A fatty acid in the MCT ketogenic diet for epilepsy treatment blocks AMPA receptors

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This scientific commentary refers to ‘Seizure control by decanoic acid through direct AMPA receptor inhibition’, by Chang et al. (doi:10.1093/brain/awv325). Dietary therapies can provide control of seizures in patients with drug-refractory epilepsy. There are several types of dietary therapies, all of which are high in fat, restrict carbohydrates to some extent, and are associated with ketosis. In the classical ketogenic diet introduced into clinical practice in the 1920s, the fat component is provided by long-chain triglycerides (LCTs). Recognizing that medium chain triglycerides (MCTs) are more ketogenic than LCTs, Huttenlocher et al. (1971) created the MCT oil diet, which permits greater amounts of carbohydrate and protein, and therefore allows a more flexible meal plan. The efficacy of the MCT oil ketogenic diet is equivalent to that of the classic LCT ketogenic diet, and the tolerability is also comparable (Neal et al. , 2009). MCTs, which are abundant in coconut and palm kernel oil, have a glycerol backbone and three fatty acid esters with 6 to 12 carbons arranged in a straight chain. The major fatty acids in MCT oil are n -octanoic acid (C8; caprylic acid; 50–80%) and n -decanoic acid (C10; capric acid; 20–50%). Following ingestion, MCTs are rapidly absorbed into the portal circulation to the liver, in contrast to LCTs which are absorbed by chylomicrons in the lymph. It was previously believed that medium chain fatty acids derived from MCTs are immediately oxidized in the liver to form ketone bodies, but it is now known that appreciable amounts appear in the circulation of patients receiving the MCT diet (Sills et al. , 1986 a ). For example, children on the MCT diet had plasma concentrations of decanoic acid in the range of 0.1–0.2 mM. Decanoic acid readily crosses the blood–brain barrier, probably by a combination of diffusion and …