Effect of l-carnitine on the kinetics of carnitine, acylcarnitines and butyrobetaine in long-term haemodialysis

Vernez, Laurence; Dickenmann, Michael; Steiger, Jürg; Wenk, Markus R.; Krähenbühl, Stephan

doi:10.1093/ndt/gfi257

Cited by 27 publications

(25 citation statements)

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“…Before L-carnitine administration, the mean plasma concentration of L-carnitine was 39.1 μmol/L, which was lower than in the other population (Angelini et al 1992;Vernez et al 2006). The baseline SOD, GSH-Px, catalase and T-AOC concentration was 25.…”

Section: Discussionmentioning

confidence: 65%

Single Dose Administration of L-Carnitine Improves Antioxidant Activities in Healthy Subjects

Cao

et al. 2011

Tohoku J. Exp. Med.

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L-carnitine has been used as a supplement to treat cardiovascular or liver disease. However, there has been little information about the effect of L-carnitine on anti-oxidation capability in healthy human subjects. This study was designed to investigate the correlation between plasma L-carnitine concentration and antioxidant activity. Liquid L-carnitine (2.0 g) was administered orally as a single dose in 12 healthy subjects. Plasma concentration of L-carnitine was detected by HPLC. The baseline concentration of L-carnitine was 39.14 ± 5.65 μmol/L. After single oral administration, the maximum plasma concentration (C max ) and area under the curve (AUC 0-∞ ) were 84.7 ± 25.2 μmol/L and 2,676.4 ± 708.3 μmol/L·h, respectively. The half-life and the time required to reach the C max was 60.3 ± 15.0 min and 3.4 ± 0.46 h, respectively. There was a gradual increase in plasma concentrations of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase and total antioxidative capacity (T-AOC) in the first 3.5 h following L-carnitine administration. The plasma concentrations of SOD, GSH-Px, catalase and T-AOC returned to baseline levels within 24 h. A positive correlation was found between L-carnitine concentration and the antioxidant index of SOD (r = 0.992, P < 0.01), GSH-Px (r = 0.932, P < 0.01), catalase (r = 0.972, P < 0.01) or T-AOC (r = 0.934, P < 0.01). In conclusion, L-carnitine increases activities of antioxidant enzymes and the total antioxidant capacity in healthy subjects. It may be useful as a supplementary therapy for chronic illnesses involving excessive oxidative stress.

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Section: Discussionmentioning

confidence: 65%

Single Dose Administration of L-Carnitine Improves Antioxidant Activities in Healthy Subjects

Cao

et al. 2011

Tohoku J. Exp. Med.

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“…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). These findings suggest that the circulating plasma carnitine exchanges with tissue where it can acylated, transported back into plasma and eventually be excreted via the urine.…”

Section: Discussionmentioning

confidence: 92%

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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“…The levels of baseline plasma L-carnitine, ALC and PLC in the Chinese subjects seem lower than in the other population. 13,14 The small intestine is the main site of L-carnitine absorption. 15,16 Absorption of L-carnitine is characterized by slow mucosal uptake, prolonged mucosal retention and slow mucosal exit into the blood.…”

Section: Discussionmentioning

confidence: 99%

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

Cao¹,

Wang²,

Liu³

et al. 2009

CIM

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Clin Invest Med 2009; 32 (1): E13-E19. AbstractPurpose: To investigate the pharmacokinetics of Lcarnitine (LC) and its analogues, acetyl-L-carnitine (ALC) and propionyl -L-carnitine (PLC) in healthy volunteers after single L-carnitine administration. Methods: Liquid L-carnitine (2.0 g) was administered orally as a single dose in 12 healthy subjects. Plasma and urine concentrations of L-carnitine, ALC and PLC were detected by HPLC. Results:The maximum plasma concentration (Cmax) and area under the curve (AUC0-) of L-carnitine was 84.7±25.2 μmol·L -1 ·h and 2676.4±708.3 μmol·L -1 ·h, respectively. The elimination half-life of L-carnitine and the time required to reach the Cmax (Tmax) was 60.3±15.0 and 3.4±0.46 h, respectively. The Cmax of ALC (12.9±5.5 μmol·L -1 ) and PLC (5.08±3.08 μmol·L -1 ) was lower than Lcarnitine (P<0.01), so as the AUC0-(166.2±77.4 and 155.6±264.2μmol·L -1 ·h, respectively, P<0.01). The half-life of ALC (35.9±28.9h) and PLC (25.7±30.3 h) was also shorter than L-carnitine (P<0.01). The 24h accumulated urinary excretion of L-carnitine, ALC and PLC were 613.5±161.7, 368.3±134.8 and 61.3±37.8μmol, respectively. Conclusion: L-carnitine has a greater maximum plasma concentration than ALC and PLC. L-carnitine also has a longer half-life than ALC and PLC. These data may have important implications in the designing of dosing regimens for L-carnitine or its analogues, such as ALC or PLC.L-carnitine (3-hydroxy-4-N-trimethylammonium butyrate) is an endogenous compound mainly derived from food stuff, such as meat and dairy products. [1][2][3] It is also synthesized in the human, in the liver and kidneys, from the essential amino acids lysine and methionine. [1][2][3] In humans, the endogenous carnitine pool, which comprises free L-carnitine and a range of short-, medium-and long-chain esters, such as acetyl-L-carnitine (ALC) and propionyl-L-carnitine (PLC), is maintained by absorption of L-carnitine from dietary sources, biosynthesis within the body and extensive renal tubular reabsorption from glomerular filtrate. [1][2][3] L-carnitine has important roles in intermediary metabolism, including the transport of long chain fatty acids across the mitochondrial inner membrane; more than 90% of the human body's store is present in skeletal and cardiac muscle. 1,2 L-carnitine is an essen-ORIGINAL RESEARCH

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Effect of l-carnitine on the kinetics of carnitine, acylcarnitines and butyrobetaine in long-term haemodialysis

Cited by 27 publications

References 24 publications

Single Dose Administration of L-Carnitine Improves Antioxidant Activities in Healthy Subjects

Single Dose Administration of L-Carnitine Improves Antioxidant Activities in Healthy Subjects

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

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

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