Triheptanoin dramatically reduces paroxysmal motor disorder in patients with GLUT1 deficiency

J Neurol Neurosurg Psychiatry. 2016 May;87(5):550-3. doi: 10.1136/jnnp-2015-311475. Epub 2015 Nov 3.


Objective: On the basis of our previous work with triheptanoin, which provides key substrates to the Krebs cycle in the brain, we wished to assess its therapeutic effect in patients with glucose transporter type 1 deficiency syndrome (GLUT1-DS) who objected to or did not tolerate ketogenic diets.

Methods: We performed an open-label pilot study with three phases of 2 months each (baseline, treatment and withdrawal) in eight patients with GLUT1-DS (7-47 years old) with non-epileptic paroxysmal manifestations. We used a comprehensive patient diary to record motor and non-motor paroxysmal events. Functional (31)P-NMR spectroscopy was performed to quantify phosphocreatine (PCr) and inorganic phosphate (Pi) within the occipital cortex during (activation) and after (recovery) a visual stimulus.

Results: Patients with GLUT1-DS experienced a mean of 30.8 (± 27.7) paroxysmal manifestations (52% motor events) at baseline that dropped to 2.8 (± 2.9, 76% motor events) during the treatment phase (p = 0.028). After withdrawal, paroxysmal manifestations recurred with a mean of 24.2 (± 21.9, 52% motor events; p = 0.043). Furthermore, brain energy metabolism normalised with triheptanoin, that is, increased Pi/PCr ratio during brain activation compared to the recovery phase (p = 0.021), and deteriorated when triheptanoin was withdrawn.

Conclusions: Treatment with triheptanoin resulted in a 90% clinical improvement in non-epileptic paroxysmal manifestations and a normalised brain bioenergetics profile in patients with GLUT1-DS.

Trial registration number: NCT02014883.


Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Chorea / drug therapy*
  • Chorea / genetics*
  • Energy Metabolism / drug effects
  • Female
  • Functional Neuroimaging
  • Glucose Transporter Type 1 / deficiency*
  • Glucose Transporter Type 1 / genetics*
  • Humans
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Occipital Lobe / metabolism
  • Phosphates / metabolism
  • Phosphocreatine / metabolism
  • Pilot Projects
  • Triglycerides / pharmacology
  • Triglycerides / therapeutic use*
  • Young Adult


  • Glucose Transporter Type 1
  • Phosphates
  • SLC2A1 protein, human
  • Triglycerides
  • Phosphocreatine
  • triheptanoin

Associated data