Plasma trimethylamine N-oxide concentration is associated with choline, phospholipids, and methyl metabolism

Obeid, Rima; Awwad, Hussain Mohamad; Rabagny, Yannick; Graeber, Stefan; Herrmann, Wolfgang; Geisel, Juergen

doi:10.3945/ajcn.115.121269

Cited by 106 publications

(94 citation statements)

References 42 publications

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“…Fasting plasma TMAO concentration in the supplemented group before starting the treatment and for the whole study period in the placebo group was similar to previously reported values in the same age and sex human subjects [23,24]. Since dietary carnitine is metabolized to TMAO in humans [25], L-carnitine supplementation induced tenfold increase in TMAO, observed in the midpoint of the study and maintained elevated until the end of the study.…”

Section: Discussion/conclusionsupporting

confidence: 88%

L-Carnitine Supplementation Increases Trimethylamine-N-Oxide but not Markers of Atherosclerosis in Healthy Aged Women

et al. 2018

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Background: L-carnitine can be metabolized to trimethylamine N-oxide (TMAO), a molecule that promotes atherogenesis through its interaction with macrophages and lipid metabolism. Objective: The aim of the present study was to assess whether L-carnitine supplementation may promote changes in selected serum biomarkers of atherosclerosis. Methods: Before the start, in the mid-point and after completing the 24-weeks supplementation protocol, fasting blood samples were taken from the antecubital vein. Plasma free L-carnitine and TMAO were determined by the UPLC/MS/MS method. Serum proteins were determined by the enzyme immunoassay method using commercially available kits. Total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglycerides have been determined using standard automatic analyzer. Results: L-carnitine supplementation elevated fasting plasma carnitine in the mid-point of our study and it remained increased until the end of supplementation period. Moreover, it induced tenfold increase in plasma TMAO concentration but did not affect serum C-reactive protein, interleukin-6, tumour necrosis factor-α, L-selectin, P-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1 or lipid profile markers. Conclusion: We demonstrated that although oral L-carnitine supplementation significantly increased plasma TMAO concentration, no lipid profile changes or other markers of adverse cardiovascular events were detected in healthy aged women over the period of 24 weeks.

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Section: Discussion/conclusionsupporting

confidence: 88%

L-Carnitine Supplementation Increases Trimethylamine-N-Oxide but not Markers of Atherosclerosis in Healthy Aged Women

et al. 2018

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“…Oxidative stress may impair betaine‐homocysteine methyltransferase, resulting in accumulation of circulating choline and betaine 38. Second, high plasma concentrations of choline and betaine have been associated with elevated concentrations of trimethylamine N‐oxide 39. This metabolite is related to microbiomic processing of dietary choline and to a lesser extent betaine, and systemic trimethylamine N‐oxide has been positively associated with adverse cardiovascular events 40.…”

Section: Discussionmentioning

confidence: 99%

Plasma Concentrations and Dietary Intakes of Choline and Betaine in Association With Atrial Fibrillation Risk: Results From 3 Prospective Cohorts With Different Health Profiles

Zuo

Svingen

Tell

et al. 2018

JAHA

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BackgroundAlthough choline metabolism has been associated with atherosclerotic heart disease, less research attention has been paid to the associations of choline and its oxidative metabolite betaine with cardiac arrhythmias.Methods and ResultsWe evaluated associations of plasma concentrations and dietary intakes of choline and betaine with long‐term atrial fibrillation (AF) risk in a community‐based cohort, HUSK ([the Hordaland Health Study] n=6949), and validated the findings in 2 patient cohorts: the Western Norway Coronary Angiography Cohort (n=4164) and the NORVIT (Norwegian B‐Vitamin) Trial (n=3733). Information on AF was obtained from the CVDNOR (Cardiovascular Disease in Norway) project. In HUSK, WECAC (Western Norway Coronary Angiography Cohort), and NORVIT, 552, 411, and 663 AF cases were identified during a median follow‐up time of 10.9, 7.3, and, 8.7 years, respectively. Plasma concentrations of choline and betaine were significantly positively associated with later AF risk after multivariable adjustments in HUSK. Such associations were independently replicated in the 2 external prospective patient cohorts. The pooled hazard ratio was 1.13 (95% confidence interval 1.08‐1.19, P<0.001) and 1.16 (95% confidence interval 1.10‐1.22, P<0.001) per SD increment for log‐transformed choline and betaine, respectively. Moreover, dietary intake of choline was marginally associated with AF risk (pooled hazard ratio 1.29, 95% confidence interval 1.01‐1.66, fifth versus first quintile), whereas no significant association was observed between dietary betaine and AF risk.ConclusionsOur findings indicate that plasma concentrations as well as dietary intake of choline, but not betaine, are associated with subsequent risk of AF, suggesting a potential role of choline metabolism in the pathogenesis of AF.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov.Unique identifier: NCT00671346.

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“…A recent prospective study indicated that higher intake of phosphatidylcholine, the precursor to the generation of TMAO, was independently associated with an increased risk of type 2 diabetes in 3 US populations (16). Previous studies have yielded inconsistent associations between plasma TMAO and type 2 diabetes (5,(17)(18)(19), and whether the association varies by FMO3 genetic variations has not yet been investigated. Our aim, therefore, was to determine the association of plasma TMAO with type 2 diabetes and to examine whether the association may be modified by a common FMO3 genetic variation in a casecontrol study.…”

Section: Introductionmentioning

confidence: 99%

Association between microbiota-dependent metabolite trimethylamine-N-oxide and type 2 diabetes

Shan

Sun

Huang

et al. 2017

The American Journal of Clinical Nutrition

166

121

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Background: The association of trimethylamine-N-oxide (TMAO), a microbiota-dependent metabolite from dietary choline and carnitine, with type 2 diabetes was inconsistent. Objective: We evaluated the association of plasma TMAO with newly diagnosed type 2 diabetes and the potential modification of TMAO-generating enzyme flavin monooxygenase 3 (FMO3) polymorphisms. Design: This was an age-and sex-matched case-control study of 2694 participants: 1346 newly diagnosed cases of type 2 diabetes and 1348 controls. Concentrations of plasma TMAO were measured, and FMO3 E158K polymorphisms (rs2266782) were genotyped. Results: Medians (IQRs) of plasma TMAO concentration were 1.47 mmol/L (0.81-2.20 mmol/L) for controls and 1.77 mmol/L (1.09-2.80 mmol/L) for type 2 diabetes cases. From the lowest to the highest quartiles of plasma TMAO, the multivariable adjusted ORs of type 2 diabetes were 1.00 (reference), 1.38 (95% CI: 1.08, 1.77), 1.64 (95% CI: 1.28, 2.09), and 2.55 (95% CI: 1.99, 3.28) (Ptrend , 0.001); each SD of ln-transformed plasma TMAO was associated with a 38% (95% CI: 26%, 51%) increment in ORs of type 2 diabetes. The FMO3 rs2266782 polymorphism was not associated with type 2 diabetes. The positive association between plasma TMAO and type 2 diabetes was consistent in each rs2266782 genotype group, and no significant interaction was observed (P = 0.093). Conclusions: Our results suggested that higher plasma TMAO was associated with increased odds of newly diagnosed type 2 diabetes and that this association was not modified by the FMO3 rs2266782 polymorphism. This study was registered at clinicaltrials.gov as NCT03130894.Am J Clin Nutr 2017;106:888-94.

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Plasma trimethylamine N-oxide concentration is associated with choline, phospholipids, and methyl metabolism

Cited by 106 publications

References 42 publications

L-Carnitine Supplementation Increases Trimethylamine-N-Oxide but not Markers of Atherosclerosis in Healthy Aged Women

L-Carnitine Supplementation Increases Trimethylamine-N-Oxide but not Markers of Atherosclerosis in Healthy Aged Women

Plasma Concentrations and Dietary Intakes of Choline and Betaine in Association With Atrial Fibrillation Risk: Results From 3 Prospective Cohorts With Different Health Profiles

Association between microbiota-dependent metabolite trimethylamine-N-oxide and type 2 diabetes

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