Reduced severity of ischemic stroke and improvement of mitochondrial function after dietary treatment with the anaplerotic substance triheptanoin

Triheptanoin: long-term effects in the very long-chain acyl-CoA dehydrogenase-deficient mouse

“…In the last 10 years there has been accumulating evidence describing the positive effects of triheptanoin, especially in the treatment of diseases associated with derangement of brain cellular metabolism. Triheptanoin has been successfully applied as a ketogenic diet in epilepsy (33,34) and reduces the severity of ischemic strokes (35). A recent study of patients with Huntington disease supplemented with triheptanoin at the early stage of the disease showed an improvement in the metabolic profile of the brain after 1 month of supplementation (36,37).…”

Anaplerotic treatment of long-chain fat oxidation disorders with triheptanoin: Review of 15years Experience

“…A recent retrospective chart review study of 20 of these same patients concluded that extension of the TH diet for three years reduced days required in hospital for clinical complications. [29] Recent animal studies with TH report significant benefit for serious complications such as correction of ventricular hypertrophy and pressure overload in rats [30], relief of ischemic stroke [31] and reduced seizures [32]. These observations indicate that an unrecognized energy deficiency exists in broad areas of disease and may also benefit from TH and carnitine therapy in humans.…”

Short- and medium-chain fatty acids in energy metabolism: the cellular perspective

“…Indeed, it has recently been shown that triheptanoin partially restores the level of citric acid cycle metabolites in an epileptic animal model (126). Triheptanoin is also able to attenuate harmful side effects associated with ischemic stroke (127). As an illustration, when mice were exposed to transient ischemia, triheptanoin reduced the extracellular level of glutamate released in the mouse striatum, maintained the cellular ATP content at the desired level, and prevented a decline of the respiratory activity of isolated brain mitochondria.…”

“…As an illustration, when mice were exposed to transient ischemia, triheptanoin reduced the extracellular level of glutamate released in the mouse striatum, maintained the cellular ATP content at the desired level, and prevented a decline of the respiratory activity of isolated brain mitochondria. The latter findings strongly suggest that mitochondrial ATP regeneration is a target of triheptanoin action (127). It is acetyl-CoA is used for the synthesis of ketone bodies (mostly acetoacetate and -hydroxybutyrate), which are delivered as fuel to nonhepatic tissues (21,22).…”