Epilepsy is a disorder where recurrent seizures (fits) are caused by abnormal electrical discharges from the brain. In most people seizures can be controlled by one or more antiepileptic medicines, but seizures may not be helped by these medicines after a while (called drug-resistant epilepsy). For people who have drug-resistant epilepsy, a special diet (called a ketogenic diet) may be considered. Ketogenic diets are high in fat and low in carbohydrate.
This review aimed to investigate the effect of ketogenic diets on seizure control, cognition (e.g. learning, concentration and academic performance in children; learning, concentration and memory in adults) and behaviour. We also investigated the side effects of the diet and the number of participants who dropped out of the studies and the reasons for this.
We searched medical databases for randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) of adults or children with epilepsy, where a ketogenic diet was compared with other treatments. We found 11 randomised controlled trials, with 778 participants. The trials were between two and 16 months long.
The short-term side effects of ketogenic diets included diarrhoea, constipation and vomiting. Long-term effects are unknown from these studies.
All studies reported participants dropping out, due to lack of improvement in seizures and poor tolerance of the diet.
One study reported upon the effect of ketogenic diets on quality of life, cognition and behaviour. No difference was found in the quality of life of those following a ketogenic diet and the group receiving care as usual, but participants following the ketogenic diet were found to be more active, more productive and less anxious. More research is needed in these areas.
Recently, other, better tolerated, ketogenic diets, such as the modified Atkins diet, found similar effects on seizure control as those more restrictive ketogenic diets. However, more research is required.
Quality of the evidence
The studies included in this review were limited by small numbers of participants and only children were included in 10 of the 11 studies, therefore, we judged the quality of the evidence to be low to very low.
There is little research at present into the use of these diets in adults, therefore, more research is required in this area.
This evidence is current to April 2017.
The RCTs discussed in this review show promising results for the use of KDs in epilepsy. However, the limited number of studies, small sample sizes and the limited studies in adults, resulted in a low to very low overall quality of evidence.
There were adverse effects within all of the studies and for all KD variations, such as short-term gastrointestinal-related disturbances and increased cholesterol. However, study periods were short, therefore the long-term risks associated with these adverse effects is unknown. Attrition rates remained a problem with all KDs and across all studies; reasons for this being lack of observed efficacy and dietary tolerance.
Only one study reported the use of KDs in adults with epilepsy; therefore further research would be of benefit.
Other more palatable but related diets, such as the MAD, may have a similar effect on seizure control as the classical KD, but this assumption requires more investigation. For people who have medically intractable epilepsy or people who are not suitable for surgical intervention, KDs remain a valid option; however, further research is required.
Ketogenic diets (KDs), being high in fat and low in carbohydrates, have been suggested to reduce seizure frequency in people with epilepsy. At present, such diets are mainly recommended for children who continue to have seizures despite treatment with antiepileptic drugs (AEDs) (drug-resistant epilepsy). Recently, there has been interest in less restrictive KDs, including the modified Atkins diet (MAD), and the use of these diets has extended into adult practice. This is an update of a review first published in 2003 and last updated in 2016.
To assess the effects of KDs for drug-resistant epilepsy by reviewing the evidence from randomised controlled trials.
For the latest update we searched the Cochrane Epilepsy Group's Specialized Register (11 April 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 11 April 2017), MEDLINE (Ovid, 11 April 2017), ClinicalTrials.gov (11 April 2017) and the WHO International Clinical Trials Registry Platform (ICTRP, 11 April 2017). We imposed no language restrictions. We checked the reference lists of retrieved studies for additional reports of relevant studies.
Randomised controlled trials or quasi-randomised controlled trials of ketogenic diets for people with drug-resistant epilepsy.
Two review authors independently applied predefined criteria to extract data and assessed study quality.
We identified 11 randomised controlled trials (RCTs) that generated 15 publications.
All trials applied an intention-to-treat analysis with varied randomisation methods. The 11 studies recruited 778 patients; 712 children and adolescents and 66 adults. We assessed all 11 studies to be at low to unclear risk of bias for the following domains: random sequence generation, allocation concealment and selective reporting. For the other domains (blinding, incomplete outcome data, other bias) assessments were varied (low, unclear and high risk of bias). We could not conduct a meta-analysis due to the heterogeneity of the studies and the quality of the evidence was low to very low (GRADE ratings).
Reported rates of seizure freedom reached as high as 55% in a classical 4:1 KD group after three months and reported rates of seizure reduction reached as high as 85% in a classical 4:1 KD group after three months (GRADE rating low).
One trial found no significant difference between the fasting-onset and gradual-onset KD for rates of seizure freedom, and reported a greater rate of seizure reduction in the gradual-onset KD group.
Studies assessing the efficacy of the MAD reported seizure freedom rates of up to 25% and seizure reduction rates of up to 60% in children. One study used a simplified MAD (sMAD) and reported seizure freedom rates of 15% and seizure reduction rates of 56% in children. One study utilised a MAD in adults and reported seizure reduction rates of 35%, but no patients became seizure free (GRADE rating low).
Adverse effects of the dietary interventions were experienced in all studies. The most commonly reported adverse effects were gastrointestinal syndromes. It was common that adverse effects were the reason for participants dropping out of trials (GRADE rating low). Other reasons for dropout included lack of efficacy and non-acceptance of the diet (GRADE rating low).
Although there was some evidence for greater antiepileptic efficacy for a classical 4:1 KD over lower ratios, the classical 4:1 KD was consistently associated with more adverse effects.
One study assessed the effect of dietary interventions on quality of life, cognition and behavioural functioning, reporting participants in the KD group to be more active, more productive and less anxious after four months, compared to the control group. However, no significant difference was found in quality-adjusted life years (QALYs) between the KD group and control group at four or 16 months (GRADE rating very low).