Cochrane for Clinicians

Putting Evidence into Practice

Ketogenic Diets for Drug-Resistant Epilepsy

 

Am Fam Physician. 2021 May 1;103(9):524-525.

Author disclosure: No relevant financial affiliations.

Clinical Question

Are ketogenic diets safe and effective at reducing seizure frequency in patients with drug-resistant epilepsy?

Evidence-Based Answer

In children with drug-resistant epilepsy, a ketogenic diet decreases the risk of seizures by 50% after three to four months (absolute risk reduction [ARR] = 37.5%; 95% CI, 19.4% to 67.6%; number needed to treat [NNT] = 3; 95% CI, 1 to 5). (Strength of Recommendation [SOR]: B, based on inconsistent or limited-quality patient-oriented evidence.) Adverse effects such as gastrointestinal symptoms do not occur more often than in children who follow their usual diet. In adults, it is unclear whether ketogenic diets are beneficial, and adverse gastrointestinal effects are common.1 (SOR: B, based on inconsistent or limited-quality patient-oriented evidence.)

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SUMMARY TABLE

Ketogenic Diets vs. Usual Care for Drug-Resistant Epilepsy

Outcomes at 3 to 6 monthsProbable outcome with normal dietProbable outcome with ketogenic diet (95% CI)NNT or NNH (95% CI)Participants (studies)Quality of evidence

Seizure freedom

Children

21 per 1,000

66 per 1,000 (25 to 174)

22 (7 to 250)

385 (4)

Very low

Adults

NA

NA

NA

141 (2)

Very low

Seizure reduction*

Children

78 per 1,000

453 per 1,000 (272 to 754)

3 (1 to 5)

385 (4)

Low

Adults

29 per 1,000

144 per 1,000 (7 to 1,000)

NA

141 (2)

Very low

Adverse effects (gastrointestinal complaints)

Children

NA

NA

NA

425 (5)

Low

Treatment withdrawal

Adults

86 per 1,000

461 per 1,000 (36 to 1,000)

NA

141 (2)

Very low


NA = not applicable (no statistical difference in outcomes); NNH = number needed to harm; NNT = number needed to treat.

*—50% or greater reduction in frequency.

SUMMARY TABLE

Ketogenic Diets vs. Usual Care for Drug-Resistant Epilepsy

Outcomes at 3 to 6 monthsProbable outcome with normal dietProbable outcome with ketogenic diet (95% CI)NNT or NNH (95% CI)Participants (studies)Quality of evidence

Seizure freedom

Children

21 per 1,000

66 per 1,000 (25 to 174)

22 (7 to 250)

385 (4)

Very low

Adults

NA

NA

NA

141 (2)

Very low

Seizure reduction*

Children

78 per 1,000

453 per 1,000 (272 to 754)

3 (1 to 5)

385 (4)

Low

Adults

29 per 1,000

144 per 1,000 (7 to 1,000)

NA

141 (2)

Very low

Adverse effects (gastrointestinal complaints)

Children

NA

NA

NA

425 (5)

Low

Treatment withdrawal

Adults

86 per 1,000

461 per 1,000 (36 to 1,000)

NA

141 (2)

Very low


NA = not applicable (no statistical difference in outcomes); NNH = number needed to harm; NNT = number needed to treat.

*—50% or greater reduction in frequency.

Practice Pointers

In 2015, approximately 3 million U.S. adults and 470,000 children were diagnosed with epilepsy.2 Worldwide, approximately 30% of people taking two or more antiepileptic medications continue to have seizures; this is termed drug-resistant epilepsy.3 Ketogenic diets have been suggested to reduce seizure frequency in people with epilepsy. Although the exact mechanism is unknown, historically, patients who fasted had less frequent seizures. Ketogenic diets mimic this fasting state by using fat as the primary fuel source. The classic ketogenic diet provides energy in a ratio of four calories of fat to every one calorie of carbohydrate or protein. The authors of this Cochrane review assessed the effectiveness of ketogenic diets, compared with usual diet, at reducing seizure frequency in children and adults with drug-resistant epilepsy.

This Cochrane review included 13 randomized controlled trials (three conducted in the United States, none in Canada; two trials included adults) and 932 participants (221 adults and 711 children).1 The follow-up time ranged from two to 16 months. Results were reported separately for children and adults, and seizure frequency was assessed via self-report. Exclusion criteria in the majority of trials involved persons with known metabolic or neurodegenerative disorders, pregnancy, hyperlipidemia, and renal disease. Primary outcomes were seizure freedom (i.e., being declared seizure-free), seizure reduction (50% or greater reduction in frequency), and adverse effects.

Children who followed a ketogenic diet had higher rates of seizure freedom (ARR = 4.5%; 95% CI, 0.4% to 15.3%; NNT = 22; 95% CI, 7 to 250) and seizure reduction (ARR = 37.5%; 95% CI, 19.4% to 67.6%; NNT = 3; 95% CI, 1 to 5) at three to four months. Adults who followed a ketogenic diet had improved seizure reduction, although the results were not statistically significant. No adult participant experienced seizure freedom.

In children, the most common adverse effects reported were vomiting, constipation, and diarrhea, but these were no more likely with ketogenic diets than with usual diets. Both adult studies demonstrated that these adverse effects were more likely in the ketogenic diet group, but this

Author disclosure: No relevant financial affiliations.

References

show all references

1. Martin-McGill KJ, Bresnahan R, Levy RG, et al. Ketogenic diets for drug-resistant epilepsy. Cochrane Database Syst Rev. 2020;(6):CD001903....

2. Zack MM, Kobau R. National and state estimates of the numbers of adults and children with active epilepsy—United States, 2015. MMWR Morb Mortal Wkly Rep. 2017;66(31):821–825.

3. Granata T, Marchi N, Carlton E, et al. Management of the patient with medically refractory epilepsy. Expert Rev Neurother. 2009;9(12):1791–1802.

4. National Institute for Health and Care Excellence. Clinical guideline [CG137]. Epilepsies: diagnosis and management. Updated February 11, 2020. Accessed October 15, 2020. https://www.nice.org.uk/guidance/cg137

These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, assistant medical editor.

A collection of Cochrane for Clinicians published in AFP is available at https://www.aafp.org/afp/cochrane.

 

 

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