Metabolic Effects of Betaine Supplementation

This study is a single site, prospective, randomized (1:1), double masked, placebo controlled
trial to assess metabolic effects of betaine compared to placebo on glycemia and insulin
sensitivity, liver fat and endothelial function.

Inclusion Criteria:

- 1) Men and women aged 21-65 years old;

- 2) Dysglycemia/prediabetes is defined as impaired fasting glucose (≥100 mg/dl),
impaired glucose tolerance (2 hour post 75 g oral glucose load 140-200 mg/dl) or HbA1c
5.7-6.5%);

- 3) Grade 1 obesity (BMI 27 to 36 kg/m2).

Exclusion Criteria:

- 1) cystathionine beta-synthase (CBS deficiency);

- 2) Presence of liver disease other than NAFLD;

- 3) Use of medications causing steatosis;

- 4) Known alcohol consumption ≥ 2 drink per day;

- 5) Use of medications known to cause insulin resistance;

- 6) Use of weight loss drugs (or program) within 3 months of screening;

- 7) Treatment with any experimental drug within the past 6 months;

- 8) Subjects must be willing to abstain from use of phosphodiesterase type 5 (PDE-5)
inhibitors;

- 9) Pregnancy or lactation, and women of child bearing potential must use adequate
contraception;

- 10) Surgery within 30 days of screening;

- 11) Heart disease defined as New York Heart Association Class III or IV cardiac status
or hospitalization for congestive heart failure, unstable angina, myocardial
infarction, cerebrovascular accident, transient ischemic attack or any
revascularization within 6 months;

- 12) Uncontrolled hypertension;

- 13) eGFR <60; 14) History of acquired immune deficiency syndrome;

- 15) History of malignancy within 5 years;

- 16) Hemoglobin <12 g/dL (males), <10 g/dL (females);

- 17) Triglycerides (TG) >500 mg/dL;

- 18) Poor mental function or any other reason to expect patient difficulty in complying
with study requirements;

- 19) Metal clips or implants that preclude magnetic resonance imaging.