Table 1.

KD in the Treatment of Refractory Seizures—Study Characteristics

Study/YearPatientsDietHospitalizationStudy DesignOutcome AssessmentCompliance (Percentage of Patients Who Discontinue Diet)Adverse Effects
Hopkins and Lynch/197034 children with seizures refractory to medications. Social environment conducive to KDClassic KD. 3:1 fat/protein ratioLength of hospital stay not specifiedClinical series. Retrospective analysisMethod NR. Response evaluated after at least 2 mo on diet32% (11/34) 9 patients could not tolerate diet from outset, 2 patients discontinued despite improvementMarked transient drowsiness—9% (3/34) Kidney stones—3% (1/34) Most patients showed moderate growth retardation
Huttenlocher et al/197112 children with seizures refractory to AEDs. Minimum of 4 seizures/wk for at least 4 moMCT diet4–10 dClinical series. Retrospective analysis (?)Method NR. Response assessed after at least 1 mo on diet17% (2/12) 1 patient discontinued attributable to adverse effects, 1 attributable to intolerabilityGI symptoms in 33% of patients (4/12), leading to discontinuation of diet in 1 patient
Janaki et al/197615 patients recalcitrant to various combinations of AEDs. 13/15 childrenClassic KD. 4:1 fat/protein ratio5–6 wkClinical series. Retrospective analysisMethod NR. Response evaluated after ≥12 wkA few patients discontinued dietNR
Huttenlocher/197618 children refractory to medications after “extensive trials…in various combinations”MCT dietNRClinical series. Retrospective analysis (?)Method NR. Response evaluated after at least 3 mo on dietNRNR. No significant increase in serum lipids while on diet
Berman/197818 children refractory to medications in various combinationsMCT diet. 8/18 children had been treated with classic KDNRClinical series. Retrospective analysisMethod NR. Variable length of time on dietNRNR
Trauner/198517 children with intractable seizures, despite numerous AEDsMCT dietNRClinical series. Retrospective assessment of outcomes (?)Seizure activity log maintained by parents. Variable length of time on diet (6 mo–4 y)29% (5/17) 17.6% (3/17) attributable to adverse effects. 11.8% (2/17) attributable to intolerability3 patients (17.6%) with severe GI symptoms—diarrhea, vomiting, abdominal pain.
Sills et al/198650 children who had failed to respond to appropriate AEDs. Exclude severely retarded or developmentally delayed.MCT dietAverage stay 18 dClinical series. Retrospective assessment of outcomes (?) Hospital records and home logs by parents. 2 wk following stabilization of diet.12% (6/50) at outset. 18% (9/50) later (time period not specified)Mild diarrhea and abdominal pain—“common”
Schwartz et al/198959 patients who had failed to respond to adequate trials of conventional AEDs, or intolerable adverse effects. 55 children/4 adultsClassic KD—15 patients MCT diet—22 patients Modified MCT—13 patientsLength of stay NRClinical series. Retrospective assessment of outcomesSeizure activity log maintained by parents. Evaluated after 6 wk on diet3.4% (2/59)GI symptoms occurred in “approximately half” of patients. Transient drowsiness in 25% of patients upon starting diet
Mixed—9 patients
Kinsman et al/199258 consecutive patients treated with KD, all refractory to multiple AEDs and adequate home environmentClassic KD. 4:1 fat/protein ratio3–4 dClinical series, consecutive patients. Retrospective analysisReports by parents and physicians. Variable length of treatment at time of assessment5.2% (3/58) Estimated 80% of patients with >50% decrease in seizures remained on diet at 12 moKidney stones—5% (3/58) Hypouricemia—3% (2/58) Acidosis—2% (1/58) Hypocalcemia—2% (1/58)
Vining et al/199851 children, 1–8 y old, >10 seizure/wk, failed at least 2 AEDs, adequate psychosocial situation, enrolled from 7 sitesClassic KD. 4:1 fat/protein ratio4 dProspective, multicenter, uncontrolled clinical trialReports by parents. Outcomes assessed at 3-, 6-, 12-mo intervals 3 mo—12% (6/51)
 6 mo—27% (14/51)
12 mo—45% (23/51)
Lethargy—4% (2/51) Acidosis—4% (2/51) Constipation—8% (4/51) Increased infections—4% (2/51) Vomiting—(2/51)
Freeman, unpublished data150 consecutive children treated with ketogenic diet. Age 1–16 y, >2 seizure/wk, failed at least 2 AEDsClassic KD. 4:1 fat/protein ratio. Some children <2 y old and adolescents put on 3:1 ratio4 dProspective, uncontrolled clinical trialReports by parents. Outcomes assessed at 3-, 6-, 12-mo intervals 3 mo—17% (25/150)
 6 mo—29% (44/150)
12 mo—45% (67/150)
Kidney stones—4% (?)
  • KD indicates ketogenic diet; MCT, medium chain triglyceride; NR, no report; GI, gastrointestinal.