While the relationships between seizure activity, oxidative stress and neuronal injury have yet to be clarified, previous studies have indicated that defects in antioxidant systems may contribute to seizure genesis and epileptogenesis (Cock, 2002; Patel, 2004; Liang & Patel, 2006; Shin et al, 2008). Earlier, the effects of a KD on mitochondrial ROS generation were discussed. Are there other mechanisms through which oxidative stress can be attenuated in epileptic brain?
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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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In support of this, Yudkoff and colleagues have published widely on the impact of ketone bodies on brain glutamate and GABA metabolism (Yudkoff et al., 2007). In one study, the addition of either acetoacetate or β-hydroxybutyrate was associated with diminished consumption of glutamate via transamination to aspartate and increased formation of labeled GABA (Daikhin et al., 1998). Ketone bodies had earlier been shown by the same group to enhance synthesis of GABA in synaptosomes prepared from rodent forebrain (Erecinska et al, 1996).
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The earliest demonstration of direct in vivo effects of ketone bodies was made by Keith in the early 1930’s, when he determined that acetoacetate, when administered intraperitoneally in rabbits, prevented seizures induced by thujone (1933), a convulsant constituent found in many essential oils and an antagonist of GABAA receptors (Höld et al., 2000). This seminal observation was later confirmed in an audiogenic seizure-susceptible mouse model (Rho et al., 2002). More intriguingly, however, Likhodii and colleagues (2003) established the broad anticonvulsant properties of acetone in four different animal models, and when injected intraperitoneally, produced plasma and cerebrospinal fluid (CSF) concentrations consistent with those used to suppress seizures. These results confirmed and extended historical observations supporting an anticonvulsant action for acetone, through as yet undetermined mechanisms (Likhodii & Burnham, 2002). And in further support of this, other investigators found that acetone was detectable (up to a concentration of 0.7 mM) in the brains of fully controlled KD-treated patients with epilepsy using proton magnetic resonance spectroscopy (Seymour et al, 1999).
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Ketogenic diets have shown great potential in weight loss, overall health and cancer treatment. Martina's valuable contributions to the low-carb community and her involvement in the cancer research project run by our team extend beyond simply helping people follow a healthy low-carb diet. Just like Martina's blog and app, her new cookbook is an amazing resource for anyone interested in healthy living with easy to follow recipes and beautiful photography.
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Lauren is the food photographer, recipe developer, and author behind the healthy living website Wicked Spatula. With a focus on mindful and sustainable living she aspires to show her audience that healthy eating doesn't have to be boring, complicated, or tasteless and that healthy living is all about getting in touch with yourself and your surroundings.
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Disisi lain, Bette Klein, seorang ahli nutrisi di Cleveland Clinic Children’s Hospital memanfaatkan metode ini untuk meringankan gejala epilepsi pada anak. Ia menyatakan bahwa diet ini efektif diterapkan pada anak yang tidak mempan diterapi dengan dua jenis obat anti-epilepsi. Sekitar 50% anak yang menjalani diet ini mengalami penurunan frekuensi kejang. Akan tetapi, sampai saat ini belum diketahui secara pasti apa yang menyebabkan hal ini terjadi.