Investigation of an Amino Acid Supplement on Glucose Levels in Obese Subjects

1. BCAA's multiple functions in cells In addition to participating in de novo protein
synthesis, Branched-Chain Amino Acids (BCAAs, including leucine, isoleucine, and valine)
regulate multiple cellular functions as nutrient signaling. For example, BCAAs regulate
insulin and glucagon secretion and thus glucose metabolism1. BCAAs, especially leucine,
is one key regulator of mTOR signaling, which is the central component of a complex
signaling network of insulin signaling, cell growth, and proliferation. BCAAs also
regulate protein synthesis and degradation in various tissues.

2. Impact of BCAA supplemental or BCAA-enriched diet on metabolism In addition to the
healthcare utilization of BCAAs for liver disorders and their complications and other
diseases, BCAA supplementation is common amongst athletes and fitness professionals to
improve muscle building and strength. Meanwhile, BCAA supplementation or BCAA-rich
protein diets are often associated with positive effects on body weight and glucose
homeostasis1. Increasing dietary uptake of BCAAs improved the parameters associated with
obesity and T2DM, such as body composition and glycemia levels. However, these
beneficial effects are not conclusive. Moreover, other studies have shown that
circulating branched-chain amino acid concentrations are associated with obesity and
future insulin resistance in children and adolescents2.

3. Summary Both beneficial and detrimental effects of BCAA on metabolism have been
established and therefore warrants further investigation. In the preliminary study, we
found that BCAAs enhanced glucose metabolism in lean mice while they promoted glucose
intolerance in obese mice. In lean mice, BCAAs decreased adiposity and enhanced glucose
utilization and insulin sensitivity in different tissues. But in obese mice, BCAAs'
effects were mediated by impaired insulin signaling in fat tissue.

Inclusion Criteria:

1. Age 20-65 years of age at screen

2. BMI between 27 to 40

3. Fasting glucose level >100, but <126 mg/dL or HgbA1c >5.7% but < 6.4%

4. Waist circumference > 40 in for men and >35 in for women

5. Subjects must read and sign the Institutional Review Board-approved written informed
consent prior to the initiation of any study specific procedures or enrollment. A
subject will be excluded for any condition that might compromise the ability to give
truly informed consent.

Exclusion Criteria:

1. Any subject with a history of diabetes mellitus on medications, or other serious
medical condition, such as chronic hepatic or renal disease, bleeding disorder,
congestive heart disease, cancer (except skin basal cell carcinoma ) chronic diarrhea
disorders, myocardial infarction, coronary artery bypass graft, angioplasty within 6
months prior to screening, current diagnosis of uncontrolled hypertension (defined as
systolic BP>160mmHg, diastolic BP>95mmHg), active or chronic gastrointestinal
disorders, bulimia, anorexia, or endocrine diseases (except thyroid disease requiring
medication) as indicated by medical history or routine physical examination.

2. Any subject with a screening laboratory value outside of the laboratory normal range
that is considered clinically significant for study participation by the investigator.

3. Any subject who currently uses tobacco products.

4. Any history of gastrointestinal disease except for appendectomy.

5. Any antibiotic or laxative use during the 2 months before the study.

6. Any subject who is unable or unwilling to comply with the study protocol.

7. Any subject allergic to soy products.