Gut Flora Metabolite Reduction After Dietary Intervention (GRADY)

This is a pilot human study to characterize the relationship between gut flora-associated
TMAO generation and dietary intervention. The investigators hypothesize that tailored dietary
interventions may help to reduce the ability for gut flora to generate TMAO in individuals
with elevated TMAO levels. Specific aims include:

1. To investigate the proportion of subjects with persistently elevated circulating TMAO
levels.

2. To compare the amount of TMAO generated from gut flora using stable-isotope-labelled
choline, carnitine, and betaine in subjects with elevated versus normal circulating TMAO
levels.

3. To evaluate the effect of dietary interventions on the amount of TMAO generated from gut
flora using stable-isotope-labelled choline, carnitine, and betaine in subjects with
elevated circulating TMAO levels.

Inclusion Criteria:

- Men and women age 18 years or above.

- Elevated TMAO metabolizers (>5 µM) based on screening test.

- Willing to remain on aspirin or able to be off aspirin or aspirin products for 1 week
prior to starting study and staying on the same aspirin regimen during the duration of
the 12-week study.

- Willing to sign consent form or to follow study protocol, which includes 12-week
dietary modification.

Exclusion Criteria:

- Significant chronic illness or end-organ dysfunction, including known history of
uncompensated heart failure, renal failure, pulmonary disease, hematologic diseases.

- Active infection or received antibiotics within 2 months of study enrollment

- Use of over-the-counter probiotic within past month, or ingestion of yogurt within
past 7 days

- Having undergone bariatric procedures or surgeries such as gastric banding or bypass.

- Pregnancy.

- Any condition which, in the judgment of the Investigator, would place a patient at
undue risk by being enrolled in the trial, or cause inability to comply with the trial