Effects of risperidone on amino acid metabolism, glucose, and kidney function in healthy adults: A pilot randomized controlled trial
d-serine administration prevents kidney damage in murine models of acute kidney injury, and risperidone inhibits the activity of d-amino acid oxidase, which regulate plasma d-amino acid levels. This pilot randomized controlled trial investigated the effects of risperidone on glucose, amino acid metabolism, and kidney function in healthy adults. Healthy adults with a homeostasis model assessment of insulin resistance (HOMA-IR) of ≥ 1.6 and estimated glomerular filtration rate (eGFR) of ≥ 60 mL/min/1.73m2 were randomly assigned to the risperidone and control groups. The risperidone group received 0.5 mg/day risperidone for 4 days. The primary outcome was mean change in HOMA-IR on day 5, and the secondary outcomes were changes in d-amino acid levels, eGFR, and urinary albumin. Seven participants were randomized to the risperidone and control groups. The changes in HOMA-IR, eGFR, and urinary albumin on day 5 were not significantly different between the two groups (all p > 0.05). Mean changes in plasma d-serine level and urinary d-serine/creatinine ratio were significantly higher in the risperidone group than in the control group (0.2 vs. -0.3 nmol/mL, p = 0.03 and 38.2 vs. -25.8 nmol/mL, p = 0.01, respectively). Short-term risperidone affects d-serine metabolism without instigating acute adverse effects on kidney or glucose homeostasis in healthy individuals. Clinical Trial Registry number: This study was registered with the Japan Registry for Clinical Trials (jRCTs041210165).
Authors
- Ryo Nishioka (ORCID: https://orcid.org/0000-0001-8654-7311)
- Yasunori Iwata (ORCID: https://orcid.org/0000-0002-4756-5207)
- Yusuke Nakade (ORCID: https://orcid.org/0000-0002-0094-359X)
- Akira Tamai
- Akihiko Koshino (ORCID: https://orcid.org/0000-0002-9432-2427)
- Masashi Kinoshita (ORCID: https://orcid.org/0000-0002-2148-8231)
- Keisuke Horikoshi
- Taro Miyagawa (ORCID: https://orcid.org/0000-0003-0186-7362)
- Mitsutoshi Nakada (ORCID: https://orcid.org/0000-0001-9419-6101)
- Masashi Mita (ORCID: https://orcid.org/0000-0002-9379-6006)
- Taichiro Minami
- Megumi Oshima (ORCID: https://orcid.org/0000-0002-4108-5229)
- Hisayuki Ogura (ORCID: https://orcid.org/0000-0001-9004-3837)
- Shiori Nakagawa (ORCID: https://orcid.org/0000-0001-6774-7959)
- Toshiaki Tokumaru (ORCID: https://orcid.org/0009-0006-5323-0688)
- Makoto Tsubomoto (ORCID: https://orcid.org/0000-0003-3633-2210)
- Ichiro Mizushima (ORCID: https://orcid.org/0000-0002-6231-0683)
- Keisuke Sako (ORCID: https://orcid.org/0000-0002-6453-8075)
- Norihiko Sakai (ORCID: https://orcid.org/0000-0001-7245-9716)
- Takashi Wada (ORCID: https://orcid.org/0000-0002-0123-3645)
- Miho Shimizu (ORCID: https://orcid.org/0000-0002-7737-935X)
- Sakae Miyagi (ORCID: https://orcid.org/0000-0002-0608-7843)
- Shinji Kitajima (ORCID: https://orcid.org/0000-0002-6532-6496)
- Takahiro Yuasa (ORCID: https://orcid.org/0009-0004-3556-935X)
- Akinori Hara (ORCID: https://orcid.org/0000-0002-0399-1474)
- Mitsuru Kikuchi (ORCID: https://orcid.org/0000-0003-3013-7844)
- Tadashi Toyama (ORCID: https://orcid.org/0000-0003-0162-6286)
- Shunsuke Tsuge
- Kiyoaki Ito
Institutions
- Kanazawa University (JP)
- University of Fukui (JP)
- Kanazawa University Hospital (JP)
- Kagami Crystal (Japan) (JP)
Publication Details
- Journal
- PLoS ONE
- Published
- 2025-12-05
- DOI
- https://doi.org/10.1371/journal.pone.0324222
- Primary Topic
- Amino Acid Enzymes and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 0.00