Authors :
First Author: Daniel Chu, PhD – University of Wisconsin School of Medicine and Public Health
Presenting Author: Elizabeth Felton, MD, PhD – University of Wisconsin-Madison
Michele Ravelli, PhD – University of Wisconsin Madison; Kelly Faltersack, RD – University of Wisconsin Madison; Arron Woods, BS – University of Wisconsin Madison; Dace Almane, PhD – University of Wisconsin Madison; zhanhai Li, MS – University of Wisconsin Madison; Emmanuel Sampene, PhD – University of Wisconsin Madison; Elizabeth Felton, MD PhD – University of Wisconsin School of Medicine and Public Health
Rationale:
Previous studies have demonstrated the safety and efficacy of the Modified Atkins Diet (MAD) in attenuating seizures in patients with intractable epilepsy. The MAD works by achieving ketosis, which is dependent on the metabolic compound, carnitine, to facilitate the transport of long-chain fatty acids across the mitochondria for beta-oxidation. Carnitine status is evaluated by measuring plasma levels of total, free, and acyl-carnitine. Because carnitine is responsible for this crucial step in the generation of ketones, MAD likely increases its demand. Although previous research has shown MAD to be highly effective in attenuating seizures, few studies have evaluated whether low plasma free carnitine plays a role in the state of ketosis while on the MAD. We investigated the effects of hypocarnitinemia on the efficacy of MAD in attenuating seizures in adults with epilepsy.
Methods:
Fifty-eight patients (18 male; mean age = 38.94 ± 14.55) were retrospectively analyzed from the database of patients with epilepsy undergoing MAD therapy at the UW Health Adult Neurology Ketogenic Diet Therapy Clinic from 2016 through 2021. Generalized linear mixed effects models were used to compare the low versus normal carnitine status groups in patient measures of seizure frequency and severity, body mass index (BMI), number of antiseizure medications (ASM), beta-hydroxybutyrate (BHB), triglyceride, and carnitine levels across baseline, three to nine month follow-up (timepoint 1), one to two year follow-up (timepoint 2), and 2+ year follow-up (timepoint 3).
Results:
The percent change in each outcome at each time point from previous visit for patients with low and normal carnitine are illustrated in Table 1. Overall, our study revealed that 38.3% of adult patients with epilepsy following MAD experienced low free carnitine at some point through the course of diet therapy. Additionally, patients with hypocarnitinemia at timepoint two demonstrated a significant percent seizure increase while seizures continued to decrease in the normal carnitine group. Additionally, triglyceride levels at timepoint one were significantly increased in the low carnitine group compared to normal carnitine group. Change in BHB, BMI, seizure severity, and number of ASMs showcased no significant differences between the low and normal carnitine groups. Figure 1 demonstrates the trend of percent change in number of seizures over the timepoints comparing the normal with low free carnitine groups.
Conclusions:
Our study demonstrates that low carnitine is fairly common for adult epilepsy patients on MAD. Additionally, hypocarnitinemia may be associated with increased seizures and triglyceride levels, which may develop over the course of the diet. Thus, it may be important for clinicians to monitor for hypocarnitinemia in adults on MAD and provide carnitine supplementation when low. Further investigations into carnitine and its effect on MAD efficacy may inform clinical decisions to maximize the therapeutic efficacy in adults with epilepsy.
Funding:
We are immensely grateful for the support from the AES Pre-doctoral Fellowship, NIH T32 GM140935, and the University of Wisconsin MSTP Radiology Fellowship.