Effect of L-carnitine on plasma glycemic and lipidemic profile in patients with type II diabetes mellitus

Rahbar, Alireza; Shakerhosseini, Rahebeh; Saadat, Navid; Taleban, Forough Azam; Pordal, Amir-Hamzeh; Gollestan, B

doi:10.1038/sj.ejcn.1602109

Cited by 81 publications

(53 citation statements)

References 24 publications

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“…Taken together, the two investigations provide compelling evidence that oral carnitine supplements administered to obese rodents not only restores tissue carnitine content, but also enhances glucose disposal and mitochondrial performance. A limited number of small scale clinical studies have likewise reported positive outcomes of L-carnitine therapy in humans (43)(44)(45). In these studies, acute carnitine infusion during a hyperinsulinemic-euglycemic clamp was found to increase glucose disposal and whole body carbohydrate oxidation in insulin-resistant subjects (43,44).…”

Section: Discussionmentioning

confidence: 85%

Carnitine Insufficiency Caused by Aging and Overnutrition Compromises Mitochondrial Performance and Metabolic Control

Noland¹,

Koves²,

Seiler³

et al. 2009

Journal of Biological Chemistry

291

339

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In addition to its essential role in permitting mitochondrial import and oxidation of long chain fatty acids, carnitine also functions as an acyl group acceptor that facilitates mitochondrial export of excess carbons in the form of acylcarnitines. Recent evidence suggests carnitine requirements increase under conditions of sustained metabolic stress. Accordingly, we hypothesized that carnitine insufficiency might contribute to mitochondrial dysfunction and obesity-related impairments in glucose tolerance. Consistent with this prediction whole body carnitine dimunition was identified as a common feature of insulin-resistant states such as advanced age, genetic diabetes, and diet-induced obesity. In rodents fed a lifelong (12 month) high fat diet, compromised carnitine status corresponded with increased skeletal muscle accumulation of acylcarnitine esters and diminished hepatic expression of carnitine biosynthetic genes. Diminished carnitine reserves in muscle of obese rats was accompanied by marked perturbations in mitochondrial fuel metabolism, including low rates of complete fatty acid oxidation, elevated incomplete ␤-oxidation, and impaired substrate switching from fatty acid to pyruvate. These mitochondrial abnormalities were reversed by 8 weeks of oral carnitine supplementation, in concert with increased tissue efflux and urinary excretion of acetylcarnitine and improvement of whole body glucose tolerance. Acetylcarnitine is produced by the mitochondrial matrix enzyme, carnitine acetyltransferase (CrAT). A role for this enzyme in combating glucose intolerance was further supported by the finding that CrAT overexpression in primary human skeletal myocytes increased glucose uptake and attenuated lipid-induced suppression of glucose oxidation. These results implicate carnitine insufficiency and reduced CrAT activity as reversible components of the metabolic syndrome.Disturbances in mitochondrial genesis, morphology, and function are increasingly recognized as components of insulin resistance and the metabolic syndrome (1-3). Still unclear is whether poor mitochondrial performance is a predisposing factor or a consequence of the disease process. The latter view is supported by recent animal studies linking diet-induced insulin resistance to a dysregulated mitochondrial phenotype in skeletal muscle, marked by excessive ␤-oxidation, impaired substrate switching during the fasted to fed transition, and coincident reduction of organic acid intermediates of the tricarboxylic acid cycle (4, 5). In these studies, both diet-induced and genetic forms of insulin resistance were specifically linked to high rates of incomplete fat oxidation and intramuscular accumulation of fatty acylcarnitines, byproducts of lipid catabolism that are produced under conditions of metabolic stress (5, 6). Most compelling, we showed that genetically engineered inhibition of fat oxidation lowered intramuscular acylcarnitine levels and preserved glucose tolerance in mice fed a high fat diet (5, 7). In aggregate, the findings established a stron...

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Section: Discussionmentioning

confidence: 85%

Carnitine Insufficiency Caused by Aging and Overnutrition Compromises Mitochondrial Performance and Metabolic Control

Noland¹,

Koves²,

Seiler³

et al. 2009

Journal of Biological Chemistry

291

339

View full text Add to dashboard Cite

show abstract

“…Additionally, a study from China [11] and another from Italy [12] found that carnitine lowered circulating lipids but did not improve fasting glucose levels. A recent study conducted in Iran [13] reported that dietary carnitine lowered fasting glucose levels, but increased triacylglycerol levels.…”

Section: Introductionmentioning

confidence: 99%

Carnitine revisited: potential use as adjunctive treatment in diabetes

et al. 2007

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Aims/hypothesis This study examined the efficacy of supplemental L-carnitine as an adjunctive diabetes therapy in mouse models of metabolic disease. We hypothesised that carnitine would facilitate fatty acid export from tissues in the form of acyl-carnitines, thereby alleviating lipidinduced insulin resistance. Materials and methods Obese mice with genetic or dietinduced forms of insulin resistance were fed rodent chow ± 0.5% L-carnitine for a period of 1-8 weeks. Metabolic outcomes included insulin tolerance tests, indirect calorimetry and mass spectrometry-based profiling of acyl-carnitine esters in tissues and plasma.Results Carnitine supplementation improved insulin-stimulated glucose disposal in genetically diabetic mice and wild-type mice fed a high-fat diet, without altering body weight or food intake. In severely diabetic mice, carnitine supplementation increased average daily respiratory exchange ratio from 0.886±0.01 to 0.914±0.01 (p<0.01), reflecting a marked increase in systemic carbohydrate oxidation. Similarly, under insulin-stimulated conditions, carbohydrate oxidation was higher and total energy expenditure increased from 172±10 to 210±9 kJ kg fatfree mass −1 h −1 in the carnitine-supplemented compared with control animals. These metabolic improvements corresponded with a 2.3-fold rise in circulating levels of acetyl-carnitine, which accounts for 86 and 88% of the total acyl-carnitine pool in plasma and skeletal muscle, respectively. Carnitine supplementation also increased several medium-and long-chain acyl-carnitine species in both plasma and tissues. Conclusions/interpretation These findings suggest that carnitine supplementation relieves lipid overload and glucose intolerance in obese rodents by enhancing mitochondrial efflux of excess acyl groups from insulin-responsive tissues. Carefully controlled clinical trials should be considered.

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“…Препарат не купировал и не провоцировал нарушения ритма сердца и проводимости. Его вве-дение хорошо переносилось больными, включая пациентов с сахарным диабетом, что соответству-ет литературным данным [17]. Не случайно лево-карнитин с успехом используют также при ожи-рении и в спортивной медицине.…”

Section: характеристика пациентов по группам исследованияunclassified

Use of L-Karnitine in Low Cardiac Output Syndrome in Patients With Acute Miocardial Infarction

Semigolovskiy

2013

Rossiĭskiĭ semeĭnyĭ vrach

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Приведены данные по применению левокарнитина у больных с различными формами ишемической болезни сердца, включая стенокардию, острый инфаркт миокарда, а также с тромбоэмболией легочной артерии и дилатационной кардиомиопатией. Пилотное клиническое исследование инфузионного препара-та «Элькар» проведено у больных острым инфарктом миокарда. Показано, что препарат обладает защит-ным эффектом при ишемии миокарда, дозозависимо повышая его сократительную способность и снижая выход кардиоспецифических ферментов и белков в кровоток.Ключевые слова: левокарнитин, ишемическая болезнь сердца, стенокардия, острый инфаркт миокар-да, фракция выброса левого желудочка, синдром малого выброса.Literature review and own data are given on use of L-carnitine in patients with various forms of ischemic heart disease, pulmonary embolism and dilated cardiomyopathy. Pilot clinical study of infusion form of L-carnitine had shown its positive dose-dependent inotropic effect in 33 patients with acute myocardial infarction and low left ventricular ejection fraction (<40%), compared with similar 24 patients, who haven't get any metabolic drugs.Keywords: L-carnitine, ischemic heart disease, angina pectoris, acute myocardial infarction, ejection fraction of left ventricle, low cardiac output syndrome.Актуальность. В 50-х гг. прошлого века по яви-лись первые научные публикации, посвященные применению в медицине карнитина, а в 70-х бы ли описаны первые заболевания, связанные с карни-тиновой недостаточностью. В настоящее время интерес к этому веществу продолжает расти. Из-вестно, что карнитин -биоактивное соединение, которое играет важную роль в выработке энергии в митохондриях. Его L-форма (левокарни тин) способствует уменьшению накопления длинно-цепочечных жирных кислот в митохондриях и ци топлазме, предупреждая тем самым их цито-токсический эффект, особенно выраженный при ишемии [1]. В условиях ишемии в митохондриях накапливается ацилкоэнзим А, баланс которого со свободным коэнзимом поддерживается именно за счет работы так называемого карнитинового чел-нока [2], транспортирующего ацильные остатки жир ных кислот. L-карнитин контролирует и ско-рость окисления длинноцепочечных жирных кис-лот, выступая в качестве специфического кофак-тора, облегчающего их перенос через внутреннюю мембрану митохондрий, и участвует в удалении их избытка из митохондрий, а затем и из цитоплазмы.Было показано, что уровень карнитина в мио-карде падает при ишемической болезни сердца (ИБС), остром инфаркте миокарда (ОИМ) и сер-дечной недостаточности различного генеза [3].Отечественный препарат «Элькар» из фар-макологической группы метаболических средств пред ставляет собой раствор левокарнитина для инъекций. К настоящему времени, главным обра-зом за рубежом, уже накоплен значительный опыт при менения L-карнитина у пациентов с различны-ми формами ИБС и кардиомиопатиями преиму-щест венно в детской практике [2,[4][5][6].Положительный клинический эффект карни-тина при стенокардии подтвержден в нескольких рандомизированных плацебо-контролируемых ис-следованиях, показавших достовер...

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Effect of L-carnitine on plasma glycemic and lipidemic profile in patients with type II diabetes mellitus

Cited by 81 publications

References 24 publications

Carnitine Insufficiency Caused by Aging and Overnutrition Compromises Mitochondrial Performance and Metabolic Control

Carnitine Insufficiency Caused by Aging and Overnutrition Compromises Mitochondrial Performance and Metabolic Control

Carnitine revisited: potential use as adjunctive treatment in diabetes

Use of L-Karnitine in Low Cardiac Output Syndrome in Patients With Acute Miocardial Infarction

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