How does the ketogenic diet work?
A ketogenic diet can help seizure control for some people with drug-resistant epilepsy, but how does it work? Researchers in China have found clues that could potentially help the development of a new epilepsy therapy. Their findings are published in the journal Experimental and Therapeutic Medicine.
A ketogenic diet is high in fat, low in carbohydrate and ‘moderate’ in protein. Its anti-seizure properties have been widely reported, but the mechanisms for these are still not clear. This type of diet requires a lot of time and commitment, and understanding how it works could lead to the development of a more simple drug treatment to replace it.
Earlier research suggests that a compound called beta hydroxybutarate (BHB), which is made in the liver during fat metabolism, has anti-convulsant properties. Some of these studies involved giving additional BHB to experimental epilepsy models, but the doses of BHB used varied between them.
Scientists in China have recently looked more closely at the effects of BHB on seizure activity and how different doses of BHB affect this.
The right epilepsy model
For the study the team needed to ensure they had an effective epilepsy model to work with, and they did this by inducing seizures in a group of rodents via a widely-used method. They analysed the resulting behaviour of the animals (using standard criteria) and found that all developed seizures.
The effects of BHB treatment
In a separate group, the scientists investigated the effects of external BHB administration on both blood BHB and blood glucose (which can also affect seizure activity) levels. They measured the ‘baseline’ levels of BHB and glucose in the animals’ blood and then administered one of three doses of BHB (2mmol/Kg, 4 mmol/Kg or 8mmol/Kg). BHB and glucose levels were recorded at set time intervals following treatment. A control group was treated in exactly the same way, except that saline (which has no effect) was given instead of BHB.
The researchers found that blood BHB levels were significantly increased after BHB administration compared with controls at all time points, and that blood glucose wasn’t affected. They also discovered that a 4mmol/Kg dose was most effective in increasing blood BHB levels.
The impact of BHB on seizures
To compare the effects of BHB administration on seizure activity with that of controls, the team treated another two groups with either 4mmol/Kg BHB and a convulsant, or saline and a convulsant. They gave the BHB/saline at a set time before the convulsant. The models’ seizure behaviour was closely monitored and then their brains were examined to find out the effects of BHB on certain neurons.
The scientists found that, in the BHB-treated group, the onset time of seizures was significantly later than that of the controls. In this group the damage associated with spontaneous recurrent seizures was also spared (this was not the case in controls).
What does this mean?
These findings are exciting, because they may, in future, help the development of a completely new therapy that is a lot easier to comply with than the ketogenic diet.
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