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Carnitine tmao

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https://www.readbyqxmd.com/read/28077467/gut-microbiota-dependent-trimethylamine-n-oxide-in-acute-coronary-syndromes-a-prognostic-marker-for-incident-cardiovascular-events-beyond-traditional-risk-factors
#1
Xinmin S Li, Slayman Obeid, Roland Klingenberg, Baris Gencer, François Mach, Lorenz Räber, Stephan Windecker, Nicolas Rodondi, David Nanchen, Olivier Muller, Melroy X Miranda, Christian M Matter, Yuping Wu, Lin Li, Zeneng Wang, Hassan S Alamri, Valentin Gogonea, Yoon-Mi Chung, W H Wilson Tang, Stanley L Hazen, Thomas F Lüscher
AIMS: Systemic levels of trimethylamine N-oxide (TMAO), a pro-atherogenic and pro-thrombotic metabolite produced from gut microbiota metabolism of dietary trimethylamine (TMA)-containing nutrients such as choline or carnitine, predict incident cardiovascular event risks in stable primary and secondary prevention subjects. However, the prognostic value of TMAO in the setting of acute coronary syndromes (ACS) remains unknown. METHODS AND RESULTS: We investigated the relationship of TMAO levels with incident cardiovascular risks among sequential patients presenting with ACS in two independent cohorts...
January 11, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28077427/serum-trimethylamine-n-oxide-carnitine-choline-and-betaine-in-relation-to-colorectal-cancer-risk-in-the-alpha-tocopherol-and-beta-carotene-study
#2
Kristin A Guertin, Xinmin S Li, Barry I Graubard, Demetrius Albanes, Stephanie J Weinstein, James J Goedert, Zeneng Wang, Stanley L Hazen, Rashmi Sinha
BACKGROUND: TMAO, a choline-derived metabolite produced by gut microbiota, and its biomarker precursors have not been adequately evaluated in relation to colorectal cancer risk. METHODS: We investigated the relationship between serum concentrations of TMAO and its biomarker precursors (choline, carnitine and betaine) and incident colorectal cancer risk in a nested case-control study of male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study...
January 11, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/27993177/diets-high-in-resistant-starch-increase-plasma-levels-of-trimethylamine-n-oxide-a-gut-microbiome-metabolite-associated-with-cvd-risk
#3
Nathalie Bergeron, Paul T Williams, Regina Lamendella, Nastaran Faghihnia, Alyssa Grube, Xinmin Li, Zeneng Wang, Rob Knight, Janet K Jansson, Stanley L Hazen, Ronald M Krauss
Production of trimethylamine-N-oxide (TMAO), a biomarker of CVD risk, is dependent on intestinal microbiota, but little is known of dietary conditions promoting changes in gut microbial communities. Resistant starches (RS) alter the human microbiota. We sought to determine whether diets varying in RS and carbohydrate (CHO) content affect plasma TMAO levels. We also assessed postprandial glucose and insulin responses and plasma lipid changes to diets high and low in RS. In a cross-over trial, fifty-two men and women consumed a 2-week baseline diet (41 percentage of energy (%E) CHO, 40 % fat, 19 % protein), followed by 2-week high- and low-RS diets separated by 2-week washouts...
December 2016: British Journal of Nutrition
https://www.readbyqxmd.com/read/27977217/identification-and-characterization-of-trimethylamine-n-oxide-uptake-and-efflux-transporters
#4
Wendy A Teft, Bridget L Morse, Brenda F Leake, Aze Wilson, Sara E Mansell, Robert A Hegele, Richard H Ho, Richard B Kim
Trimethylamine-N-oxide (TMAO) is a recently identified predictor of cardiovascular and chronic kidney disease. TMAO is primarily generated through gut-microbiome mediated conversion of dietary choline and carnitine to TMA, which is converted to TMAO by hepatic flavin monooxygenase 3 (FMO3) and subsequently undergoes renal elimination. We investigated the role of uptake and efflux drug transporters in TMAO disposition in vitro and in vivo. After screening a large array of uptake transporters, we show organic cation transporter 2 (OCT2) is the key transporter for TMAO cellular uptake...
January 3, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27935219/the-influence-of-a-chronic-l-carnitine-administration-on-the-plasma-metabolome-of-male-fischer%C3%A2-344-rats
#5
Christoph H Weinert, Michael T Empl, Ralf Krüger, Lara Frommherz, Björn Egert, Pablo Steinberg, Sabine E Kulling
SCOPE: L-carnitine has been advertised as a fat-lowering and performance-enhancing supplement, although scientific evidence for its effectiveness is lacking. The uptake of about 1-2 g of L-carnitine per day may result in the formation of metabolites like trimethylamine-N-oxide (TMAO), which in turn may be converted to potential carcinogens or promote the development of cardiovascular diseases. METHODS AND RESULTS: To assess whether an L-carnitine supplementation changes overall metabolism or causes the formation of previously unknown metabolites, we analyzed plasma samples from Fischer 344 rats originating from a previous study 2 using a multi-platform metabolomics approach comprising LC-MS/MS and GC×GC-MS methods...
December 9, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27855528/dietary-anthropometric-and-biochemical-factors-influencing-plasma-choline-carnitine-trimethylamine-and-trimethylamine-n-oxide-concentrations
#6
Anna M Malinowska, Artur Szwengiel, Agata Chmurzynska
The objective of the study was to evaluate the nutritional, anthropometric, and biochemical factors that influence choline, l-carnitine, trimethylamine (TMA), and trimethylamine-N-oxide (TMAO) metabolism in elderly women. The volunteers' diet was assessed using a food frequency questionnaire. Dietary patterns were estimated using a self-established score method. Body mass index (BMI), serum glucose, total, HDL, LDL cholesterol, triacylglycerol, homocysteine (tHcy), free choline (fchol), L-carnitine, TMA, and TMAO were assessed...
November 17, 2016: International Journal of Food Sciences and Nutrition
https://www.readbyqxmd.com/read/27834801/trimethylamine-n-oxide-the-good-the-bad-and-the-unknown
#7
REVIEW
Manuel T Velasquez, Ali Ramezani, Alotaibi Manal, Dominic S Raj
Trimethylamine N-oxide (TMAO) is a small colorless amine oxide generated from choline, betaine, and carnitine by gut microbial metabolism. It accumulates in the tissue of marine animals in high concentrations and protects against the protein-destabilizing effects of urea. Plasma level of TMAO is determined by a number of factors including diet, gut microbial flora and liver flavin monooxygenase activity. In humans, a positive correlation between elevated plasma levels of TMAO and an increased risk for major adverse cardiovascular events and death is reported...
November 8, 2016: Toxins
https://www.readbyqxmd.com/read/27669507/simultaneous-targeted-analysis-of-trimethylamine-n-oxide-choline-betaine-and-carnitine-by-high-performance-liquid-chromatography-tandem-mass-spectrometry
#8
Jia Liu, Mingming Zhao, Juntuo Zhou, Changjie Liu, Lemin Zheng, Yuxin Yin
Trimethylamine-N-oxide (TMAO) is a metabolite generated from choline, betaine and carnitine in a gut microbiota-dependent way. This molecule is associated with development of atherosclerosis and cardiovascular events. A sensitive liquid chromatographic electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) has been developed and validated for the simultaneous determination of TMAO related molecules including TMAO, betaine, choline, and carnitine in mouse plasma. Analytes are extracted after protein precipitation by methanol and subjected to LC-ESI-MS/MS without preliminary derivatization...
November 1, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/27573063/the-metabolite-trimethylamine-n-oxide-is-an-emergent-biomarker-of-human-health
#9
Amit Sharma, Jyoti Chhibber-Goel, Varsha Singhal, Neeraj Parakh, Balram Bhargava
Trimethylamine-N-oxide (TMAO) is a low molecular weight metabolite whose production is dependent on metabolism of its precursors choline, carnitine, creatinine, betaine or lecithin by host gut microbes resulting in the synthesis of trimethylamine (TMA) and subsequent oxidation to TMAO via the hepatic flavin monooxygenase (FMO) enzyme or bacterial Trimethylamine Monooxygenase (TMM). TMAO is associated with microbial dysbiosis and it is being studied for its linkage with cardiovascular disorders. In addition, dysregulated levels of TMAO has been linked with renal diseases, neurological disorders, and cancer...
August 30, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27377678/trimethylamine-n-oxide-tmao-response-to-animal-source-foods-varies-among-healthy-young-men-and-is-influenced-by-their-gut-microbiota-composition-a-randomized-controlled-trial
#10
Clara E Cho, Siraphat Taesuwan, Olga V Malysheva, Erica Bender, Nathan F Tulchinsky, Jian Yan, Jessica L Sutter, Marie A Caudill
SCOPE: Trimethylamine-N-oxide (TMAO), a metabolite linked to the gut microbiota, is associated with excess risk of heart disease. We hypothesized that (i) TMAO response to animal source foods would vary among healthy men and (ii) this response would be modified by their gut microbiome. METHODS AND RESULTS: A crossover feeding trial in healthy young men (n = 40) was conducted with meals containing TMAO (fish), its dietary precursors, choline (eggs) and carnitine (beef), and a fruit control...
January 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27189968/new-insight-into-the-dietary-cause-of-atherosclerosis-implications-for-pharmacology
#11
Reynold Spector
At present, the guideline approach to the medical treatment and prevention of atherosclerotic cardiovascular disease (ASCVD) is to classify patients by risk and treat the known risk factors (contributory causes), e.g., hypertension, diabetes, obesity, smoking, and poor diet, as appropriate. All high-risk patients should receive statins. This approach has had substantial success but ASCVD still remains the number one cause of death in the United States. Until recently, the underlying cause of ASCVD remained unknown, although a potential dietary cause was suggested by the fact that vegetarians, especially vegans, have a much lower incidence of ASCVD than animal flesh eaters...
July 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27155921/dioxin-like-pollutants-increase-hepatic-flavin-containing-monooxygenase-fmo3-expression-to-promote-synthesis-of-the-pro-atherogenic-nutrient-biomarker-trimethylamine-n-oxide-from-dietary-precursors
#12
Michael C Petriello, Jessie B Hoffman, Manjula Sunkara, Banrida Wahlang, Jordan T Perkins, Andrew J Morris, Bernhard Hennig
The etiology of cardiovascular disease (CVD) is impacted by multiple modifiable and non-modifiable risk factors including dietary choices, genetic predisposition, and environmental exposures. However, mechanisms linking diet, exposure to pollutants, and CVD risk are largely unclear. Recent studies identified a strong link between plasma levels of nutrient-derived Trimethylamine N-oxide (TMAO) and coronary artery disease. Dietary precursors of TMAO include carnitine and phosphatidylcholine, which are abundant in animal-derived foods...
July 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27123785/diabetes-is-associated-with-higher-trimethylamine-n-oxide-plasma-levels
#13
M Dambrova, G Latkovskis, J Kuka, I Strele, I Konrade, S Grinberga, D Hartmane, O Pugovics, A Erglis, E Liepinsh
Recent studies have revealed strong associations between systemic trimethylamine N-oxide (TMAO) levels, atherosclerosis and cardiovascular risk. In addition, plasma L-carnitine levels in patients with high TMAO concentrations predicted an increased risk for cardiovascular disease and incident major adverse cardiac events. The aim of the present study was to investigate the relation between TMAO and L-carnitine plasma levels and diabetes. Blood plasma samples were collected from 12 and 20 weeks old db/db mice and patients undergoing percutaneous coronary intervention...
April 2016: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/27122669/urinary-nuclear-magnetic-resonance-spectroscopy-of-a-bangladeshi-cohort-with-hepatitis-b-hepatocellular-carcinoma-a-biomarker-corroboration-study
#14
I Jane Cox, Abil E Aliev, Mary Me Crossey, Mahvish Dawood, Mamun Al-Mahtab, Sheikh M Akbar, Salimur Rahman, Antonio Riva, Roger Williams, Simon D Taylor-Robinson
AIM: To establish if a distinct urinary metabolic profile could be identified in Bangladeshi hepatitis-B hepatocellular carcinoma (HCC) patients compared to cirrhosis patients and controls. METHODS: Urine samples from 42 Bangladeshi patients with HCC (39 patients with hepatitis-B HCC), 47 with cirrhosis on a background of hepatitis B, 46 with chronic hepatitis B, and seven ethnically-matched healthy controls were analyzed using nuclear magnetic resonance (NMR) spectroscopy...
April 28, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27083288/advanced-chronic-kidney-disease-populations-have-elevated-trimethylamine-n-oxide-levels-associated-with-increased-cardiovascular-events
#15
MULTICENTER STUDY
Richard B Kim, Bridget L Morse, Ognjenka Djurdjev, Mila Tang, Norman Muirhead, Brendan Barrett, Daniel T Holmes, Francois Madore, Catherine M Clase, Claudio Rigatto, Adeera Levin
Cardiovascular disease is more common in patients with chronic kidney disease (CKD), and traditional risk factors do not adequately predict those at risk for cardiovascular (CV) events. Recent evidence suggests elevated trimethylamine N-oxide (TMAO), created by gut microflora from dietary L-carnitine and choline, is associated with CV events. We investigated the relationship of TMAO levels in patients with stages 3b and 4 CKD to ischemic CV events using the CanPREDDICT cohort, a Canada-wide observational study with prospective 3-year follow-up of adjudicated CV events...
May 2016: Kidney International
https://www.readbyqxmd.com/read/27081744/major-increase-in-microbiota-dependent-proatherogenic-metabolite-tmao-one-year-after-bariatric-surgery
#16
Marius Trøseid, Johannes R Hov, Torunn Kristin Nestvold, Hanne Thoresen, Rolf K Berge, Asbjørn Svardal, Knut Tore Lappegård
BACKGROUND: Trimethylamine-N-oxide (TMAO) is formed in the liver from trimethylamine (TMA), a product exclusively generated by the gut microbiota from dietary phosphatidylcholine and carnitine. An alternative pathway of TMAO formation from carnitine is via the microbiota-dependent intermediate γ-butyrobetaine (γBB). Elevated TMAO levels are associated with cardiovascular disease (CVD), but little is known about TMAO in obesity. Given the proposed contribution of microbiota alterations in obesity and type 2 diabetes (T2D), we investigated the potential impact of obesity, lifestyle-induced weight loss, and bariatric surgery on plasma levels of TMAO, its microbiota-dependent intermediate γBB, and its diet-dependent precursors carnitine and choline...
May 2016: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/27036856/a-multiplexed-targeted-assay-for-high-throughput-quantitative-analysis-of-serum-methylamines-by-ultra-performance-liquid-chromatography-coupled-to-high-resolution-mass-spectrometry
#17
Hanane Kadar, Justine Dubus, Jérémie Dutot, Lyamine Hedjazi, Suman Srinivasa, Kathleen V Fitch, Steven K Grinspoon, Jeremy K Nicholson, Marc-Emmanuel Dumas, Dominique Gauguier
Methylamines are biologically-active metabolites present in serum and urine samples, which play complex roles in metabolic diseases. Methylamines can be detected by proton nuclear magnetic resonance (NMR), but specific methods remain to be developed for their routine assay in human serum in clinical settings. Here we developed and validated a novel reliable "methylamine panel" method for simultaneous quantitative analysis of trimethylamine (TMA), its major detoxification metabolite trimethylamine-N-oxide (TMAO), and precursors choline, betaine and l-carnitine in human serum using Ultra Performance Liquid Chromatography (UPLC) coupled to High Resolution Mass Spectrometry (HRMS)...
May 1, 2016: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/26936850/chronic-oral-l-carnitine-supplementation-drives-marked-plasma-tmao-elevations-in-patients-with-organic-acidemias-despite-dietary-meat-restrictions
#18
Marcus J Miller, Bret L Bostwick, Adam D Kennedy, Taraka R Donti, Qin Sun, V Reid Sutton, Sarah H Elsea
Recent studies have implicated trimethylamine N-oxide (TMAO) in atherosclerosis, raising concern about L-carnitine, a common supplement for patients with inborn errors of metabolism (IEMs) and a TMAO precursor metabolized, in part, by intestinal microbes. Dietary meat restriction attenuates carnitine-to-TMAO conversion, suggesting that TMAO production may not occur in meat-restricted individuals taking supplemental L-carnitine, but this has not been tested. Here, we mine a metabolomic dataset to assess TMAO levels in patients with diverse IEMs, including organic acidemias...
2016: JIMD Reports
https://www.readbyqxmd.com/read/26873789/lean-seafood-intake-decreases-urinary-markers-of-mitochondrial-lipid-and-energy-metabolism-in-healthy-subjects-metabolomics-results-from-a-randomized-crossover-intervention-study
#19
Mette Schmedes, Eli Kristin Aadland, Ulrik Kraemer Sundekilde, Hélène Jacques, Charles Lavigne, Ingvild Eide Graff, Øyvin Eng, Asle Holthe, Gunnar Mellgren, Jette Feveile Young, Hanne Christine Bertram, Bjørn Liaset, Morten Rahr Clausen
SCOPE: Proteins constitute an important part of the human diet, but understanding of the effects of different dietary protein sources on human metabolism is sparse. We aimed to elucidate diet-induced metabolic changes through untargeted urinary metabolomics after four weeks of intervention with lean-seafood or nonseafood diets. It is shown that lean-seafood intake reduces urinary excretion of metabolites involved in mitochondrial lipid and energy metabolism possibly facilitating a higher lipid catabolism in healthy subjects...
July 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/26868510/the-carnitine-butyrobetaine-trimethylamine-n-oxide-pathway-and-its-association-with-cardiovascular-mortality-in-patients-with-carotid-atherosclerosis
#20
Karolina Skagen, Marius Trøseid, Thor Ueland, Sverre Holm, Azhar Abbas, Ida Gregersen, Martin Kummen, Vigdis Bjerkeli, Frode Reier-Nilsen, David Russell, Asbjørn Svardal, Tom Hemming Karlsen, Pål Aukrust, Rolf K Berge, Johannes E R Hov, Bente Halvorsen, Mona Skjelland
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...
April 2016: Atherosclerosis
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