Greene A E, Todorova M T, McGowan R, Seyfried T N
Biology Department, Boston College, Chestnut Hill, Massachusetts 02167, USA.
Epilepsia. 2001 Nov;42(11):1371-8. doi: 10.1046/j.1528-1157.2001.17601.x.
Caloric restriction (CR) involves underfeeding and has long been recognized as a dietary therapy that improves health and increases longevity. In contrast to severe fasting or starvation, CR reduces total food intake without causing nutritional deficiencies. Although fasting has been recognized as an effective antiseizure therapy since the time of the ancient Greeks, the mechanism by which fasting inhibits seizures remains obscure. The influence of CR on seizure susceptibility was investigated at both juvenile (30 days) and adult (70 days) ages in the EL mouse, a genetic model of multifactorial idiopathic epilepsy.
The juvenile EL mice were separated into two groups and fed standard lab chow either ad libitum (control, n=18) or with a 15% CR diet (treated, n=17). The adult EL mice were separated into three groups; control (n=15), 15% CR (n=6), and 30% CR (n=3). Body weights, seizure susceptibility, and the levels of blood glucose and ketones (beta-hydroxybutyrate) were measured over a 10-week treatment period. Simple linear regression and multiple logistic regression were used to analyze the relations among seizures, glucose, and ketones.
CR delayed the onset and reduced the incidence of seizures at both juvenile and adult ages and was devoid of adverse side effects. Furthermore, mild CR (15%) had a greater antiepileptogenic effect than the well-established high-fat ketogenic diet in the juvenile mice. The CR-induced changes in blood glucose levels were predictive of both blood ketone levels and seizure susceptibility.
We propose that CR may reduce seizure susceptibility in EL mice by reducing brain glycolytic energy. Our preclinical findings suggest that CR may be an effective antiseizure dietary therapy for human seizure disorders.
热量限制（CR）涉及减少进食量，长期以来一直被视为一种改善健康和延长寿命的饮食疗法。与严重禁食或饥饿不同，CR减少总食物摄入量而不会导致营养缺乏。尽管自古希腊时代起禁食就被认为是一种有效的抗癫痫疗法，但禁食抑制癫痫发作的机制仍不清楚。在EL小鼠（一种多因素特发性癫痫的遗传模型）中，研究了热量限制对幼年（30天）和成年（70天）小鼠癫痫易感性的影响。
将幼年EL小鼠分为两组，一组自由进食标准实验室饲料（对照组，n = 18），另一组给予15%热量限制饮食（处理组，n = 17）。将成年EL小鼠分为三组：对照组（n = 15）、15%热量限制组（n = 6）和30%热量限制组（n = 3）。在为期10周的治疗期间，测量体重、癫痫易感性以及血糖和酮体（β-羟基丁酸）水平。使用简单线性回归和多元逻辑回归分析癫痫发作、血糖和酮体之间的关系。
热量限制在幼年和成年阶段均延迟了癫痫发作的起始并降低了发作发生率，且无不良副作用。此外，在幼年小鼠中，轻度热量限制（15%）比成熟的高脂肪生酮饮食具有更大的抗癫痫作用。热量限制引起的血糖水平变化可预测血酮水平和癫痫易感性。
我们提出热量限制可能通过减少脑糖酵解能量来降低EL小鼠的癫痫易感性。我们的临床前研究结果表明，热量限制可能是一种治疗人类癫痫疾病的有效抗癫痫饮食疗法。
