In mice genetically predisposed to artery plaque buildup, a diet extremely high in fat and very low in carbohydrates led to lower levels of specific blood fats known to contribute to plaque formation, compared to a diet with less fat and more carbohydrates.
Evidence from Studies
No evidence studies found yet.
What Would Prove This
Per GRADE and EBM methodology, here is what ideal scientific evidence would look like to definitively prove or disprove this claim, ordered from strongest to weakest.
Whether the reduction in phosphatidylcholines, cholesterol esters, sphingomyelins, and ceramides is a consistent effect of ketogenic diets across multiple independent studies in ApoE-deficient mice.
A systematic review and meta-analysis of all controlled animal studies comparing ketogenic (≥70% kcal fat, ≤5% kcal carbohydrate) versus non-ketogenic high-fat diets in ApoE-deficient mice, with standardized lipidomics using mass spectrometry to quantify phosphatidylcholines, cholesterol esters, sphingomyelins, and ceramides, reporting standardized mean differences and confidence intervals.
Whether the ketogenic diet directly causes a reduction in these specific atherogenic lipid metabolites compared to a control diet in ApoE-deficient mice.
A double-blind, randomized controlled trial in 60 male ApoE-deficient mice, randomly assigned to either a ketogenic diet (81% kcal fat, 1% kcal carbohydrate, 18% kcal protein) or an isocaloric non-ketogenic high-fat diet (40% kcal fat, 42% kcal carbohydrate, 18% kcal protein), with plasma lipid metabolites quantified via mass spectrometry at baseline and week 12 as primary endpoints, and analysts blinded to group assignment.
Whether the ketogenic diet is consistently associated with lower levels of these lipid metabolites across different strains of mice with varying metabolic profiles.
A prospective cohort study following 200 male and female mice across five different atherosclerosis-prone strains (ApoE−/−, LDLR−/−, B6, C57BL/6J, and mixed backgrounds), each fed either a ketogenic or non-ketogenic high-fat diet for 12 weeks, with serial lipid metabolite measurements adjusted for sex, age, and baseline lipid levels.
Whether a snapshot of these lipid metabolites correlates with dietary fat and carbohydrate composition in a broader population of mice.
A cross-sectional analysis of plasma lipid metabolites in 500 mice from multiple laboratories fed diverse high-fat diets (ranging from 30–90% kcal fat and 0–50% kcal carbohydrate), with dietary composition and lipid profiles recorded at a single time point without intervention.
Whether rare individual mice on ketogenic diets show extreme suppression of these lipid metabolites not seen in the group average.
A case series documenting plasma levels of phosphatidylcholines, cholesterol esters, sphingomyelins, and ceramides in five ApoE-deficient mice that exhibited exceptionally low levels (<10th percentile) despite being on the same ketogenic diet as others with moderate reductions.