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Triheptanoin Ups Brain Energy in Huntington’s Dementia

Triheptanoin (brand name Dojolvi), an MCT oil
Triheptanoin is available as a supplement or by prescription. A series of studies suggest it improves brain energy metabolism for people with Huntington's disease. Learn how. (Video+Article)

Triheptanoin is an MCT (Medium Chain Triglyceride) oil. The synthetic oil appears to increase the efficacy of the ketogenic diet as a treatment for certain brain disorders, such as Huntington’s disease. Triheptanoin produces helpful ketone bodies with five carbon atoms. These ketone bodies easily cross the blood–brain barrier and enter the brain.

First Study

One early study, suggesting hope for people with Huntington’s disease, is published in the online issue of Neurology®, the medical journal of the American Academy of Neurology. (Continued below video…)

Huntington’s disease is inherited and causes nerve cells to break down in the brain, especially areas involved in the control of movements, memory and thinking abilities, and emotions and behavior. A child of a parent with Huntington’s disease has a 50 percent chance of developing the disease. Symptoms usually appear between the ages of 30 to 50.

Improved Movement & Motor Skills in Huntington’s

“Our study suggests that this drug in the form of oil may be able to improve the brain metabolic profile in early stages of the disease,” said study author Fanny Mochel, MD, PhD, with Pitié-Salpêtrière University hospital in Paris, France. “Although the results should be taken with great caution because researchers and participants in the study knew whether or not they were getting the drug, we saw improvement in movement and motor skills in people with Huntington’s after one month of therapy.”

For the study, researchers used MRI brain scans to analyze the energy profile before, during and after the brain was visually stimulated in nine people in the early stages of Huntington’s disease and 13 people without the disease. The average age of the participants was 46. The test was then repeated one month later. In the people without the disease, the brain’s metabolism increased during the stimulation, then returned to the normal level. In people with Huntington’s disease, there was no change in metabolism.

Brain Metabolism Now Normal

For the second part of the study, only people with Huntington’s disease received triheptanoin, a compound made up of special fatty acids that can provide alternative energy to glucose in the brain. The 10 participants, which included five of the participants in the first part of the study, had the flavorless, odorless oil during meals three or four times a day for a month. Then they had the visual stimulation test again. The brain metabolism was now normal.

“If confirmed in other studies, the findings may be hopeful for people who have the family gene for Huntington’s and will eventually develop the disease,” Mochel said.

Second Trial

A Phase 2 clinical trial (NCT02453061) of triheptanoin, called TRIHEP3, studied approximately 100 participants with early Huntington’s disease having a Unified Huntington’s Disease Rating Scale (UHDRS) score between 5 and 40. UHDRS assesses clinical features and course of the disease.

The trial was a randomized, double-blind, controlled study that took place at one center each in France and the Netherlands, and treated patients with triheptanoin oil at 1g/kg of body weight daily for six months, followed by an open-label and six-month extension study. Its primary outcomes are an increase in brain energy restoration and a decrease in the rate of caudate atrophy, a common brain feature of Huntington’s that worsens over time. The caudate nucleus is part of the basal ganglia.

Extensive testing at 6 and 12 months included motor, psychiatric, and cognitive assessments as well as patient autonomy evaluations.

The results showed that treatment with triheptanoin was associated with clinical stability and decreased caudate atrophy in HD.

Rationale Behind Triheptanoin as a Treatment for Huntington’s Disease

Fanny Mochel, MD, PhD, APHP, is from the Sorbonne Université, Pitié-Salpêtrière University Hospital, Paris, France. In the video above, she discusses the rationale behind the development of triheptanoin as a treatment option in Huntington’s disease (HD) and shares evidence from the 6-month randomized, controlled, bicentric TRIHEP3 trial (NCT02453061).

Triheptanoin is a synthetic medium-chain triglyceride. It acts as an anaplerotic compound for the Krebs cycle. It breaks down into acetyl-CoA and propionyl-CoA, which can replenish the Krebs cycle via succinyl-CoA.

Prior investigations have shown that energy deficiencies seen in HD are associated with increased substrate requirements for the Krebs cycle. Observed decreases in branched-chain amino acids, precursors of acetyl-CoA and succinyl-CoA, led to the hypothesis that the body was trying to compensate for an energy deficiency by using these amino acids to keep the Krebs cycle running. Therefore, the ability of triheptanoin to improve energy homeostasis through acetyl-CoA and propionyl-CoA supply was investigated. Treatment with triheptanoin for 12 months was associated with stabilization of Unified Huntington’s Disease Rating Scale (UHDRS) scores and decreased caudate atrophy.

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P. Berger

This site was inspired by my Mom’s autoimmune dementia.

It is a place where we separate out the wheat from the chafe, the important articles & videos from each week’s river of news. Google gets a new post on Alzheimer’s or dementia every 7 minutes. That can overwhelm anyone looking for help. This site filters out, focuses on and offers only the best information. it has helped hundreds of thousands of people since it debuted in 2007. Thanks to our many subscribers for your supportive feedback.

The site is dedicated to all those preserving the dignity of the community of people living with dementia.

Peter Berger, Editor

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This site was inspired by my Mom’s autoimmune dementia.

It is a place where we separate out the wheat from the chafe, the important articles & videos from each week’s river of news. Google gets a new post on Alzheimer’s or dementia every 7 minutes. That can overwhelm anyone looking for help. This site filters out, focuses on and offers only the best information. it has helped hundreds of thousands of people since it debuted in 2007. Thanks to our many subscribers for your supportive feedback.

The site is dedicated to all those preserving the dignity of the community of people living with dementia.

Peter Berger, Editor

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This site was inspired by my Mom’s autoimmune dementia.

It is a place where we separate out the wheat from the chafe, the important articles & videos from each week’s river of news. Google gets a new post on Alzheimer’s or dementia every 7 minutes. That can overwhelm anyone looking for help. This site filters out, focuses on and offers only the best information. It has helped hundreds of thousands of people since it debuted in 2007. Thanks to our many subscribers for your supportive feedback.

The site is dedicated to all those preserving the dignity of the community of people living with dementia.

Peter Berger, Editor

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