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The principal goal for the study is to examine the role gut flora plays in modulating metabolism of dietary carnitine and choline in humans.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Carnitine (No antibiotics, No aspirin) | Active Comparator | L-Carnitine 500 mg capsule by mouth, twice daily for 2 months. No aspirin for 1 month prior to starting study and remains off aspirin during study. |
|
| Choline (No Antibiotics, No aspirin) | Active Comparator | Choline 500 mg capsule by mouth, twice daily for 2 months. No aspirin for 1 month prior to starting study and remains off aspirin during study. |
|
| Antibiotics | Active Comparator | Antibiotics (Ciprofloxacin, Vancomycin, Metronidazole and Neomycin) Drug: Ciprofloxacin 500 mg, po, twice daily for 7 days (Other Names: Cipro) Drug: Metronidazole 500 mg, po, twice daily for 7 days (Other Names: Flagyl, Noritate, Rosadan, Vandazole, Flagyl ER, Vitazol) Drug: Vancomycin 125 mg, po, 4 times daily for 7 days (Other Names: Vancocin, Vancocin HCl, Pulvules, Vancoled, Novaplus, PremierPro Rx, Vancomycin HCl) Drug: Neomycin 1 gram, po, four times daily for 7 days (Other Names: Aminoglycoside) |
|
| Choline and Aspirin | Active Comparator | Choline supplement 500 mg capsule by mouth, twice daily for 2 months Drug: aspirin 81 mg by mouth, daily for 3 months (on aspirin for 1 month prior to starting study and 2 months with Choline supplementation during study) Other Names: Ecotrin, Bufferin, Ascriptin, Fasprin, Norwich Aspirin, Durlaza, Bayer Genuine Aspirin, Genacote, Bayer, Halfprin, Aspirtab, Aspir Low, Aspir-Trin |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Carnitine | Dietary Supplement | Group 1: Carnitine supplement for 2 months, No antibiotics, no aspirin for 3 months (1 month prior and during study) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Primary Outcome Measure | Plasma levels of carnitine and multiple gut flora metabolites | December 2017 |
| Measure | Description | Time Frame |
|---|---|---|
| Secondary Outcome Measures | Alterations in plasma levels of cardio-metabolic risk factors. | December 2017 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Stanley L Hazen, MD, PhD | The Cleveland Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cleveland Clinic | Cleveland | Ohio | 44195 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30530985 | Derived | Koeth RA, Lam-Galvez BR, Kirsop J, Wang Z, Levison BS, Gu X, Copeland MF, Bartlett D, Cody DB, Dai HJ, Culley MK, Li XS, Fu X, Wu Y, Li L, DiDonato JA, Tang WHW, Garcia-Garcia JC, Hazen SL. l-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans. J Clin Invest. 2019 Jan 2;129(1):373-387. doi: 10.1172/JCI94601. Epub 2018 Dec 10. |
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|
| Carnitine and Aspirin | Active Comparator | Carnitine supplement 500 mg capsule by mouth, twice daily for 2 months Drug: aspirin 81 mg by mouth, daily for 3 months (on aspirin for 1 month prior to starting study and 2 months with Carnitine supplementation during study) Other Names: Ecotrin, Bufferin, Ascriptin, Fasprin, Norwich Aspirin, Durlaza, Bayer Genuine Aspirin, Genacote, Bayer, Halfprin, Aspirtab, Aspir Low, Aspir-Trin |
|
| Choline | Dietary Supplement | Group 2: Choline supplement for 2 months, No antibiotics, no aspirin for 3 months (1 month prior and during study) |
|
| Antibiotics | Drug | Group 3: Carnitine or Choline for 2 months, antibiotic cocktail (Ciprofloxacin, Flagyl, Vancomycin, and Neomycin) for 1 week |
|
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| Choline and Aspirin | Drug | 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). |
|
|
| Carnitine and Aspirin | Drug | 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). |
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|
| ID | Term |
|---|---|
| D002331 | Carnitine |
| D002794 | Choline |
| D000900 | Anti-Bacterial Agents |
| D002939 | Ciprofloxacin |
| D008795 | Metronidazole |
| D014640 | Vancomycin |
| D009355 | Neomycin |
| D001241 | Aspirin |
| ID | Term |
|---|---|
| D050337 | Trimethyl Ammonium Compounds |
| D000644 | Quaternary Ammonium Compounds |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009861 | Onium Compounds |
| D000890 | Anti-Infective Agents |
| D045506 | Therapeutic Uses |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D009593 | Nitroimidazoles |
| D009574 | Nitro Compounds |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006020 | Glycopeptides |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D012459 | Salicylates |
| D062385 | Hydroxybenzoates |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
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