The Effects of the Telomerase Activator TA-65 on Insulin Resistance, Inflammation, and Metabolic Syndrome

This is double blind cross over randomized clinical trial. The supplement and placebo will
be provided by TA Science, Inc. and prepared as described below. Subjects will be randomly
allocated to consume either a daily serving of TA-65 (two capsules per day of 8 mg each)
(please see attached label) or a placebo for 12 weeks. Randomization will be done in a
sequential manner; the first subject will be allocated to supplement A and the next one to
supplement B and so on. After a 3-week washout, they will be allocated to the alternate
treatment for additional 12 weeks. Supplements (TA-65 or placebo) will be taken twice daily
with a meal.

Participants will be advised not to change their diet or exercise protocols during the 27
week intervention. Volunteers will be required to provide a 5-day dietary record before
starting the study, at the end of each supplement period (TA-65 or placebo) and at the end
of the washout period. Subjects will have to fill an exercise questionnaire during the same
times to ensure that there are no changes in physical activity. Participants will be asked
to report to the department every 4 weeks for checking compliance on supplement intake and
to assess weight and blood pressure.

Inclusion Criteria:

The inclusion criteria are:

men and women (40-70 y) with metabolic syndrome which means having at least 3 of the
following characteristics:

- Blood pressure > 130/85 mm Hg

- plasma glucose > 100 mg/dL

- plasma triglycerides > 150 mg/dL

- HDL cholesterol < 40 mg/dL (men) and < 50 mg/dL (women)

- waist circumference >102 cm (men) and ≥ 88 cm (women)

- Women of childbearing age should be using contraception

Exclusion Criteria:

Exclusion criteria will be

- self-reported diabetes mellitus

- coronary heart disease

- triglycerides greater than 400 mg/dL

- Fasting glucose greater than 126 mg/dL

- Blood pressure greater than 140/100 mmg Hg

- history of stroke

- Use of alcohol at an elevated rate (more than two drinks per day)

- Renal problems

- liver disease

- cancer

- pregnancy and lactation

- severe infectious diseases

- autoimmune disease currently under treatment

- current hormone therapy

- previous treatment with TA-65.

- Intake of glucose-lowering prescriptions

- Use of immunosuppressants, lithium or supplements such as Sulphonylureas (Glucotrol,
Amaryl), Thiazolidinedione (Avandia, ACTOS,), Meglitinides (Prandin, Starlix),
Biguanides (Metformin), Alpha-glucosidase inhibitors (Precose, Glyset), dipeptidyl
peptidase (DPP)-4 inhibitors (Januvia, Onglyza)

- high dose chromium or cinnamon supplements

- Consistent intake of vitamin, mineral, or multivitamin supplements prior to
recruitment may be admitted into the study if they plan on maintaining their current
supplement program.

However, subjects may not participate if they begin taking a new supplement during the
27-wk study period.

-Subjects will also be asked to refrain from taking any additional supplements, including
fish oil, herb and concentrated antioxidant sources.