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Carnitine cardiovascular risk

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...
December 2, 2016: Lipids
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
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
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
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
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
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
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
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
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
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
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
Daniel M Mueller, Martina Allenspach, Alaa Othman, Christoph H Saely, Axel Muendlein, Alexander Vonbank, Heinz Drexel, Arnold von Eckardstein
BACKGROUND: After ingestion of phosphatidylcholine, l-carnitine or betaine, trimethylamine-N-oxide (TMAO) is formed by gut microbiota and liver enzymes. Elevated TMAO plasma levels were associated with increased cardiovascular risk and other diseases. Also betaine and choline itself were recently associated with increased cardiovascular risk. METHODS: A newly developed LC-HRMS method was applied to measure the plasma concentrations of TMAO, betaine and choline in a cohort of 339 patients undergoing coronary angiography for the evaluation of suspected coronary artery disease...
December 2015: Atherosclerosis
Alex P Kitson, Kristin A Marks, Juan J Aristizabal Henao, A Russell Tupling, Ken D Stark
Menopause is associated with higher plasma and liver triacylglycerol (TAG) and increased risk for cardiovascular disease. Lowering TAG in menopause may be beneficial; however, the mechanism underlying menopause-induced TAG accumulation is not clear. Ovariectomy is a model for menopause and is associated with metabolic alterations and hyperphagia. This study investigated the role of hyperphagia in ovariectomy-induced increases in blood and tissue TAG, as well as differences in lipid metabolism enzymes and resting metabolic measures...
December 2015: Nutrition Research
Bodil Bjørndal, Marie S Ramsvik, Carine Lindquist, Jan E Nordrehaug, Inge Bruheim, Asbjørn Svardal, Ottar Nygård, Rolf K Berge
Seafood is assumed to be beneficial for cardiovascular health, mainly based on plasma lipid lowering and anti-inflammatory effects of n-3 polyunsaturated fatty acids. However, other plasma risk factors linked to cardiovascular disease are less studied. This study aimed to penetrate the effect of a phospholipid-protein complex (PPC) from Antarctic krill on one-carbon metabolism and production of trimethylamine-N-oxide (TMAO) in rats. Male Wistar rats were fed isoenergetic control, 6%, or 11% PPC diets for four weeks...
September 2015: Marine Drugs
Marcin Ufnal, Anna Zadlo, Ryszard Ostaszewski
Trimethylamine N-oxide (TMAO) is a small organic compound whose concentration in blood increases after ingesting dietary l-carnitine and phosphatidylcholine. Recent clinical studies show a positive correlation between elevated plasma levels of TMAO and an increased risk for major adverse cardiovascular events defined as death, myocardial infarction, or stroke. Several experimental studies suggest a possible contribution of TMAO to the etiology of cardiovascular diseases by affecting lipid and hormonal homeostasis...
November 2015: Nutrition
Kati Hanhineva, Carl Brunius, Agneta Andersson, Matti Marklund, Risto Juvonen, Pekka Keski-Rahkonen, Seppo Auriola, Rikard Landberg
SCOPE: Whole grain (WG) intake is associated with decreased risk of developing colorectal cancer, type 2 diabetes, and cardiovascular disease and its comorbidities. However, the role of specific grains is unclear. Moreover, intake of specific WG is challenging to measure accurately with traditional dietary assessment methods. Our aim was to use nontargeted metabolite profiling to discover specific urinary biomarkers for WG rye to objectively reflect intake under free-living conditions...
November 2015: Molecular Nutrition & Food Research
Andrew Mente, Kenneth Chalcraft, Handan Ak, A Darlene Davis, Eva Lonn, Ruby Miller, Murray A Potter, Salim Yusuf, Sonia S Anand, Matthew J McQueen
BACKGROUND: Microflora-dependent trimethylamine-N-oxide (TMAO) formation, which results from intake of choline and L-carnitine-rich food, shows promise as a predictor of cardiovascular disease (CVD) risk, but these associations have not been examined in ethnically diverse populations. In a multiethnic population-based study of adults in Canada, we assessed the stability of TMAO and L-carnitine in stored serum samples and their association with intimal medial thickness, prevalent risk factors, and clinical events...
September 2015: Canadian Journal of Cardiology
Daniel Li, Jennifer Kirsop, W H Wilson Tang
What we understand about diabetes from decades of genetics research is now being supplemented with exciting new evidence based on a better understanding of how one of the biggest "environmental" factors the body is exposed to is influencing the pathogenesis of disease. The recent discovery that certain dietary nutrients possessing a trimethylamine (TMA) moiety (namely choline/phosphatidylcholine and L-carnitine) participate in the development of atherosclerotic heart disease has renewed attention towards the contributions of gut microbiota in the development of cardiovascular diseases...
September 2015: Current Diabetes Reports
Sunil K Panchal, Hemant Poudyal, Leigh C Ward, Jennifer Waanders, Lindsay Brown
Obesity and dyslipidaemia are metabolic defects resulting from impaired lipid metabolism. These impairments are associated with the development of cardiovascular disease and non-alcoholic fatty liver disease. Correcting the defects in lipid metabolism may attenuate obesity and dyslipidaemia, and reduce cardiovascular risk and liver damage. L-Carnitine supplementation was used in this study to enhance fatty acid oxidation so as to ameliorate diet-induced disturbances in lipid metabolism. Male Wistar rats (8-9 weeks old) were fed with either corn starch or high-carbohydrate, high-fat diets for 16 weeks...
August 2015: Food & Function
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