Synthesis of triheptanoin and formulation as a solid diet for rodents
2012
Semak, Vladislav | Semakova, Jana | Halbaut, Lyda | Aso, Ester | Ferrer, Isidro | Calpena, Ana | Escolano, Carmen | Perales, Jose Carlos
Triheptanoinâenriched 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 the daily caloric intake. However, preâclinical studies using triheptanoinârich diets are hindered by the difficulty of administering to laboratory animals as a solid foodstuff. In the present study, we successfully synthesized triheptanoin to the highest standards of purity from glycerol and heptanoic acid, using sulfonated charcoal as a catalyst. Triheptanoin oil was then formulated as a solid, stable and palatable preparation 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 15âweek period, comparing overall status and body weight change. Practical applications: This work provides a complete description of (i) an efficient and costâeffective synthesis of triheptanoin and (ii) its formulation as a solid, stable, and palatable ketogenic diet (triheptanoinârich; 39% of the caloric intake) for rodents. Triheptanoinârich diets will be helpful on preâclinical experiments testing the therapeutic efficacy of triheptanoin in different rodent models of human diseases. In addition, using the same solidification procedure, other oils could be incorporated into rodent ketogenic diet to study their dosage and longâterm effects on mammal health and development. This approach could be extremely valuable as ketogenic diet is widely used clinically for epilepsy treatment.
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