Mechanism of Ketogenic Diet-Induced Hypercholesterolemia

This study will evaluate the mechanism of ketogenic diet-induced hypercholesterolemia in susceptible normal-weight adults. The first stage of screening will identify eligible young adults who are normal-weight and at low cardiovascular risk. The second stage of screening will identify "responders" who demonstrate susceptibility to ketogenic diet-induced hypercholesterolemia by displaying an increase in LDL-cholesterol concentration after a 3-week screening ketogenic diet. Responders will be eligible to complete a randomized crossover clinical study at Washington University School of Medicine in St. Louis, MO. The randomized crossover study will involve isotope tracer studies of lipoprotein and cholesterol kinetics after two separate 4-week dietary interventions [ketogenic diet and control diet], conducted in random order with a 4-week washout period between interventions. All food will be provided to the participants as packed-out meals. Certain outcomes will use data from the screening process, comparing screen successes and screen failures to evaluate factors that could influence susceptibility to ketogenic diet-induced hypercholesterolemia.

Inclusion criteria

• age ≥ 18 and < 40 years
• BMI ≥ 18.5 and < 25.0 kg/m2
• baseline serum LDL-c < 150 mg/dL (< 3.9 mmol/L)
• baseline serum TG < 100 mg/dL (< 1.1 mmol/L)
• HbA1c ≤ 5.6%.

Exclusion criteria

• personal or family history of familial hypercholesterolemia
• current use of lipid-lowering drugs
• currently on a ketogenic diet and unwilling to change diet
• current tobacco use
• hypertension
• prediabetes or diabetes
• elevated Lp(a) > 6.5% of ApoB-containing lipoproteins at baseline
• oral contraceptive use
• contraindication to heparin
• known atherosclerotic cardiovascular disease
• unwilling to abstain from alcohol