 0.040). The change in NPi from baseline to the end of NoT was significant (-2.8%, p = 0.048). In conclusion, NoT showed little change in NBC but resulted in decreased nighttime frequency with a tendency toward reduced NPi.
Journal of clinical medicine. 2023 Apr 07*** epublish ***
Haruki Ito, Hiromitsu Negoro, Jin Kono, Naoki Hayata, Takayoshi Miura, Yumi Manabe, Yu Miyazaki, Mutsuki Mishina, Je Tae Woo, Naoki Sakane, Hiroshi Okuno
Department of Urology, National Hospital Organization, Kyoto Medical Center, Kyoto 612-8555, Japan., Department of Urology, Institute of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan., Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan., Department of Biological Chemistry, College of Bioscience and Biotechnology, Chubu University, Kasugai 487-8501, Japan., Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization, Kyoto Medical Center, Kyoto 612-8555, Japan.