Effect of egg ingestion on trimethylamine-N-oxide production in humans: a randomized, controlled, dose-response study

Am J Clin Nutr. 2014 Sep;100(3):778-86. doi: 10.3945/ajcn.114.087692. Epub 2014 Jun 18.


Background: It is important to understand whether eating eggs, which are a major source of dietary choline, results in increased exposure to trimethylamine-N-oxide (TMAO), which is purported to be a risk factor for developing heart disease.

Objective: We determined whether humans eating eggs generate TMAO and, if so, whether there is an associated increase in a marker for inflammation [ie, high-sensitivity C-reactive protein (hsCRP)] or increased oxidation of low-density lipoprotein (LDL).

Design: In a longitudinal, double-blind, randomized dietary intervention, 6 volunteers were fed breakfast doses of 0, 1, 2, 4, or 6 egg yolks. Diets were otherwise controlled on the day before and day of each egg dose with a standardized low-choline menu. Plasma TMAO at timed intervals (immediately before and 1, 2, 4, 8, and 24 h after each dose), 24-h urine TMAO, predose and 24-h postdose serum hsCRP, and plasma oxidized LDL were measured. Volunteers received all 5 doses with each dose separated by >2-wk washout periods.

Results: The consumption of eggs was associated with increased plasma and urine TMAO concentrations (P < 0.01), with ∼14% of the total choline in eggs having been converted to TMAO. There was considerable variation between individuals in the TMAO response. There was no difference in hsCRP or oxidized LDL concentrations after egg doses.

Conclusions: The consumption of ≥2 eggs results in an increased formation of TMAO. Choline is an essential nutrient that is required for normal human liver and muscle functions and important for normal fetal development. Additional study is needed to both confirm the association between TMAO and atherosclerosis and identify factors, microbiota and genetic, that influence the generation of TMAO before policy and medical recommendations are made that suggest reduced dietary choline intake.

Trial registration: ClinicalTrials.gov NCT01906554.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Biomarkers / urine
  • C-Reactive Protein / analysis
  • Choline / administration & dosage
  • Choline / adverse effects*
  • Cross-Over Studies
  • Double-Blind Method
  • Egg Yolk / adverse effects
  • Eggs / adverse effects*
  • Female
  • Heart Diseases / blood
  • Heart Diseases / epidemiology
  • Heart Diseases / etiology*
  • Heart Diseases / urine
  • Humans
  • Lipoproteins, LDL / blood
  • Longitudinal Studies
  • Male
  • Methylamines / blood*
  • Methylamines / urine
  • Middle Aged
  • North Carolina / epidemiology
  • Pilot Projects
  • Risk Factors
  • Up-Regulation*


  • Biomarkers
  • Lipoproteins, LDL
  • Methylamines
  • oxidized low density lipoprotein
  • C-Reactive Protein
  • trimethyloxamine
  • Choline

Associated data

  • ClinicalTrials.gov/NCT01906554