Plasma Concentrations of Trimethylamine-N-oxide Are Directly Associated with Dairy Food Consumption and Low-Grade Inflammation in a German Adult Population

J Nutr. 2016 Feb;146(2):283-9. doi: 10.3945/jn.115.220103. Epub 2015 Dec 16.


Background: Trimethylamine-N-oxide (TMAO) is a metabolite of carnitine, choline, and phosphatidylcholine, which is inversely associated with survival of cardiovascular disease (CVD) patients.

Objective: We examined the associations of diet with plasma concentrations of TMAO, choline, and betaine and the associations of TMAO with plasma concentrations of various cytokines.

Methods: Plasma TMAO, choline, and betaine concentrations were measured using LC-high resolution mass spectrometry in 271 participants, ≥18 y old, of the Second Bavarian Food Consumption Survey, conducted in 2002 and 2003. Food consumption was assessed using at least two 24-h dietary recalls. Cytokines were measured in plasma with enzyme-linked immunosorbent assays. Geometric mean concentrations of TMAO, choline, and betaine by categories of meat, dairy food, egg, and fish consumption were computed, adjusted for sex, age, and BMI. Multivariable-adjusted geometric mean concentrations of cytokines [tumor necrosis factor-α (TNF-α), soluble TNF receptors (sTNF-R) p55, sTNF-R p75, interleukin-6 (IL-6), and C-reactive protein (CRP)] were computed by quartiles of TMAO concentration using general linear models.

Results: Meat, egg, or fish consumption was not associated with TMAO, choline, or betaine concentrations (all P-trend ≥ 0.05). With increases in milk and other dairy food consumption, the plasma TMAO concentration increased [geometric mean bottom quartile of milk consumption: 2.08 μM (95% CI: 1.69, 2.57 μM); compared with top quartile: 3.13 μM (95% CI: 2.56, 3.84 μM); P-trend = 0.008]. Participants in the top TMAO quartile had higher plasma concentrations of TNF-α, sTNF-R p55, and sTNF-R p75 than participants in the bottom quartile (percentage difference ranging between 14.4% and 17.3%; all P-trend < 0.05), but there were no differences in plasma concentrations of CRP and IL-6 (all P-trend ≥ 0.05).

Conclusions: Results of this study conducted among healthy adults from the general population do not indicate a strong effect of diet on plasma concentrations of TMAO, choline, or betaine, with the exception of a positive association between dairy food consumption and plasma TMAO concentrations. Also, plasma TMAO concentrations were positively associated with inflammation. Whether habitual diet is strongly linked to the plasma TMAO concentration, a potential marker of CVD risk, needs to be determined in further studies.

Keywords: Trimethylamine-N-oxide; cheese; inflammation; milk; red meat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Betaine / blood
  • C-Reactive Protein / metabolism
  • Choline / blood
  • Dairy Products*
  • Diet Surveys
  • Diet*
  • Feeding Behavior*
  • Female
  • Germany
  • Humans
  • Inflammation* / blood
  • Inflammation* / etiology
  • Interleukin-6 / blood
  • Male
  • Methylamines* / adverse effects
  • Methylamines* / blood
  • Middle Aged
  • Milk
  • Receptors, Tumor Necrosis Factor, Type I / blood
  • Tumor Necrosis Factor-alpha / blood


  • Interleukin-6
  • Methylamines
  • Receptors, Tumor Necrosis Factor, Type I
  • Tumor Necrosis Factor-alpha
  • Betaine
  • C-Reactive Protein
  • trimethyloxamine
  • trimethylamine
  • Choline