Ketogenic Diet Efficacy

The ketogenic diet reduces seizure frequency by more than 50% in half of the patients who try it and by more than 90% in a third of patients. Three-quarters of children who respond do so within two weeks, though experts recommend a trial of at least three months before assuming it has been ineffective. Children with refractory epilepsy are more likely to find the ketogenic diet to be effective than to benefit from trying another anticonvulsant drug. There is some evidence that adolescents and adults may also benefit from the diet.

Trial design

Early studies reported high success rates: in one study in 1925, 60% of patients became seizure-free, and another 35% of patients had a 50% reduction in seizure frequency. These studies generally examined a cohort of patients recently treated by the physician (what is known as a retrospective study) and selected patients who had successfully maintained the dietary restrictions. However, these studies are difficult to compare to modern trials. One reason is that these older trials suffered from selection bias, as they excluded patients who were unable to start or maintain the diet and thereby selected from patients who would generate better results. In an attempt to control for this bias, modern study design prefers a prospective cohort (the patients in the study are chosen before therapy begins) in which the results are presented for all patients regardless of whether they started or completed the treatment (known as intent-to-treat analysis).

Another difference between older and newer studies is that the type of patients treated with the ketogenic diet has changed over time. When first developed and used, the ketogenic diet was not a treatment of last resort; in contrast, the children in modern studies have already tried and failed a number of anticonvulsant drugs, so may be assumed to have more difficult-to-treat epilepsy. Early and modern studies also differ because the treatment protocol has changed. In older protocols, the diet was initiated with a prolonged fast, designed to lose 5–10% body weight, and heavily restricted the calorie intake. Concerns over child health and growth led to a relaxation of the diet's restrictions. Fluid restriction was once a feature of the diet, but this led to increased risk of constipation and kidney stones, and is no longer considered beneficial.

Outcomes

The largest modern study with an intent-to-treat prospective design was published in 1998 by a team from the Johns Hopkins Hospital and followed-up by a report published in 2001. As with most studies of the ketogenic diet, there was no control group (patients who did not receive the treatment). The study enrolled 150 children. After three months, 83% of them were still on the diet, 26% had experienced a good reduction in seizures, 31% had had an excellent reduction and 3% were seizure-free. At twelve months, 55% were still on the diet, 23% had a good response, 20% had an excellent response and 7% were seizure-free. Those who had discontinued the diet by this stage did so because it was ineffective, too restrictive or due to illness, and most of those who remained were benefiting from it. The percentage of those still on the diet at two, three and four years was 39%, 20% and 12% respectively. During this period the most common reason for discontinuing the diet was because the children had become seizure-free or significantly better. At four years, 16% of the original 150 children had a good reduction in seizure frequency, 14% had an excellent reduction and 13% were seizure-free, though these figures include many who were no longer on the diet. Those remaining on the diet after this duration were typically not seizure-free but had had an excellent response.

It is possible to combine the results of several small studies to produce evidence that is stronger than that available from each study alone—a statistical method known as meta-analysis. One of four such analyses, conducted in 2006, looked at 19 studies on a total of 1,084 patients. It concluded that half the patients achieved a 50% reduction in seizures and a third achieved a 90% reduction.

The first randomised controlled trial was published in 2008, which had an intent-to-treat prospective design, but no blinding. This study enrolled 145 children, half of whom were randomly selected to start the ketogenic diet immediately and half to start after a three-month delay. The children who received delayed treatment acted as a control, which is particularly important for medical conditions such as epilepsy where patients may get better or worse regardless of treatment. Of the children in the diet group, 38% had at least a 50% reduction in seizure frequency, 7% had at least a 90% reduction, and one child became seizure-free. Only 6% of the control group saw a greater than 50% reduction in seizure frequency and no children had a 90% reduction. The mean seizure frequency of the diet group fell by a third; the control group's mean seizure frequency actually got worse.

Further Reading

• What is the Ketogenic Diet?
• Ketogenic Diet and Epilepsy
• History of the Ketogenic Diet
• Ketogenic Diet Indications and Contra-Indications
• Ketogenic Diet Side Effects
• Ketogenic Diet Types
• Ketogenic Diet Mechanism

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