Cardiovascular Risk FactorEGGSNCT03039023
Effects of Choline From Eggs vs. Supplements on the Generation of TMAO in Humans
A study testing Choline Bitartrate, Pre-cooked, pre-peeled whole hardboiled eggs and Egg whites from pre-cooked, pre-peeled hardboiled eggs in people with Cardiovascular Risk Factor, run by The Cleveland Clinic at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Risk Factor
- What is being tested?
- Choline Bitartrate, Pre-cooked, pre-peeled whole hardboiled eggs and Egg whites from pre-cooked, pre-peeled hardboiled eggs
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 86 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Sep 2016to 3 Sep 2020
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Choline From Eggs vs. Supplements on the Generation of TMAO in Humans (EGGS)
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.
Read the 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.
- Conditions
- Cardiovascular Risk Factor
- Being tested
- Choline Bitartrate, Pre-cooked, pre-peeled whole hardboiled eggs, Egg whites from pre-cooked, pre-peeled hardboiled eggs, Phosphatidylcholine capsules
- Keywords
- TMAO, choline, eggs, gastrointestinal microbiome, healthy volunteers
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Choline BitartrateDietary supplement
500mg choline bitartrate tablets
Pre-cooked, pre-peeled whole hardboiled eggsOther
Obtained from a commercial source.
Egg whites from pre-cooked, pre-peeled hardboiled eggsOther
Egg whites from pre-cooked, pre-peeled hardboiled eggs. The yolks are removed and discarded.
Phosphatidylcholine capsulesDietary supplement
420 mg phosphatidylcholine capsules obtained from a commercial source.
| Study group | Role | What they receive |
|---|---|---|
| Whole Hardboiled Eggs | Experimental | Subjects will consume four (4) pre-cooked, pre-peeled whole hardboiled eggs per day for 28 days. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Dietary Supplement: Phosphatidylcholine capsules |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline, Day 28
Secondary outcomes (8)
Changes in Levels of Fasting Trimethylamine-N-oxide (TMAO) in 24-hour Urine Collections
Changes in levels of non-labeled TMAO from baseline to Day 28 measured by established mass spectrometry techniques.
Measured: Baseline, Day 28
Changes in Plasma Levels of Fasting Choline
Fasting plasma levels of choline from samples obtained at baseline and at day 28 were compared.
Measured: Baseline, Day 28
Changes in Plasma Levels of Fasting Carnitine.
Fasting plasma levels of carnitine from samples obtained at baseline and at day 28 were compared.
Measured: Baseline, Day 28
Changes in Plasma Levels of Fasting Betaine.
Fasting plasma levels of betaine from samples obtained at baseline and at day 28 were compared.
Measured: Baseline, Day 28
Changes in Lipid Profile, Total Cholesterol
Changes in total cholesterol levels between baseline and Day 28
Measured: Baseline, Day 28
Changes in Lipid Profile, HDL
Changes in measured HDL levels between baseline and Day 28
Measured: Baseline, Day 28
Changes in Lipid Profile, LDL
Changes in measured LDL levels between baseline and Day 28
Measured: Baseline, Day 28
Changes in Lipid Profile, Triglycerides
Changes in measured triglyceride levels between baseline and Day 28
Measured: Baseline, Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2017 (estimated)
- Study start2 Sep 2016
- Primary completion10 Apr 2018
- Study completion3 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular Risk FactorStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wilson Tang, The Cleveland Clinic
- Investigators
- W. H. Wilson Tang, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03039023
- Sponsor's protocol ID
- 16-1048
- Acronym
- EGGS
- Status last verified
- Jun 2026
- First submitted
- 19 Jan 2017
- Last updated
- 13 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 21475195Rebouche 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.
PubMed 2007906Bidulescu 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.
PubMed 19232103Wilcox 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.
PubMed 33872583
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Choline From Eggs vs. Supplements on the Generation of TMAO in Humans (EGGS)
- ClinicalTrials.gov ID
- NCT03039023
- Acronym / sponsor ID
- EGGS / 16-1048
- Conditions
- Cardiovascular Risk Factor
- Keywords
- TMAO, choline, eggs, gastrointestinal microbiome, healthy volunteers
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Study start
- 2 Sep 2016 (actual)
- Primary completion
- 10 Apr 2018 (actual)
- Study completion
- 3 Sep 2020 (actual)
- First posted
- 1 Feb 2017 (estimated)
- Results
- Posted 14 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Whole Hardboiled Eggs | Experimental | Other: Pre-cooked, pre-peeled whole hardboiled eggsSubjects will consume four (4) pre-cooked, pre-peeled whole hardboiled eggs per day for 28 days. |
| Choline Bitartrate Tablets | Experimental | Dietary Supplement: Choline BitartrateSubjects will consume two (2) 500mg choline bitartrate tablets per day for 28 days. |
| Hardboiled Eggs + Choline Bitartrate Tablets | Experimental | Dietary Supplement: Choline Bitartrate, Other: Pre-cooked, pre-peeled whole hardboiled eggsSubjects will consume both four (4) whole, pre-cooked, pre-peeled hardboiled eggs and two (2) 500mg choline bitartrate tablets per day for 28 days. |
| Egg Whites + Choline Bitartrate Tablets | Experimental | Dietary Supplement: Choline Bitartrate, Other: Egg whites from pre-cooked, pre-peeled hardboiled eggsSubjects 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. |
| Phosphatidylcholine Capsules | Experimental | Dietary Supplement: Phosphatidylcholine capsulesSubjects will consume six (6) 420 mg phosphatidylcholine capsules by mouth per day for 28 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Choline Bitartrate500mg choline bitartrate tablets | Dietary supplement | Choline Bitartrate Tablets, Egg Whites + Choline Bitartrate Tablets, Hardboiled Eggs + Choline Bitartrate Tablets |
| Pre-cooked, pre-peeled whole hardboiled eggsObtained from a commercial source. | Other | Hardboiled Eggs + Choline Bitartrate Tablets, Whole Hardboiled Eggs |
| Egg whites from pre-cooked, pre-peeled hardboiled eggsEgg whites from pre-cooked, pre-peeled hardboiled eggs. The yolks are removed and discarded. | Other | Egg Whites + Choline Bitartrate Tablets |
| Phosphatidylcholine capsules420 mg phosphatidylcholine capsules obtained from a commercial source. | Dietary supplement | Phosphatidylcholine Capsules |
Primary outcome
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.
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.
8 secondary outcomes
Changes in Levels of Fasting Trimethylamine-N-oxide (TMAO) in 24-hour Urine Collections
Time frame: Baseline, Day 28
Changes in Plasma Levels of Fasting Choline
Time frame: Baseline, Day 28
Changes in Plasma Levels of Fasting Carnitine.
Time frame: Baseline, Day 28
Changes in Plasma Levels of Fasting Betaine.
Time frame: Baseline, Day 28
Changes in Lipid Profile, Total Cholesterol
Time frame: Baseline, Day 28
Changes in Lipid Profile, HDL
Time frame: Baseline, Day 28
Changes in Lipid Profile, LDL
Time frame: Baseline, Day 28
Changes in Lipid Profile, Triglycerides
Time frame: Baseline, Day 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21475195Wang 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.
- Background: PubMed 2007906Rebouche 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.
- Background: PubMed 19232103Bidulescu 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.
- Derived from this study: PubMed 33872583Wilcox 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.
- Patterson K, Bhagwat S, Williams J, Howe J, and Holden J. USDA Database for the Choline Content of Common Foods, Release Two. January 2008.Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
W. H. Wilson Tang, MD principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Choline Bitartrate, Pre-cooked, pre-peeled whole hardboiled eggs and Egg whites from pre-cooked, pre-peeled hardboiled eggs in people with Cardiovascular Risk Factor, run by The Cleveland Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Plasma Levels of Fasting Trimethylamine-N-oxide (TMAO), a Choline Metabolite (time frame: Baseline, 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03039023, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2026.