Rationale:
The modified Atkins diet (MAD) is a ketogenic diet-variant and a well-established treatment for drug resistant epilepsy in children and adults. High-fat, low-carbohydrate diets may lead to changes in lipid biomarkers that impact cardiovascular health. The aim of this study was to further assess cardiovascular risk markers by evaluating changes in lipid biomarkers and carotid intima-media thickness (CIMT) in adults with epilepsy following MAD for one year.
Methods:
Eighty-five diet-naïve adults were enrolled in an ongoing prospective study at the Johns Hopkins Adult Epilepsy Diet Center. Participants were instructed to follow a 20 gram/day net carbohydrate limit MAD. Collected baseline demographic measures included age at study and diet onset, gender, self-identified ethnicity, smoking history, personal history of diabetes, hypertension, cardiovascular disease, and dyslipidemia, physical activity levels, and family history of myocardial infarction and stroke. Anthropometric (weight and body mass index) and serologic measures were collected at baseline and one year. Serum levels of total cholesterol, triglycerides, HDL, LDL, apolipoproteins B and A1, LDL particle number, LDL sub-class, and LDL peak size were measured. CIMT was measured using B-mode ultrasonography at end-diastole in the far wall of the bilateral distal common carotid arteries according to a standard protocol. Mean left and right CIMT from anterior, lateral, and posterior approaches were averaged and reported. Paired sample t-tests were used for the analysis of continuous variables using IBM SPSS Version 30 for Mac.
Results:
Of the initially enrolled cohort, thirty participants completed their one year follow up visit. There were eighteen (60%) males and twelve (40%) females. The average age was thirty-nine years (SD = 14). Significant increases in lipid biomarkers included total cholesterol (32 mg/dL ± 20, p = 0.003), LDL-C (27 mg/dL ± 17, p = 0.003), ApoB (15 mg/dL ± 11, p = 0.12), and LDL-peak size (3 angstrom ± 2, p = 0.007). Triglycerides were the only biomarker to decrease but this change was not significant. The remaining serologic biomarkers demonstrated no significant change over time. There was no significant change in average left or right CIMT (L = 0.008, p = 0.791, R = 0.018, p = 0.515).
Conclusions:
Adults with epilepsy following MAD for one year experienced significant increases in total cholesterol, LDL-C, ApoB, and LDL-peak size. In the general population, lifetime exposure to LDL-C and ApoB may increase risk of cardiovascular disease. However, it is unknown if lipid changes associated with MAD confers similar risk. CIMT is a surrogate marker for atherosclerotic cardiovascular disease and there was no significant change in CIMT over one year in this cohort. However, atherosclerosis is an insidious process which increases with age. The relatively short follow up of one year and young age of the cohort may be limitations of this study. These findings suggest further study is warranted on the impacts of MAD on long-term cardiovascular health.
Funding:
The Johns Hopkins Center for Refractory Status Epilepticus and Neuroinflammation and a grant from the American Epilepsy Society.