Ketogenic diets exacerbating dyslipidemia: The role of lipid testing, genetic testing and advanced cardiac imaging

Low carb/high fat ketogenic diets (LCHF/KD) have gained recent popularity in the United States for its benefits on weight loss and type 2 diabetes mellitus management. However, it can potentially exacerbate significant dyslipidemia , particularly in those with certain genetic predispositions . Individual response to ketogenic diets varies largely based on the quantity and composition of the diet as well as individual genetics . The hyper-response of dyslipidemia from a LCHF/KD has not been widely reported in the medical literature. In this article, we present three patients, and compare them to an additional eleven patients we found on a PubMed literature search, all of whom developed severe hyperlipidemia in response to LCHF/KDs, and in whom such a diet should have been otherwise contraindicated. We studied a series of 3 patients along with 11 patients found on literature search (Table 1) all of whom underwent exacerbation of hyperlipidemia after initiation of a ketogenic diet. We compared age, sex, past medical history , medications, LDL levels pre- and post- ketogenic diet, genetic testing, and availability of imaging among our patients with those reported in the literature. Compared to the 11 patients found in the literature search, our patients were of similar age, had similar levels of hyperlipidemia exacerbation, and similar genetic mutations (apolipoprotein gene mutations) (Table 2). All 3 of our patients underwent cardiovascular risk screening with imaging and had cholesterol hyper-absorbance testing. One of our patients was found to be a cholesterol hyper-absorber and responded well to ezetimibe therapy. Dyslipidemia is caused by various genetic factors including familial hypercholesterolemia (FH), caused by mutations in either LDL receptor , apolipoprotein B(ApoB) or proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. Additionally, less commonly known genetic factors of dyslipidemia include apolipoprotein E (ApoE) variants. We recommend that all patients initiate ketogenic diet with an appropriate health care provider and have their baseline and routine lipid panel monitored. If there is a significant increase in their lipid profile , they should also undergo genetic testing, coronary CT angiogram for early detection of atherosclerosis as well as to establish clinically relevant plaque stages, and initiate lipid lowering therapy when clinically indicated. A suggested algorithm for patients initiating ketogenic diet is included in Figure 1.