Severe diet-induced hypercholesterolemia mimicking familial hypercholesterolemia in atypical lean mass hyper-responders on ketogenic diets: a case series

Background The lean mass hyper-responder (LMHR) phenotype describes marked increases in low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (ApoB) during carbohydrate-restricted ketogenic diets, usually in lean, metabolically healthy individuals with high high-density lipoprotein cholesterol (HDL-C) and low triglycerides. Case presentations We report three Western European patients referred for suspected familial hypercholesterolemia (FH) after severe hypercholesterolemia developed during ketogenic dieting. None consistently met all current LMHR laboratory criteria. One patient was overweight before diet initiation, one was on the low side of the normal BMI range upon referral, and one was within the normal weight BMI range and became markedly underweight during diet exposure. Peak LDL-C during ketogenic dieting ranged from 364 to 682 mg/dL. After modest carbohydrate reintroduction, LDL-C and ApoB decreased substantially without lipid-lowering pharmacotherapy. Conclusion These cases suggest that ketogenic diet-associated severe hypercholesterolemia may extend beyond classical LMHR criteria and can closely mimic FH. Dietary patterns, weight trajectory, and secondary causes should be assessed before assigning an FH diagnosis. Because ApoB-containing lipoproteins are causal in atherosclerosis, severe diet-induced ApoB elevation should not be assumed to be benign.