Neuro-Oncology Research, Barrow Neurological Institute® of St. Joseph's Hospital and Medical Center, Phoenix, Arizona, United States of America.
PLoS One. 2012;7(5):e36197. doi: 10.1371/journal.pone.0036197. Epub 2012 May 1.
The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that alters metabolism by increasing the level of ketone bodies in the blood. KetoCal® (KC) is a nutritionally complete, commercially available 4:1 (fat:carbohydrate+protein) ketogenic formula that is an effective non-pharmacologic treatment for the management of refractory pediatric epilepsy. Diet-induced ketosis causes changes to brain homeostasis that have potential for the treatment of other neurological diseases such as malignant gliomas.
We used an intracranial bioluminescent mouse model of malignant glioma. Following implantation animals were maintained on standard diet (SD) or KC. The mice received 2×4 Gy of whole brain radiation and tumor growth was followed by in vivo imaging.
Animals fed KC had elevated levels of β-hydroxybutyrate (p = 0.0173) and an increased median survival of approximately 5 days relative to animals maintained on SD. KC plus radiation treatment were more than additive, and in 9 of 11 irradiated animals maintained on KC the bioluminescent signal from the tumor cells diminished below the level of detection (p<0.0001). Animals were switched to SD 101 days after implantation and no signs of tumor recurrence were seen for over 200 days.
KC significantly enhances the anti-tumor effect of radiation. This suggests that cellular metabolic alterations induced through KC may be useful as an adjuvant to the current standard of care for the treatment of human malignant gliomas.
生酮饮食（KD）是一种高脂肪、低碳水化合物的饮食，通过增加血液中酮体的水平来改变代谢。 KetoCal®（KC）是一种营养全面、市售的 4:1（脂肪：碳水化合物+蛋白质）生酮配方，是治疗难治性小儿癫痫的有效非药物治疗方法。饮食诱导的酮症引起大脑内稳态的变化，有可能治疗其他神经疾病，如恶性胶质瘤。
我们使用颅内生物发光小鼠恶性胶质瘤模型。植入后，动物维持在标准饮食（SD）或 KC 上。小鼠接受 2×4 Gy 全脑照射，并通过体内成像跟踪肿瘤生长。
喂养 KC 的动物β-羟丁酸水平升高（p = 0.0173），中位生存期延长约 5 天，与维持在 SD 的动物相比。KC 加放射治疗的效果超过了相加作用，在 11 只接受 KC 治疗的照射动物中，有 9 只肿瘤细胞的生物发光信号降至检测水平以下（p<0.0001）。动物在植入后 101 天切换到 SD，200 多天后没有肿瘤复发的迹象。
KC 显著增强了放射治疗的抗肿瘤效果。这表明，通过 KC 诱导的细胞代谢改变可能作为目前恶性胶质瘤治疗标准护理的辅助手段是有用的。
