Comparison of pharmacokinetics of L-carnitine, Acetyl-L-carnitine and Propionyl-Lcarnitine after single oral administration of L-carnitine in healthy volunteers

Cao, Yu; Wang, Yun-xiao; Liu, Cheng-juan; Wang, Lexin; Han, Ze‐Guang; Wang, Chunbo

doi:10.25011/cim.v32i1.5082

Cited by 33 publications

(22 citation statements)

References 20 publications

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“…Whereas propionylcarnitine was below the limit of quantification in the urine of control mice, it was present in the urine of all treated animals, also of the mice supplemented with carnitine or acetylcarnitine. Similarly, in humans treated with oral carnitine, elevated concentrations of acetylcarnitine and propionylcarnitine have been observed in plasma and urine (Cao et al, 2009). Furthermore, in patients with endstage renal failure undergoing hemodialysis, intravenous administration of carnitine was associated with increased plasma concentrations of many acylcarnitines and increased elimination of acylcarnitines by dialysis (Vernez et al, 2006).…”

Section: Discussionmentioning

confidence: 95%

Effect of carnitine, acetyl-, and propionylcarnitine supplementation on the body carnitine pool, skeletal muscle composition, and physical performance in mice

et al. 2013

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Reprint requestUnfortunately, due to copyright-relatedt issues, we are not able to post the post-print pdf version of our manuscript -in some cases, not even any version of our manuscript. Thus, if you would like to request a post-production, publisher pdf reprint, please click send an email with the request to christoph-dot-handschin_at_unibas-dot-ch (see http://www.biozentrum.unibas.ch/handschin).Information about the Open Access policy of different publishers/journals can be found on the SHERPA/ROMEO webpage: http://www.sherpa.ac.uk/romeo/ Reprint AnfragenAufgrund fehlender Copyright-Rechte ist es leider nicht möglich, dieses Manuskript in der finalen Version, z.T. sogar in irgendeiner Form frei zugänglich zu machen. Anfragen für Reprints per Email an christoph-dot-handschin_at_unibas-dot-ch (s. http://www.biozentrum.unibas.ch/handschin). AbstractCarnitine has key functions in energy metabolism. In most studies in animals or humans, carnitine supplementation did not influence muscle composition and function, but the effects of the carnitine esters acetylcarnitine or propionylcarnitine are not well characterized. We therefore investigated the influence of carnitine, acetylcarnitine and propionylcarnitine on body carnitine homeostasis, energy metabolism and physical performance in mice. Animals were orally supplemented with approximately 2 mmol/kg/d carnitine, acetylcarnitine or propionylcarnitine for four weeks, before being subjected to exhaustive exercise and analysis of skeletal muscle energy metabolism and morphology.In supplemented groups, the total plasma and urine carnitine concentrations were significantly higher than in the control group, whereas the skeletal muscle carnitine content remained unchanged. The bioavailability of supplemented carnitine or acylcarnitines was in the range of 20 to 23% as determined by urinary excretion of total carnitine. The supplemented acylcarnitines were hydrolyzed in the intestine and in the liver before reaching the systemic circulation. Skeletal muscle morphology including fiber type composition was not affected by treatment with carnitine or acylcarnitines. Oxygen consumption by muscle fibers obtained from soleus or gastrocnemius was not different between the groups. The supplementation of carnitine or acylcarnitines had no significant impact on the running capacity and on key substrates of skeletal muscle energy metabolism such as glycogen, ATP, phosphocreatine or creatine.In conclusion, oral supplementation of carnitine, acetylcarnitine or propionylcarnitine is associated with increased plasma concentrations of total carnitine and increased urinary excretion of carnitine, but does not affect the skeletal muscle carnitine content. Accordingly, physical performance, skeletal muscle energy metabolism, and muscle fiber type composition are not affected by high oral doses of carnitine or acylcarnitines in mice.

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Section: Discussionmentioning

confidence: 95%

Effect of carnitine, acetyl-, and propionylcarnitine supplementation on the body carnitine pool, skeletal muscle composition, and physical performance in mice

et al. 2013

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“…This method was first established in our lab [27]. A Waters2695 High Performance Liquid Chromatography system (Waters, America) equipped with a Hypersil C18 column (5 μm particle size, 200 mm length, 4.6 mm internal diameter) and a Waters474 fluorescence detector (Waters, America) was used.…”

Section: Methodsmentioning

confidence: 99%

L-carnitine ameliorated fatty liver in high-calorie diet/STZ-induced type 2 diabetic mice by improving mitochondrial function

Xia

Zhong

et al. 2011

Diabetol Metab Syndr

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BackgroundThere are an increasing number of patients suffering from fatty liver caused by type 2 diabetes. We intended to study the preventive and therapeutic effect of L-carnitine (LC) on nonalcoholic fatty liver disease (NAFLD) in streptozotocin (STZ)-induced type 2 diabetic mice and to explore its possible mechanism.MethodsThirty male Kungming mice were randomly divided into five groups: control group, diabetic group, pre-treatment group (125 mg/kg BW), low-dose (125 mg/kg BW) therapeutic group and high-dose (250 mg/kg BW) therapeutic group. The morphology of hepatocytes was observed by light and electron microscopy. LC and ALC (acetyl L-carnitine) concentrations in the liver were determined by high-performance liquid chromatography (HPLC). Moreover, liver weight, insulin levels and free fatty acid (FFA) and triglyceride (TG) levels in the liver and plasma were measured.ResultsAverage liver LC and ALC levels were 33.7% and 20% lower, respectively, in diabetic mice compared to control mice (P < 0.05). After preventive and therapeutic treatment with LC, less hepatocyte steatosis, clearer crista and fewer glycogen granules in the mitochondria were observed. Decreased liver weight, TG levels, and FFA concentrations (P < 0.05) in the liver were also observed after treatment with LC in diabetic mice. Moreover, liver LC and ALC levels increased upon treatment with LC, whereas the ratio of LC and ALC decreased significantly (P < 0.01).ConclusionLC supplements ameliorated fatty liver in type 2 diabetic mice by increasing fatty acid oxidation and decreasing the LC/ALC ratio in the liver. Therefore, oral administration of LC protected mitochondrial function in liver.

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“…Since AcCT excreted from skeletal muscle to blood is finally eliminated in urine, (14) blood AcCT may be increased in CKD patients. Fouque et al (15) showed that serum concentrations of acylated CT (acyl-CT) were significantly higher in CKD patients than in normal subjects.…”

Section: Introductionmentioning

confidence: 99%

Retention of acetylcarnitine in chronic kidney disease causes insulin resistance in skeletal muscle

Miyamoto

Miyazaki

Honda

et al. 2016

J. Clin. Biochem. Nutr.

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Insulin resistance occurs frequently in patients with chronic kidney disease. However, the mechanisms of insulin resistance associated with chronic kidney disease are unclear. It is known that an increase in the mitochondrial acetyl-CoA (AcCoA)/CoA ratio causes insulin resistance in skeletal muscle, and this ratio is regulated by carnitine acetyltransferase that exchanges acetyl moiety between CoA and carnitine. Because excess acetyl moiety of AcCoA is excreted in urine as acetylcarnitine, we hypothesized that retention of acetylcarnitine might be a cause of insulin resistance in chronic kidney disease patients. Serum acetylcarnitine concentrations were measured in chronic kidney disease patients, and were significantly increased with reduction of renal function. The effects of excess extracellular acetylcarnitine on insulin resistance were studied in cultured skeletal muscle cells (C2C12 and human myotubes), and insulin-dependent glucose uptake was significantly and dose-dependently inhibited by addition of acetylcarnitine. The added acetylcarnitine was converted to carnitine via reverse carnitine acetyltransferase reaction, and thus the AcCoA concentration and AcCoA/CoA ratio in mitochondria were significantly elevated. The results suggest that increased serum acetylcarnitine in CKD patients causes AcCoA accumulation in mitochondria by stimulating reverse carnitine acetyltransferase reaction, which leads to insulin resistance in skeletal muscle.

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Comparison of pharmacokinetics of L-carnitine, Acetyl-L-carnitine and Propionyl-Lcarnitine after single oral administration of L-carnitine in healthy volunteers

Cited by 33 publications

References 20 publications

Effect of carnitine, acetyl-, and propionylcarnitine supplementation on the body carnitine pool, skeletal muscle composition, and physical performance in mice

Effect of carnitine, acetyl-, and propionylcarnitine supplementation on the body carnitine pool, skeletal muscle composition, and physical performance in mice

L-carnitine ameliorated fatty liver in high-calorie diet/STZ-induced type 2 diabetic mice by improving mitochondrial function

Retention of acetylcarnitine in chronic kidney disease causes insulin resistance in skeletal muscle

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