The ketogenic diet (KD) is characterized by a diet ratio of 4:1 fat to non-fat energy sources. For decades KD has been successfully used to control seizures in epilepsy patients. Investigations into its mechanism of action suggest that it may have an effect on the metabolic, nervous, immune, and digestive systems. In this review, we postulate that KD may also improve depressive symptoms – for that, we highlight the similarities between depression and epilepsy, describe the extent to which body systems involved in both conditions are affected by the KD, and ultimately hypothesize how KD could improve MDD outcomes. Research into animal models and human patients have reported that KD can increase mitochondrial biogenesis and increase cellular resistance to oxidative stress both at the mitochondrial and genetic levels. Its effect on neurotransmitters alters cell-to-cell communication in the brain and may decrease hyperexcitability by increasing Gamma Aminobutyric Acid (GABA) and decreasing excitatory neurotransmitter levels. Its anti-inflammatory effects are mediated by decreasing chemo- and cytokine levels, including TNF-alpha and IL-1 levels. Finally, KD can alter gut microbiota (GM). Certain strains of microbiota predominate in major depressive disorder (MDD) when compared to healthy individuals. Recent evidence points to Bacteroidetes as a potential treatment predictor as it seems to increase in KD treatment responders for epilepsy. Each of these observations contributes to the presumed modulatory effects of KD on mood and supports its potential role as antidepressant.

中文翻译：

---

探索生酮饮食抗抑郁作用的作用机制。

生酮饮食 (KD) 的特点是脂肪与非脂肪能量来源的饮食比例为 4:1。几十年来，KD 已成功用于控制癫痫患者的癫痫发作。对其作用机制的研究表明，它可能对代谢、神经、免疫和消化系统产生影响。在这篇综述中，我们假设 KD 也可能改善抑郁症状——为此，我们强调了抑郁症和癫痫之间的相似性，描述了这两种情况下涉及的身体系统受 KD 影响的程度，并最终假设 KD 如何改善MDD 结果。对动物模型和人类患者的研究报告称，KD 可以在线粒体和基因水平上增加线粒体生物发生并增加细胞对氧化应激的抵抗力。它对神经递质的影响会改变大脑中细胞间的通讯，并可能通过增加伽马氨基丁酸 (GABA) 和降低兴奋性神经递质水平来降低过度兴奋。其抗炎作用是通过降低化学和细胞因子水平介导的，包括 TNF-α 和 IL-1 水平。最后，KD 可以改变肠道微生物群 (GM)。与健康个体相比，某些微生物群在重度抑郁症 (MDD) 中占主导地位。最近的证据表明 与健康个体相比，某些微生物群在重度抑郁症 (MDD) 中占主导地位。最近的证据表明 与健康个体相比，某些微生物群在重度抑郁症 (MDD) 中占主导地位。最近的证据表明拟杆菌作为潜在的治疗预测因子，因为它似乎会增加癫痫的 KD 治疗反应者。这些观察中的每一个都有助于推测 KD 对情绪的调节作用，并支持其作为抗抑郁药的潜在作用。