Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03039023
Recruitment Status : Active, not recruiting
First Posted : February 1, 2017
Last Update Posted : July 24, 2019
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 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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 80 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
Estimated Study Completion Date : December 31, 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.




Primary Outcome Measures :
  1. Changes in plasma levels of fasting trimethylamine-N-oxide (TMAO), a choline metabolite [ Time Frame: 1 week, 1 month ]
    Changes in levels of non-labeled TMAO over time will be measured by established techniques by mass spectrometry.

  2. Changes in plasma levels of fasting trimethylamine (TMA), a choline metabolite [ Time Frame: 1 week, 1 month ]
    Changes in levels of non-labeled TMA over time will be measured by established techniques by mass spectrometry.

  3. Changes in plasma levels of fasting crotonobetaine, a choline metabolite [ Time Frame: 1 week, 1 month ]
    Changes in levels of non-labeled crotonobetaine over time will be measured by established techniques by mass spectrometry.

  4. Changes in plasma levels of fasting betaine, a choline metabolite [ Time Frame: 1 week, 1 month ]
    Changes in levels of non-labeled betaine over time will be measured by established techniques by mass spectrometry.

  5. Changes in plasma levels of fasting gammabutyrobetaine (GBB), a choline metabolite [ Time Frame: 1 week, 1 month ]
    Changes in levels of non-labeled GBB over time will be measured by established techniques by mass spectrometry.


Secondary Outcome Measures :
  1. Changes in urine levels of fasting trimethylamine-N-oxide (TMAO) [ Time Frame: 1 week, 1 month ]
    Changes in levels of non-labeled TMAO over time will be measured by established techniques by mass spectrometry.

  2. Changes in urine levels of fasting trimethylamine (TMA) [ Time Frame: 1 week, 1 month ]
    Changes in levels of non-labeled TMA over time will be measured by established techniques by mass spectrometry.

  3. Changes in urine levels of fasting crotonobetaine [ Time Frame: 1 week, 1 month ]
    Changes in levels of non-labeled crotonobetaine over time will be measured by established techniques by mass spectrometry.

  4. Changes in urine levels of fasting betaine [ Time Frame: 1 week, 1 month ]
    Changes in levels of non-labeled betaine over time will be measured by established techniques by mass spectrometry.

  5. Changes in urine levels of fasting gammabutyrobetaine (GBB) [ Time Frame: 1 week, 1 month ]
    Changes in levels of non-labeled GBB over time will be measured by established techniques by mass spectrometry.

  6. Changes in platelet function with increased choline intake [ Time Frame: 1 month ]
    The activation and functioning of platelets within a single subject will be compared before and after increased choline intake.

  7. Changes in metabolic markers [ Time Frame: 1 week, 1 month ]
    Changes in lipid profile and other markers of metabolism will be measured over time.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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
Layout table for location information
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
The Cleveland Clinic
Investigators
Layout table for investigator information
Principal Investigator: W. H. Wilson Tang, MD The Cleveland Clinic

Additional Information:
Publications:
Layout table for additonal information
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     History of Changes
Other Study ID Numbers: 16-1048
First Posted: February 1, 2017    Key Record Dates
Last Update Posted: July 24, 2019
Last Verified: July 2019
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:
Layout table for MeSH terms
Choline
Lipotropic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Agents
Lipid Regulating Agents
Nootropic Agents