Dietary Modification
Conditions
Keywords
carnitine metabolism, gut flora, phosphatidylcholine
Brief summary
The principal goal for the study is to examine the role gut flora plays in modulating metabolism of dietary carnitine and choline in humans.
Detailed description
The principal goal for the study is to examine the role gut flora plays in modulating metabolism of dietary trimethylamine nutrients in humans. We have recently shown that dietary intake of two trimethylamines abundant in animal products, carnitine and the choline group of phosphatidylcholine (PC), are mechanistically linked to cardiovascular disease risk. We wish to further explore the metabolism of these nutrients in humans, and to test the hypothesis that the intestinal micro flora (gut flora) plays a critical role in generation of metabolites from dietary carnitine and choline/PC linked to cardiometabolic disease. We further hypothesize that the production of specific metabolites of carnitine and choline/PC are influenced by the composition of gut flora, and these may be altered by the preceding dietary patterns of the subjects. We therefore wish to test whether dietary supplementation with carnitine and/or choline alters the metabolism of carnitine and choline/PC in subjects. We also hypothesize that transient suppression or modulation of gut flora via short-term broad spectrum antibiotic therapy, or by reconstitution of micro flora composition via probiotic therapy, in healthy subjects, can alter the metabolism of carnitine and choline/PC. We will also examine the impact of low dose aspirin on these pathways by examining subjects before versus after taking aspirin.
Interventions
DIETARY_SUPPLEMENTCarnitine
Group 1: Carnitine supplement for 2 months, No antibiotics, no aspirin for 3 months (1 month prior and during study)
DIETARY_SUPPLEMENTCholine
Group 2: Choline supplement for 2 months, No antibiotics, no aspirin for 3 months (1 month prior and during study)
DRUGAntibiotics
Group 3: Carnitine or Choline for 2 months, antibiotic cocktail (Ciprofloxacin, Flagyl, Vancomycin, and Neomycin) for 1 week
DRUGCholine and Aspirin
Group 4: Choline supplement for 2 months plus aspirin 81 mg for 3 months (1 month prior to starting the study and 2 months during the study).
DRUGCarnitine and Aspirin
Group 5: Carnitine supplement for 2 months plus aspirin 81 mg for 3 months (1 month prior to starting the study and 2 months during the study).
Sponsors
The Cleveland Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Men and women age 18 years or above. * Able to provide informed consent and comply with study protocol
Exclusion criteria
* Significant chronic illness or end-organ dysfunction, including known history of heart failure, renal failure, pulmonary disease, hematologic diseases or pregnancy. * Active infection or received antibiotics within 2 months of study enrollment * Use of Over-The-Counter (OTC) probiotic within past 2 months, or ingestion of yogurt within past 7 days * Chronic gastrointestinal disorders, or intolerance to probiotic therapy * Having undergone Bariatric procedures or surgeries such as gastric banding or bypass
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Outcome Measure | December 2017 | Plasma levels of carnitine and multiple gut flora metabolites |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Outcome Measures | December 2017 | Alterations in plasma levels of cardio-metabolic risk factors. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORStanley L Hazen, MD, PhD
The Cleveland Clinic
Outcome results
None listed