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Trimethylamine-N-oxide

tmao
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Updated 22/11/2023

What is measured?

Synonym: TMAO.
Method(s): LC-MS/MS (1).

What is trimethylamine-N-oxide?

Choline, phosphatidylcholine and L-carnitine are cleaved by the gut microbiota to trimethylamine (TMA), which is oxidized to trimethylamine-N-oxide (TMAO) in the liver. TMAO seems to be proatherogenic in animal models and plasma levels are associated with risk of cardiovascular and other diseases in humans (2, 3). Circulating TMAO increases during renal failure, and has been regarded as an uremic toxin (4).

Indication(s)

Assessment of choline status in relation to cardiovascular risk.

Specimen, collection and processing

Patient/subject:
Matrix: EDTA plasma is preferred if sarcosine is not measured simultaneously.
Volume: Minimum volume is 60 µL, but 200 µL is optimal and allows reanalysis.
Preparation and stability: The blood sample must be centrifuged and the plasma/serum fraction put on ice, and frozen.

Transportation

Frozen, on dry ice. (for general instruction on transportation, click here)

Reported values, interpretation

Reported values: 0.5-60.0 µmol/L
Intraclass correlation coefficient (ICC): 0.17–0.38.

Literature

1. Midttun, O., Kvalheim, G., and Ueland, P.M. (2013). High-throughput, low-volume, multianalyte quantification of plasma metabolites related to one-carbon metabolism using HPLC-MS/MS. Anal Bioanal Chem 405, 2009-017.
2. Cho, C.E., and Caudill, M.A. (2017). Trimethylamine-N-oxide: Friend, foe, or simply caught in the cross-fire? Trends Endocrinol Metab 28, 121-130.
3. Subramaniam, S., and Fletcher, C. (2018) Trimethylamine N-oxide: breathe new life. Br J Pharmacol 175, 1344-1353.
4. Rysz, J., Franczyk, B., Ławiński, J., Olszewski, R., Ciałkowska-Rysz, A., & Gluba-Brzózka, A. (2021). The impact of CKD on uremic toxins and gut microbiota. Toxins (Basel), 13, 252.

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Cardiometabolic
Inflammation
Microbiome
Nutrition
Categories

Amino acids, amino acid catabolites, acylcarnitines, TCA metabolites, ketone bodies, AGEs

Kynurenines, proteins, ratio-derived metabolites



SCFAs, indoles, choline metabolites, amino acid derived



B-vitamins, functional markers, and methyl donors, fat-soluble vitamins, essential amino acids, meat & fish intake, tobacco use & coffee intake
Biomarkers
65
18
20
41
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Amino acids: Alanine, Arginine, Asparagine, Aspartic acid, Glutamic acid, Glutamine, Glycine, Histidine, Isoleucine, Kynurenine, Leucine, Lysine, Methionine, Ornithine, Phenylalanine, Proline, Sarcosine, Serine, Threonine, Total cysteine, Tryptophan, Tyrosine, Valine

Amino acids and catabolites: 2-Aminoadipic acid, 2-Hydroxybutyrate, 3-Hydroxysiobutyrate, α-Hydroxyglutaric acid, β-Alanine, β-Aminoisobutyrate, β-Hydroxy B-methylbutyric acid, Phenylacetylglutamine

Acylcarnities: BB, C0, C2, C3, C3, DC, C4, C4-OH , C4-DC , iC5 , C5-DC, C5:1 , C6 , C8, C10, C12, C14 , C14-OH, C16, C16-OH, C18 , C18-OH, C18:1, C18:2

TCA metabolites: α-Ketoglutarate, Citrate, Fumarate, Isocitrate, Lactate, Malate, Pyruvate, Ketone bodies, 3-Hydroxybutyrate, Acetoacetate

AGEs: Carboxyethyllysine, Carboxymethyllysine

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Kynurenines: Kynurenine, Kynurenic acid, Quinaldic acid, Anthranilic acid, 3-Hydroxykynurenine, Xanthurenic acid, 3-Hydroxyanthranilic acid, Picolinic acid, Quinolinic acid, Nicotinic acid, Nicotinamide, N1-methylnicotinamide

Neopterin

Proteins: C-Reactive protein, Calprotectin, Serum Amyloid A

Ratio-derived: Kynurenine/tryptophan ratio, PAr index (PLP, PL, PA)

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SCFAs: Acetate, Butyrate, Formate, Isobutyrate, Isovalerate, Propionate, Valerate, α-Methylbutyrate

Indoles: 3-Indoxyl sulfate, Imidazole propionate, Indole-3-acetamide, Indole-3-acetate, Indole-3-aldehyde, Indole-3-lactate, Indole-3-propionate

Choline metabolites: Choline ,Betaine, DMG, TMAO

Amino acid derived: Phenylacetylglutamine

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B-vitamins, functional markers, and methyl donors: 4-Pyridoxic acid, Betaine, Choline, Cobalamin, Flavin mononucleotide, Folate, Methylmalonic acid, N1-methylnicotinamide, Nicotinamide, Nicotinic acid, Pyridoxal, Pyridoxal 5-phosphate, Pyridoxine, Riboflavin, Thiamine, Thiamine monophosphate, Total homocysteine

Fat-soluble vitamins: 25-hydroxy vitamin D2, 25-hydroxy vitamin D3, α-Tocopherol (Vit. E), All-trans retinol (Vit. A), Phylloquinone (Vit. K1), y-Tocopherol (Vit. E)

Essential amino acids: Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine

Meat and fish intake: 1-Methylhistidine, 3-Methylhistidine, B-Alanine, Creatine, Creatinine, TMAO

Tobacco use and coffee intake: Cotinine, Trans-3-hydroxycotinine, Trigonelline

Volume (ul)
150
100
200
200
Analytical technique
GC- and LC-MS/MS
LC- and MALDI-MS
GC- and LC-MS/MS
GC- and LC-MS/MS
Turnaround time (weeks)
1
1
1
1
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