Low-density lipoprotein cholesterol elevation, ketogenic diets, body mass index, and heterozygous ABCG5 genetic variation: Review, case report, and large population analysis

BACKGROUND: Low body mass index (BMI) has been associated with marked low-density-lipoprotein-cholesterol (LDL-C) elevations in response to very-low-carbohydrate diets (VLCD). METHODS: ) whose LDL-C was >500 mg/dL on a VLCD. We characterized her plasma lipoproteins and noncholesterol-sterols (gas chromatography/mass spectrometry) and the DNA sequences of her genes affecting lipid metabolism. We also carried out a large population analysis (224,126 subjects, 54% female, mean age 54 years) examining interrelationships between BMI and serum lathosterol/total cholesterol and β-sitosterol/total cholesterol ratios. RESULTS: had mean β-sitosterol/total cholesterol values that were significantly higher (+63%, P < .00001) than values in obese women. The converse was true for the plasma lathosterol/total cholesterol ratio. Similar findings were noted in men. CONCLUSIONS: Our data are consistent with the concepts that low BMI predisposes to increased plasma β-sitosterol/total cholesterol ratios and an increased serum LDL-C when on high cholesterol VLCD, and that this response may be markedly enhanced in subjects with pathogenic heterozygous ABCG5 variants.