The Metabolic Response to Reduced Branched-chain Amino Acids in Humans

Study Overview
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Brief Summary
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Branched-chain amino acids (BCAAs) are essential nutrients that the body obtains from proteins found in food, especially meat, diary products, and legumes. Data from rodent studies suggest that reduction of dietary BCAAs will promote fat mass loss and improved control of blood glucose. The purpose of this study is to test if reduction of dietary BCAAs without reducing calorie intake will lead to similar metabolic benefits in humans. Here the investigators test the feasibility of reducing dietary BCAAs using BCAA-free meal replacement beverages for two months.

Detailed Description
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This study, which will be completed over three months, involves replacing two meals a day with meal replacement beverages for two months, with a one month follow-up visit. These beverages will be made up by subjects using either a complete protein powder or BCAD2, a BCAA-free medical food. Participants will complete food diaries at baseline and at one month intervals during the study, and compliance will be assessed via food diaries, weekly telephone contact, and measuring returned food powder.

Official Title
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The Metabolic Response to Reduced Branched-chain Amino Acids in Humans

Conditions
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Diabetes, Obesity, Insulin Resistance

Intervention / Treatment
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* Other: Whey protein powder
* Other: BCAD2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male between the age of 35 - 65 BMI between 28 - 35 (mildly obese/overweight) Fasting glucose level of 101 - 125 mg/dL Able and willing to give written informed consent Stable weight (within 5 lbs. for at least 3 months) Not taking (or willing to cease taking) over the counter vitamin/mineral supplements Not planning to begin an exercise or diet program Exclusion Criteria: Female Outside required age range of 35 - 65 BMI not within range of 28 - 35 Fasting glucose not within range of 101 - 125 mg/dL Use of prescription medications for diabetes or weight-loss Use of and unwillingness to discontinue over the counter supplements (e.g. cinnamon, chromium, protein powders) or weight loss beverage or meal plans (e.g. SlimFast or Jenny Craig). Low baseline albumin or pre-albumin levels (below normal reference range) Significant anemia (Hemoglobin < 11 g/dL) Known bleeding disorder or platelet dysfunction Already eating a low protein diet (less than 14% total caloric intake from protein), as calculated from food diaries provided by subjects Participating in intensive exercise training program (high to moderate intensity exercise greater than 210 minutes per week) or planning to start new exercise program during study period. Significant co-morbidities (including kidney disease, liver disease, GI disease, cardiovascular disease, respiratory disease, malnutrition, substance abuse, psychiatric disease, or a diagnosed eating disorder). Planned smoking cessation or attempt at smoking cessation during study period Inability to tolerate meal replacement beverages due to palatability Recent weight loss (> 5 lbs within 3 months). Bariatric surgery, gastric banding or liposuction Current or past (within 1 year) use of illicit drugs Claustrophobia

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Whey protein powder<br>Participants in the Placebo Arm will replace two-thirds of participants dietary protein intake with meal replacement beverages utilizing a complete protein powder. | Other: Whey protein powder<br>* Participants in the Control Arm will replace two-thirds of participants dietary protein intake with a commercially available whey protein powder.<br>|
| Experimental: Experimental<br>Participants in the Experimental Arm will replace two-thirds of participants dietary protein intake with BCAD2 (Mead Johnson), a BCAA-free medical food. | Other: BCAD2<br>* Participants in the Experimental Arm will replace two-thirds of participants dietary protein intake with BCAD2 (Mead Johnson), a BCAA-free medical food.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of BCAA intake | The principle outcome of this study is to determine if replacing 2/3rds of the subjects baseline protein intake with BCAA-free meal replacement beverages are a feasible method of selectively reducing BCAA consumption. Our principle outcome is to reduce BCAA intake by 50% or more in the Experimental Arm (BCAD2) of the study as compared to baseline intake. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight | Weight in kg | 3 months | 
| Fat mass | Fat mass in kg | 3 months | 
| BMI | Weight in kg and height in meters will be combined to report BMI in kg/m^2 | 3 months | 
| Resting metabolic rate | Resting metabolic rate in kcal/hour | 3 months | 
| Fasting blood glucose | Fasting blood glucose in mg/dL | 3 months | 
| Insulin | Insulin in ng/dL | 3 months | 
| HbA1c | HbA1c in mmol/mol | 3 months | 
| Glucose tolerance | Area under the curve in mg/dL/min | 3 months |