Carnitine supplementation

Atroshi F, Rizzo A F, Westermarck T and Ali-Vehmas T (1998), Effects of tamoxifen, melatonin, coenzyme Q10 and L-carnitine supplementation on bacterial growth in the presence of mycotoxins , Pharmacol. Res., 38 (4), 289-295. 

Special diet low in isoleucine, valine, methionine, threonine. Carnitine supplementation. Liver transplantation may be beneficial. 

Generalized carnitine deficiency, in its primary form and inherited as an autosomal recessive trait, is due to a defect of the specific high-affinity, low-concentration, carrier-mediated carnitine-uptake mechanism. The defect has been documented in cultured fibroblasts and muscle cultures, but the same uptake system is probably shared by heart and kidney, thus explaining the cardiomyopathy and the excessive leakage of carnitine into the urine. Oral L-carnitine supplementation results in dramatic improvement in cardiac function [4,8]. 

Both these disorders are treated by avoidance of fasting, dietary restriction of LCFAs, and carnitine supplementation the objective is to stimulate whatever carnitine shuttle activity is present. 

I. (1998) L-carnitine supplementation in childhood epilepsy current perspectives. Epilepsia 39 1216-1225. 

Adefovir dipivoxil is well tolerated. A dose-dependent nephrotoxicity has been observed in clinical trials, manifested by increased serum creatinine with decreased serum phosphorous and more common in patients with baseline renal insufficiency and those receiving high doses (60 mg/d). Other potential adverse effects are headache, diarrhea, asthenia, and abdominal pain. As with other NRTI agents, lactic acidosis and hepatic steatosis are considered a risk owing to mitochondrial dysfunction. No clinically important drug-drug interactions have been recognized to date. Pivalic acid, a by-product of adefovir dipivoxil metabolism, can esterify free carnitine and result in decreased carnitine levels. However, it is not felt necessary to administer carnitine supplementation with the low doses used to treat patients with HBV (10 mg/d). 

Acylcarnitine profiles are dependent on the clinical status of the patient at the time of sample collection [56, 57]. It is therefore important to provide the biochemical genetics laboratory with information regarding the clinical context during which the sample was collected. The laboratory must be conscientious of the fact that carnitine deficiency states can be associated with acylcarnitine profiles that lack any acylcarnitine species that are elevated above the reference range. Therefore, it is essential that the complete profiles are reviewed and even borderline elevated acylcarnitines should prompt further follow up in the presence of abnormally low free acetylcar-nitine (Fig. 3.2.2). If clinically indicated, a repeat sample should be collected at least 24 h after L-carnitine supplementation. 

Normal persons excrete very little TMA in the urine. However, slight TMA excretion may be observed after meals with a high content of TMA precursors like choline or lecithin, or after eating marine fish due to its high TMA N-oxide content. Healthy women may have a short episode of trimethylaminuria at the onset and during menstruation. TMA has also found to be increased in the urine of some patients using carnitine supplementation. Advanced liver and renal disease may result in TMA excretion and this constitutes the so-called secondary trimethylaminurias. 

Life-threatening cardiac dysfunction in a 7-year-old boy required urgent carnitine supplementation (SEDA-17, 74). 

De Vivo DC, Bohan TP, Coulter DL, Dreifuss FE, Greenwood RS, Nordli DR Jr, Shields WD, Stafstrom CE, Tein I. L-carnitine supplementation in childhood epilepsy current perspectives. Epilepsia 1998 39(11) 1216—25. 

Acylcamitines or amino acids may also be important in disease monitoring and treatment or as markers for new therapies, toxicities, etc. In one application using dried plasma spots, carnitine and acylcamitines may be useful in detecting possible carnitine deficiency as a result of kidney dialysis for patients with end-stage renal disease (36,37). A deficiency should result in carnitine supplementation in those patients that cannot replenish their levels fast enough. In fact, this is one of the first pharmaceutical-related applications of screening. The measurement of certain amino acids such as Phe and Tyr and their ratio is also routinely performed to monitor the effectiveness of dietary intervention in patients with PKU. 

Understanding the biochemical bases for carnitine deficiency and the resulting clinical syndrome forms the foundation for the two major approaches to therapy avoidance of biochemical stressors and carnitine supplementation. 

Carnitine supplementation is also critical in these patients. In acute severe metabolic crises, carnitine can be administered intravenously. Oral carnitine supplementation can be used for chronic maintenance therapy. Note that as the primary transport defect will still be present, carnitine supplementation cannot normalize the patient s carnitine homeostasis. 

The antipsychotic chlorpromazine is a prototype heptotoxicant for production of cholestasis. Pleiotropic effects of chlorpromazine on membrane permeability and associated ion gradients and microfilament-mediated canalicular contraction have been attributed to detergent effects. Valproic acid, an anticonvulsant, is associated with microvesicular steatosis. Inhibition of mitochondial fatty acid (S-oxidation is an important component of this toxic effect and is apparently related to carnitine availability as evidenced by the protection afforded by L-carnitine supplements. The hypolipidemic drugs clofibrate, fenofibrate, and gemfibrozil are peroxisome prolif-erators in rodent liver, but not in humans. Isoniazid, an antibiotic used to treat tuberculosis, exhibits an approximately 1 % incidence of hepatotoxicity. Although toxicity is known to be metabolism-dependent and protein adduction has been well-... 

Although carnitine is not generally nutritionally important, it may be required for premature infants, because tbey have a limited capacity to synthesize it. However, there is inadequate evidence to support routine carnitine supplementation of parenteraUy fed premature infants (Cairns and Stalker, 2000). Carnitine depletion occurs in patients undergoing hemodialysis, but there is Utde evidence that supplements are effective in treating the associated dyslipidemia (Raskind and El-Chaar, 2000 Hurot et al., 2002). 

Cairns PA and Stalker DJ (2000) Carnitine supplementation of parenterally fed neonates. Cochrane Database Systematic Reviews, CD000950. 

Hurot JM, Cucherat M, Haugh M, and Fouque D (2002) Effects of L-carnitine supplementation in maintenance hemodialysis patients a systematic review. Journal of the American Society of Nephrology 13,708-14. 

Raskind JY and El-Chaar GM (2000) The role of carnitine supplementation during valproic acid therapy. Annals of Pharmacotherapy 34, 630-8. 

Carnitine supplementation has been proposed for the treatment of symptomatic hyperammonemia caused by valproate. 

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