Effect of a Low Advanced Glycation End Products (AGE) Diet in the Metabolic Syndrome

The metabolic syndrome (MetSyn), a well-defined cluster of pathogenic conditions, includes
glucose intolerance, insulin resistance (pre-diabetes), hypertension, abdominal obesity, and
dyslipidemia. The MetSyn has a strong inflammatory component and raises the risk for
cardiovascular disease (CVD) by five-fold and of diabetes by two fold in aging. Although,
excessive caloric intake, i.e. "over nutrition" is known to be involved in developing the
MetSyn, the actual causative agents of MetSyn in human nutrition have not been determined.

The investigators have previously shown that Advanced Glycation End products (AGEs) can
induce oxidant stress and inflammatory responses and modulate insulin signaling in animal
models and more recently in humans. These studies separated the effects of "over-nutrition"
from the pro-inflammatory effects of AGEs, a factor not previously considered. These data
support our hypothesis that AGE-restriction could be an important intervention in the MetSyn
in aging.

The investigators would like to demonstrate that this safe, practical and economical
intervention can arrest the progression of three major "epidemics" of aging: diabetes,
obesity, and vascular disease associated with the metabolic syndrome. This simple
intervention could have significant health and economic implications.

Our hypothesis is that dietary AGE restriction can reverse several cardinal manifestation of
the MetSyn, specifically insulin resistance, abdominal obesity and cardiovascular disease.

Inclusion Criteria:

- Non-smoking adult subjects with at least three of the following five characteristics
of the metabolic syndrome (MetSyn):

- Waist circumference:

Men: > 102 cm Women: > 88 cm

- Blood pressure: > 130/85 mm Hg (or use of anti-Blood Pressure medication)

- HDL-cholesterol:

Men: < 40 mg/dL Women: < 50 mg/dL

- Triglycerides: > 150 mg/dL (or use of medications for high triglycerides such as
fibrates or nicotinic acid)

- Fasting blood sugar > 100 mg/dl (or use of metformin), but a Glycated hemoglobin
(HbA1c) <6.5%

- Any gender and race 50 years old or above

- Dietary AGE intake > 12 AGE Eq/day

(Before randomization all participants will be screened with a 3-day food record and 7-day
food frequency questionnaire (AGE Quick Score) to determine their average spontaneous
daily intake of AGEs. Only those subjects whose daily intake is > 12 AGE Eq/day will
participate in the study.)

Exclusion Criteria:

- Diagnosis of diabetes (HbA1C > 6.5 %)

- Glomerular Filtration Rate (GFR) less than 60 ml/min

- Any major cardiovascular event within the preceding 3 months

- Inability to understand or unwillingness to follow study diets

- Any unstable medical condition requiring medication adjustment or treatment within
the preceding 3 months

- Any severe illness with an expected participant survival less than 1 year

- Diagnosis of HIV

- Currently receiving treatment for any inflammatory condition

- Currently receiving cancer treatment, such as radiation, chemotherapy, hormone
therapy, or stem cell transplant

- Currently participating in any other research study requiring a special diet,
medications, supplements or other lifestyle change