Work

Effect of Oral Creatine Supplementation on Plasma, Central, and Peripheral Creatine Levels in Creatine Transporter Deficiency Mice

Year: 2026

Type: article

Abstract: PURPOSE: Creatine transporter deficiency (CRTD) is characterized by severe brain creatine depletion due to creatine transporter (CRT) dysfunction. Although oral creatine supplementation has been explored as a therapy, its effects under CRT-deficient conditions remain unclear. Here, we aimed to investigate the impact of oral creatine supplementation on creatine distribution in plasma, brain, and peripheral tissues using CRTD model mice. METHODS: , CRT-KI), and wild-type male mice (WT). RESULTS: Oral creatine supplementation significantly increased plasma creatine in both CRT-KO and CRT-KI mice but failed to restore creatine levels in the brain. Conversely, creatine levels increased markedly in the liver and kidney. Urinary creatine and the creatine-to-creatinine ratio, a key diagnostic biomarker for CRTD, were substantially elevated, exceeding diagnostic thresholds even in WT mice. CONCLUSIONS: Oral creatine increases systemic creatine but fails to restore brain creatine under CRT-deficient conditions, underscoring the crucial role of CRT-mediated blood-brain barrier (BBB) uptake and the need to restore creatine transport across the BBB to elevate brain creatine levels. Furthermore, creatine intake should be controlled for proper diagnostic biomarker interpretation.

Source: Pharmaceutical Research

DOI: 10.1007/s11095-026-04217-x