Oregon Health & Science University
The ketogenic diet (KD) is a very high fat and low carbohydrate diet that reduces seizure frequency in some children with epilepsy. The KD may increase risk for deficiency of carnitine, a nutrient required for fatty acid oxidation and ketone production. Although carnitine is supplemented during KD therapy by many medical centers, supplemental carnitine may be cost prohibitive, poorly tolerated, and possibly unnecessary. This study aimed to evaluate: 1) the impact of the KD on plasma carnitine concentrations, 2) possible correlations between plasma carnitine and β9 hydroxybutyrate concentrations, and 3) the association between plasma carnitine concentration and reduction in seizure frequency and number of antiepileptic drugs (AEDs) prescribed.
We reviewed medical records for pediatric patients at Doernbecher Children’s Hospital (Portland, OR) who were treated by the KD (3:1 ratio or higher) for epilepsy who were not prescribed supplemental carnitine during KD therapy. Mean plasma concentrations of free carnitine, acylcarnitine, total carnitine, and acyl/free carnitine concentration ratio were calculated before and 1, 3, and 5 – 8 months after KD initiation. Mean plasma concentrations of individual acylcarnitine species were calculated before and 5 – 8 months after KD initiation. Difference in means was assessed, linear regression was performed, and odds ratios were calculated.
Medical records of 22 patients were analyzed (mean age 3.9 ± 4.8 years, range 0.08 – 16.0 years). Mean plasma free carnitine was lower than baseline at 1, 3, and 5 — 8 months after KD initiation (not statistically significant). Mean plasma concentration of total carnitine was significantly higher than baseline at 1 and 5 — 8 months after KD initiation. Mean plasma concentration of acylcarnitine and acyl/free carnitine concentration ratio were significantly higher than baseline at 1, 3, and 5 — 8 months after KD initiation. Mean plasma concentrations were significantly higher than baseline at 5 – 8 months after KD initiation for the acylcarnitine species: C2, C49OH, C8, C10, C10:1, C14:1, C18 – C18:2. Plasma β9hydroxybutyrate concentration was significantly negatively correlated with plasma concentration of free (p=0.00) and total (p<0.01) carnitine, and significantly positively correlated with plasma acyl/free carnitine concentration ratio (p=0.01) and plasma concentrations of C2 (p=0.04) and C3 (p<0.01). Participants with a plasma acyl/free carnitine concentration ratio of at least 1.5 were 10 times more likely to achieve at least a 50% reduction in seizure frequency (p<0.05). No statistically significant odds ratios were observed for likelihood of withdrawal of at least one AED.
Discussion and Conclusion
The KD significantly impacted mean plasma carnitine concentrations for pediatric patients who were not prescribed supplemental carnitine. We observed increased: plasma acylcarnitine and total carnitine concentrations, acyl/free carnitine concentration ratio, and concentrations of certain acylcarnitine species. Degree of ketosis was higher for children with: lower plasma concentrations of free and total carnitine, higher plasma acyl/free carnitine concentration ratio, and higher plasma concentrations of C2 and C3. Children with plasma acyl/free carnitine concentration ratios of at least 1.5 may be more likely to experience reduction in seizure frequency. We found insufficient evidence to suggest that AED withdrawal was influenced by plasma carnitine concentration.
Graduate Programs in Human Nutrition
School of Medicine
Riebold, Jane E., "Carnitine status of children treated with the ketogenic diet for intractable epilepsy" (2015). Scholar Archive. 3651.