Triheptanoin improves brain energy metabolism in patients with Huntington disease

Neurology. 2015 Feb 3;84(5):490-5. doi: 10.1212/WNL.0000000000001214. Epub 2015 Jan 7.


Objective: Based on our previous work in Huntington disease (HD) showing improved energy metabolism in muscle by providing substrates to the Krebs cycle, we wished to obtain a proof-of-concept of the therapeutic benefit of triheptanoin using a functional biomarker of brain energy metabolism validated in HD.

Methods: We performed an open-label study using (31)P brain magnetic resonance spectroscopy (MRS) to measure the levels of phosphocreatine (PCr) and inorganic phosphate (Pi) before (rest), during (activation), and after (recovery) a visual stimulus. We performed (31)P brain MRS in 10 patients at an early stage of HD and 13 controls. Patients with HD were then treated for 1 month with triheptanoin after which they returned for follow-up including (31)P brain MRS scan.

Results: At baseline, we confirmed an increase in Pi/PCr ratio during brain activation in controls-reflecting increased adenosine triphosphate synthesis-followed by a return to baseline levels during recovery (p = 0.013). In patients with HD, we validated the existence of an abnormal brain energy profile as previously reported. After 1 month, this profile remained abnormal in patients with HD who did not receive treatment. Conversely, the MRS profile was improved in patients with HD treated with triheptanoin for 1 month with the restoration of an increased Pi/PCr ratio during visual stimulation (p = 0.005).

Conclusion: This study suggests that triheptanoin is able to correct the bioenergetic profile in the brain of patients with HD at an early stage of the disease.

Classification of evidence: This study provides Class III evidence that, for patients with HD, treatment with triheptanoin for 1 month restores an increased MRS Pi/PCr ratio during visual stimulation.

Trial registration: NCT01696708 NCT01882062.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain / drug effects
  • Brain / metabolism*
  • Energy Metabolism / drug effects
  • Energy Metabolism / physiology*
  • Female
  • Humans
  • Huntington Disease / drug therapy*
  • Huntington Disease / metabolism*
  • Magnetic Resonance Spectroscopy / methods
  • Male
  • Middle Aged
  • Triglycerides / pharmacology
  • Triglycerides / therapeutic use*
  • Young Adult


  • Triglycerides
  • triheptanoin

Associated data