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Trimethylamine-N-oxide (TMAO), a metabolite produced by gut microbial metabolism of dietary choline, has recently been causally linked to atherosclerosis in animal models and has been shown to be predictive of cardiovascular disease (CVD) risk in some but not all cohort studies. The relevance of observations in animals to humans is unclear and little information is available on the mechanisms linking TMAO to increased CVD risk. Vascular dysfunction plays a critical role in the initiation and progression of atherothrombotic disease. Whether TMAO impairs vascular function in humans is not known. The purpose of this study is to determine if short term supplementation of dietary choline, which increase TMAO, impairs vascular function.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Short Term Choline Supplementation | Experimental | Participants will be asked to consume 1000 mg of choline bitartrate for 4 weeks prior to and during the testing period. |
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| Short Term Placebo Supplementation | Placebo Comparator | Participants will be asked to consume 1000 mg of placebo (maltodextrin) for 4 weeks prior to and during the testing period. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Choline | Dietary Supplement | Participants will consume 1000 mg (2x500 mg) of choline bitartrate (over-the-counter supplement) for 28 consecutive days. At baseline, some participants will also be randomly assigned to consume 1000 mg of choline bitartrate the evening before the third testing session to study its acute effects. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in brachial artery function after supplementation | Brachial artery function or flow mediated dilation (FMD), the blood flow and diameter of the brachial artery in the forearm (fMD), will be measured using a duplex ultrasound machine before and after the inflation of a blood pressure cuff on the forearm for 5 minutes and after placing a nitroglycerine tablet (0.4 mg) under the participant's tongue. This test will be conducted once at baseline and then once after each 5-day period of the randomly-assigned supplement (choline or placebo), including a 1-week washout period (crossover design). Off-line analysis of baseline and post-reactive hyperemic diameters and velocities will be performed using edge detection software (Vascular Analysis Tools, Medical Imaging Applications, Inc.). | 30-minute measurement in laboratory |
| Measure | Description | Time Frame |
|---|---|---|
| Change in arterial stiffness after supplementation | The blood flow and diameter in the common arteries in the neck will be measured from the image obtained from an ultrasound unit (GE Vivid S6) equipped with a high resolution linear array transducer. For applanation tonometry, the carotid, brachial, radial and femoral artery pressure waveform and amplitude will be obtained by a fingertip probe incorporating a high-fidelity strain gauge transducer. Each of these measures are used to calculate arterial stiffness. These tests will be conducted once at baseline and then once after each 5-day period of the randomly-assigned supplement (choline or placebo), including a 1-week washout period (crossover design). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kevin Davy, PhD | Virginia Polytechnic Institute and State University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Virginia Polytechnic and State University | Blacksburg | Virginia | 24061 | United States |
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| ID | Term |
|---|---|
| D002794 | Choline |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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Double-blind, placebo-controlled, crossover design
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| Placebo | Dietary Supplement | Participants will consume 1000 mg (2x500 mg) of placebo for 28 consecutive days. At baseline, some participants will also be randomly assigned to consume 1000 mg of placebo the evening before the third testing session to study its acute effects. |
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| 45-minute measurement in laboratory |
| Change in gut-mediated TMAO levels after supplementation | At baseline, a fasting blood sample will be collected to measure plasma TMAO concentration after supplementation consumption 8 hours prior to the third testing session. | 5-minute measurement in laboratory |
| D000588 |
| Amines |
| D050337 | Trimethyl Ammonium Compounds |
| D000644 | Quaternary Ammonium Compounds |
| D009861 | Onium Compounds |