Mechanism of Ketogenic Diet-Induced Hypercholesterolemia
ID: NCT06894004
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Very-low carbohydrate ketogenic diets can dramatically increase blood cholesterol levels, particularly in normal-weight people, for reasons that are not well understood. This study will enroll normal-weight adults, will identify "responders" who develop high cholesterol on a ketogenic diet, and will measure rates of production and removal of certain types of cholesterol-carrying particles called lipoproteins in responders. The results will clarify the mechanism by which a ketogenic diet can cause high cholesterol in certain susceptible people.
Read Full Scientific Objectives & Methods
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.
Participants will consume an isocaloric ketogenic diet for 4 weeks with all food provided as packed-out meals.
Participants will consume an isocaloric control diet for 4 weeks with all food provided as packed-out meals.
Treatment Arms Description
Arm A will complete the Ketogenic Diet intervention first, followed by the Control Diet intervention after a 4-week washout period.
Arm B will complete the Control Diet intervention first, followed by the Ketogenic Diet intervention after a 4-week washout period.
- 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%.
- 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
Primary Outcome Measures
- VLDL-ApoB100 production rate — Time Frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Determined by using plasma and VLDL-ApoB100 leucine isotopic enrichment and compartmental modeling
View Secondary Outcome Measures (18)
- VLDL-ApoB100 fractional catabolic rate — Time Frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Determined by using plasma and VLDL-ApoB100 leucine isotopic enrichment and compartmental modeling
- IDL-ApoB100 production rate — Time Frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Determined by using plasma and IDL-ApoB100 leucine isotopic enrichment and compartmental modeling
- IDL-ApoB100 fractional catabolic rate — Time Frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Determined by using plasma and IDL-ApoB100 leucine isotopic enrichment and compartmental modeling
- LDL-ApoB100 production rate — Time Frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Determined by using plasma and LDL-ApoB100 leucine isotopic enrichment and compartmental modeling
- LDL-ApoB100 fractional catabolic rate — Time Frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Determined by using plasma and LDL-ApoB100 leucine isotopic enrichment and compartmental modeling
- VLDL-triglyceride production rate — Time Frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Determined by using plasma and VLDL glycerol isotopic enrichment and compartmental modeling
- VLDL-triglyceride fractional catabolic rate — Time Frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Determined by using plasma and VLDL glycerol isotopic enrichment and compartmental modeling
- Plasma lipoprotein lipase activity — Time Frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Determined by assaying lipoprotein lipase activity in post-heparin plasma
- Plasma lipoprotein profile — Time Frame: At baseline, immediately after the screening ketogenic diet, immediately after the 4-week ketogenic diet intervention period, and immediately after the 4-week control diet intervention period.
Determined by standard clinical chemistry methods and by advanced lipoprotein profiling
- Whole-body lipolytic rate — Time Frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Determined by using plasma palmitate isotopic enrichment
This trial is recruiting at 1 study facilities worldwide. Click below to see if there is a clinic or hospital in your area:
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View Official Medical/Scientific Title
Mechanism of Ketogenic Diet-Induced Hypercholesterolemia