Hypercholesterolemia Induced by a High-Fat, Low-Carbohydrate Diet in a 16-year-old Male and 6-year-old Female.
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Background: The ketogenic diet is a high-fat, low-carbohydrate (HFLC) diet that has been linked to hypercholesterolemia. There are ongoing studies on the connection between hypercholesterolemia and adherence to the ketogenic diet. Medically supervised HFLC ketogenic diets with up to 90% fat have been used successfully in children as an alternative treatment for epilepsy. Although safety and efficacy data are limited in children, this high-fat diet has also been used for weight loss. Case information: Patient 1:A 16-year-old previously healthy African American male was concerned about his weight and his mother started him on a ketogenic diet. Before diet implementation, he weighed 93.2 kg (BMI of 31.6 kg/m2; 99%) and had a low-density lipoprotein cholesterol (LDL-C) of 114 mg/dL (normal LDL-C is below 110 mg/dL). During the following months, the patient lost weight and his LDL-C levels continuously increased and peaked at 348 mg/dL after losing 59lbs on the ketogenic diet. The patient was offered pharmacotherapy but the parents declined. During his most recent follow-up appointment, the patient stopped adhering to the ketogenic diet and increased his weight to 79.2 kg (BMI of 26.2 kg/m2; 87.5%), and his LDL-C level dropped to 182 mg/dL. Throughout appointments, triglycerides remained normal. No pathological variants for APOB, LDLR, LDLRAP1, and PCSK9were found on genetic testing. Patient 2: A 6-year-old female with a history of idiopathic ketotic hypoglycemia and growth hormone deficiency was started on the ketogenic diet as a way to help control hypoglycemic episodes. The diet helped keep her blood glucose levels stable but she demonstrated severe hypercholesterolemia on her lipid screening. Her LDL-C levels were significantly elevated at 310 mg/dL 37 months after her first appointment. She was taken off the ketogenic diet for 6-8 weeks with significant improvement in her LDL-C dropping down to 116 mg/dL. At 42 months, the patient was admitted to the hospital for hypoglycemia. It was noted that the mother had started the patient on the ketogenic diet again due to recurrent episodes of hypoglycemia. On lipid screening, her LDL-C was back up to 397 mg/dL. Genetic testing for APOB, LDLR, LDLRAP1, and PCSK9 were all negative. Conclusions: Several mechanisms have been proposed to explain the adverse effect of hypercholesterolemia in individuals participating in the ketogenic diet. This includes increased saturated fatty acid intake causing downregulation of LDL receptors, genetic polymorphisms, and cholesterol mobilization associated with weight loss. Although there is ongoing research regarding the mechanism behind hypercholesterolemia associated with HFLC diets, there is no clear, definitive explanation yet. Our case study and other case series in adults on the ketogenic diet for weight loss show the importance of ruling out HFLC diets when patients present with hypercholesterolemia and have no known genetic mutations suggesting familial hypercholesterolemia (FH).