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Carnitine cardiovascular risk

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https://www.readbyqxmd.com/read/28624482/nmr-quantification-of-trimethylamine-n-oxide-in-human-serum-and-plasma-in-the-clinical-laboratory-setting
#1
Erwin Garcia, Justyna Wolak-Dinsmore, Zeneng Wang, Xinmin S Li, Dennis W Bennett, Margery A Connelly, James D Otvos, Stanley L Hazen, Elias J Jeyarajah
BACKGROUND AND OBJECTIVES: Trimethylamine-N-oxide (TMAO) produced by gut microbiota metabolism of dietary choline and carnitine has been shown to be associated with increased risk of cardiovascular disease (CVD) and to provide incremental clinical prognostic utility beyond traditional risk factors for assessing a patient's CVD risk. The aim of this study was to develop an automated nuclear magnetic resonance (NMR) spectroscopy assay for quantification of TMAO concentration in serum and plasma using a high-throughput NMR clinical analyzer...
June 14, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/28498348/nutrients-turned-into-toxins-microbiota-modulation-of-nutrient-properties-in-chronic-kidney-disease
#2
REVIEW
Raul Fernandez-Prado, Raquel Esteras, Maria Vanessa Perez-Gomez, Carolina Gracia-Iguacel, Emilio Gonzalez-Parra, Ana B Sanz, Alberto Ortiz, Maria Dolores Sanchez-Niño
In chronic kidney disease (CKD), accumulation of uremic toxins is associated with an increased risk of death. Some uremic toxins are ingested with the diet, such as phosphate and star fruit-derived caramboxin. Others result from nutrient processing by gut microbiota, yielding precursors of uremic toxins or uremic toxins themselves. These nutrients include l-carnitine, choline/phosphatidylcholine, tryptophan and tyrosine, which are also sold over-the-counter as nutritional supplements. Physicians and patients alike should be aware that, in CKD patients, the use of these supplements may lead to potentially toxic effects...
May 12, 2017: Nutrients
https://www.readbyqxmd.com/read/28469156/impaired-renal-function-and-dysbiosis-of-gut-microbiota-contribute-to-increased-trimethylamine-n-oxide-in-chronic-kidney-disease-patients
#3
Kai-Yu Xu, Geng-Hong Xia, Jun-Qi Lu, Mu-Xuan Chen, Xin Zhen, Shan Wang, Chao You, Jing Nie, Hong-Wei Zhou, Jia Yin
Chronic kidney disease (CKD) patients have an increased risk of cardiovascular diseases (CVDs). The present study aimed to investigate the gut microbiota and blood trimethylamine-N-oxide concentration (TMAO) in Chinese CKD patients and explore the underlying explanations through the animal experiment. The median plasma TMAO level was 30.33 μmol/L in the CKD patients, which was significantly higher than the 2.08 μmol/L concentration measured in the healthy controls. Next-generation sequence revealed obvious dysbiosis of the gut microbiome in CKD patients, with reduced bacterial diversity and biased community constitutions...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28161804/tryptophan-depletion-under-conditions-that-imitate-insulin-resistance-enhances-fatty-acid-oxidation-and-induces-endothelial-dysfunction-through-reactive-oxygen-species-dependent-and-independent-pathways
#4
Theodoros Eleftheriadis, Georgios Pissas, Maria Sounidaki, Georgia Antoniadi, Christos Rountas, Vassilios Liakopoulos, Loannis Stefanidis
In atherosclerosis-associated pathologic entities characterized by malnutrition and inflammation, L-tryptophan (TRP) levels are low. Insulin resistance is an independent cardiovascular risk factor and induces endothelial dysfunction by increasing fatty acid oxidation. It is also associated with inflammation and low TRP levels. Low TRP levels have been related to worse cardiovascular outcome. This study evaluated the effect of TRP depletion on endothelial dysfunction under conditions that imitate insulin resistance...
April 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28159823/serum-acylcarnitines-and-risk-of-cardiovascular-death-and-acute-myocardial-infarction-in-patients-with-stable-angina-pectoris
#5
Elin Strand, Eva R Pedersen, Gard F T Svingen, Thomas Olsen, Bodil Bjørndal, Therese Karlsson, Jutta Dierkes, Pål R Njølstad, Gunnar Mellgren, Grethe S Tell, Rolf K Berge, Asbjørn Svardal, Ottar Nygård
BACKGROUND: Excess levels of serum acylcarnitines, which are intermediate products in metabolism, have been observed in metabolic diseases such as type 2 diabetes mellitus. However, it is not known whether acylcarnitines may prospectively predict risk of cardiovascular death or acute myocardial infarction in patients with stable angina pectoris. METHODS AND RESULTS: This study included 4164 patients (median age, 62 years; 72% men). Baseline serum acetyl-, octanoyl-, palmitoyl-, propionyl-, and (iso)valerylcarnitine were measured using liquid chromatography/tandem mass spectrometry...
February 3, 2017: Journal of the American Heart Association
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
#6
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...
March 14, 2017: European Heart Journal
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
#7
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 using a multi-platform metabolomics approach comprising LC-MS/MS and GC×GC-MS methods...
May 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27931027/anthracycline-induced-cardiotoxicity-in-young-cancer-patients-the-role-of-carnitine
#8
Saro H Armenian
While the increased rates of survival in childhood cancers have increased progressively in recent decades, many childhood cancer survivors will have at least one chronic health condition within 40 years of age. In this regard, cardiovascular complications have emerged as a leading cause of long-term morbidity and mortality in long-term survivors of childhood cancer, likely due to exposure to anthracycline chemotherapy, and outcomes in patients with anthracycline-related cardiomyopathy remain poor. Some progress has been made in understanding the mechanisms at the basis of anthracycline-related cardiomyopathy, which appear to involve generation of reactive oxygen species, leading to mitochondrial dysfunction, followed by myocyte apoptosis and maladaptive left ventricular remodeling...
2016: Annals of Nutrition & Metabolism
https://www.readbyqxmd.com/read/27914033/l-carnitine-simvastatin-reduces-lipoprotein-a-levels-compared-with-simvastatin-monotherapy-a-randomized-double-blind-placebo-controlled-study
#9
M Florentin, M S Elisaf, C V Rizos, V Nikolaou, E Bilianou, C Pitsavos, E N Liberopoulos
Lipoprotein (a) [Lp(a)] is an independent risk factor for cardiovascular disease. There are currently limited therapeutic options to lower Lp(a) levels. L-Carnitine has been reported to reduce Lp(a) levels. The aim of this study was to compare the effect of L-carnitine/simvastatin co-administration with that of simvastatin monotherapy on Lp(a) levels in subjects with mixed hyperlipidemia and elevated Lp(a) concentration. Subjects with levels of low-density lipoprotein cholesterol (LDL-C) >160 mg/dL, triacylglycerol (TAG) >150 mg/dL and Lp(a) >20 mg/dL were included in this study...
January 2017: Lipids
https://www.readbyqxmd.com/read/27834801/trimethylamine-n-oxide-the-good-the-bad-and-the-unknown
#10
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/27189968/new-insight-into-the-dietary-cause-of-atherosclerosis-implications-for-pharmacology
#11
REVIEW
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/27126549/the-complex-metabolism-of-trimethylamine-in-humans-endogenous-and-exogenous-sources
#13
REVIEW
Jyoti Chhibber-Goel, Anamika Gaur, Varsha Singhal, Neeraj Parakh, Balram Bhargava, Amit Sharma
Trimethylamine (TMA) is a tertiary amine with a characteristic fishy odour. It is synthesised from dietary constituents, including choline, L-carnitine, betaine and lecithin by the action of microbial enzymes during both healthy and diseased conditions in humans. Trimethylaminuria (TMAU) is a disease typified by its association with the characteristic fishy odour because of decreased TMA metabolism and excessive TMA excretion. Besides TMAU, a number of other diseases are associated with abnormal levels of TMA, including renal disorders, cancer, obesity, diabetes, cardiovascular diseases and neuropsychiatric disorders...
April 29, 2016: Expert Reviews in Molecular Medicine
https://www.readbyqxmd.com/read/27123785/diabetes-is-associated-with-higher-trimethylamine-n-oxide-plasma-levels
#14
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/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/27069868/mitochondrial-gene-polymorphisms-alter-hepatic-cellular-energy-metabolism-and-aggravate-diet-induced-non-alcoholic-steatohepatitis
#17
Torsten Schröder, David Kucharczyk, Florian Bär, René Pagel, Stefanie Derer, Sebastian Torben Jendrek, Annika Sünderhauf, Ann-Kathrin Brethack, Misa Hirose, Steffen Möller, Axel Künstner, Julia Bischof, Imke Weyers, Jörg Heeren, Dirk Koczan, Sebastian Michael Schmid, Senad Divanovic, Daniel Aaron Giles, Jerzy Adamski, Klaus Fellermann, Hendrik Lehnert, Jörg Köhl, Saleh Ibrahim, Christian Sina
OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is associated with an enhanced risk for liver and cardiovascular diseases and mortality. NAFLD can progress from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH). However, the mechanisms predisposing to this progression remain undefined. Notably, hepatic mitochondrial dysfunction is a common finding in patients with NASH. Due to a lack of appropriate experimental animal models, it has not been evaluated whether this mitochondrial dysfunction plays a causative role for the development of NASH...
April 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/26918530/leptin-induces-oxidative-stress-through-activation-of-nadph-oxidase-in-renal-tubular-cells-antioxidant-effect-of-l-carnitine
#18
Antonio J Blanca, María V Ruiz-Armenta, Sonia Zambrano, Rocío Salsoso, José L Miguel-Carrasco, Ana Fortuño, Elisa Revilla, Alfonso Mate, Carmen M Vázquez
Leptin is a protein involved in the regulation of food intake and in the immune and inflammatory responses, among other functions. Evidences demonstrate that obesity is directly associated with high levels of leptin, suggesting that leptin may directly link obesity with the elevated cardiovascular and renal risk associated with increased body weight. Adverse effects of leptin include oxidative stress mediated by activation of NADPH oxidase. The aim of this study was to evaluate the effect of L-carnitine (LC) in rat renal epithelial cells (NRK-52E) exposed to leptin in order to generate a state of oxidative stress characteristic of obesity...
October 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/26868510/the-carnitine-butyrobetaine-trimethylamine-n-oxide-pathway-and-its-association-with-cardiovascular-mortality-in-patients-with-carotid-atherosclerosis
#19
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
https://www.readbyqxmd.com/read/26687352/non-lethal-inhibition-of-gut-microbial-trimethylamine-production-for-the-treatment-of-atherosclerosis
#20
Zeneng Wang, Adam B Roberts, Jennifer A Buffa, Bruce S Levison, Weifei Zhu, Elin Org, Xiaodong Gu, Ying Huang, Maryam Zamanian-Daryoush, Miranda K Culley, Anthony J DiDonato, Xiaoming Fu, Jennie E Hazen, Daniel Krajcik, Joseph A DiDonato, Aldons J Lusis, Stanley L Hazen
Trimethylamine (TMA) N-oxide (TMAO), a gut-microbiota-dependent metabolite, both enhances atherosclerosis in animal models and is associated with cardiovascular risks in clinical studies. Here, we investigate the impact of targeted inhibition of the first step in TMAO generation, commensal microbial TMA production, on diet-induced atherosclerosis. A structural analog of choline, 3,3-dimethyl-1-butanol (DMB), is shown to non-lethally inhibit TMA formation from cultured microbes, to inhibit distinct microbial TMA lyases, and to both inhibit TMA production from physiologic polymicrobial cultures (e...
December 17, 2015: Cell
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