Disposition and Metabolite Kinetics of Oral L‐carnitine in Humans

Abstract

The pharmacokinetics of L-carnitine and its metabolites were investigated in 7 healthy subjects following the oral administration of 0, 0.5, 1, and 2 g 3 times a day for 7 days. Mean plasma concentrations of L-carnitine across an 8-hour dose interval increased significantly (P < .05) from a baseline of 54.2 +/- 9.3 microM to 80.5 +/- 12.5 microM following the 0.5-g dose; there was no further increase at higher doses. There was a significant increase (P < .001) in the renal clearance of L-carnitine indicating saturation of tubular reabsorption. Trimethylamine plasma levels increased proportionately with L-carnitine dose, but there was no change in renal clearance. A significant increase in the plasma concentrations of trimethylamine-N-oxide from baseline was evident only for the 2-g dose of L-carnitine (from 34.5 +/- 2.0 to 149 +/- 145 microM), and its renal clearance decreased with increasing dose (P < .05). There was no evidence for nonlinearity in the metabolism of trimethylamine to trimethylamine-N-oxide. In conclusion, the pharmacokinetics of oral L-carnitine display nonlinearity above a dose of 0.5 g 3 times a day.

Effect of intravenous l-carnitine in Chinese patients with chronic heart failure

“…27,28 This process may override the beneficial effects of correcting carnitine insufficiency since the increase in some acyl-carnitine derivatives in plasma may have a detrimental effect on cardiovascular function. 29,30 The paradoxical dose-effect relationship of carnitine on plasma triglycerides, showing a beneficial effect at low doses that disappears at high doses, 31 may be due to a similar mechanism; (ii) an increase in oral dose of carnitine above a critical level is associated with an increase in plasma trimethylamine 32 which may promote atherosclerosis. 33 Our results are not relevant to the first treatment approach based on carnitine insufficiency since the increased risk of developing major cardiac AEs has only been detected in humans with carnitine plasma concentrations .45.1 mmol/L.…”

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

“…butyrate) is an endogenous compound derived from the diet, such as meat and dairy products, or being synthesized in the liver or kidneys from the essential amino acids lysine and methionine (Vaz and Wanders 2002;Bain et al 2006;Tsakiris et al 2008). L-carnitine plays an important role in intermediary metabolism, including the transport of long chain fatty acids across the mitochondrial inner membrane (Vaz and Wanders 2002;Bain et al 2006).…”

“…L-carnitine plays an important role in intermediary metabolism, including the transport of long chain fatty acids across the mitochondrial inner membrane (Vaz and Wanders 2002;Bain et al 2006). L-carnitine is an essential cofactor in the β-oxidation of long-chain fatty acids.…”

Efeitos ergogênicos da L-carnitina no metabolismo lipídico

“…Concomitante a esses resultados, a biodisponibilidade da L-carnitina dietética pode ser superior a 75%, demonstrando que os suplementos são absorvidos em menores quantidades quando em comparação aos alimentos (BAIN et al, 2006;REBOUCHE, 2004.). A fração não absorvida da carnitina pode ser transformada em trimetilamina e Ybutirobetaína pelas enterobactérias, as quais serão eliminadas do organismo pelas fezes (EVANS & FORNASINI, 2003;BAIN et al, 2006) No organismo, tem sido reportado existir três locais de compartimentalização da L-carnitina, o fluído extracelular, tecidos de equilíbrio rápido (fígado e rins) e de equilíb r io lento (músculo esquelético e cardíaco) (COELHO, et al 2005;EVANS & FORNASINI, 2003). O tempo de turnover nesses locais é de, respectivamente, 1 hora, 12 horas e 191 horas aproximadamente, sendo o turnover corporal total aproximado de 66 dias (EVANS & FORNASINI, 2003).…”