Synthesis of triheptanoin and formulation as a solid diet for rodents

Abstract

SummaryTriheptanoin enriched diets have been successfully used in the experimental treatment of various metabolic disorders. Maximal therapeutic effect is achieved in the context of a ketogenic diet where triheptanoin oil provides 30-40% of daily caloric intake. However, studies using triheptanoin-rich diets in the pre-clinical setting are hindered by the difficulty to administer to lab animals as a solid foodstuff. In the present study, we have successfully synthesized triheptanoin to the highest standards of purity from glycerol and heptanoic acid, using sulfonated charcoal, previously studied in esterification reactions by Yurui and Prager (Aust. J. Chem. 1989Chem. , 42, 1003Chem. -1005, as a catalyst. Then, triheptanoin oil was formulated as a solid, stable and palatable diet using a ketogenic base and a combination of four commercially available formulation agents; hydrophilic fumed silica, hydrophobic fumed silica, microcrystalline cellulose and talc.Diet compliance and safety was tested on C57Bl/6 mice over a 15-week period, comparing overall status and body weight change.Formulation of Solid Triheptanoin-Rich Ketogenic Diet for Rodents. 3 Practical applicationsThis work provides a complete description of, (i) an effective and cost-effective synthesis of triheptanoin and, (ii) the formulation of a solid, stable and palatable triheptanoin-rich (39% of caloric intake) ketogenic diet for rodents. Rodent triheptanoin-rich diets have practical applications in pre-clinical screening of the therapeutic efficacy of triheptanoin in different rodent models of human diseases. On the other hand, using the same solidification procedure, other oils could be incorporated into rodent ketogenic diet to study its high dose/long term effect on mammal health and development. This approach could be extremely valuable as ketogenic diet is widely used clinically for epilepsy treatment.

Impairments in Oxidative Glucose Metabolism in Epilepsy and Metabolic Treatments Thereof

“…Triheptanoin is an uneven medium chain triglyceride, namely of the C7 heptanoate, which is only found in minute amounts in certain seeds. Therefore, triheptanoin is commercially produced through chemical breakdown of long-chain triglycerides ( Semak et al, 2012 ). Triheptanoin has been used in the treatment of various metabolic disorders associated with metabolic enzyme deficiency and long-chain fat oxidation disorders ( Roe et al, 2002 , 2008 , 2010 ; Mochel et al, 2005 ; Roe and Brunengraber, 2015 ; Gillingham et al, 2017 ; Vockley et al, 2017 ).…”