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

Cardiovascular Risk Factor Clinical Trial

— EGGS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03039023
• Other study ID #: 16-1048
• Status: Completed
• Phase: N/A
• Start date: September 2, 2016
• Est. completion date: September 3, 2020

Study information

• Verified date: March 2023
• Source: The Cleveland Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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 However, another pilot study by a collaborator (unpublished) did not show the same increase in plasma TMAO levels following the ingestion of whole eggs, a major dietary source of choline.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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: September 3, 2020
• Est. primary completion date: April 10, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cardiovascular Risk Factor

Intervention

Dietary Supplement:
• Choline Bitartrate
500mg choline bitartrate tablets

Other:
• Pre-cooked, pre-peeled whole hardboiled eggs
Obtained from a commercial source.
• Egg whites from pre-cooked, pre-peeled hardboiled eggs
Egg whites from pre-cooked, pre-peeled hardboiled eggs. The yolks are removed and discarded.

Dietary Supplement:
• Phosphatidylcholine capsules
420 mg phosphatidylcholine capsules obtained from a commercial source.

Locations

Country	Name	City	State
United States	Cleveland Clinic Foundation	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
The Cleveland Clinic

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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.	Baseline, Day 28
Secondary	Changes in Plasma Levels of Fasting Choline	Fasting plasma levels of choline from samples obtained at baseline and at day 28 were compared.	Baseline, Day 28
Secondary	Changes in Plasma Levels of Fasting Carnitine.	Fasting plasma levels of carnitine from samples obtained at baseline and at day 28 were compared.	Baseline, Day 28
Secondary	Changes in Plasma Levels of Fasting Betaine.	Fasting plasma levels of betaine from samples obtained at baseline and at day 28 were compared.	Baseline, Day 28
Secondary	Changes in Lipid Profile, Total Cholesterol	Changes in total cholesterol levels between baseline and Day 28	Baseline, Day 28
Secondary	Changes in Lipid Profile, HDL	Changes in measured HDL levels between baseline and Day 28	Baseline, Day 28
Secondary	Changes in Lipid Profile, LDL	Changes in measured LDL levels between baseline and Day 28	Baseline, Day 28
Secondary	Changes in Lipid Profile, Triglycerides	Changes in measured triglyceride levels between baseline and Day 28	Baseline, Day 28

External 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.