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.

Abstract

Background: Choline is a dietary precursor to the gut microbial generation of the prothrombotic and proatherogenic metabolite trimethylamine-N-oxide (TMAO). Eggs are rich in choline, yet the impact of habitual egg consumption on TMAO levels and platelet function in human subjects remains unclear.

Methods: Healthy volunteers (41% male, 81% Caucasian, median age 28 years) with normal renal function (estimated glomerular filtration rate >60) were recruited and assigned to 1 of 5 daily interventions for 4 weeks: 1) hardboiled eggs (n = 18); 2) choline bitartrate supplements (n = 20); 3) hardboiled eggs + choline bitartrate supplements (n = 16); 4) egg whites + choline bitartrate supplements (n = 18); 5) phosphatidylcholine supplements (n = 10). Fasting blood and urine samples were collected for quantification of TMAO, its precursors, and platelet aggregometry.

Results: Participants' plasma TMAO levels increased significantly in all 3 intervention arms containing choline bitartrate (all P < .0001), but daily ingestion of 4 large eggs (P = .28) or phosphatidylcholine supplements (P = .27) failed to increase plasma TMAO levels. Platelet reactivity also significantly increased in the 3 intervention arms containing choline bitartrate (all P < .01), but not with eggs (P = .10) or phosphatidylcholine supplements (P = .79).

Conclusions: Despite high choline content in egg yolks, healthy participants consuming 4 eggs daily showed no significant increase in TMAO or platelet reactivity. However, choline bitartrate supplements providing comparable total choline raised both TMAO and platelet reactivity, demonstrating that the form and source of dietary choline differentially contributes to systemic TMAO levels and platelet responsiveness.

Trial registration: ClinicalTrials.gov NCT03039023.

Keywords: Choline; Eggs; TMAO.

Publication types

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

MeSH terms

  • Adult
  • Choline* / administration & dosage
  • Choline* / blood
  • Choline* / metabolism
  • Diet / methods*
  • Drug Monitoring / methods
  • Egg White
  • Egg Yolk
  • Female
  • Healthy Volunteers
  • Humans
  • Lipotropic Agents / administration & dosage
  • Lipotropic Agents / blood
  • Lipotropic Agents / metabolism
  • Male
  • Methylamines / blood*
  • Phosphatidylcholines* / administration & dosage
  • Phosphatidylcholines* / blood
  • Phosphatidylcholines* / metabolism
  • Platelet Function Tests / methods*
  • Treatment Outcome

Substances

  • Lipotropic Agents
  • Methylamines
  • Phosphatidylcholines
  • trimethyloxamine
  • Choline

Associated data

  • ClinicalTrials.gov/NCT03039023