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Effects of Choline From Eggs vs. Supplements on the Generation of TMAO in Humans (EGGS)

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ClinicalTrials.gov Identifier: NCT03039023
Recruitment Status : Completed
First Posted : February 1, 2017
Results First Posted : May 14, 2021
Last Update Posted : June 2, 2021
Sponsor:
Information provided by (Responsible Party):
Wilson Tang, The Cleveland Clinic

Brief Summary:
The investigators are interested in learning more about choline, a nutrient required by the body. The body does make some choline, but it does not make enough to support health and the rest must be acquired through diet. Eggs, and especially egg yolks, are a major dietary source of choline. Choline can also be given as a dietary supplement. Ingestion of choline supplements has been linked to an increased concentration of a compound called TMAO (trimethylamine N-oxide). Elevated TMAO levels have been linked to higher heart disease risk. With this study, the investigators hope to learn whether there is a difference in the way your body responds to the ingestion of a choline supplement versus the choline found within eggs.

Condition or disease Intervention/treatment Phase
Cardiovascular Risk Factor Dietary Supplement: Choline Bitartrate Other: Pre-cooked, pre-peeled whole hardboiled eggs Other: Egg whites from pre-cooked, pre-peeled hardboiled eggs Dietary Supplement: Phosphatidylcholine capsules Not Applicable

Detailed Description:

The principal goal for the study is to examine whether there is a difference between the ingestion of choline through supplements versus choline found within eggs on plasma TMAO levels. The investigators have previously shown that dietary intake of trimethylamines, including the choline group of phosphatidylcholine (PC), is mechanistically linked to cardiovascular disease risk and that the metabolism of these trimethylamine nutrients in humans is modulated by the intestinal microbes (gut microbes). Additionally, extensive animal studies link an essential role of gut microbiota to the metabolism of choline and the production of metabolites that promote / accelerate atherosclerotic processes. The investigators have also recently shown a 10-fold increase in plasma TMAO levels following supplementation with choline bitartrate supplements. However, another pilot study by a collaborator (unpublished) did not show the same increase in plasma TMAO levels following the ingestion of whole eggs, a major dietary source of choline. Therefore, with this study the investigators wish to examine the differences, if any, between the ingestion of an equivalent mass of total choline in the free form (as bitartrate salt) as a supplement vs. within whole eggs.

Eggs, and specifically the egg yolk, contain a large amount of total choline. However, egg white contains potential anti-microbial peptides that could influence gut microbial composition and function, and therefore impact conversion of choline into TMA and TMAO observed in subjects. Therefore, the investigators hypothesize that the consumption of whole eggs (hardboiled) will not elevate plasma TMAO levels to the same extent as a comparable amount of total choline ingested in capsule form as the choline bitartrate salt. The investigators further hypothesize that the consumption of egg white with choline bitartrate tablets may result in less of a rise in TMAO levels than ingestion of the choline bitartrate supplement alone.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 86 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Effects of Choline From Eggs vs. Supplements on the Generation of TMAO in Humans (EGGS)
Actual Study Start Date : September 2, 2016
Actual Primary Completion Date : April 10, 2018
Actual Study Completion Date : September 3, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Whole Hardboiled Eggs
Subjects will consume four (4) pre-cooked, pre-peeled whole hardboiled eggs per day for 28 days.
Other: Pre-cooked, pre-peeled whole hardboiled eggs
Obtained from a commercial source.

Experimental: Choline Bitartrate Tablets
Subjects will consume two (2) 500mg choline bitartrate tablets per day for 28 days.
Dietary Supplement: Choline Bitartrate
500mg choline bitartrate tablets

Experimental: Hardboiled Eggs + Choline Bitartrate Tablets
Subjects will consume both four (4) whole, pre-cooked, pre-peeled hardboiled eggs and two (2) 500mg choline bitartrate tablets per day for 28 days.
Dietary Supplement: Choline Bitartrate
500mg choline bitartrate tablets

Other: Pre-cooked, pre-peeled whole hardboiled eggs
Obtained from a commercial source.

Experimental: Egg Whites + Choline Bitartrate Tablets
Subjects will consume both the egg whites (no yolks) of four (4) pre-cooked, pre-peeled hardboiled eggs and two (2) 500mg choline bitartrate tablets per day for 28 days.
Dietary Supplement: Choline Bitartrate
500mg choline bitartrate tablets

Other: Egg whites from pre-cooked, pre-peeled hardboiled eggs
Egg whites from pre-cooked, pre-peeled hardboiled eggs. The yolks are removed and discarded.

Experimental: Phosphatidylcholine Capsules
Subjects will consume six (6) 420 mg phosphatidylcholine capsules by mouth per day for 28 days.
Dietary Supplement: Phosphatidylcholine capsules
420 mg phosphatidylcholine capsules obtained from a commercial source.




Primary Outcome Measures :
  1. Changes in Plasma Levels of Fasting Trimethylamine-N-oxide (TMAO), a Choline Metabolite [ Time Frame: Baseline, 28 days ]
    Changes in levels of non-labeled TMAO from baseline to end-of-study (day 28) as measured by established techniques by mass spectrometry.

  2. Changes in Platelet Function With Increased Choline Intake [ Time Frame: Baseline, Day 28 ]
    The activation and functioning of platelets within a single subject will be compared before and after increased choline intake.


Secondary Outcome Measures :
  1. Changes in Levels of Fasting Trimethylamine-N-oxide (TMAO) in 24-hour Urine Collections [ Time Frame: Baseline, Day 28 ]
    Changes in levels of non-labeled TMAO from baseline to Day 28 measured by established mass spectrometry techniques.

  2. Changes in Plasma Levels of Fasting Choline [ Time Frame: Baseline, Day 28 ]
    Fasting plasma levels of choline from samples obtained at baseline and at day 28 were compared.

  3. Changes in Plasma Levels of Fasting Carnitine. [ Time Frame: Baseline, Day 28 ]
    Fasting plasma levels of carnitine from samples obtained at baseline and at day 28 were compared.

  4. Changes in Plasma Levels of Fasting Betaine. [ Time Frame: Baseline, Day 28 ]
    Fasting plasma levels of betaine from samples obtained at baseline and at day 28 were compared.

  5. Changes in Lipid Profile, Total Cholesterol [ Time Frame: Baseline, Day 28 ]
    Changes in total cholesterol levels between baseline and Day 28

  6. Changes in Lipid Profile, HDL [ Time Frame: Baseline, Day 28 ]
    Changes in measured HDL levels between baseline and Day 28

  7. Changes in Lipid Profile, LDL [ Time Frame: Baseline, Day 28 ]
    Changes in measured LDL levels between baseline and Day 28

  8. Changes in Lipid Profile, Triglycerides [ Time Frame: Baseline, Day 28 ]
    Changes in measured triglyceride levels between baseline and Day 28



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Men and women age 18 years or above.
  • Willing to remain on aspirin or stay off aspirin or aspirin products for 1 week prior to starting the study and throughout the study period.
  • Able to provide informed consent and comply with study protocol.
  • Able to be off all other supplements during the study period.

Exclusion Criteria:

  • Significant chronic illness.
  • Active infection or received antibiotics within 1 month of study enrollment.
  • Use of over-the-counter probiotic within the past month
  • Chronic gastrointestinal disorders, such as ulcerative colitis or Crohn's disease.
  • Allergy to eggs or lactose.
  • Having undergone bariatric procedures or surgeries such as gastric banding or bypass.
  • Pregnancy.
  • Any condition that, 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03039023


Locations
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United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
The Cleveland Clinic
Investigators
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Principal Investigator: W. H. Wilson Tang, MD The Cleveland Clinic
  Study Documents (Full-Text)

Documents provided by Wilson Tang, The Cleveland Clinic:
Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Wilson Tang, Staff, Cardiovascular Medicine, The Cleveland Clinic; Staff, Cellular and Molecular Medicine, The Cleveland Clinic Lerner Research Institute, The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT03039023    
Other Study ID Numbers: 16-1048
First Posted: February 1, 2017    Key Record Dates
Results First Posted: May 14, 2021
Last Update Posted: June 2, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Wilson Tang, The Cleveland Clinic:
TMAO
choline
eggs
gastrointestinal microbiome
healthy volunteers
Additional relevant MeSH terms:
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Choline
Lipotropic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Agents
Lipid Regulating Agents
Nootropic Agents