L-Carnitine

Monograph

Chemical Structure of L-Carnitine

L-Carnitine
Introduction
A trimethylated amino acid, roughly similar in structure to choline, L-camitine is a cofactor required for transformation of free long-chain fatty acids into acylcarnitines, and for their subsequent transport into the mitochondrial matrix, where they undergo beta-oxidation for cellular energy production. Conditions that appear to benefit from exogenous supplementation of L-carnitine include anorexia, chronic fatigue, cardiovascular disease, diphtheria, hypoglycemia. male infertility, tnuscular myopathies. and Rett syndrome. Preterm infants, dialysis patients, and HIV-positive individuals seem to be prone to a deficiency of L-carnitine and benefit from supplementation. Although discovered in 1905, the crucial role of L-camitine in metabolism was not elucidated until 1955, and its deficiency was not described until 1972. The most significant source of L-carnitine in human nutrition is meat, although humans can synthesize L-camitine from dietary amino acids.

Biochemistry and Pharmacokinetics
Synthesis of carnitine begins with methylation of the amino acid L-lysine by S-adenosylmethionine (SAMe). Magnesium, vitamin C, iron, vitamins B3 and B6. and alpha-ketoglutarate - along with the cofactors responsible for creating SAMe (methionine. folic acid, vitamin BI2. and betaine)-are all required for endogenous carnitine synthesis. Evidence indicates L-camitine is absorbed in the intestine by a combination of active transport and passive diffusion.' Reports of bioavailability following an oral dose have varied substantially, with estimates as low as 16-18 percent-' and as high as 54-87 percent.""'^ Oral supplementation of L-camitine in individual dosages greater than 2 g appears to offer no advantage, since the mucosal absorption of camitine appears to be saturated at about a 2-g dose.- Maximum blood concentration is reached approximately 3.5 hours after an oral dose and slowly decreases, with a half-life of about 15 hours."^ Elimination of carnitine occurs primarily through the kidneys.^ The heart, skeletal muscle, liver, kidneys, and epididymis have specific transport systems for camitine that concentrate carnitine within these tissues. Despite evidence indicating increased levels of free carnitine and carnitine metabolites in the blood and urine following an oral dose, no significant change in red blood cell carnitine levels was noted in healthy subjects, suggesting either a slow repletion of tissue stores of carnitine following an oral dose or a low capability to transport camitine into tissues under normal conditions.''

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Alternative Medicine Review • Volume 10, Number 1 • 2005

although rare. hypotonia.'. Primary camitine deficiency. Secondary carnitine deficiency is not as rare and is most commonly associated with dialysis in chronic renal failure.000 mg daily) has been shown to moderately improve exercise tolerance and reduce ECG indices of ischemia in patients with stable angina. progressive myasthenia. although it can also be induced by intestinal resection. an increase in maximal systolic arterial blood pressure. nomialize gastrointestinal function. In addition. and malondialdehyde.diabetes. a concomitant increase in the number of patients belonging to class I of the NYHA classification (as opposed to classes II and III) and a reduction in the consumption of cardioactive drugs has been reported. congestive heart failure.-" Alternative Medicine Review • Volume 10. and a reduction in ST-segment depression during maximal effort." A small study on L-camitine"s effect on high-repetition squat exercise found significant benefit from 2 g carnitine daily compared to placebo on blood parameters of muscle recovery .-^ Angina patients receiving L-carnitine have experieticed functional improvement."* In contrast.'"-' Cardiovascular Disease Angina and Ischemia L-camitine (oral doses ranging from 9003. and isoleucine . Camitine deficiency can be acquired or a result of inborn errors of metabolism. and improve physical performance.-."^ Clinical Indications Anorexia Combined use of L-camitine and adenosylcobalamin in patients with anorexia nervosa has been shown to accelerate body weight gain.^ Carnitine is involved in the tnetabolism of ketones for energy** and the conversion of branchedchain amino acids .myoglobin. evidence suggests both primary and secondary deficiencies do occur. Number 1 • 2005 Page 43 ." Deficiency can result in cardiomyopathy. or lethargy. and neuromuscular disorders.'" Pre-temi infants are at risk for developing a carnitine deficiency due to impaired synthesis and insufficient renal tubular resorption. severe infection. including a reduction in the number of premature ventricular contractions at rest. encephalopathy. other research has shown no ergogenic effects of either chronic or acute L-camitine supplementation. decrease fatigue.'^ while other researchers reported increased maximal oxygen uptake and decreased plasma lactate when L-carnitine was supplemented acutely one hour prior to beginning exercise. and tissue levels of camitine. Athletic Performance A clinical study reported improved running speed and decreased average oxygen consumption and heart rate following prolonged L-camitine supplementation. Alzheimer's disease. Increasing benefits are often observed with longer suppletnentation. hepatomegaly. and liver: a disruption of muscle fibers: and an accumulation of large aggregates of mitochondria within skeletal and smooth muscle. Additional symptoms of chronic carnitine deliciency can include hypoglycemia. and liver disease. is characterized by low plasma. leucine.into energy. and myoglobinetnia following exercise." '^ Children with infantile anorexia responded to a combination of carnitine and adenosylcobalamin with improved appetite. cardiac muscle. red blood cell.''' Deficiency States and Symptoms Although L-carnitine is supplied exogenously as a component of the diet and can also be synthesized endogenously.valine. cramps.Monograph L-Carnitine Mechanisms of Action Carnitine's primary mechanism of action is apparently attributable to its role as a cofactor in the transformation of free long-chain fatty acids into acylcarnitines for subsequent transport into the mitcxrhondrial matrix. impaired growth and development in infants. and heart failure. Other conditions associated with a carnitine deficiency include cancer. creatine kinase. Estimates suggest upward of 22 percent of subjects might become angina-free during supplementation periods. and generally presents with symptoms such as muscle fatigue." Pathological manifestations of chronic deficiency include accumulation of neutral lipid within skeletal muscle.

Insulin-mediated glueose uptake was significantly higher in both groups receiving L-earnitine compared to the saline groups.*' In a study of pediatrie patients on dialysis. Significant improvements were also noted in heart rate and anginal attacks. Other measurements taken but not significantly impacted by L-carnitine were body mass index. fasting glucose. walking distance improved from an average of 174 minutes with placebo to 306 minutes with L-carnitine at a dose of 2 g twiee daily for three weeks.'^'^ Page 44 Alternative Medicine Review • Volume 10.'** In healthy subjects."-'^ Diabetes/Insulin Resistance Healthy volunteers and type 2 diabetics received an infusion of L-carnitine or saline.^' L-eamitine (2 g daily) significantly reduced lipoprotein(a) (Lp(a)) levels in 14 of 18 subjects. oral L-carnitine at 50 mg/kg/day for 30 days resulted in significant decrease in apolipoprotein B levels. maximal time of cardiopulmonary exercise test. Normalization of lipid levels occurred in a substantial number of subjects with continued supplementation for one year. in a significant number of subjeets the reduction of Lp(a) resulted in a return to the normal range.L-Carnitine In subjects with ischemia-induced NYHA II or III cardiac insufliciency. L-carnitine supplementation {1 g three times daily for 120 days).5%).-^"-" Cardiomyopathy Long-term supplementation of L-carnitine (2 g daily) for the treatment of heart failure caused by dilated cardiomyopathy resulted in improvement in survival rate.'*^ Myocardial Infarction Following a recent myocardial infarction (MI). glycosylated hemoglobin. nitrates). resulted in improvements in exercise performance and hemodynamic parameters.-^ Monograph Hyperlipidemia L-carnitine (2-3 g daily) resulted in improved lipid profiles in individuals with hyperlipidemia. arterial and pulmonary biood pressure.^""^^ L-camitine supplementation (2 g daily) also deereased triglycerides in individuals with essential hypertension. Number 1 • 2005 . Weber classification. triglycerides. Lcarnitine was found to inhibit fatty-acid induced endothelial dysfunction intended to simulate that seen in obesity or type 2 diabetes. indicating improved insulin sensitivity from carnitine. and apolipoproteins A-1 and B / ' Peripheral Vascular Disease In a double-blind. Reductions in Lp(a) were greater in individuals with more marked elevations prior to supplementation.*Similar results were found in hypercholesterolemie patients newly diagnosed with type 2 diabetes. crossover study of subjects with peripheral vascular disease. calcium antagonists.^'' Additional research confirms a benefit in terms of redueed mortality in individuals given L-earnitine following MI. a marked reduction in mortality was observed with 12-month supplementation of 4 g daily L-carnitine (1. LDL. consumption. ejection fraction. after which plasma glueose and insulin levels were analyzed.2%) when compared to controls (12. with reductions in total and LDL-choIesterol and increased plasma apolipoprotein A-1 and B levels. with no changes in other lipid parameters.-'* Cardiogenic Shock L-camitine supplementation during cardiogenie shock improved metabolic acidosis and survival rate in hospitalized individuals. in addition lo the usual medications (digitalis. total cholesterol. beta-blockers. Benefits were maintained beyond the L-carnitine supplementation period. postprandial glucose.^ A small study found 500-mg intramuscular injections ofL-carnitine twice daily for 15 days resulted in improvement in painful diabetic neuropathy.and HDL-cholesterol. peak VO. and cardiac output. with significant deereases in Lp(a) levels noted after three and six months of 1 g L-carnitine twice daily.

Each substance was administered for two months with a two-week washout period. sixmonth trial reported both 2.^' In another study on HIV patients on AZT and didanosine (DDl).^•' Hepatic Effects Fatty Liver L-carnitine ameliorates ethanol-induced fatty liver in animals. and acylcarnitine compared to controls. Mental function was also significantly improved by L-carnitine. double-blind. No toxicity or decrease in drug effectiveness was noted.^' Male Infertility Oral administration of L-carnitinc (3 g daily for four months) resulted in significant improvements in sperm number. and sleep quality. quality. including apoptosis of CD4 and CD8 cells and oxidative stress.'. In addition. the patient progressed from comatose to normal mental status. followed by a two-month washout period.Dosage began at 250 mg/day. and low free carniline levels responded to IV L-earnitine. an accepted psychometric test for mental status in cirrhotic patients. The researchers speculate L-carnitine decreases brain and blood ammonia levels by stimulating urcagenesis. Addition of carnitine greatly reduced the negative effects of the drugs. placebti-controlled. patients experienced significant improvement in fatigue.Monograph L-Carnitine Hepatic Encephalopathy from Cirrhosis L-carnitine (2 g twice daily) or placebt) was administered to 120 patients with hepatic encephalopathy for 6(J days. A randomized. 15/18 cancer patients presented with carnitine deliciency. Fasting scrum ammonia levels were significantly lower at 30 and 60 days compared to baseline and placebo. crossover trial.^' Hepatitis A study found plasma carnitine levels were significantly lower in children with chronic hepatitis B than in healthy controls.'•'''^^ In another double-blind. After one week of supplementation. to a maximum dose of 3 g daily. and motility in patients with inadequate sperm. Within three hours of a single 2-g dose. it has not been investigated in humans for this condition. and finally Alternative Medicine Review # Volume 10. the carnitine supplementation resulted in only one dropout and improvement in !2 of 18 parameters studied. with a statistically significant correlation between total and free carnitine levels and clinical symptomology. Hyperthyroidism L-camitine is believed to be a peripheral antagonist of thyroid hormone activity in some tissues. 100 infertile males were supplemented with 2 g L-carnitine daily or placebo for two months. carnitine levels corresponded inversely to extent of liver fibrosis and inflammation/'* In a single case report. which was postulated to be a significant cause of fatigue in this population." Administration of L-carnitine (6 g daily for two weeks) to AIDS patients treated with zidovudine (AZT) resulted in improved immunity and a reduction in scrum levels of tumor necrosis factor-alpha. a subgroup was assigned to also receive 6 g L-carnitine daily.^' HIV and Immunity Daily infusions of L-carnitine (6 g) for four months resulted in an increase in CD4 counts in HIVpositive subjects who were not taking anti-retro viral therapy.**' Fatigue Cancer-Associated Fatigue In a small study. including exerting a beneficial effect on bone mineralization. 30 patients with CFS were treated with L-carnitine or amantadine (a drug that provides benefit for fatigue in patients with multiple sclerosis). Chronic Fatigue Syndrome Thirty-five patients with chronic fatigue syndrome (CFS) were found to have low free carnitine. as measured by NCT-A. dialysis.""* however. increasing in increments of 500 mg. mainly due to intolerance of the amantadine. depression.""' In a crossover study. Number 1 ^ 2005 Page 45 . total carnitine. a patient with hyperammonemia associated with a combination of hepatitis C. However.and 4-g daily doses of L-carnitine prevented and reversed hyperthyroidismrelated symptoms. Half of the patients dropped out of the study.

when used concurrently with AZT.'"^ The National Kidney Foundation .*" A case report suggests carnitine deficiency was induced in a patient receiving sulfadiazine and pyrimethamine. suggests L-carnitine might prevent some cases of sudden infant death syndrome.xtensively studied for patients in renal failure." The antibiotic pivampicillin negatively impacts carnitine metabolism. weight gain. valproic acid.'^L-carnitine supplementation helps prevent elevation in liver enzymes. if at all. A case of siblings presenting with apnea and periodic breathing. resulted in improved left ventricular ejection fraction.""^ L-carnitine should be used cautiously. including phenobarbital. mitigates some of the disorders associated with dialysis.'" The same researchers conducted a second study on 56 infertile males and found the combination of L-carnitine (2 g daily) and acetyl-L-carnitine (1 g daily) led to significant improvement in sperm motility. and prevent the accumulation of lipids. cardiac dysfunction.'^'' Monograph Weight Loss In a double-blind study. administered IV during dialysis sessions. have a significant lowering effect on camitine levels.''^ In rats.Kidney Disease Outcome Quality Initiative recommends the use of L-carnitine for the treatment of anemia associated with chronic renal failure/'^ Drug-Nutrient Interactions Anticonvulsant medications.'''' L-carnitine supplementation to preterm infants at a dose of 30 mg/kg/day in one study''^ and 15 mg/kg/day in a second study"^ did not result in significant differences between supplementation and placebo groups in frequency of apnea. preserve the structure and volume of mitochondria.**' L-carnitine. and carbamazepine. Statistically signilicant improvements in sperm count and motility were observed in the L-carnitine group. appears to prevent the drug-induced destruction of myotubcs. since evidence suggests the combination might exacerbate the side effects of the drug. or length of hospital stays. insulin resistance. weakness. Number 1 • 2005 .L-Carnitine two months on the opposite treatment. From the above studies." A case report describes normalization of carnitine levels following administration with riboflavin. and oxidative stress." Choline supplementation appears to decrease carnitine synthesis.^^ Emetine (ipecac) appears to promote camitine deficiency. as well as the myalgia. either orally or intravenously. lipid abnormalities. along with biochemical defects consistent with a non-specific abnormality of betaoxidation. supplementing the diet with ascorbic acid increased carnitine biosynthesis. phenytoin.^" Nutrient-Nutrient Interactions A deficiency of ascorbic acid may decrease endogenous biosynthesis of carnitine. administration of vitamin B12 increased carnitine biosynthesis."^ Respiratory Distress in Premature Infants A combination of L-carnitine (4 g daily for five days) and betamethasone given to women in the prenatal period reduced both the incidence of respiratory distress syndrome and the mortality of pretnature newborns. including renal anemia."" Page 46 Alternative Medicine Review • Volume 10. Supplementation. it appears prenatal supplementation may be of more benefit than newborn supplementation.^'' Renal Failure!Dialysis L-caniitine has been e. with pentyienetetrazote. and hypotension induced by isotretinoin. investigators found no effect of L-carnitine supplementation on weight loss or any variable of body composition measured.^^ Evidence suggests supplemental L-carnitine might prevent cardiac complications secondary to interleukin-2 immunotherapy in cancer patients'"' and cardiac toxicity secondary to adriamycin."^.In guinea pigs.*'*"'' Treatment for eight months with 1 g L-carnitine three times weekly.

JogI G. L-carnitine has been given to pregnant women late in pregnancy with resulting positive outcomes. Loots JM. J Gastroenierol Hi'patol 2{)()ih\5:706-l\l. Mitchell GA. Rossouw J. Perrotti G.4:211219. 9. J Nulr 1991:121:539-546. 13. Korchak GM. 1033:42-51. Nutr Res 1997:17:405-414. DeAngelis B. Pathways and control of ketone body metabolism: on the fringe of lipid biochemistry. 8. and diarrhea. Multiple dose pharmacokinetics and bioequivalence of L-camitine 330-mg tablet versus 1 -g chewable tablet versus enteral solution in healthy adult male volunteers. Pharmacokinetics of intravenous and oral bolus doses of L-carnitine in healthy subjects. Fukao T. et al. 14. Vlassopoulos D. 11. et al. 7. Int J Vitani NiitrRes 1993:63:22-26. Effects of carnitine and cobamaniide on the dynamics of mental work capacity in patients with anorexia nervosa. Stanley CA. Bach AC. Ann N Y Acad Sci 2004:1033:17-29. Gudjonsson H. Baker ER. Cruciani RA. [Article in Russian| Korkina MV. 17. Zh Nevropalol Psikhiatr Im S S Korsakova l989. Lloyd ML. Schirardin H. Number 1 • 2005 . Frank O. Vecchiet L. Influence of L-carnitinc administration on maximal physical exercise. |Article in Russian] Giordano C. The LD. 15. Sihr MO. use of the racemic mixture has been correlated with myasthenia-like symptoms in some individuals. Metabolic fate of dietary carnitine in human adults: identification and quantification of urinary and fecal metabolites. Storck D. Helton ED. Pieralisi G. Zh Nevropatol Psikhiatr hn S S Korsakova 1992:92:99-102. LI B. Dosage The average therapeutic dose is I -2 g two to three times daily for a total of 2-6 g daily. Ann N Y Acad Sci 2004. The effect of enteral carnitine administration in humans. 16. J Pharm Sci 1995:84:627-633.when supplementation is necessary? Curr Pharm Bioteclmo! 2OO3. Mutagenicity data indicate no mutagenicity. References 1. Siihajwaiki CG. Kruger MC.L-carnitine) should be avoided. 10. Medvedev DI. Kong SE. Ccderblad G.89:82-87. Prosia^kiiuUns Leukat Esscnt Fatty Acids 2004:70:243-251. Cliu Ter 1979:88:51-60. Rebouche CJ. Di Lisa F. Free and total carnitine in human serum after oral insestion of L-Ciirnitine. The effect of L-camitine supplementation on plasma camitine levels and various performance parameters of male marathon athletes. since absorption studies indicate saturation at this dose. 3.. Page 47 Evidence also suggests L-carnitine potentiates the anti-arrhythmic effect of propafenone and mexiletine in patients with ischemia/'* Side Effects and Toxicity A variety of mild gastrointestinal symptoms have been reported. 12. Lopaschuk GD. Chenard CA. McCauley R. Platell C. et al. Alternative Medicine Review • Volume 10. Hiirpcr P. Carniiine deficiency disorders in children. Ann N YAcad 5a2004:l033:168-I76. indicating animal studies have revealed no harm to the fetus but that no adequate studies in pregnant women have been conducted. Carnitine metabolism and deficit . Clinical studies of the effects of treatment with a combination of carnitine and cobamamide in infantile anorexia. Structure and function of carnitine acyltransferases. Korchak GM. Eur J Clin Pharmacol 1988:35:555-562. L-camitine supplementation for the treatment of fatigue and depressed mood in cancer patients with carnitine deficiency: a preliminary analysis. Elwin CE. Tong L. Hsiao YS. Homel P. however. Hall J C Branched-chain amino acids. including transient nausea and vomiting. Korkina MB. Clinicoexperimental substantiation of the use of carnitine and cobalamin in the treatment of anorexia nervosa. No advantage appears to exist in giving an oral dose greater than 2 g at one time. In uremic patients. Eur J Appl Physiol Occup Phvsiol 1990:61:486-490. 2.. 5. Warnings and Contraindications L-carniiine is listed as pregnancy category B. Am J Clin Nutr 1992:55:838-845. experiments to determine long-term carcinogenic ity have not been conducted. et al. Evangeliou A. abdominal cramps. 6. Absorption and excretion of L-camitine during single or multiple dosings in humans. in mice is 19. Kareva MA. [Article in Italian] Swart I. Dvorkin E. Purich ED.Monograph L-Carnitine 4.2 g/kg. Baker H. The racemic mixture (D. Diabete Merah 1983:9:121-124. D-carnitine is not biologically active and might interfere with the proper utilization of the L isomer.

Lettieri B. Pediatr /Vf/. Camitine supplementation improves apolipoprotein B levels in pediatric peritoneal dialysis patients. Bisi G. |Article in Italian| Digiesi V. Bruzzi P. Page 48 Alternative Medicine Review • Volume 10. Effect of L-carnitine on plasma lipoprotein fatty acids pattern in patients with primary hyperlipoproteinemia. Ciarimboli M. L-carnitine reduces plasma lipt>protein(a) levels in patients with hyper Lp(a). Femandez C. e ai. //// J Clin Pharmacol Ther Toxicol 1985:23:569-572. Bicycle ergometer and echocardiographic study in healthy subjects and patients with angina pectoris after administration of L-camitine: semiautomatic computerized analysis of M-mtnle tracing. Canale C. Khan AA. Iyer RN. A randomi. Chiariello M. et al. Cantini F. 31. Scrutinio D. Lamanna F.48:IO5(}-1()52.sed. 39. 35.26:380-387. De Pasquale B. Davini P. Kosan C. Carnitine supplementation: effect on muscle carnitine and glycogen content during exercise.scle mittKhi>ndriaI activities and antio. Ferrara S. Dru^s E. Med Sci Sports Ewrc 1994:26:1122-1129. Akcil E. Clin Ter 1994:144:391-395. EtirJ Hear! Fail 2O(K):2:189-193. placebo-controlled trial of L-carnitine in suspected acute myocardial infarction. Cherchi A. 13:8791. double-blind. Terrachini V. Gurlek A.1():247-25I. Int J Clin Pharmacol '/'her Toxicol 1988:26:221-224. 23. Three-year survival of patients with heart failure caused by dilated cardiomyopathy and Lcarnitine administration. Controlled study on L-camitine therapeutic efficacy in post-infarction. Kun/ I. Cardiogenic shock and Lcarnitine: clinical data and therapeutic perspectives. Jones DA. 40. placebo controlled crossover study. Effects of Lcamitine on exercise tolerance in chronic stable angina: a multicenter. Ann N Y Acad Sci 2004:1033:189-197. et al. Lcarnitine L-iartrale supplcmcniation favorably aifects markers of recover)' from exercise stress. et al. Corbueci GG. double-blind.L-Carnitine 18. Kobayashi A.xp Clin Res 1991:17:225-235. Tutar E. L-camitine miKierately improves the exercise tolerance in chronic stable angina. et al. Sever L. 26. Number 1 • 2005 . et al. [Article in Italian| Singh RB. The effects of L-camitinc treatment on left ventricular function and erythriKyte superoxide dismutase activity in patients with ischemic cardiomyopathy. Int J Clin Pharmacol Res 1993. J Sports Sci 1986:4:79-87. cross-over study. Effects of L-camitine administration on left ventricular remodeling after acute anterior myocardial infarction: the L-Camitine Ecocardiografia Digitalizzata Infarto Mioeardico (CEDIM) Trial. 42. 27. 36. Am Heart J 2000:139: SI20-S123. ei al. 34. Righetti G. L-carnitine may attenuate free fatty acid-induced endothelial dysfunction. Vivenzio A. et al.282:E474E482. EurJ Appl Physiol Occnp Physiol 1996:73:434-439. L-carnitine in the treatment of chronic mywardial ischemia. Rizos I. Sirtori CR. L-camitine for the treatment of acute myocardial infarct. Cardiovasc Drugs Ther 1999:13:537-546. Suzuki Y. Int J Clin Pharmacol Res 1991:11:283-293. Steinberg HO. Kraemcr WJ. Circulation 1988:77:767-773. Loche F L-camitine in cardiogenic shock therapy: pharmacodynamic aspects and clinica! data. Lucani G. The C therapeutic effect of L-camitine in patients with exercise-induced stable angina: a controlled study. 22. Gupta A. An analysis of 3 multicenter studies and a bibliographic review. Niaz MA. Monograph 30. 19. Angelino F. Agarwal P. Prolonged oral L-carnitine substitution increases bicycle ergometer performance in patients with severe. Am J Physiol Endocrinol Metah 2002. Effects of L-camitine on exercise tolerance in patients with stable angina pectoris. Boem A. 38. 37. J Am Coll Cardiol 1995. 33. et al. et al. 21. Fink WJ. lncrea. 24. Edwards RH. Arisoy N. Voiek JS. Ferulano G. Caiabresi L. randomized.ses in walking distance in patients with peripheral vascular disease treated with L-eamitine: a double-blind. ischemically induced cardiac insufficiency. et al. Cardiohfiia 1990:35:591-596. Costill DL. Cerio R. Proto C. Punzel M. Corbueci GG. [iiceto S. 25./im/2003:l8:ll84-ll88. ct al. Menotti A. The effect of marathon running on carnitine metabolism and on some aspects of mu. Nutr Metah Cardiovasc Dis 2(X)O. Miehe K. Cooper MB.xp Clin Res 1992:18:355-365. Lai C. 20. Cacciatore L. 41. 32. et al. Vukovich MD. Mirzaniohanimadi B. Clin 7£T 1998:149:115-119. Clin Ter 1992:140:353-377.Kidani mechanisms. Kamikawa T. Biagini A. Colombani P. et al. Wenk C. Bigalli A. Jpn Heart J 1984:25:587597. Brevetti G. et al. Rubin MR. Postgrad Med J 1996:72:45-50. J Assoc Physicians India 2(K)O. Stefanutti C. Loster H. Walsh JP. L-camitine adjuvant therapy in essential hypertension. Effects of Lcarnitine supplementation on physical performance and energy metabolism of endurance-trained athletes: a double-blind crossover field study. 29. et al. Shankar SS. Drtt^s E. et al. 28.

Melotti C. Drugs K\p Clin Res 1995:21:157-159. placebo-controlled clinical trial. Plioplys S. Bairaktari E. Pediatrics 2003:111:477--482. et al. 56. 45. Di Marzio L. Alesse E. High dose L-carnitine improves imniunologic and metabolic parameters in AIDS patients. Z Gehurtshilfe /'('r//i«/f»/'i993:l97:215-2l9. L-eamitine in idiopathic asthenozoospermia: a multicenter study. Racek J. Finer NN. £)/> Dis 2003:21:271-275. Lidestri V Beneficial effects of L-carnitine in dialysis patients with impaired left ventricular function: an observational study. Sgro P. Blood 1998:91:3817-3824. Usefulness of L-carnitine. Moretti S. UUian ME. Astuto M. Trefil L. Lcamitine reduces lymphocyte apoptosis and oxidant stress in HIV-1-infected subjects treated with zidovudine and didanosine. et al. Greco AV.xid Redox Signal 2002:4:391-403. Elisaf M. Famularo G. 51. Curr Ther Res Clin Exp 2000:61:871-876. Browning IB 3rd. a naturally occurring peripheral antagonist of thyroid hormone action. Donder E. Sachan DS.Monograph L-Carnitine 57. The effect of L-carnitine on insulin resistance in hemodialysed patients with chronic renal failure. Parente R. Clin Nephrol 2002:57:402-405. 60. Celiker H. Number 1 • 2005 Page 49 . et al. Plioplys AV. Gunal SY. in iatrogenic hyperthyroidism: a randomized. Famularo G. Plioplys S. Am J Clin Nutr I984. Lenzi A. Italian Study Group on Carnitine and Male Infertility. Pliopiys AV. Antio. 58. Eertil 5/^7 2004:81:1578-1584. et ai. 66. Role of Lcamitine in apnea of prematurity: a randomized. Iafolla AK. 47. Hirose S. Bhuid Purif 2001:19:24-32. 63. Sgro P. et al. Effect of L-camitine on human immunodeficiency vims-l infection-associated apoptosis: a pilot study. 55. 69.39:738744. VeselaE. Lcarnitine in the treatment of mild or moderate hepatic encephalopathy. Obennair A. Clin Hie/-2003:25:1429-1439. J Clin Gastroenterol 2004:38:130-133. Whitfield J. Roe CR. Pediatr Pulmonol 1995:20:167-171. 49. 52. 65. Rhew TH. 68.xicol 1993:15:1 -12. DaVanzo WJ. Becker BN. et al. Ruggeri RM. Pistone G. 50. Tzantzoglou S. Vitali G. The effect of L-carnitine on plasma lipoprotein(a) levels in hypercholesterolemic patients with type 2 diabetes mellitus. V Am Coll Nutr 1999:18:77-82. Lcarnitine improves glucose disposal in type 2 diabetic patients. et al. Gaddi A. De Simone C. L-carnitinebetamethasone combination therapy versus betamethasone therapy alone in prevention of respiratory distress syndrome. Amantadine and Lcamitine treatment of chronic fatigue syndrome. et al. 46. Gunal Al. doubleblind. et al. Malaguamera M. Yetkin 1. Katopodis K. 48. Neuropsychohioloi'v 1997:35:16-23. Arbeiter K. J Nephrol 1999:12:38-40. 67. Karakoc A. Matsumoto Y. 62. Familial infantile apnea and immature beta oxidation. Effect of Lcarnitine supplementation in hemodialysis patients. et al. Golper TA. 64. Romagnoli GF. 61. Mingrone G. 44. Semm levels of carnitine in chronic fatigue syndrome: clinical correlates. Am J Nephrol 1998:18:416421.so A. et al. Sollohub H. Marcellini S. Langman CB. Salacone P. Kurz C. Curr Med Res Opin 2002:18:172-175. Cakir N. 53. |Article in Gemian] O'Donnell J. Use of camitine therapy in selected cases of male factor infertility: a double-blind crossover trial. controlled trial. Smith T. et al. Lenzi A. L-carnitine administration reverses acute mental status changes in a chronic hemodialysis patient with hepatitis C infection. L-camitine in the treatment of painful diabetic neuropathy and its effect on plasma beta-endorphin levels. Alternative Medicine Review • Volume 10. et al. Derosa G. Yagci RV Plasma and liver camitine levels of children with chronic hepatitis B. Capristo E. 43. Clinical effects of L-camitine supplementation on apnea and growth in very low birth weight infants. Moretti S. J Clin Endocrinol Metah 2001:86:3579-3594. et al. 54. Filicori M. L-camitine treatment of anemia. Androhgia 1994:26:155-159. Russo A. Benvenga S. Carraro G. Ameliorating effects of carnitine and its precursors on alcoholinduced fatty liver. Ruark RA. 59. Carnitine supplementation in human idiopathic asthenospermia: clinica! results. Selimoglu MA. Canale D. A placebocontrolled double-blind randomized trial of the use of combined L-camitine and L-acetyl-carnitine treatment in men with asthenozoospermia. Am J Kidnev Dis 2003:41 :S27-S34. Lombardo F. Goral S. Eeriil Steril 2003:79:292-300. Amano 1. Immimopharmacol tmmunoto. Netiropsychohiology 1995:32:132-138. et al. Na. Costa M. et al. Cicero AF. Rich W. Effect of L-carnitine supplementation on lipid parameters in hemodialysis patients. Effects of L-camitine supplementation on renal anemia in poor responders to erythropoietin. Pediatrics 2002:109:622-626. et al.

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