Highlights

\* Ketogenic diet-induced severe hypercholesterolemia may extend beyond classical lean mass hyper-responder criteria.

\* Severe low-density lipoprotein cholesterol (LDL-C) elevation on ketogenic diets can closely mimic familial hypercholesterolemia.

\* In 3 cases, LDL-C peaked at 364 to 682 mg/dL during ketogenic dieting.

\* LDL-C decreased substantially after modest carbohydrate reintroduction without lipid-lowering therapy.

\* When ketosis is medically required, dietary modification plus pharmacological apolipoprotein B-lowering therapy should be considered.

Abstract

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 and low triglycerides.

CASE PRESENTATIONS

We report 3 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, 1 was on the low side of the normal body mass index (BMI) range upon referral, and 1 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.

**Because ApoB-containing lipoproteins are causal in atherosclerosis, severe diet-induced ApoB elevation should not be dismissed as harmless.15 If strict ketosis is medically necessary, eg, for refractory epilepsy, pharmacological ApoB-lowering therapy should be considered within shared decision-making.**