Trimethylamine-N-oxide (TMAO) determined by LC-MS/MS: distribution and correlates in the population-based PopGen cohort

Gessner, Arne; Giuseppe, Romina di; Koch, Manja; Fromm, Martin F.; Lieb, Wolfgang; Maas, Renke

doi:10.1515/cclm-2019-1146

Cited by 30 publications

(28 citation statements)

References 39 publications

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“…Moreover, data collected in the current study did not support the hypothesis that TMAO is directly associated with CVD. We observed similar plasma TMAO levels in patients with confirmed angiographically CAD and control subjects with no medical history of CVD, and plasma TMAO concentration were coherent with values previously measured in the general population 27 . Moreover, no significant pure associations between the CETP genotypes and TMAO metabolism has been found.…”

Section: Discussionsupporting

confidence: 89%

Trimethylamine N-oxide and the reverse cholesterol transport in cardiovascular disease: a cross-sectional study

Bordoni

Samulak

Sawicka

et al. 2020

Sci Rep

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The early atherosclerotic lesions develop by the accumulation of arterial foam cells derived mainly from cholesterol-loaded macrophages. Therefore, cholesterol and cholesteryl ester transfer protein (CETP) have been considered as causative in atherosclerosis. Moreover, recent studies indicate the role of trimethylamine N-oxide (TMAO) in development of cardiovascular disease (CVD). The current study aimed to investigate the association between TMAO and CETP polymorphisms (rs12720922 and rs247616), previously identified as a genetic determinant of circulating CETP, in a population of coronary artery disease (CAD) patients (n = 394) and control subjects (n = 153). We also considered age, sex, trimethylamine (TMA) levels and glomerular filtration rate (GFR) as other factors that can potentially play a role in this complex picture. We found no association of TMAO with genetically determined CETP in a population of CAD patients and control subjects. Moreover, we noticed no differences between CAD patients and control subjects in plasma TMAO levels. On the contrary, lower levels of TMA in CAD patients respect to controls were observed. Our results indicated a significant correlation between GFR and TMAO, but not TMA. The debate whether TMAO can be a harmful, diagnostic or protective marker in CVD needs to be continued.

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Section: Discussionsupporting

confidence: 89%

Trimethylamine N-oxide and the reverse cholesterol transport in cardiovascular disease: a cross-sectional study

Bordoni

Samulak

Sawicka

et al. 2020

Sci Rep

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“…27 studies were considered for this review [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. Their major features such as study design, methodology used for TMAO determination, and the effects of foods on TMAO are given in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

“…15 studies evaluated the possible relationship between fish and TMAO. 13 studies demonstrated that levels of urinary or plasma TMAO and/or TMA are significantly associated with the intake of fish [ 11 , 12 , 20 , 21 , 24 , 27 , 28 , 30 , 31 , 32 , 33 , 34 , 36 ]. One of the earliest studies evaluated 46 different foods and demonstrated that only fish and other sea-products significantly increase urinary TMAO [ 12 ].…”

Section: Resultsmentioning

confidence: 99%

“…Cho et al [ 21 ] supposed that the rapid rise in circulating TMAO in response to fish consumption might demonstrate that the absorption of intact dietary TMAO is independent of the microbiota. In one paper, the association of fish and shellfish intake with TMAO plasma concentrations was limited to men only [ 31 ]. Only two papers demonstrated no association.…”

Section: Resultsmentioning

confidence: 99%

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Association of Urinary and Plasma Levels of Trimethylamine N-Oxide (TMAO) with Foods

Lombardo

Aulisa²,

Marcon³

et al. 2021

Nutrients

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Introduction: Trimethylamine N-oxide (TMAO) may play a key mediator role in the relationship between the diet, gut microbiota and cardiovascular diseases, particularly in people with kidney failure. The aim of this review is to evaluate which foods have a greater influence on blood or urinary trimethylamine N-oxide (TMAO) levels. Methods: 391 language articles were screened, and 27 were analysed and summarized for this review, using the keywords “TMAO” AND “egg” OR “meat” OR “fish” OR “dairy” OR “vegetables” OR “fruit” OR “food” in December 2020. Results: A strong correlation between TMAO and fish consumption, mainly saltwater fish and shellfish, but not freshwater fish, has been demonstrated. Associations of the consumption of eggs, dairy and meat with TMAO are less clear and may depend on other factors such as microbiota or cooking methods. Plant-based foods do not seem to influence TMAO but have been less investigated. Discussion: Consumption of saltwater fish, dark meat fish and shellfish seems to be associated with an increase in urine or plasma TMAO values. Further studies are needed to understand the relationship between increased risk of cardiovascular disease and plasma levels of TMAO due to fish consumption. Interventions coupled with long-term dietary patterns targeting the gut microbiota seem promising.

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“…Gut microbiota modified by diet may also play a role in the relationships between acylcarnitines, phosphatidylcholine and cardiometabolic traits [ 35 , 36 ]. Numerous metabolites such as acylcarnitines and phosphatidylcholine, are involved in gut microbe–dependant pathways that contribute to the formation of hepatic production of trimethylamine-N-oxide (TMAO) from choline and sequentially into trimethylamine in the microbiota, which may increase risk of atherosclerosis [37] and glucose metabolism [ 36 , 38 ]. TMAO has been shown to play a causal role in cardiovascular disease via promotion of macrophage foam cell accumulation, leading to inhibition of the reverse cholesterol transport that affect aspects of bile and sterol metabolism, which in turn enhances platelet hyperactivity and initiates atherosclerotic plaque formation [ 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Dietary metabolite profiling brings new insight into the relationship between nutrition and metabolic risk: An IMI DIRECT study

et al. 2020

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Summary Background Dietary advice remains the cornerstone of prevention and management of type 2 diabetes (T2D). However, understanding the efficacy of dietary interventions is confounded by the challenges inherent in assessing free living diet. Here we profiled dietary metabolites to investigate glycaemic deterioration and cardiometabolic risk in people at risk of or living with T2D. Methods We analysed data from plasma collected at baseline and 18-month follow-up in individuals from the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohort 1 n = 403 individuals with normal or impaired glucose regulation (prediabetic) and cohort 2 n = 458 individuals with new onset of T2D. A dietary metabolite profile model (T pred ) was constructed using multivariable regression of 113 plasma metabolites obtained from targeted metabolomics assays. The continuous T pred score was used to explore the relationships between diet, glycaemic deterioration and cardio-metabolic risk via multiple linear regression models. Findings A higher T pred score was associated with healthier diets high in wholegrain (β=3.36 g, 95% CI 0.31, 6.40 and β=2.82 g, 95% CI 0.06, 5.57) and lower energy intake (β=-75.53 kcal, 95% CI -144.71, -2.35 and β=-122.51 kcal, 95% CI -186.56, -38.46), and saturated fat (β=-0.92 g, 95% CI -1.56, -0.28 and β=–0.98 g, 95% CI -1.53, -0.42 g), respectively for cohort 1 and 2. In both cohorts a higher T pred score was also associated with lower total body adiposity and favourable lipid profiles HDL-cholesterol (β=0.07 mmol/L, 95% CI 0.03, 0.1), (β=0.08 mmol/L, 95% CI 0.04, 0.1), and triglycerides (β=-0.1 mmol/L, 95% CI -0.2, -0.03), (β=-0.2 mmol/L, 95% CI -0.3, -0.09), respectively for cohort 1 and 2. In cohort 2, the T pred score was negatively associated with liver fat (β=-0.74%, 95% CI -0.67, -0.81), and lower fasting concentrations of HbA1c (β=-0.9 mmol/mol, 95% CI -1.5, -0.1), glucose (β=-0.2 mmol/L, 95% CI -0.4, -0.05) and insulin (β=-11.0 pmol/mol, 95% CI -19.5, -2.6). Longitudinal analysis showed at 18-month follow up a higher T pred score was also associated lower total body adiposity in both cohorts and lower fasting glucose (β=-0.2 mmol/L, 95% CI -0.3, -0.01) and insulin (β=-9.2 pmol/mol, 95% CI -17.9, -0.4) concentrations in cohort 2. Interpretation Plasma dietary metabolite profiling provides objective measures of diet intake, showing a relationship to glycaemic deterioration and cardiometabolic health. Funding This work was supported by the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115,317 (DIRECT), resources of which are composed of financial contribution from the European Unio...

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Trimethylamine-N-oxide (TMAO) determined by LC-MS/MS: distribution and correlates in the population-based PopGen cohort

Cited by 30 publications

References 39 publications

Trimethylamine N-oxide and the reverse cholesterol transport in cardiovascular disease: a cross-sectional study

Trimethylamine N-oxide and the reverse cholesterol transport in cardiovascular disease: a cross-sectional study

Association of Urinary and Plasma Levels of Trimethylamine N-Oxide (TMAO) with Foods

Dietary metabolite profiling brings new insight into the relationship between nutrition and metabolic risk: An IMI DIRECT study

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