The scientific rationale for elucidating mechanisms of disease pathogenesis or of therapeutic interventions has been traditionally based upon the lofty goal of discovering novel treatments, ones that would be more efficacious than existing options and also be devoid of side-effects altogether. Moreover, in epilepsy research, disease prevention or modification has become the “holy grail”, such that we are no longer complacent with symptomatic treatment and increasing attention is being given to understanding the processes of anti-epileptogenesis itself. Researchers in the field of the ketogenic diet (KD) have also embraced these tenets and recently embarked on that all-too-familiar Quixotic journey, with the ultimate aim of reducing the “difficult” KD regimen to a simple pill. If achieved, this result would represent an ironic recapitulation of the early history of the KD in the United States. Although the KD experienced an initial surge of interest following its introduction in the early 1920’s, it was relegated to near obscurity by the emergence of a familiar drug known as phenytoin. Henceforth, until the mid 1990’s, clinicians – for obvious practical reasons – found it simpler to prescribe a pill rather than an exacting diet.
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One highly studied mechanism implicated in the clinical benefits of calorie restriction involves sirtuins, a large and diverse family of enzymes that regulate gene expression. The first sirtuin, silent information regulator 2 (Sir2), was described in yeast. Sir2 is a class III histone deacetylase that uses the cofactor nicotinamide adenine dinucleotide (NAD+) in a catalytic reaction that releases nicotinamide (a feedback inhibitor) and O-acetyl ADP ribose (Imai et al. 2000; Marmorstein 2004; Sauve et al. 2006). It has been reported that increased Sir2 activity lengthens life span, and that calorie restriction increases Sir2 levels and does not promote longevity in SIR2 knockouts (Kaeberlein et al. 1999; Lin et al. 2000, 2004; Tissenbaum and Guarente 2001; Rogina and Helfand 2004). In mammals, calorie restriction increases the expression of Sirt1, the Sir2 mammalian ortholog, in various tissues, including brain. Resveratrol, a natural Sirt1 activator found in red wine, lengthens the life span of mice and prevents the age-related deterioration of their motor function (Cohen et al. 2004; Baur et al. 2006). Additionally, resveratrol stimulates AMP kinase activity in neurons (Dasgupta & Milbrandt, 2007), and more importantly, protects against kainic acid-induced seizures and oxidative stress in rats (Gupta et al., 2002).
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Many of our existing anticonvulsant medications exert effects on inhibitory neurotransmission, and more specifically, by enhancing synaptic levels of γ-aminobutyric acid (GABA) or modulating post-synaptic GABAA receptors (Meldrum & Rogawski, 2007; White et al., 2007). Examples of such agents include tiagabine, vigabatrin, benzodiazepines, barbiturates, felbamate, and topiramate. Thus, given the wealth of information regarding GABAergic neurotransmission, one possibility is that the KD, perhaps through ketone bodies, might be responsible for elevating synaptic levels of GABA, which would then yield an inhibitory (and potentially anticonvulsant) effect.
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While the effects of leptin on seizure susceptibility and its relationship to KD-induced weight loss are intriguing, there are as yet no direct data supporting leptin as an anticonvulsant mediator of the KD. Certainly, the clinical implications of the study by Xu et al. (2008) are intriguing, namely, that intranasal administration of leptin might be efficacious in aborting acute seizure activity. And if the clinical effects of the KD are due in part to increased leptin levels, then accelerated development and validation of leptin as a novel anticonvulsant medication would be warranted.
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Selalu perhatikan porsi makan Anda. Idealnya, bagilah piring Anda menjadi 4 bagian. Seperempat untuk daging atau sumber protein Anda, seperempat lagi untuk karbohidrat, dan dua perempat terakhir untuk sayuran hijau dan berwarna-warni. Ingat, hindari makanan berat yang berlemak atau makanan tinggi gula ketika makan malam agar berat badan Anda tetap terkontrol dengan baik.