The Carnitine-butyrobetaine-trimethylamine-N-oxide pathway and its association with cardiovascular mortality in patients with carotid atherosclerosis - PubMed (original) (raw)

doi: 10.1016/j.atherosclerosis.2016.01.033. Epub 2016 Feb 5.

Marius Trøseid 2, Thor Ueland 3, Sverre Holm 4, Azhar Abbas 5, Ida Gregersen 6, Martin Kummen 7, Vigdis Bjerkeli 6, Frode Reier-Nilsen 8, David Russell 9, Asbjørn Svardal 10, Tom Hemming Karlsen 11, Pål Aukrust 12, Rolf K Berge 13, Johannes E R Hov 14, Bente Halvorsen 15, Mona Skjelland 9

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The Carnitine-butyrobetaine-trimethylamine-N-oxide pathway and its association with cardiovascular mortality in patients with carotid atherosclerosis

Karolina Skagen et al. Atherosclerosis. 2016 Apr.

Abstract

Background and purpose: γ-butyrobetaine (γBB) is a metabolite from dietary Carnitine, involved in the gut microbiota-dependent conversion from Carnitine to the pro-atherogenic metabolite trimethylamine-N-oxide (TMAO). Orally ingested γBB has a pro-atherogenic effect in experimental studies, but γBB has not been studied in relation to atherosclerosis in humans. The aim of this study was to evaluate associations between serum levels of γBB, TMAO and their common precursors Carnitine and trimethyllysine (TML) and carotid atherosclerosis and adverse outcome.

Methods: Serum γBB, Carnitine, TML and TMAO were quantified by high performance liquid chromatography in patients with carotid artery atherosclerosis (n = 264) and healthy controls (n = 62).

Results: Serum γBB (p = 0.024) and Carnitine (p = 0.001), but not TMAO or TML, were increased in patients with carotid atherosclerosis. Higher levels of γBB and TML, but not TMAO or Carnitine were independently associated with cardiovascular death also after adjustment for age and eGFR (adjusted HR [95%] 3.3 [1.9-9.1], p = 0.047 and 6.0 [1.8-20.34], p = 0.026, respectively).

Conclusions: Patients with carotid atherosclerosis had increased serum levels of γBB, and elevated levels of γBB and its precursor TML were associated with cardiovascular mortality. Long-term clinical studies of γBB, as a cardiovascular risk marker, and safety studies regarding dietary supplementation of γBB, are warranted.

Keywords: Carotid atherosclerosis; Microbiota; Stroke; TMAO; γBB.

Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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