The ketogenic diet was first developed in the 1920s to treat children with epilepsy. It is a high-fat, low carbohydrate, adequate protein diet which mimics the effect of starvation on the body. One of the side-effects of breaking down fats instead of carbohydrates for energy is the production of a chemical state in the body which inhibits seizures.

The process in which carbohydrates are broken down into sugars for energy is called glycolysis. Because the ketogenic diet is low in carbohydrate, it causes very little glycolysis. Dr Avtar Roopra and colleagues at the University of Wisconsin in Madison, USA, theorised that low rate of glycolysis was related to the anti-convulsive effect of the diet. So could a drug that inhibits glycolysis have the same effect?

In the October issue of Nature Neuroscience, they reported a study in which they treated rats at risk of developing temporal lobe epilepsy with a glycolysis blocker called 2-deoxy-D-glucose. This compound is structurally closely related to glucose, and is sweet tasting. It is currently being investigated as an add-on to chemotherapy treatment for cancer, and has been used for years in medical scanning.

The researchers found that rats treated with 2-deoxy-D-glucose developed epilepsy more slowly, and then experienced fewer, milder seizures than those which were not treated. They also characterised the indirect mechanism by which the sugar works: it stops damage caused by the seizures themselves. These tend to increase the presence in brain cells of an excitatory protein called BDNF and its corresponding receptors, which in turn increases the likelihood of seizures. 2-deoxy-D-glucose interacts with genes in the cell and prevents the increase in BDNF and its receptors happening.

This research suggests that 2-deoxy-D-glucose has anti-convulsant properties, at least in this model of epilepsy. The next step will be to establish that 2-deoxy-D-glucose or other glycolysis blockers have the same effect in humans. No current anti-epileptic drugs work on this basis, so this could be the first clue to a new type of anti-seizure compound. The researchers also pointed out that influencing brain cell genes by diet is a potential powerful new treatment angle for other neurological disorders and cancer.

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