Clinical trial NCT03039023: Effects of Choline From Eggs vs. Supplements on the Generation of TMAO in Humans
Official title: Effects of Choline From Eggs vs. Supplements on the Generation of TMAO in Humans (EGGS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Risk Factor
Keywords: TMAO
choline
eggs
gastrointestinal microbiome
healthy volunteers
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2017-02-01
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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 However, another pilot study by a collaborator (unpublished) did not show the same increase in plasma TMAO levels following the ingestion of whole eggs, a major dietary source of choline.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

Eligibility 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.

Primary outcomes:
measure: Changes in Plasma Levels of Fasting Trimethylamine-N-oxide (TMAO), a Choline Metabolite
timeFrame: Baseline, 28 days
measure: Changes in Platelet Function With Increased Choline Intake
timeFrame: Baseline, Day 28
Secondary outcomes:
measure: Changes in Levels of Fasting Trimethylamine-N-oxide (TMAO) in 24-hour Urine Collections
timeFrame: Baseline, Day 28
measure: Changes in Plasma Levels of Fasting Choline
timeFrame: Baseline, Day 28
measure: Changes in Plasma Levels of Fasting Carnitine.
timeFrame: Baseline, Day 28
measure: Changes in Plasma Levels of Fasting Betaine.
timeFrame: Baseline, Day 28
measure: Changes in Lipid Profile, Total Cholesterol
timeFrame: Baseline, Day 28
measure: Changes in Lipid Profile, HDL
timeFrame: Baseline, Day 28
measure: Changes in Lipid Profile, LDL
timeFrame: Baseline, Day 28
measure: Changes in Lipid Profile, Triglycerides
timeFrame: Baseline, Day 28
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: W. H. Wilson Tang, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: 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.
citation: 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.