Mechanism of Ketogenic Diet-Induced Hypercholesterolemia
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- VLDL-ApoB100 production rate
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 39 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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%.
排除标准
- •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
研究组 & 干预措施
A
Arm A will complete the Ketogenic Diet intervention first, followed by the Control Diet intervention after a 4-week washout period.
干预措施: Ketogenic Diet (Behavioral)
A
Arm A will complete the Ketogenic Diet intervention first, followed by the Control Diet intervention after a 4-week washout period.
干预措施: Control Diet (Behavioral)
B
Arm B will complete the Control Diet intervention first, followed by the Ketogenic Diet intervention after a 4-week washout period.
干预措施: Ketogenic Diet (Behavioral)
B
Arm B will complete the Control Diet intervention first, followed by the Ketogenic Diet intervention after a 4-week washout period.
干预措施: Control Diet (Behavioral)
结局指标
主要结局
VLDL-ApoB100 production rate
时间窗: 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
次要结局
- Adipokines(Immediately after the screening ketogenic diet)
- VLDL-ApoB100 fractional catabolic rate(Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.)
- IDL-ApoB100 production rate(Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.)
- LDL-ApoB100 production rate(Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.)
- LDL-ApoB100 fractional catabolic rate(Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.)
- IDL-ApoB100 fractional catabolic rate(Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.)
- VLDL-triglyceride production rate(Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.)
- VLDL-triglyceride fractional catabolic rate(Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.)
- Plasma lipoprotein lipase activity(Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.)
- Plasma lipoprotein profile(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(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(Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.)
- Thyroid function(Immediately after the screening ketogenic diet)
- Cholesterol synthetic rate(Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.)
- Fat mass(Immediately after the screening ketogenic diet)
- Fat-free mass(Immediately after the screening ketogenic diet)
- Insulin sensitivity(Immediately after the screening ketogenic diet)
- Cholesterol absorption markers(Immediately after the screening ketogenic diet)