Strategies to Augment Ketosis: Impact of Exogenous Ketones on Indices of Keto-Adaptation in Obese Subjects on Weight Reducing Diets.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Insulin (mIU/L)
研究概览
简要总结
This project will be a three-group controlled 6-wk feeding study where all meals are prepared and provided to obese participants. All participants will be fed a 25% energy-restricted diet. Two diets will be very low in carbohydrate (i.e., ketogenic diets) designed to induce nutritional ketosis and fat loss. Another diet will be low in fat and saturated fat but contain the same total calories. Participants will be randomly assigned to a Ketone Supplement group who are provided an exogenous pre-formed source of beta-hydroxybutyrate (BOHB) or a Control group that only receives the standard ketogenic diet. Randomization will be stratified based on insulin resistance, sex, and body composition to ensure balanced group assignment. Because of timing of recruitment (i.e., after most of the ketogenic groups have already completed the study), the low-fat group will not be randomized. Outcome measurements will be made at various intervals over the 6-wk intervention.
详细描述
This project will be a three-group controlled 6-wk feeding study where all meals are prepared and provided to obese participants. All participants will be fed a 25% energy-restricted diet. Two diets will be very low in carbohydrate (i.e., ketogenic diets) designed to induce nutritional ketosis and fat loss. Another diet will be low in fat and saturated fat but contain the same total calories. Participants will be randomly assigned to a Ketone Supplement group (n=12) who are provided an exogenous pre-formed source of beta-hydroxybutyrate (BOHB) or a Control group (n=12) that only receives the standard ketogenic diet. Randomization will be stratified based on insulin resistance, sex, and body composition to ensure balanced group assignment. Because of timing of recruitment (i.e., after most of the ketogenic groups have already completed the study), the low-fat group will not be randomized. Outcome measurements will be made at various intervals over the 6-wk intervention. Key outcome variables will include: 1) Markers of Ketosis/Keto-Adaptation: a. Daily measures of BOHB (capillary blood) b. Fasting serum BOHB and total ketones (venous blood) c. Diurnal capillary blood ketones and urinary loss of BOHB and total ketones 2) Energy Balance and Body Composition: a. Body mass (scale) b. Whole body and regional composition (DXA) c. Nitrogen balance (daily nitrogen intake - 24-hr urinary nitrogen loss) d. Resting energy expenditure and substrate oxidation (indirect calorimetry) e. Adiposity (myocardial/epicardial fat, liver fat, visceral fat, skeletal muscle fat by MRI) f. Microbiome (stool collection to observe microbiota and the response to diet alteration) 3) Cognitive and Behavioral: a. Computer-based cognitive function (ANAM) b. Behavioral responses (surveys) 4) Cardio-Metabolic Risk: a. Metabolic panel b. Circulating lipid panel (total cholesterol, LDL-C, HDL-C, TG) c. Glucose, insulin, HOMA
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 21 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •BMI >27 and =35 kg/m2
排除标准
- •have diabetes, liver, kidney, or other metabolic or endocrine dysfunction, or using diabetic medications.
- •Currently consuming a low-carbohydrate diet
- •Weight loss of >10% in past 6 months -Currently pregnant or nursing, or planning to become pregnant during the study
- •Major psychiatric disorder (e.g., schizophrenia, bipolar disorder)
- •Excessive alcohol intake (acute or chronic) defined as average consumption of 3 or more alcohol-containing beverages daily or consumption of more than 14 alcoholic beverages per week
研究组 & 干预措施
Ketogenic Diet
Participants will have all their meals prepared in the Instructional Kitchen in the Ohio Union, irrespective of group assignment. They will receive a daily caloric intake equal to 75% of their estimated requirement to maintain weight, which should result in weight loss over the 6-week period. For those in the ketogenic groups, daily macronutrient intake will consist of 35 g of carbohydrates and moderate protein calculated as 1.5 g/kg of reference weight. The remaining caloric intake will consist of fat. A wide range of whole foods will be incorporated into the meals, including non-starchy vegetables, meats, nuts and seeds, oils, cheese, butter, cream, and eggs. The menu will be shared with participants prior to enrolling in the study so they know what to expect in terms of the meal plans.
干预措施: Diet (Other)
Ketogenic Diet
Participants will have all their meals prepared in the Instructional Kitchen in the Ohio Union, irrespective of group assignment. They will receive a daily caloric intake equal to 75% of their estimated requirement to maintain weight, which should result in weight loss over the 6-week period. For those in the ketogenic groups, daily macronutrient intake will consist of 35 g of carbohydrates and moderate protein calculated as 1.5 g/kg of reference weight. The remaining caloric intake will consist of fat. A wide range of whole foods will be incorporated into the meals, including non-starchy vegetables, meats, nuts and seeds, oils, cheese, butter, cream, and eggs. The menu will be shared with participants prior to enrolling in the study so they know what to expect in terms of the meal plans.
干预措施: Blood Draw (Biological)
Ketogenic Diet
Participants will have all their meals prepared in the Instructional Kitchen in the Ohio Union, irrespective of group assignment. They will receive a daily caloric intake equal to 75% of their estimated requirement to maintain weight, which should result in weight loss over the 6-week period. For those in the ketogenic groups, daily macronutrient intake will consist of 35 g of carbohydrates and moderate protein calculated as 1.5 g/kg of reference weight. The remaining caloric intake will consist of fat. A wide range of whole foods will be incorporated into the meals, including non-starchy vegetables, meats, nuts and seeds, oils, cheese, butter, cream, and eggs. The menu will be shared with participants prior to enrolling in the study so they know what to expect in terms of the meal plans.
干预措施: Ketone/Glucose Monitoring (Biological)
Ketogenic Diet
Participants will have all their meals prepared in the Instructional Kitchen in the Ohio Union, irrespective of group assignment. They will receive a daily caloric intake equal to 75% of their estimated requirement to maintain weight, which should result in weight loss over the 6-week period. For those in the ketogenic groups, daily macronutrient intake will consist of 35 g of carbohydrates and moderate protein calculated as 1.5 g/kg of reference weight. The remaining caloric intake will consist of fat. A wide range of whole foods will be incorporated into the meals, including non-starchy vegetables, meats, nuts and seeds, oils, cheese, butter, cream, and eggs. The menu will be shared with participants prior to enrolling in the study so they know what to expect in terms of the meal plans.
干预措施: Body Composition (Other)
Ketogenic Diet
Participants will have all their meals prepared in the Instructional Kitchen in the Ohio Union, irrespective of group assignment. They will receive a daily caloric intake equal to 75% of their estimated requirement to maintain weight, which should result in weight loss over the 6-week period. For those in the ketogenic groups, daily macronutrient intake will consist of 35 g of carbohydrates and moderate protein calculated as 1.5 g/kg of reference weight. The remaining caloric intake will consist of fat. A wide range of whole foods will be incorporated into the meals, including non-starchy vegetables, meats, nuts and seeds, oils, cheese, butter, cream, and eggs. The menu will be shared with participants prior to enrolling in the study so they know what to expect in terms of the meal plans.
干预措施: Urine Analysis (Biological)
Ketogenic Diet
Participants will have all their meals prepared in the Instructional Kitchen in the Ohio Union, irrespective of group assignment. They will receive a daily caloric intake equal to 75% of their estimated requirement to maintain weight, which should result in weight loss over the 6-week period. For those in the ketogenic groups, daily macronutrient intake will consist of 35 g of carbohydrates and moderate protein calculated as 1.5 g/kg of reference weight. The remaining caloric intake will consist of fat. A wide range of whole foods will be incorporated into the meals, including non-starchy vegetables, meats, nuts and seeds, oils, cheese, butter, cream, and eggs. The menu will be shared with participants prior to enrolling in the study so they know what to expect in terms of the meal plans.
干预措施: Neuropsychological Measures - ANAM (Behavioral)
Ketogenic Diet + Ketone Salt
Participants will have all their meals prepared in the Instructional Kitchen in the Ohio Union, irrespective of group assignment. They will receive a daily caloric intake equal to 75% of their estimated requirement to maintain weight, which should result in weight loss over the 6-week period. For those in the ketogenic groups, daily macronutrient intake will consist of 35 g of carbohydrates and moderate protein calculated as 1.5 g/kg of reference weight. The remaining caloric intake will consist of fat. A wide range of whole foods will be incorporated into the meals, including non-starchy vegetables, meats, nuts and seeds, oils, cheese, butter, cream, and eggs. The menu will be shared with participants prior to enrolling in the study so they know what to expect in terms of the meal plans. This group will also be provided a ketone salt supplement to take x2 daily.
干预措施: Diet (Other)
Ketogenic Diet + Ketone Salt
Participants will have all their meals prepared in the Instructional Kitchen in the Ohio Union, irrespective of group assignment. They will receive a daily caloric intake equal to 75% of their estimated requirement to maintain weight, which should result in weight loss over the 6-week period. For those in the ketogenic groups, daily macronutrient intake will consist of 35 g of carbohydrates and moderate protein calculated as 1.5 g/kg of reference weight. The remaining caloric intake will consist of fat. A wide range of whole foods will be incorporated into the meals, including non-starchy vegetables, meats, nuts and seeds, oils, cheese, butter, cream, and eggs. The menu will be shared with participants prior to enrolling in the study so they know what to expect in terms of the meal plans. This group will also be provided a ketone salt supplement to take x2 daily.
干预措施: Blood Draw (Biological)
Ketogenic Diet + Ketone Salt
Participants will have all their meals prepared in the Instructional Kitchen in the Ohio Union, irrespective of group assignment. They will receive a daily caloric intake equal to 75% of their estimated requirement to maintain weight, which should result in weight loss over the 6-week period. For those in the ketogenic groups, daily macronutrient intake will consist of 35 g of carbohydrates and moderate protein calculated as 1.5 g/kg of reference weight. The remaining caloric intake will consist of fat. A wide range of whole foods will be incorporated into the meals, including non-starchy vegetables, meats, nuts and seeds, oils, cheese, butter, cream, and eggs. The menu will be shared with participants prior to enrolling in the study so they know what to expect in terms of the meal plans. This group will also be provided a ketone salt supplement to take x2 daily.
干预措施: Ketone/Glucose Monitoring (Biological)
Ketogenic Diet + Ketone Salt
Participants will have all their meals prepared in the Instructional Kitchen in the Ohio Union, irrespective of group assignment. They will receive a daily caloric intake equal to 75% of their estimated requirement to maintain weight, which should result in weight loss over the 6-week period. For those in the ketogenic groups, daily macronutrient intake will consist of 35 g of carbohydrates and moderate protein calculated as 1.5 g/kg of reference weight. The remaining caloric intake will consist of fat. A wide range of whole foods will be incorporated into the meals, including non-starchy vegetables, meats, nuts and seeds, oils, cheese, butter, cream, and eggs. The menu will be shared with participants prior to enrolling in the study so they know what to expect in terms of the meal plans. This group will also be provided a ketone salt supplement to take x2 daily.
干预措施: Body Composition (Other)
Ketogenic Diet + Ketone Salt
Participants will have all their meals prepared in the Instructional Kitchen in the Ohio Union, irrespective of group assignment. They will receive a daily caloric intake equal to 75% of their estimated requirement to maintain weight, which should result in weight loss over the 6-week period. For those in the ketogenic groups, daily macronutrient intake will consist of 35 g of carbohydrates and moderate protein calculated as 1.5 g/kg of reference weight. The remaining caloric intake will consist of fat. A wide range of whole foods will be incorporated into the meals, including non-starchy vegetables, meats, nuts and seeds, oils, cheese, butter, cream, and eggs. The menu will be shared with participants prior to enrolling in the study so they know what to expect in terms of the meal plans. This group will also be provided a ketone salt supplement to take x2 daily.
干预措施: Urine Analysis (Biological)
Ketogenic Diet + Ketone Salt
Participants will have all their meals prepared in the Instructional Kitchen in the Ohio Union, irrespective of group assignment. They will receive a daily caloric intake equal to 75% of their estimated requirement to maintain weight, which should result in weight loss over the 6-week period. For those in the ketogenic groups, daily macronutrient intake will consist of 35 g of carbohydrates and moderate protein calculated as 1.5 g/kg of reference weight. The remaining caloric intake will consist of fat. A wide range of whole foods will be incorporated into the meals, including non-starchy vegetables, meats, nuts and seeds, oils, cheese, butter, cream, and eggs. The menu will be shared with participants prior to enrolling in the study so they know what to expect in terms of the meal plans. This group will also be provided a ketone salt supplement to take x2 daily.
干预措施: Neuropsychological Measures - ANAM (Behavioral)
Low Fat Diet +Placebo
The low-fat comparison group will also be provided all their food. Their diet will also be restricted in calories and have the same level of protein, but it will be lower in fat and higher in carbohydrate. The low-fat diet will consist of approximately 25% fat, with the remaining calories coming from carbohydrates (approximately 55% after accounting for protein at around 20%). Added sugars will be kept relatively low (less than 25 g/day) with a focus on unprocessed carbohydrate-rich foods. Saturated fat will be limited to less than 10% of total energy, with a focus on unsaturated fat sources.
干预措施: Diet (Other)
Low Fat Diet +Placebo
The low-fat comparison group will also be provided all their food. Their diet will also be restricted in calories and have the same level of protein, but it will be lower in fat and higher in carbohydrate. The low-fat diet will consist of approximately 25% fat, with the remaining calories coming from carbohydrates (approximately 55% after accounting for protein at around 20%). Added sugars will be kept relatively low (less than 25 g/day) with a focus on unprocessed carbohydrate-rich foods. Saturated fat will be limited to less than 10% of total energy, with a focus on unsaturated fat sources.
干预措施: Blood Draw (Biological)
Low Fat Diet +Placebo
The low-fat comparison group will also be provided all their food. Their diet will also be restricted in calories and have the same level of protein, but it will be lower in fat and higher in carbohydrate. The low-fat diet will consist of approximately 25% fat, with the remaining calories coming from carbohydrates (approximately 55% after accounting for protein at around 20%). Added sugars will be kept relatively low (less than 25 g/day) with a focus on unprocessed carbohydrate-rich foods. Saturated fat will be limited to less than 10% of total energy, with a focus on unsaturated fat sources.
干预措施: Ketone/Glucose Monitoring (Biological)
Low Fat Diet +Placebo
The low-fat comparison group will also be provided all their food. Their diet will also be restricted in calories and have the same level of protein, but it will be lower in fat and higher in carbohydrate. The low-fat diet will consist of approximately 25% fat, with the remaining calories coming from carbohydrates (approximately 55% after accounting for protein at around 20%). Added sugars will be kept relatively low (less than 25 g/day) with a focus on unprocessed carbohydrate-rich foods. Saturated fat will be limited to less than 10% of total energy, with a focus on unsaturated fat sources.
干预措施: Body Composition (Other)
Low Fat Diet +Placebo
The low-fat comparison group will also be provided all their food. Their diet will also be restricted in calories and have the same level of protein, but it will be lower in fat and higher in carbohydrate. The low-fat diet will consist of approximately 25% fat, with the remaining calories coming from carbohydrates (approximately 55% after accounting for protein at around 20%). Added sugars will be kept relatively low (less than 25 g/day) with a focus on unprocessed carbohydrate-rich foods. Saturated fat will be limited to less than 10% of total energy, with a focus on unsaturated fat sources.
干预措施: Urine Analysis (Biological)
Low Fat Diet +Placebo
The low-fat comparison group will also be provided all their food. Their diet will also be restricted in calories and have the same level of protein, but it will be lower in fat and higher in carbohydrate. The low-fat diet will consist of approximately 25% fat, with the remaining calories coming from carbohydrates (approximately 55% after accounting for protein at around 20%). Added sugars will be kept relatively low (less than 25 g/day) with a focus on unprocessed carbohydrate-rich foods. Saturated fat will be limited to less than 10% of total energy, with a focus on unsaturated fat sources.
干预措施: Neuropsychological Measures - ANAM (Behavioral)
结局指标
主要结局
Insulin (mIU/L)
时间窗: up to six weeks
Fasting venous blood will be collected biweekly.
Daily Ketone/Glucose Monitoring
时间窗: Up to 6 weeks
Daily fasting glucose/ketones will be assessed using capillary finger stick lancing. A small drop of blood will be obtained once daily, while fasting, using enzymatic strips fitted for a handheld analyzer (KetoMojo). All the data will be stored in the device's internal memory.
Lean Mass (kg)
时间窗: up to six weeks
DEXA Scanning will be biweekly to assess lean mass
Fat Mass (kg)
时间窗: up to six weeks
DEXA Scanning will be biweekly to assess fat mass
Cholesterol (mg/dl)
时间窗: up to six weeks
Fasting venous blood will be collected biweekly to measure cholesterol.
Glucose (mg/dL)
时间窗: up to six weeks
Fasting venous blood will be collected biweekly.
次要结局
- Neuropsychological Outcome 1 - Spatial Processing (Throughput)(up to six weeks)
- Neuropsychological Outcome 1 - Visual Short Term Memory (Throughput)(up to six weeks)
- Neuropsychological Outcome 1 - Reaction time (Throughput)(up to six weeks)
- Urine Chemistries(up to 6 weeks)