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

Not Applicable

Completed

Conditions: Cardiovascular Risk Factor

Interventions: Dietary Supplement: Choline Bitartrate
Dietary Supplement: Phosphatidylcholine capsules
Other: Pre-cooked, pre-peeled whole hardboiled eggs
Other: Egg whites from pre-cooked, pre-peeled hardboiled eggs

Registration Number: NCT03039023

Lead Sponsor: 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.

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 However, another pilot study by a collaborator (unpublished) did not show the same increase in plasma TMAO levels following the ingestion of whole eggs, a major dietary source of choline.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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 86

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Hardboiled Eggs + Choline Bitartrate Tablets	Pre-cooked, pre-peeled whole hardboiled eggs	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.
Egg Whites + Choline Bitartrate Tablets	Choline Bitartrate	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.
Egg Whites + Choline Bitartrate Tablets	Egg whites from pre-cooked, pre-peeled hardboiled eggs	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.
Whole Hardboiled Eggs	Pre-cooked, pre-peeled whole hardboiled eggs	Subjects will consume four (4) pre-cooked, pre-peeled whole hardboiled eggs per day for 28 days.
Phosphatidylcholine Capsules	Phosphatidylcholine capsules	Subjects will consume six (6) 420 mg phosphatidylcholine capsules by mouth per day for 28 days.
Choline Bitartrate Tablets	Choline Bitartrate	Subjects will consume two (2) 500mg choline bitartrate tablets per day for 28 days.
Hardboiled Eggs + Choline Bitartrate Tablets	Choline Bitartrate	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.

Primary Outcome Measures

Name	Time	Method
Changes in Platelet Function With Increased Choline Intake	Baseline, Day 28	The activation and functioning of platelets within a single subject will be compared before and after increased choline intake.
Changes in Plasma Levels of Fasting Trimethylamine-N-oxide (TMAO), a Choline Metabolite	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.

Secondary Outcome Measures

Name	Time	Method
Changes in Lipid Profile, Total Cholesterol	Baseline, Day 28	Changes in total cholesterol levels between baseline and Day 28
Changes in Plasma Levels of Fasting Betaine.	Baseline, Day 28	Fasting plasma levels of betaine from samples obtained at baseline and at day 28 were compared.
Changes in Lipid Profile, Triglycerides	Baseline, Day 28	Changes in measured triglyceride levels between baseline and Day 28
Changes in Levels of Fasting Trimethylamine-N-oxide (TMAO) in 24-hour Urine Collections	Baseline, Day 28	Changes in levels of non-labeled TMAO from baseline to Day 28 measured by established mass spectrometry techniques.
Changes in Plasma Levels of Fasting Choline	Baseline, Day 28	Fasting plasma levels of choline from samples obtained at baseline and at day 28 were compared.
Changes in Plasma Levels of Fasting Carnitine.	Baseline, Day 28	Fasting plasma levels of carnitine from samples obtained at baseline and at day 28 were compared.
Changes in Lipid Profile, HDL	Baseline, Day 28	Changes in measured HDL levels between baseline and Day 28
Changes in Lipid Profile, LDL	Baseline, Day 28	Changes in measured LDL levels between baseline and Day 28