Polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA, C22: 6ω-3), arachidonic acid (AA, C20: 4ω-3), or eicosapentaenoic acid (EPA, C20: 5ω-3) have been reported to suppress voltage-gated sodium channels and L-type calcium channels in seizure-prone structures such as the hippocampus (Vreugdenhil et al., 1996). The KD produces elevations of both AA and DHA in serum (Fraser et al., 2003; Cunnane et al., 2002) and brain (Taha et al., 2005) of patients and animals, respectively, suggesting that these substrates might exert anticonvulsant effects by inhibiting sodium and calcium channels, like many anticonvulsant drugs (Xiao et al., 1997, 1998).

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Given these findings, it is not surprising that investigators have studied the effects of dietary supplementation with PUFAs alone, to determine whether these substrates can render an anticonvulsant effect. Early case reports suggested that seizures might be better controlled with this approach (Schlanger et al., 2002). However, a recent randomized trial in adult patients with epilepsy failed to demonstrate superiority of a PUFA supplement (EPA) plus DHA, 2.2 mg/day in a 3:2 ratio) over placebo (Bromfield et al., 2008). Thus, the jury is still out as to whether PUFAs alone can mirror the clinical effects of the KD.

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