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Martindale: The Complete Drug Reference
Carnitine Derivatives
Date of monograph review: 08-Mar-2006; 24-Jul-2006; 18-Aug-2008; 28-Apr-2009; 23Aug-2010; (latest modification: 13-Aug-2011)
Drug Nomenclature (Latest modification: 20-Aug-2011)
Synonyms: Производные Карнитина
Martindale code: 22640-h
Acetylcarnitine Hydrochloride
Date of monograph review: 24-Feb-1998; 01-Sep-1998; 19-Apr-2001; 08-Nov-2001;
24-Feb-2003; 01-Jul-2004; 08-Mar-2006; 24-Jul-2006; 18-Aug-2008; 28-Apr-2009; 23Aug-2010; (latest modification: 13-Aug-2011)
Drug Nomenclature (Latest modification: 20-Aug-2011)
Synonyms: Acetilcarnitina, hidrocloruro de; Acetyl-L-carnitine Chloride; Levacecarnine
Hydrochloride; Levocarnitinum acetilum hydrochloricum; ST-200; Ацетилкарнитина
Гидрохлорид
Chemical name: (3-Carboxy-2-hydroxypropyl)trimethylammonium acetate (ester)
chloride
Molecular formula: C9H17NO4,HCl =239.7
CAS: 5080-50-2
ATC code: N06BX12
ATC code (veterinary): QN06BX12
UNII code: NDW10MX58T
Martindale code: 3015-f
Chemical Structure of Acetyl-L-carnitine
Carnitine
Martindale: The Complete Drug Reference
Date of monograph review: 31-Aug-1999; 19-Oct-2001; 25-May-2004; 08-Mar-2006;
24-Jul-2006; 18-Aug-2008; 28-Apr-2009; 23-Aug-2010; (latest modification: 13-Aug2011)
Drug Nomenclature (Latest modification: 26-Feb-2011)
Synonyms: Carnitina; Karnitin; ST-198; Vitamin BT; Vitamina BT
INN: Carnitine [rINN (en)]
INN: Carnitina [rINN (es)]
INN: Carnitine [rINN (fr)]
INN: Carnitinum [rINN (la)]
INN: Карнитин [rINN (ru)]
INN: ‫[ ك ارن ي ت ين‬rINN (ar)]
INN: 卡尼汀 [rINN (cn)]
Chemical name: (3-Carboxy-2-hydroxypropyl)trimethylammonium hydroxide, inner
salt; 3-Hydroxy-4-trimethylammoniobutyrate
Molecular formula: C7H15NO3 =161.2
CAS: 461-06-3
UNII code: S7UI8SM58A
Martindale code: 20298-e
Chemical Structure of Carnitine
Levocarnitine
Date of monograph review: 24-Mar-1998; 31-Aug-1999; 19-Oct-2001; 25-May-2004;
08-Mar-2006; 24-Jul-2006; 18-Aug-2008; 28-Apr-2009; 23-Aug-2010; (latest
modification: 13-Aug-2011)
Drug Nomenclature (Latest modification: 20-Aug-2011)
Synonyms: L-Carnitina; L-Carnitine; L-Karnitin; Levocarnitin; Levocarnitina;
Lévocarnitine; Levocarnitinum; Levokarnitiini; Levokarnitin; Levokarnitinas;
レボカルニチン
BAN: Levocarnitine
Martindale: The Complete Drug Reference
USAN: Levocarnitine
INN: Levocarnitine [rINN (en)]
INN: Levocarnitina [rINN (es)]
INN: Lévocarnitine [rINN (fr)]
INN: Levocarnitinum [rINN (la)]
INN: Левокарнитин [rINN (ru)]
INN: ‫[ ل ي فوك ارن ي ت ين‬rINN (ar)]
INN: 左卡尼汀 [rINN (cn)]
Chemical name: (R)-(3-Carboxy-2-hydroxypropyl)trimethylammonium hydroxide,
inner salt; (R)-3-Hydroxy-4-trimethylammoniobutyrate
Molecular formula: C7H15NO3 =161.2
CAS: 541-15-1
ATC code: A16AA01
ATC code (veterinary): QA16AA01
UNII code: 0G389FZZ9M
Martindale code: 12528-s
Chemical Structure of Levocarnitine
Pharmacopoeias:
In Eur. (see
) and US.
Ph. Eur. 7.3 (Levocarnitine). A white or almost white, hygroscopic, crystalline powder
or colourless crystals. Freely soluble in water; soluble in warm alcohol; practically
insoluble in acetone. A 5% solution in water has a pH of 6.5 to 8.5. Store in airtight
containers.
USP 34 (Levocarnitine). White, hygroscopic, crystals or crystalline powder. Freely
soluble in water and in hot alcohol; practically insoluble in acetone, in ether, and in
benzene. pH of a 5% solution in water is between 5.5 and 9.5. Store in airtight
containers.
Levocarnitine Hydrochloride
Martindale: The Complete Drug Reference
Date of monograph review: 08-Mar-2006; 24-Jul-2006; 18-Aug-2008; 28-Apr-2009; 23Aug-2010; (latest modification: 13-Aug-2011)
Drug Nomenclature (Latest modification: 23-Aug-2010)
BAN: Levocarnitine Hydrochloride [BANM]
INN: Levocarnitine Hydrochloride [rINNM (en)]
INN: Hidrocloruro de levocarnitina [rINNM (es)]
INN: Lévocarnitine, Chlorhydrate de [rINNM (fr)]
INN: Levocarnitini Hydrochloridum [rINNM (la)]
INN: Левокарнитина Гидрохлорид [rINNM (ru)]
Chemical name: (R)-3-Hydroxy-4-trimethylammoniobutyrate hydrochloride
Molecular formula: C7H15NO3,HCl =197.7
CAS: 6645-46-1
UNII code: J3Y5E6IKS3
Martindale code: 20704-s
Levocarnitine Propionate
Date of monograph review: 08-Mar-2006; 24-Jul-2006; 18-Aug-2008; 28-Apr-2009; 23Aug-2010; (latest modification: 13-Aug-2011)
Drug Nomenclature (Latest modification: 04-Jan-2011)
Synonyms: L-Carnitine propionate; Propionyl-L-carnitine; Propionylcarnitine; LPropionylcarnitine; ST-261
INN: Levocarnitine propionate [rINNM (en)]
INN: Propionato de levocarnitina [rINNM (es)]
INN: Lévocarnitine, Propionate de [rINNM (fr)]
INN: Levocarnitini Propionas [rINNM (la)]
INN: Левокарнитина Пропионат [rINNM (ru)]
Molecular formula: C10H19NO4 =217.3
CAS: 20064-19-1
UNII code: 0HU2UI27HF
Martindale code: 15216-k
Levocarnitine Propionate Hydrochloride
Martindale: The Complete Drug Reference
Date of monograph review: 08-Mar-2006; 24-Jul-2006; 18-Aug-2008; 28-Apr-2009; 23Aug-2010; (latest modification: 13-Aug-2011)
Drug Nomenclature (Latest modification: 13-Aug-2011)
Synonyms: Propionyl-L-carnitine Hydrochloride; STI-261;
レボカルニチンプロピオナート塩酸塩
USAN: Levocarnitine Propionate Hydrochloride
Chemical name: (2R)-3-Carboxy-N,N,N-trimethyl-2-(propanoyloxy)propan-1-aminium
chloride
Molecular formula: C10H20ClNO4 =253.7
CAS: 119793-66-7
UNII code: 12FW2YBF04
Martindale code: 20729-a
Adverse Effects and Precautions (Latest modification: 21-Jul-2008)
Gastrointestinal disturbances such as nausea, vomiting, diarrhoea, and abdominal
cramps have been reported after the use of levocarnitine. Body odour has also been
noticed in some patients, possibly due to the formation of the metabolite trimethylamine
(see Fish Odour Syndrome,
). Decreasing the dosage may reduce or eliminate these
effects; oral levocarnitine should be consumed slowly to decrease gastrointestinal
disturbances. Seizures have been reported.
Patients with severe renal impairment should not be given high oral doses of
levocarnitine for long periods, because of the accumulation of the metabolites
trimethylamine and trimethylamine-N-oxide. This is said not to occur to the same extent
after intravenous dosage. Diabetic patients given carnitine while receiving insulin or
hypoglycaemic drugs should be monitored for hypoglycaemia.
(last reviewed 2010-08-23; last modified 2008-07-21)
Renal impairment (Latest modification: 26-Oct-2005)
Of 30 patients given
DL-carnitine
intravenously after dialysis sessions 3 developed
myasthenia-like symptoms but when these 3 were given only levocarnitine the
symptoms did not occur.1 It was considered that in anuric uraemic patients the D-isomer
Martindale: The Complete Drug Reference
was not excreted adequately and that accumulation had blocked neuromuscular
transmission. It was therefore suggested that levocarnitine, rather than the
DL-form,
should be used. (High and prolonged oral doses of levocarnitine should, however, be
avoided—see
.)
(last reviewed 2010-08-23; last modified 2005-10-26)
1. 1. Bazzato G, et al. Myasthenia-like syndrome after D,L but not L-carnitine. Lancet
1981; i: 1209. PubMed
Pharmacokinetics (Latest modification: 18-Aug-2010)
Oral doses of levocarnitine are absorbed slowly and incompletely from the small
intestine. Bioavailability has been reported to be only about 10 to 15%, with peak
plasma concentrations occurring about 3 to 4 hours after an oral dose. Plasma
concentrations after oral doses represent the sum of endogenous and exogenous
material. Levocarnitine does not appear to bind to plasma proteins. It is mainly
eliminated by the kidneys, undergoing extensive tubular reabsorption. After intravenous
doses, levocarnitine appears to undergo minimal metabolism. Levocarnitine given orally
may undergo degradation in the gastrointestinal tract, leading to the formation of
metabolites such as trimethylamine-N-oxide and γ-butyrobetaine, recovered in the urine
and faeces, respectively.
(last reviewed 2010-08-23; last modified 2010-08-18)
References.
(last reviewed 2010-08-23; last modified 2008-07-21)
1. 1. Evans AM, Fornasini G. Pharmacokinetics of L-carnitine. Clin Pharmacokinet 2003;
42: 941–67. PubMed
2. 2. Bain MA, et al. Disposition and metabolite kinetics of oral L-carnitine in humans. J
Clin Pharmacol 2006; 46: 1163–70. PubMed
3. 3. Fornasini G, et al. A pharmacokinetic model for L-carnitine in patients receiving
haemodialysis. Br J Clin Pharmacol 2007; 64: 335–45. PubMed
Uses and Administration (Latest modification: 03-Sep-2010)
Martindale: The Complete Drug Reference
Carnitine is an amino acid derivative that is an essential cofactor of fatty acid
metabolism.
Carnitine is used in the treatment of primary carnitine deficiency and in carnitine
deficiency secondary to a variety of defects of intermediary metabolism or other
conditions such as haemodialysis. Both the L- and the
DL-isomers
have been used, but it
is believed that only levocarnitine is effective and in addition, that
DL-carnitine
supplementation can lead to carnitine deficiency.
In the UK, depending on the condition, up to 200 mg/kg daily of levocarnitine is given
orally, in 2 to 4 divided doses. Rarely, higher doses of up to 400 mg/kg daily may be
needed. In the USA, lower doses up to about 3 g daily are recommended.
When given intravenously, up to 100 mg/kg daily is given in 3 to 4 divided doses by
slow intravenous injection over 2 to 3 minutes. Higher intravenous doses have been
given, but are associated with an increased incidence of adverse effects.
Similar doses are used in children, although initial dose recommendations may vary in
different countries, see Administration in Children,
.
In patients with carnitine deficiency secondary to haemodialysis, the recommended dose
of levocarnitine is 10 to 20 mg/kg intravenously after each dialysis session, adjusted
according to plasma-carnitine concentrations. An oral maintenance dose of 1 g daily may
be considered (but see Adverse Effects and Precautions,
).
Levocarnitine is under investigation for the treatment of zidovudine-induced
mitochondrial myopathy. Carnitine derivatives have been used to treat conditions
including cardiovascular disease, peripheral arterial disease, cerebrovascular
insufficiency, peripheral neuropathies, and neurological disorders, see
.
Carnitine chloride, carnitine hydrochloride, carnitine orotate, carnitine tartrate,
levocarnitine fumarate, levocarnitine tartrate, acetylcarnitine or its hydrochloride, and
bicarnitine chloride have also been used.
(last reviewed 2010-08-23; last modified 2010-09-03)
Administration in children (Latest modification: 18-Aug-2010)
Martindale: The Complete Drug Reference
In the treatment of primary and secondary carnitine deficiency and organic acidaemias
in children, levocarnitine is given in doses similar to those used in adults, see Uses and
Administration,
. In the USA, an initial oral dose of 50 mg/kg daily is suggested for
infants and children, increased gradually if necessary to a maximum of 3 g daily. The
BNFC 2009 suggests that carnitine may also be given to neonates and children up to 18
years of age by intravenous infusion for primary deficiency and organic acidaemias,
diluted in sodium chloride 0.9%, or glucose 5 or 10%; an initial dose of 100 mg/kg over
30 minutes is followed by a continuous infusion of 4 mg/kg per hour.
(last reviewed 2010-08-23; last modified 2010-08-18)
Carnitine supplementation (Latest modification: 18-Aug-2010)
Carnitine occurs as distinct L- and D-isomers although naturally-occurring carnitine is
almost exclusively the L-isomer.1 Carnitine is an essential co-factor of fatty acid
metabolism in the heart, liver, and skeletal muscle.1,2 It is normally synthesised in the
liver, brain, and kidneys in sufficient quantities to meet human requirements but dietary
sources such as meat and dairy products also provide carnitine.1-4 In plasma and tissues
carnitine is present in the free form and as acylated esters of which acetylcarnitine is the
most abundant.
Although
DL-carnitine
is the form often present in over-the-counter preparations and
dietary supplements, levocarnitine should be preferred, as the two isomers differ in their
actions. Levocarnitine acts as a substrate for carnitine acetyltransferase while D-carnitine
acts as a competitive inhibitor; also, levocarnitine-induced stimulation of palmitate
oxidation is competitively inhibited by D-palmitoylcarnitine. Such differences are believed
to account for findings of benefit only with the L-isomer, or unwanted effects when Dcarnitine or
DL-carnitine
was used.1,5
Primary carnitine deficiency is a disorder of the membrane transport of carnitine and
patients have presented with hypoglycaemia and encephalopathy, skeletal myopathy,
and cardiomyopathy. Therapy with carnitine in these primary deficiency states is
considered to have a rational basis.2,4-6 Secondary carnitine deficiency occurs in many
inherited metabolic disorders, especially in the organic acidurias and disorders of betaoxidation. The value of carnitine for these conditions is controversial.2,4,6-8
Martindale: The Complete Drug Reference
Carnitine deficiency may also arise during the long-term use of drugs such as valproic
acid,5,9-11 pivampicillin,12,13 or pivmecillinam,12 which are conjugated with carnitine.
Whether carnitine supplementation can prevent or reverse this type of deficiency is
unclear: although treatment with carnitine raised plasma-carnitine concentrations, it had
no more effect than placebo on the well-being of children receiving valproic acid therapy
in one study,14 but others have found levocarnitine supplementation of value in
attenuating valproate-induced hyperammonaemia after a protein-rich meal,15 and some
paediatric neurologists consider supplementation justified in selected children with
epilepsy,16,17 including those with, or at risk of, valproate-induced hepatotoxicity and
hyperammonaemic encephalopathy. There is some suggestion that carbamazepine and
phenobarbital can also decrease carnitine concentrations.10,11 Therapy with cisplatin18 or
ifosfamide19 has been reported to cause increased urinary excretion of carnitine.
There is also some evidence5,20 that carnitine supplements may be of benefit to low birthweight preterm infants, but a double-blind study21 failed to confirm this effect. A
systematic review concluded that there are insufficient data to support the use of
carnitine supplementation for the treatment of apnoea of prematurity, despite a
plausible rationale for such treatment.22 While some evidence of benefit exists for
carnitine supplementation of neonates receiving parenteral nutrition,5 a systematic
review found no evidence of effect on weight gain, fat utilisation, or ketogenesis.23
Low concentrations of carnitine have also been reported to occur in a variety of other
conditions (see below).
(last reviewed 2010-08-23; last modified 2010-08-18)
1. 1. Li Wan Po A. Carnitine: a scientifically exciting molecule. Pharm J 1990; 245: 388–9.
2. 2. Anonymous. Carnitine deficiency. Lancet 1990; 335: 631–3. PubMed
3. 3. Anonymous. L-carnitine. Med Lett Drugs Ther 2004; 46: 95–6. PubMed
4. 4. Scaglia F, Longo N. Primary and secondary alterations of neonatal carnitine
metabolism. Semin Perinatol 1999; 23: 152–61. PubMed
5. 5. Goa KL, Brogden RN. L-Carnitine: a preliminary review of its pharmacokinetics, and
its therapeutic use in ischaemic cardiac disease and primary and secondary carnitine
deficiencies in relationship to its role in fatty acid metabolism. Drugs 1987; 34: 1–24.
PubMed
6. 6. Evangeliou A, Vlassopoulos D. Carnitine metabolism and deficit when
supplementation is necessary? Curr Pharm Biotechnol 2003; 4: 211–9. PubMed
Martindale: The Complete Drug Reference
7. 7. Rinaldo P, et al. Effect of treatment with glycine and L-carnitine in medium-chain
acyl-coenzyme A dehydrogenase deficiency. J Pediatr 1993; 122: 580–4. PubMed
8. 8. Winter SC. Treatment of carnitine deficiency. J Inherit Metab Dis 2003; 26: 171–80.
PubMed
9. 9. Lheureux PE, Hantson P. Carnitine in the treatment of valproic acid-induced toxicity.
Clin Toxicol 2009; 47: 101–111. PubMed
10.10. Verrotti A, et al. Carnitine deficiency and hyperammonemia in children receiving
valproic acid with and without other anticonvulsant drugs. Int J Clin Lab Res 1999; 29:
36–40. PubMed
11.11. Castro-Gago M, et al. Serum carnitine levels in epileptic children before and during
treatment with valproic acid, carbamazepine, and phenobarbital. J Child Neurol 1998;
13: 546–9. PubMed
12.12. Holme E, et al. Carnitine deficiency induced by pivampicillin and pivmecillinam
therapy. Lancet 1989; ii: 469–73. PubMed
13.13. Melegh B. Carnitine supplementation in pivampicillin treatment. Lancet 1989; ii:
1096. PubMed
14.14. Freeman JM, et al. Does carnitine administration improve the symptoms attributed
to anticonvulsant medications?: a double-blinded, crossover study. Pediatrics 1994; 93:
893–5. PubMed
15.15. Gidal BE, et al. Diet- and valproate-induced transient hyperammonemia: effect of Lcarnitine. Pediatr Neurol 1997; 16: 301–5. PubMed
16.16. De Vivo DC, et al. L-carnitine supplementation in childhood epilepsy: current
perspectives. Epilepsia 1998; 39: 1216–25. PubMed
17.17. Lheureux PER, et al. Science review: carnitine in the treatment of valproic acidinduced toxicity—what is the evidence? Crit Care 2005; 9: 431–40. PubMed
18.18. Heuberger W, et al. Increased urinary excretion of carnitine in patients treated with
cisplatin. Eur J Clin Pharmacol 1998; 54: 503–8. PubMed
19.19. Marthaler NP, et al. Increased urinary losses of carnitine during ifosfamide
chemotherapy. Cancer Chemother Pharmacol 1999; 44: 170–2. PubMed
20.20. Shortland GJ, Walter JH. L-carnitine. Lancet 1990; 335: 1215. PubMed
21.21. Shortland GJ, et al. Randomised controlled trial of L-carnitine as a nutritional
supplement in preterm infants. Arch Dis Child Fetal Neonatal Ed 1998; 78: F185–F188.
PubMed
22.22. Kumar M, et al. Carnitine supplementation for preterm infants with recurrent apnea.
Available in The Cochrane Database of Systematic Reviews; Issue 4. Chichester: John
Wiley; 2003 (accessed 08/11/05). PubMed
Martindale: The Complete Drug Reference
23.23. Cairns PA, Stalker DJ. Carnitine supplementation of parenterally fed neonates.
Available in The Cochrane Database of Systematic Reviews; Issue 4. Chichester: John
Wiley; 2000 (accessed 08/11/05). PubMed
Cardiovascular disease
There is some evidence that carnitine supplementation may exert a cardioprotective
role. Benefit in patients with cardiomyopathies,1-3 reduction of infarct size in patients
with myocardial infarction,4 and increased exercise performance in patients with angina5
or intermittent claudication,6-9 have all been described in patients given carnitine. While
variable effects on cholesterol and triglyceride plasma concentrations have been
described,5 studies in diabetic10 and hyperlipoproteinaemic11 patients have reported
reductions in plasma lipoprotein(a) concentrations. However, carnitine supplementation
in patients with chronic heart failure failed to increase exercise capacity,12 and its value
outside of actual deficiency is still considered uncertain.5
(last reviewed 2010-08-23; last modified 2010-08-24)
1. 1. Winter SC, Buist NRM. Cardiomyopathy in childhood, mitochondrial dysfunction, and
the role of L-carnitine. Am Heart J 2000; 39 (suppl): S63–S69. PubMed
2. 2. Helton E, et al. Metabolic aspects of myocardial disease and a role for L-carnitine in
the treatment of childhood cardiomyopathy. Pediatrics 2000; 105: 1260–70. PubMed
Correction. ibid.; 106: 623.
3. 3. Rizos I. Three-year survival of patients with heart failure caused by dilated
cardiomyopathy and L-carnitine administration. Am Heart J 2000; 139 (suppl): S120–
S123. PubMed
4. 4. Pauly DF, Pepine CJ. The role of carnitine in myocardial dysfunction. Am J Kidney Dis
2003; 41 (suppl): S35–S43. PubMed
5. 5. Arsenian MA. Carnitine and its derivatives in cardiovascular disease. Prog Cardiovasc
Dis 1997; 40: 265–86. PubMed
6. 6. Hiatt WR, et al. Propionyl-L-carnitine improves exercise performance and functional
status in patients with claudication. Am J Med 2001; 110: 616–22. PubMed
7. 7. Brevetti G, et al. European multicenter study on propionyl-L-carnitine in intermittent
claudication. J Am Coll Cardiol 1999; 34: 1618–24. PubMed
8. 8. Wiseman LR, Brogden RN. Propionyl-L-carnitine. Drugs Aging 1998; 12: 243–8.
PubMed
9. 9. Andreozzi GM. Propionyl L-carnitine: intermittent claudication and peripheral arterial
disease. Expert Opin Pharmacother 2009; 10: 2697–2707. PubMed
Martindale: The Complete Drug Reference
10.10. Derosa G, et al. The effect of L-carnitine on plasma lipoprotein(a) levels in
hypercholesterolemic patients with type 2 diabetes mellitus. Clin Ther 2003; 25: 1429–
39. PubMed
11.11. Sirtori CR, et al. L-carnitine reduces plasma lipoprotein(a) levels in patients with
hyper Lp(a). Nutr Metab Cardiovasc Dis 2000; 10: 247–51. PubMed
12.12. The Investigators of the Study on Propionyl-L-Carnitine in Chronic Heart Failure.
Study on propionyl-L-carnitine in chronic heart failure. Eur Heart J 1999; 20: 70–6.
PubMed
Exercise performance
Improved exercise performance in patients with angina or peripheral vascular disease
has been described in patients given carnitine supplementation (see Cardiovascular
Disease,
). However, evidence of benefit from the use of carnitine in healthy subjects
in an attempt to improve athletic performance is lacking.1,2 Nonetheless, interest in, and
research into, the possible effects in healthy subjects and their mechanisms has
continued.3-6
(last reviewed 2010-08-23; last modified 2010-09-03)
1. 1. Tonda ME, Hart LL. N,N dimethylglycine and L-carnitine as performance enhancers in
athletes. Ann Pharmacother 1992; 26: 935–7. PubMed
2. 2. Brass EP. Supplemental carnitine and exercise. Am J Clin Nutr 2000; 72 (suppl):
618S–623S. PubMed
3. 3. Karlic H, Lohninger A. Supplementation of L-carnitine in athletes: does it make
sense? Nutrition 2004; 20: 709–15. PubMed
4. 4. Brass EP. Carnitine and sports medicine: use or abuse? Ann N Y Acad Sci 2004;
1033: 67–78. PubMed
5. 5. Kraemer WJ, et al. L-carnitine supplementation: influence upon physiological
function. Curr Sports Med Rep 2008; 7: 218–23. PubMed
6. 6. Broad EM, et al. Carbohydrate, protein, and fat metabolism during exercise after oral
carnitine supplementation in humans. Int J Sport Nutr Exerc Metab 2008; 18: 567–84.
PubMed
Fatigue
Placebo-controlled studies in elderly subjects found that levocarnitine supplementation
significantly reduced physical and mental fatigue,1,2 while an open study in patients with
chronic fatigue syndrome reported improvement in mental fatigue with acetylcarnitine,
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and general fatigue improvement with propionylcarnitine.3 In a crossover study with
amantadine, patients with chronic fatigue syndrome given levocarnitine for 8 weeks
showed improvement in 12 out of 18 parameters measuring fatigue; patients who were
most ill at the start of the study improved the most.4 There is also some suggestion that
levocarnitine supplementation may be of benefit in alleviating fatigue induced by
antineoplastic chemotherapy,5 or interferon.6 For reports of carnitine use for fatigue in
multiple sclerosis patients, see Neurological Disorders,
.
(last reviewed 2010-08-23; last modified 2009-09-05)
1. 1. Pistone G, et al. Levocarnitine administration in elderly subjects with rapid muscle
fatigue: effect on body composition, lipid profile and fatigue. Drugs Aging 2003; 20:
761–7. PubMed
2. 2. Malaguarnera M, et al. L-Carnitine treatment reduces severity of physical and mental
fatigue and increases cognitive functions in centenarians: a randomized and controlled
clinical trial. Am J Clin Nutr 2007; 86: 1738–44. PubMed
3. 3. Vermeulen RCW, Scholte HR. Exploratory open label, randomized study of acetyland propionylcarnitine in chronic fatigue syndrome. Psychosom Med 2004; 66: 276–82.
PubMed
4. 4. Plioplys AV, Plioplys S. Amantadine and L-carnitine treatment of chronic fatigue
syndrome. Neuropsychobiology 1997; 35: 16–23. PubMed
5. 5. Graziano F, et al. Potential role of levocarnitine supplementation for the treatment of
chemotherapy-induced fatigue in non-anaemic cancer patients. Br J Cancer 2002; 86:
1854–7. PubMed
6. 6. Neri S, et al. L-carnitine decreases severity and type of fatigue induced by interferonα in the treatment of patients with hepatitis C. Neuropsychobiology 2003; 47: 94–7.
PubMed
Haemodialysis
Carnitine homoeostasis is altered in renal failure1 and a functional deficiency may
develop in patients on dialysis.2 This dialysis-related carnitine disorder manifests notably
as anaemia, intradialytic hypotension, cardiomyopathy, and muscle weakness and
fatigability. Treatment with intravenous levocarnitine 20 mg/kg after each dialysis
session has been recommended. Clinical response should be evaluated at 3-monthly
intervals, and treatment stopped if no improvement is seen within 9 to 12 months.2 A
systematic review suggested a beneficial effect of levocarnitine for the management of
anaemia in haemodialysis patients.3 Since carnitine supplementation has been
Martindale: The Complete Drug Reference
associated with a reduction4,5 in the incidence of haemodialysis-induced cramps (
) it
has been suggested that these cramps might be due in part to carnitine deficiency. A
meta-analysis6 considered the evidence for benefit in cramp and hypotension to be
suggestive, but not conclusive.
(last reviewed 2010-08-23; last modified 2009-04-07)
1. 1. Matera M, et al. History of L-carnitine: implications for renal disease. J Ren Nutr
2003; 13: 2–14. PubMed
2. 2. Eknoyan G, et al. Practice recommendations for the use of L-carnitine in dialysisrelated carnitine disorder: National Kidney Foundation Carnitine Consensus Conference.
Am J Kidney Dis 2003; 41: 868–76. PubMed
3. 3. Hurot J-M, et al. Effects of L-carnitine supplementation in maintenance hemodialysis
patients: a systematic review. J Am Soc Nephrol 2002; 13: 708–14. PubMed
4. 4. Ahmad S, et al. Multicenter trial of L-carnitine in maintenance hemodialysis patients
II: clinical and biochemical effects. Kidney Int 1990; 38: 912–18. PubMed
5. 5. Sakurauchi Y, et al. Effects of L-carnitine supplementation on muscular symptoms in
hemodialyzed patients. Am J Kidney Dis 1998; 32: 258–64. PubMed
6. 6. Lynch KE, et al. Effects of L-carnitine on dialysis-related hypotension and muscle
cramps: a meta-analysis. Am J Kidney Dis 2008; 52: 962–71. PubMed
HIV infection
Carnitine deficiency has been reported in HIV-infected patients. Causes may include
malabsorption or increased excretion due to a wasting syndrome commonly found in
these patients, or toxicity from antiretroviral drugs causing metabolic changes or altered
lipid metabolism in the patient.1 Small, mostly uncontrolled studies have suggested
benefit from supplementation with levocarnitine or acetylcarnitine in relieving
complications of HIV infection and adverse effects of antiretroviral drugs,2 notably toxic
neuropathy.3,4
(last reviewed 2010-08-23; last modified 2008-07-21)
1. 1. Vilaseca MA, et al. Low serum carnitine in HIV-infected children on antiretroviral
treatment. Eur J Clin Nutr 2003; 57: 1317–22. PubMed
2. 2. Ilias I, et al. L-Carnitine and acetyl-L-carnitine in the treatment of complications
associated with HIV infection and antiretroviral therapy. Mitochondrion 2004; 4: 163–8.
PubMed
Martindale: The Complete Drug Reference
3. 3. Herzmann C, et al. Long-term effect of acetyl-L-carnitine for antiretroviral toxic
neuropathy. HIV Clin Trials 2005; 6: 344–50. PubMed
4. 4. Osio M, et al. Acetyl-l-carnitine in the treatment of painful antiretroviral toxic
neuropathy in human immunodeficiency virus patients: an open label study. J Peripher
Nerv Syst 2006; 11: 72–6. PubMed
Male infertility
Increases in sperm motility have been reported in some infertile men treated with
carnitine,1-3 and some studies have reported improvements in pregnancy rates,4 although
clinical benefit needs to be further evaluated.4,5
(last reviewed 2010-08-23; last modified 2010-08-24)
1. 1. Lenzi A, et al. Use of carnitine therapy in selected cases of male factor infertility: a
double-blind crossover trial. Fertil Steril 2003; 79: 292–300. PubMed
2. 2. Lenzi A, et al. A placebo-controlled double-blind randomized trial of the use of
combined L-carnitine and L-acetyl-carnitine treatment in men with asthenozoospermia.
Fertil Steril 2004; 81: 1578–84. PubMed
3. 3. Vicari E, Calogero AE. Effects of treatment with carnitines in infertile patients with
prostato-vesiculo-epididymitis. Hum Reprod 2001; 16: 2338–42. PubMed
4. 4. Zhou X, et al. Effect of L-carnitine and/or L-acetyl-carnitine in nutrition treatment for
male infertility: a systematic review. Asia Pac J Clin Nutr 2007; 16 (suppl 1): 383–90.
PubMed
5. 5. Agarwal A. Carnitines and male infertility. Reprod Biomed Online 2004; 8: 376–84.
PubMed
Neurological disorders
A meta-analysis of 21 studies concluded that acetylcarnitine improved mild cognitive
impairment and prevented deterioration in patients with mild Alzheimer's disease.1
However, a systematic review of 11 of these trials concluded that, although some
evidence of benefit on clinical global impression exists, use of acetylcarnitine could not
be routinely recommended in the treatment of Alzheimer's disease.2
Although no differences were found in serum carnitine concentrations in multiple
sclerosis patients with or without disabling fatigue,3 there is some suggestion of benefit
with acetylcarnitine treatment for those patients with fatigue,4 although a systematic
Martindale: The Complete Drug Reference
review5 considered the evidence of benefit insufficient. Carnitine has been reported to be
of benefit in other cases of fatigue (see
).
In Rett syndrome, a severe neurodevelopmental disorder, supplementation with
levocarnitine led to improvements in sleep efficiency, energy levels, and communication
skills.6 Parental and medical assessment of patient well-being improved in another
study;7 girls with classical Rett syndrome also improved in motor behaviour as assessed
medically.
(last reviewed 2010-08-23; last modified 2010-08-24)
1. 1. Montgomery SA, et al. Meta-analysis of double-blind randomized controlled clinical
trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment
and mild Alzheimer's disease. Int Clin Psychopharmacol 2003; 18: 61–71. PubMed
2. 2. Hudson S, Tabet N. Acetyl-l-carnitine for dementia. Available in The Cochrane
Database of Systematic Reviews; Issue 2. Chichester: John Wiley; 2003 (accessed
08/11/05). PubMed
3. 3. Fukazawa T, et al. Serum carnitine and disabling fatigue in multiple sclerosis.
Psychiatry Clin Neurosci 1996; 50: 323–5. PubMed
4. 4. Tomassini V, et al. Comparison of the effects of acetyl L-carnitine and amantadine for
the treatment of fatigue in multiple sclerosis: results of a pilot, randomised, doubleblind, crossover trial. J Neurol Sci 2004; 218: 103–8. PubMed
5. 5. Tejani AM, et al. Carnitine for fatigue in multiple sclerosis. Available in The Cochrane
Database of Systematic Reviews; Issue 2. Chichester: John Wiley; 2010 (accessed
10/06/10). PubMed
6. 6. Ellaway CJ, et al. Medium-term open label trial of L-carnitine in Rett syndrome. Brain
Dev 2001; 23 (suppl): S85–S89. PubMed
7. 7. Ellaway C, et al. Rett syndrome: randomized controlled trial of L-carnitine. J Child
Neurol 1999; 14: 162–7. PubMed
Preparations (Latest modification: 23-Aug-2011)
Single-ingredient Preparations (Latest modification: 23-Aug-2011)
The symbol ¤ denotes a preparation which is discontinued or no longer actively
marketed.
Argentina: Albicar; Fertilix; Laremide; Neurex; Neuroactil; Austria: Nefrocarnit;
Brazil: Levocarnin¤; Canada: Carnitor; Chile: Actigeron; Carnicor¤; France:
Martindale: The Complete Drug Reference
Bicarnesine¤; Flatistine¤; Levocarnil; Germany: Biocarn; L-Carn; Nefrocarnit; Greece:
Aminocer; Aveptol; Bicarnesine; Bitobionil; Carniben; Carnidose; Carnil; Carniprol;
Carnitop; Corubin; Energocarnil; Ensial; Ergogen; Frutenor; Growart; Inestom;
Intelecta; Koptilan; Lecarna; Levalastine; Levamin; Levars; Levocarnil; Levocuor;
Levosan; Lisefor; Listover; Locar; Lofostin; Maledrol; Medicardin; Merlit; Mevamyst;
Minartine; Minoa; Oskana; Phacovit; Ridovet; Soludamin; Superamin; Tonovit; Trian;
Trinalin; Xaritic; Hong Kong: Carnitene; Carnitor; India: Carnitor; L-Tine; Italy:
Acilen¤; Anetin¤; Bio-Vis; Branigen; Branitil¤; Briocor¤; Cardimet¤; Cardiobil¤;
Cardiogen¤; Carnicor¤; Carnidex¤; Carnitene; Carnitolo¤; Carnitop¤; Carnovis;
Carnum¤; Carrier¤; Carvis¤; Carvit¤; Ceredor¤; Dromos; Elleci; Eucar¤; Eucarnil;
Eufertil; Farnitin; Framil¤; Karrer¤; Kernit¤; Lefcar; Levocarvit; Medocarnitin; Megavis;
Metina¤; Miocardin; Miocor; Miotonal; Neo Cardiol¤; Nicetile; Normobren; Transfert¤;
Zibren; Mexico: Cardispan; Lipovitasi D; Provicar; Netherlands: Nefrocarnit;
Philippines: Carnicor; Cartine; Levocetile; Poland: Carnivit¤; Portugal: Cartine¤;
Disocor; Lacetilina¤; Russia: Carniten (Карнитен); Elcar (Элькар); Spain: Carnicor;
Secabiol; Switzerland: Elcarnitol¤; Turkey: Carnitene; Nefro-Carnitin; United
Kingdom: Carnitor; Elcarn¤; United States: Carnitor; VitaCarn; Venezuela: Carnisin;
Kativil; Lixi; Provicar;
Multi-ingredient Preparations (Latest modification: 23-Aug-2011)
The symbol ¤ denotes a preparation which is discontinued or no longer actively
marketed.
Argentina: Azodac; Biocell; Biomag Vital; Cistidac; Dermasolutions¤; Desgras Burner
Fat; Durgel; Enlinea¤; Fingras¤; Garcinol Max; Herbaccion Diet; Metabolic; Natural Diet;
Reductase; Redumax; Ripped Max; Silueta Plus¤; Tonekin Plus¤; Top Life Energizante¤;
Australia: PM Kids Intelligent; Brazil: Apetin¤; Bucliamin¤; Buclitina¤; Carnabol;
Carnizin¤; Enzivital¤; Ferrotrat B12 Plus; Ferrotrat B12¤; Hepanisan¤; Kelavitam¤;
Nutri-Ped¤; Nutrimaiz SM; Pepsivit¤; Trimetabol; Useton¤; Vitalisin¤; Chile: Cellenergy;
Grisetin Con Carnitina¤; Peracon; Ubiten; France: Aminox¤; Arkotonic¤; Hungary:
Metabol; Indonesia: Betaslim; Bexicom Fit; Bioquinone; Canergy¤; Car-Q; Carni Plus;
Carnon; Combes¤; Corsel; DFM; Enercore; Immunace; Procardio¤; Vitaslim; Italy: AlOxin¤; Anasten Plus; Atlantis; Betaplus¤; Binfolipase; Biocarnil¤; Briovitase Sostegno;
Carfosid; Carpantin¤; Cerebrix¤; Co-Carnetina B12; Creavit; Enercomplex¤; Linfolipase;
Lipoenergy; Memorandum¤; Memovigor; Normo-Calcium¤; Phototrop; Riduton Ergo;
Martindale: The Complete Drug Reference
Salovit; Tripondil; Vitalmix Action¤; Vitavir¤; Malaysia: Hovid Q-10 SupraBio + LCarnitine; Olivenol livin' Vigor¤; Mexico: Redumed; Slim-D; Philippines: Fit-N-Trim;
Fitrum¤; Godex¤; Memorx IQ Plus; Mitodex; Nutrafit; Optigrow; Zeman; Poland:
Kofevit¤; Singapore: Cardio-Essentials; Olivenol Livin' Vigor; Spain: Anabolico
Navarro¤; Ascorbamina Infantil¤; Carnitina Lasa¤; Glotone¤; Grovixim¤; Hepadif;
Malandil; Pranzo; Transfusine Infantil¤; United Kingdom: Slimswift Day Trim¤;
Ukraine: Cardonat (Кардонат); Hepadif (Гепадиф); Trimetabol (Триметабол);
Pharmacopoeial Preparations (Latest modification: 09-Apr-2011)
USP 34: Levocarnitine Injection; Levocarnitine Oral Solution; Levocarnitine Tablets