Ketogenic Diet

The ketogenic diet (KD) is a high-fat, low-carb, moderate-protein dietary strategy used as an effective alternative therapy for medically refractory epilepsy.

The term "ketogenic" refers to the shift from a glucose-based energy mode to a ketone-based energy mode through fat oxidation. After 

3 days on the ketogenic diet, ketones can provide the brain with 30% of its energy, increasing to up to 70% after 40 days. 

Ketones encompass acetoacetate, β-hydroxybutyrate, and acetone.

Ketogenic Mechanism

The ketogenic diet restricts carbohydrate intake, leading the body to increase gluconeogenesis pathway activity （utilizing oxaloacetate to 

generate glucose）to maintain blood sugar balance. This reduces the decomposition and consumption of acetyl-CoA (produced by fatty 

acid beta-oxidation) through the TCA pathway (requires the participation of oxaloacetate). The excess acetyl-CoA is converted to ketone bodies, such as acetoacetate and β-hydroxybutyrate, which are released into circulation and utilized by tissues like the brain and heart as alternative energy sources to glucose.

Ketone bodies(KB)’s function - KB can exert broad neuroprotective effects and have been shown to block acutely induced and spontaneous recurrent seizures in various animal models.

Potential Anti-Epileptic Mechanisms of Ketone Bodies

1.ketone bodies can suppress neuronal excitability by inhibiting the presynaptic release of glutamate, directly competing with  Cl− for allosteric modulation of VGLUTs. 

2. Enhancing ATP-sensitive potassium channel activity to promote opening, leading to neuronal depolarization or hyperpolarization,reducing cell excitability and inhibiting seizures.

3. By indirectly regulating cyclophilin D, the mitochondrial permeability transition threshold is increased, making mitochondria more resistant to changes in the internal and external environment and protecting neurons from damage.

4. Inhibits NLRP3 inflammasome assembly by preventing K+ efflux(Others suggested that it may occur through suppression of oxidative stress in the endoplasmic reticulum), the anti-inflammatory effect of ketone bodies partially explains the effects of the ketogenic diet on 

neuroinflammation-induced Improvement of epilepsy such as FIRES (febrile infection-related epilepsy syndrome).

5. BHB was shown to inhibit histone deacetylases (HDACs) both in vitro and in vivo， HDAC inhibitors considered potential treatments for ischemic stroke-induced neurodegeneration

（Potential Mechanisms of Ketone Bodies in Anti-Epileptic Action.）

Four Ketogenic Diet Methods：

• Classical Ketogenic Diet (CKD): High-fat, low-protein, and low-carbohydrate ratio diet, commonly at a ratio of 4:1 or 3:1.

• Medium-Chain Triglyceride Diet (MCTD): In CKD, swapping long-chain for medium-chain triglycerides speeds up absorption and metabolism,boosts ketone production, and lowers fat intake, making room for more carbs and proteins.

• Modified Atkins Diet (MAD): A more flexible and less restrictive diet compared to CKD, requiring no hospitalization,often used in adolescents and adults for self-administration ease.

• Low Glycemic Index Treatment (LGIT): Easing carb limits by including low GI (under 50) foods like meats, dairy, certain fruits, and whole-grainbread, with a daily cap of 40-60 grams.

(Due to side effects like hypoglycemia, liver damage, and bad breath, long-term keto dieting (≤3 months) is generally not recommended.)

Goldencoco MCT Oil-Keto Diet Essential Tool

MCT oil, key in the keto diet, quickly reaches the liver to produce energy via ketones within 30 minutes. It also helps reduce appetite, 

cut calorie intake, boost thermogenesis, and increase fat burning.