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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
100
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.
Washington University School of Medicine
St Louis, Missouri, United States
RECRUITINGVLDL-ApoB100 production rate
Determined by using plasma and VLDL-ApoB100 leucine isotopic enrichment and compartmental modeling
Time frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
VLDL-ApoB100 fractional catabolic rate
Determined by using plasma and VLDL-ApoB100 leucine isotopic enrichment and compartmental modeling
Time frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
IDL-ApoB100 production rate
Determined by using plasma and IDL-ApoB100 leucine isotopic enrichment and compartmental modeling
Time frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
IDL-ApoB100 fractional catabolic rate
Determined by using plasma and IDL-ApoB100 leucine isotopic enrichment and compartmental modeling
Time frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
LDL-ApoB100 production rate
Determined by using plasma and LDL-ApoB100 leucine isotopic enrichment and compartmental modeling
Time frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
LDL-ApoB100 fractional catabolic rate
Determined by using plasma and LDL-ApoB100 leucine isotopic enrichment and compartmental modeling
Time frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
VLDL-triglyceride production rate
Determined by using plasma and VLDL glycerol isotopic enrichment and compartmental modeling
Time frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
VLDL-triglyceride fractional catabolic rate
Determined by using plasma and VLDL glycerol isotopic enrichment and compartmental modeling
Time frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Plasma lipoprotein lipase activity
Determined by assaying lipoprotein lipase activity in post-heparin plasma
Time frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Plasma lipoprotein profile
Determined by standard clinical chemistry methods and by advanced lipoprotein profiling
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.
Whole-body lipolytic rate
Determined by using plasma palmitate isotopic enrichment
Time frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Relative contribution of systemic fatty acids to VLDL-triglyceride
Determined by using plasma and VLDL-triglyceride palmitate isotopic enrichment and compartmental modeling
Time frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Cholesterol synthetic rate
Determined by using mass isotopomer distribution analysis of deuterium enrichment in plasma cholesterol after labeling the total body water pool with deuterium oxide
Time frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Fat mass
Determined by using dual-energy X-ray absorptiometry
Time frame: Immediately after the screening ketogenic diet
Fat-free mass
Determined by using dual-energy X-ray absorptiometry
Time frame: Immediately after the screening ketogenic diet
Insulin sensitivity
Determined by measuring fasting plasma glucose, insulin, and C-peptide
Time frame: Immediately after the screening ketogenic diet
Thyroid function
Determined by measuring TSH, free T4, and free T3
Time frame: Immediately after the screening ketogenic diet
Adipokines
Determined by measuring plasma leptin and adiponectin
Time frame: Immediately after the screening ketogenic diet
Cholesterol absorption markers
Determined by measuring serum campesterol, sitosterol, and cholestanol
Time frame: Immediately after the screening ketogenic diet
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