Clinical UM Guideline

Subject: Ketogenic Diet for Treatment of Intractable Seizures
Guideline #:  CG-MED-05 Current Effective Date:    09/27/2017
Status: Reviewed Last Review Date:    08/03/2017


This document addresses the use of a ketogenic diet to treat seizures.

Clinical Indications

Medically Necessary: 

The use of a ketogenic diet for children and teenagers with seizures refractory to antiepileptic drugs is considered medically necessary.

Not Medically Necessary:

The use of a ketogenic diet for all other indications is considered not medically necessary.


The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

99499 Unlisted evaluation and management service [when specified as services related to ketogenic diet]
ICD-10 Diagnosis  
G40.011-G40.019 Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset, intractable
G40.111-G40.119 Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures, intractable
G40.211-G40.219 Localization-related (focal) (partial) symptomatic epilepsy and epileptics syndromes with complex partial seizures, intractable
G40.311-G40.319 Generalized idiopathic epilepsy and epileptic syndromes, intractable
G40.A11-G40.A19 Absence epileptic syndrome, intractable
G40.B11-G40.B19 Juvenile myoclonic epilepsy, intractable
G40.411-G40.419 Other generalized epilepsy and epileptic syndromes, intractable
G40.803-G40.804 Other epilepsy, intractable
G40.813-G40.814 Lennox-Gastaut syndrome, intractable
G40.823-G40.824 Epileptic spasms, intractable
G40.89 Other seizures
G40.911-G40.919 Epilepsy, unspecified, intractable
Discussion/General Information

The ketogenic diet is a high-fat, low-protein, low-carbohydrate diet which has been used for the treatment of uncontrolled seizures. The diet has a 4:1 ratio of fats to carbohydrates. The composition of the diet induces ketosis, a physiologic state in which circulating ketone bodies are used as the primary fuel source in the absence of simple sugars. Ketosis is thought to inhibit seizures, although the mechanism is unknown. The ketogenic diet is quite restrictive, requiring the cooperation of the individual, family and an appropriately trained dietician. The diet may be initiated in the inpatient or outpatient setting. In the inpatient setting, children are admitted to the hospital and fasted for one to two days. The diet is then instituted gradually over a number of days. The main reason for hospitalization is to monitor the period of initial fasting, which exposes children to metabolic derangements and dehydration. In a study by Kossoff (2008), it was reported that individuals who responded to the diet, did so quickly (often within one to two weeks), but universally within the first two months. In children in whom the seizures are not improved after two months, the study suggests a regular diet could be reintroduced and other treatment options considered.

Published data shows that some children benefit from the ketogenic diet, as demonstrated by a significant reduction in seizure frequency. A meta-analysis by Henderson and colleagues (2006) supports the current uncontrolled case series reporting on the therapeutic effect of the ketogenic diet in the treatment of seizures in pediatric epileptic individuals. The analysis of 1,084 pooled individuals demonstrated a greater than 50% seizure reduction in individuals who stayed on the ketogenic diet versus those who discontinued the diet.

Neal (2008) studied the effectiveness of a ketogenic diet on intractable seizures in a randomized controlled trial. Of 145 children initially enrolled, 103 completed the study and were included in the final analysis. Dropout reasons varied from changing their mind to diet intolerance. After 3 months of ketogenic diet, the mean percentage of seizures in the 54 children on the diet fell to 62% of baseline. For the 49 children in the control group, seizures increased to 137% of baseline. The authors were surprised by the increase in seizures of the control group. Their most probable explanation is an unusual increase in seizure frequency of three of the children in the control group. When that data was excluded, the seizure frequency increase in the control group over 3 months was only 12%.

In 2014, Taub and colleagues looked at the records of 276 children who had been initiated on the ketogenic diet. A total of 65 children achieved freedom from seizures for a minimum of one month. The median time to seizure freedom after initiation of ketogenic diet was 1.5 months. Seizures recurred in 53 children with a median time to seizure recurrence of 3 months. The recurrence of seizures was reported as an occasional breakthrough and not a return to baseline seizure frequency.

A 2015 study by Lambrechts and colleagues assessed the long-term efficacy and tolerability of a ketogenic diet as an add-on treatment for children with refractory epilepsy. A total of 48 children were included initially in the study. Evaluation was done at baseline, 6 weeks, and every 3 months after initiation of diet. At each visit, the children were evaluated for seizure severity, side effects and blood and urine samples. At the one-year follow-up, 16 children remained on the diet and at 11 remained on the diet at 2 years. In terms of seizure frequency, seizure outcome for 35 children was analyzed and the highest response was seen at 6 and 9 months of treatment. A total of 15 children had seizure clusters during baseline. After 3 months, 9 children were responders for cluster reduction. After 3 months of treatment, most of the children on the ketogenic diet had a decrease in seizure severity. Side effects included abdominal pain, vomiting, and fatigue. There were no reported abnormalities on electrocardiograms and no kidney stones. While there are limitations to this study including non-randomization, uncontrolled selection of children, and limited sample size, the results concluded that ketogenic diet was effective for children with drug-resistant epilepsy with response to diet noted after 6 months of treatment.

In a 2017 randomized controlled trial by Lambrechts and colleagues, the authors reported on the tolerability and efficacy of ketogenic diet in 48 participants (age 1 to 18 years of age) with refractory epilepsy. Primary outcome was reduction of seizure frequency by greater than or equal to 50% when compared with seizure frequency at baseline. Participants were randomized to either the ketogenic diet or to care as usual. At a 4 month follow-up, of the participants who received ketogenic diet treatment, 13 responded to the treatment (3 were seizure free while another 3 had greater than 90% reduction in seizure frequency). In the care as usual group, 2 participants were seizure free and 1 participant had a greater than 90% reduction in seizure frequency. The most commonly reported side effect occurred in the ketogenic diet group was gastrointestinal symptoms.

A 2016 study by Ozdemir and colleagues reported on the effect of ketogenic diet on cardiac functions. A total of 61 participants with intractable epilepsy on the ketogenic diet for at least 12 months were followed. All participants received baseline serum carnitine, selenium levels, electrocardiographic and echocardiographic exams. During the 12 month follow-up, the participants received Doppler imaging to look at the ventricular systolic and diastolic functions. During the year of ketogenic diet, 33 participants were seizure free, 25 participants had seizures decreased by greater than or equal to 90%, and 3 participants had seizures decreased by greater than or equal to 50%. After one year of ketogenic diet, the only significant difference when compared to baseline values was decreased A-wave velocity. Ketogenic diet does not appear to have a disturbing effect on ventricular functions in the midterm, however additional longer term studies are necessary to assess the long-term effect of ketogenic diet on cardiac functions.

The ketogenic diet has been initiated in an inpatient setting, primarily to monitor the individual during the initial fasting period, but also to provide the intense education required to maintain a ketogenic diet once discharged. However, studies have suggested that the diet can be safely initiated in the outpatient setting. In 2004, Vaisleib and colleagues reported on a case series of 37 individuals who underwent outpatient induction of the ketogenic diet, whose outcomes were compared retrospectively to those who underwent inpatient dietary induction. The mean age of the individuals was 6.6 years, with a range of 1.8 to 14 years. The authors reported that there was no evidence that inpatient initiation of the ketogenic diet was superior to outpatient initiation.

The use of a ketogenic diet is being studied for population groups other than children and teenagers. The peer-reviewed published literature is limited to small group sizes and observational studies or retrospective reviews (Cervenka, 2017; Thakur, 2014).


Peer Reviewed Publications:

  1. Cervenka MC, Hocker S, Koenig M, et al. Phase I/II multicenter ketogenic diet study for adult superrefractory status epilepticus. Neurology. 2017; 88(10):938-943.
  2. Henderson CB, Filloux FM, Alder SC, et al. Efficacy of the ketogenic diet as a treatment option for epilepsy: Meta-analysis. J Child Neurol. 2006; 21(3):193-198.
  3. Klein P, Janousek J, Barber A, Weissberger R. Ketogenic diet treatment in adults with refractory epilepsy. Epilepsy Behav. 2010; 19(4):575-579.
  4. Kossoff EH, Laux LC, Blackford R, et al. When do seizures usually improve with the ketogenic diet? Epilepsia. 2008; 49(2):329-333.
  5. Lambrechts DA, de Kinderen RJ, Vles HS, et al. The MCT-ketogenic diet as a treatment option in refractory childhood epilepsy: A prospective study with 2-year follow-up. Epilepsy Behav. 2015; 51:261-266.
  6. Lambrechts DA, de Kinderen RJ, Vles JS, et al. A randomized controlled trial of the ketogenic diet in refractory childhood epilepsy. Acta Neurol Scand. 2017; 135(2):231-239.
  7. Neal EG, Chaffe H, Schwartz RH, et al. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol. 2008; 7(6):500-506.
  8. Ozdemir R, Kucuk M, Guzel O, et al. Does ketogenic diet have any negative effect on cardiac systolic and diastolic functions in children with intractable epilepsy?: One-year follow-up results. Brain Dev. 2016; 38(9):842-847.
  9. Taub KS, Kessler SK, Bergqvist AG. Risk of seizure recurrence after achieving initial seizure freedom on the ketogenic diet. Epilepsia. 2014; 55(4):579-583.
  10. Thakur KT, Probasco JC, Hocker SE, et al. Ketogenic diet for adults in super-refractory status epilepticus. Neurology. 2014; 82(8):665-670.
  11. Vaisleib II, Buchhalter JR, Zupanc ML. Ketogenic diet: outpatient initiation, without fluid, or caloric restrictions. Pediatr Neurol. 2004; 31(3):198-202.
Websites for Additional Information
  1. National Institute of Neurological Disorders and Stroke (NINDS). NINDS Epilepsy Information Page. Available at Accessed on June 5, 2017.

Ketogenic Diet

Status Date Action
Reviewed 08/03/2017 Medical Policy & Technology Assessment Committee (MPTAC) review. Updated Discussion/General Information, References, and Index sections.
Reviewed 08/04/2016 MPTAC review. Updated Discussion/General Information and References sections. Removed ICD-9 codes from Coding section.
Reviewed 08/06/2015 MPTAC review. Updated Discussion/General Information and References.
Reviewed 08/14/2014 MPTAC review. Updated Discussion/General Information and References.
Reviewed 08/08/2013 MPTAC review. Updated Discussion/General Information.
Reviewed 08/09/2012 MPTAC review. Updated Discussion/General Information and References.
Reviewed 08/18/2011 MPTAC review. Updated Discussion/General Information and References.
Reviewed 08/19/2010 MPTAC review. No change in Clinical Indications.
Reviewed 08/27/2009 MPTAC review. Removed "Place of Service" section. Updated Discussion and References.
Revised 08/28/2008 MPTAC review. References, Coding and Web Sites updated. Added "not medically necessary" statement.
Revised 08/23/2007 MPTAC review. Deleted "highly motivated" from Clinical Indication statement. Rationale and References updated.
Reviewed 09/14/2006 MPTAC review. No change in position; References updated.
Revised 09/22/2005 MPTAC Revision based on Pre-merger Anthem and Pre-merger WellPoint Harmonization.
Pre-Merger Organizations Last Review Date Document Number Title
Anthem, Inc.


  No document
Anthem SE Memo


Memo 1113 Ketogenic Diet for Refractory Epilepsy
WellPoint Health Networks, Inc.


2.10.01 Ketogenic Diet for Intractable Seizure Disorder