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

NCT03039023 | Completed Results

• 1 other identifier: 16-1048
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

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.

Conditions

Cardiovascular Risk Factor

Keywords

TMAO; choline; eggs; gastrointestinal microbiome; healthy volunteers

Outcome Measures

Primary Outcomes (2)

• Changes in Plasma Levels of Fasting Trimethylamine-N-oxide (TMAO), a Choline Metabolite

  Changes in levels of non-labeled TMAO from baseline to end-of-study (day 28) as measured by established techniques by mass spectrometry.

  Baseline, 28 days

• Changes in Platelet Function With Increased Choline Intake

  The activation and functioning of platelets within a single subject will be compared before and after increased choline intake.

  Baseline, Day 28

Secondary Outcomes (8)

• Changes in Levels of Fasting Trimethylamine-N-oxide (TMAO) in 24-hour Urine Collections

  Baseline, Day 28

• Changes in Plasma Levels of Fasting Choline

  Baseline, Day 28

• Changes in Plasma Levels of Fasting Carnitine.

  Baseline, Day 28

• Changes in Plasma Levels of Fasting Betaine.

  Baseline, Day 28

• Changes in Lipid Profile, Total Cholesterol

  Baseline, Day 28

Study Arms (5)

Whole Hardboiled Eggs

EXPERIMENTAL

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

Choline Bitartrate Tablets

EXPERIMENTAL

Subjects will consume two (2) 500mg choline bitartrate tablets per day for 28 days.

Dietary Supplement: Choline Bitartrate

Hardboiled Eggs + Choline Bitartrate Tablets

EXPERIMENTAL

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; Other: Pre-cooked, pre-peeled whole hardboiled eggs

Egg Whites + Choline Bitartrate Tablets

EXPERIMENTAL

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; Other: Egg whites from pre-cooked, pre-peeled hardboiled eggs

Phosphatidylcholine Capsules

EXPERIMENTAL

Subjects will consume six (6) 420 mg phosphatidylcholine capsules by mouth per day for 28 days.

Dietary Supplement: Phosphatidylcholine capsules

Interventions

Choline Bitartrate DIETARY_SUPPLEMENT

500mg choline bitartrate tablets

Choline Bitartrate Tablets; Egg Whites + Choline Bitartrate Tablets; Hardboiled Eggs + Choline Bitartrate Tablets

Pre-cooked, pre-peeled whole hardboiled eggs OTHER

Obtained from a commercial source.

Hardboiled Eggs + Choline Bitartrate Tablets; Whole Hardboiled Eggs

Egg whites from pre-cooked, pre-peeled hardboiled eggs OTHER

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

Egg Whites + Choline Bitartrate Tablets

Phosphatidylcholine capsules DIETARY_SUPPLEMENT

420 mg phosphatidylcholine capsules obtained from a commercial source.

Phosphatidylcholine Capsules

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Cleveland Clinic: lead

Study Sites (1)

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Related Publications (4)

• Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011 Apr 7;472(7341):57-63. doi: 10.1038/nature09922.

  PMID: 21475195 BACKGROUND

• Rebouche CJ, Chenard CA. Metabolic fate of dietary carnitine in human adults: identification and quantification of urinary and fecal metabolites. J Nutr. 1991 Apr;121(4):539-46. doi: 10.1093/jn/121.4.539.

  PMID: 2007906 BACKGROUND

• Bidulescu A, Chambless LE, Siega-Riz AM, Zeisel SH, Heiss G. Repeatability and measurement error in the assessment of choline and betaine dietary intake: the Atherosclerosis Risk in Communities (ARIC) study. Nutr J. 2009 Feb 20;8:14. doi: 10.1186/1475-2891-8-14.

  PMID: 19232103 BACKGROUND

• Wilcox J, Skye SM, Graham B, Zabell A, Li XS, Li L, Shelkay S, Fu X, Neale S, O'Laughlin C, Peterson K, Hazen SL, Tang WHW. Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial. Am J Med. 2021 Sep;134(9):1160-1169.e3. doi: 10.1016/j.amjmed.2021.03.016. Epub 2021 Apr 17.

  PMID: 33872583 DERIVED

Related Links

• Patterson K, Bhagwat S, Williams J, Howe J, and Holden J. USDA Database for the Choline Content of Common Foods, Release Two. January 2008.

MeSH Terms

Interventions

Choline; Phosphatidylcholines

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Onium Compounds; Glycerophospholipids; Phosphatidic Acids; Glycerophosphates; Phospholipids; Membrane Lipids; Lipids

Limitations and Caveats

Small sample sizes within each group created uneven distributions of some baseline characteristics; participants' dietary intake beyond the assigned interventions was not controlled during the study period; using only healthy controls makes the translatability of the results to other patient populations, like those with impaired renal function, unclear.

Results Point of Contact

• Title: Jennifer Wilcox
• Organization: Cleveland Clinic Foundation

kirsopj@ccf.org

216-636-6153

Study Officials

• W. H. Wilson Tang, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff, Cardiovascular Medicine, The Cleveland Clinic; Staff, Cellular and Molecular Medicine, The Cleveland Clinic Lerner Research Institute

Study Record Dates

• First Submitted: January 19, 2017
• First Posted: February 1, 2017
• Study Start: September 2, 2016
• Primary Completion: April 10, 2018
• Study Completion: September 3, 2020
• Last Updated: November 4, 2025
• Results First Posted: May 14, 2021

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)