Carnitine is an amino acid derivative.
Carnitine is sometimes known as vitamin BT; it is not an officially recognised vitamin.
Carnitine exists as two distinct isomers, L-carnitine (naturally occurring carnitine) and D-carnitine (synthetic carnitine). Dietary supplements contain L-carnitine or a DL-carnitine mixture.
No proof of a dietary need exists. Carnitine is synthesised in sufficient quantities to meet human requirements.
The average omnivorous diet is estimated to provide 100–300 mg of carnitine daily.
Meat and dairy products are the best sources. Fruit, vegetables and cereals are poor sources of carnitine. Carnitine is added to infant milk formulae.
Carnitine has the following physiological functions:
Regulation of long-chain fatty acid transport across cell membranes.
Facilitation of beta-oxidation of long-chain fatty acids and ketoacids.
Transportation of acyl CoA compounds.
Dietary carnitine is absorbed rapidly from the intestine by both passive and active transport mechanisms. Carnitine is synthesised in the liver, brain and kidney from the essential amino acids, lysine and methionine.
Primary carnitine deficiency is caused by impairment in the membrane transport of carnitine. Symptoms may include: chronic muscle weakness (due to muscle carnitine deficiency); recurrent episodes of coma and hypoglycaemia (usually in infants and children); encephalopathy; and cardiomyopathy.
Secondary carnitine deficiency occurs in several inherited disorders of metabolism (especially organic acidurias and disorders of beta-oxidation). Despite the fact that plant foods are poor sources of carnitine, there is no evidence that vegetarians are deficient in carnitine. Endogenous synthesis prevents deficiencies.
Carnitine supplementation has been investigated for its potential benefit in CVD, exercise performance, chronic fatigue syndrome and Alzheimer’s disease.
Carnitine may be beneficial in patients with ischaemic heart disease, but only those who have low serum carnitine levels.
Orally administered L-carnitine (2 g daily) has been shown to improve symptoms of angina, and to reduce anginal attacks and glyceryl trinitrate consumption. In a dose of 900 mg daily for 12 weeks, it has also been shown to improve exercise tolerance in patients with stable angina.
Carnitine supplementation (4 g daily) has also been reported to improve heart rate, arterial pressures, angina and lipid patterns in a controlled study of patients who had experienced a recent myocardial infarction. Yet another study showed that L-carnitine (1 g twice daily for 45 days) may be beneficial in congestive heart failure (CHF), by reducing heart rate, dyspnoea and oedema, and increasing diuresis. Supplementation also allowed for a reduction in daily digoxin dose.
Another study has provided some evidence that L-carnitine (2 g twice a day for 3 weeks) increases walking distance in patients with intermittent claudication.
Preliminary studies have shown that L-carnitine may reduce blood cholesterol levels. Oral administration of L-carnitine (3–4 g daily) significantly reduced serum levels of total cholesterol or triglyceride or both, and increased those of high-density lipoprotein (HDL) cholesterol.
There is a potential for carnitine to improve athetic performance by increasing lipid utilisation and conserving glycogen supplies in the muscles. An increase in maximal aerobic power was observed in subjects who received L-carnitine 2 g daily and 4 g daily. Other studies have shown no effect of supplemental carnitine on muscle carnitine. Double-blind placebo-controlled trials have shown no benefit of oral carnitine 2 g, 3 g or 4 g on exercise performance in healthy subjects.
Chronic fatigue syndrome
Patients with chronic fatigue syndrome have been reported to have low carnitine levels. One crossover (not blinded) parallel design study randomised 30 patients with chronic fatigue syndrome to either 3 g L-carnitine or 100 mg amantadine. At the end of the 2-month study, the carnitine group experienced clinical improvement in 12 out of the 18 studied parameters. However, no statistical comparison between carnitine and amantadine was conducted.
Preliminary evidence from two double-blind, placebo-controlled trials suggests that carnitine supplementation could reduce the deterioration in some symptoms of Alzheimer’s disease. A meta-analysis of 21 double-blind RCTs of acetyl-L-carnitine (ALC) versus placebo in the treatment of mild cognitive impairment and mild Alzheimer’s disease concluded that ALC improved mild cognitive impairment or pre-vented deterioration, and was well tolerated. More recent evidence from a Cochrane review of 16 trials suggests evidence of benefit for acetyl-L-carnitine on clinical global impression and on the Mini Mental State Examination (MMSE – test for Alzheimer’s disease), but there is no evidence using objective assessments in any other area of outcome. In many cases the trial methodologies were poor with vague descriptions of dementia. The Cochrane review concluded that at present there is no evidence to recommend the use of acetyl-L-carnitine in clinical practice.
There is some evidence that carnitine improves insulin resistance in type II diabetes.23 ALC is also a promising treatment for symptoms, particularly pain, of diabetic neuropathy.24,25 It may support treatment for epilepsy and complement antiretroviral therapy in patients with HIV but studies have not assessed the effect of carnitine on morbidity and mortality from AIDS.
The administration of the D-isomer (including a DL-mixture, contained in some supplements) may interfere with the normal function of the L-isomer and should not be used. Only the L-isomer has been used in studies.
Pregnancy and breast-feeding
No problems have been reported, but there have not been sufficient studies to guarantee the safety of carnitine in pregnancy and breast-feeding.
Serious toxicity has not been reported. Nausea, vomiting and diarrhoea may occur with high doses. The risk of toxicity is greater with the D-isomer than with L-carnitine (see Precautions/contraindications); myasthenia has been reported with ingestion of DL-carnitine.
Anticonvulsants: increased excretion of carnitine.
Pivampicillin: increased excretion of carnitine.
Pivmecillinam: increased excretion of carnitine.
L-carnitine supplements are available in the form of tablets and capsules.
The dose is not established. In studies, doses of 1–6 g L-carnitine daily have been used.
Preliminary evidence suggests that carnitine supplementation may be of benefit in several cardiovascular disorders, such as angina, hyperlipidaemia, myocardial infarction, CHF and intermittent claudication. Evidence also exists that carnitine may be beneficial in Alzheimer’s disease, chronic fatigue syndrome and diabetic neuropathy. While these results are clearly of interest, further evidence is required before the role of carnitine, if any, in the management of these conditions can be defined. Despite a theoretical rationale, there is as yet no good evidence that carnitine supplementation improves exercise performance.
Cherchi A, Lai C, Angelino F, Trucco G, Caponnetto S. Effects of L-carnitine in exercise tolerance in chronic stable angina: a multicenter, double-blind, randomized placebo controlled crossover study. Int J Clin Pharmacol Ther Toxicol 1985; 23: 569–572.
Garyza G, Amico RM. Comparative study on the activity of racemic and laevorotatory carnitine in stable angina pectoris. Int J Tissue React 1980; 2: 175–180.
Kamikawa T, Suzuki Y, Kobayashi A, et al. Effects of L-carnitine on exercise tolerance in patients with stable angina pectoris. Jpn Heart J 1984; 25: 587–597.
Davini P, Bigalli A, Lamanna F, et al. Con-trolled study on L-carnitine therapeutic efficacy in post-infarction. Drugs Exp Clin Res 1992; 18: 355–365.
Ghidini O, Azzurro M, Vita G, et al. Evaluation of the therapeutic efficacy of L-carnitine in congestive heart failure. Int J Clin Pharmacol Ther Toxicol 1988; 26: 217–220.
Brevetti G, Chiariello M, Ferulano G, et al. Increases in walking distance in patients with peripheral vascu-lar disease treated with L-carnitine: a double-blind, cross-over study. Circulation 1988; 77: 767–773.
Pola P, Savi L, Grilli M, et al. Carnitine in the therapy of dyslipidemic patients. Curr Ther Res 1979; 27: 208–216.
Pola P, Tondi P, Dal Lago A, et al. Statisti-cal evaluation of long-term L-carnitine therapy in hyperlipoproteinaemias. Drugs Exp Clin Res 1983; 12: 925–935.
Rossi CS, Silprandi N. Effect of carnitine on serum HDL-cholesterol: report of two cases. Johns Hop-kins Med J 1982; 150: 51–54.
Swart I, Rossouw J, Loots J, et al. The effect of L-carnitine supplementation on plasma carnitine levels and various parameters of male marathon athletes. Nutr Res 1997; 17: 405–414.
Angelini C, Vergani L, Costa L, et al. Clinical study of efficacy of L-carnitine and metabolic observations in exercise physiology. In: Borum D, ed. Clinical Aspects of Human Carnitine Deficiency. New York: Pergamon Press, 1986: 36–42.
Marconi C, Sassi G, Carpinelli A, Cerretelli P. Effects of L-carnitine loading on the aerobic and aerobic performance of endurance athletes. Eur J Appl Physiol 1985; 54: 131–135.
Barnett C, Costill D, Vukovitch M, et al. Effect of L-carnitine supplementation on muscle and blood carnitine content and lactate accumulation during high-intensity spring cycling. Int J Sport Nutr 1994; 4: 280–288.
Vukovitch M, Costill D, Fink W, et al. Carnitine supplementation: effect on muscle carnitine and glycogen content during exercise. Med Sci Sports Exerc 1994; 26: 1122–1129.
Colombani P, Wenk C, Kunz I, et al. Effects of L-carnitine supplementation on physical performance and energy metabolism of endurance trained ath-letes: a double-blind crossover field study. Eur J Appl Physiol 1996; 73: 434–439.
Trappe SW, Costill DL, Goodpaster P, et al. The effects of L-carnitine on performance during interval swimming. Int J Sports Med 1994; 15: 181–185.
Giamberardino MA, Dragani L, Valente R, et al. Effects of prolonged L-carnitine administration on delayed muscle pain and CK release after eccentric effort. Int J Sports Med 1996; 17: 320–324.
Pliophys A, Pliophys S. Amantadine and L-carnitine treatment of chronic fatigue syndrome. Neuropsy-chobiology 1997; 35: 16–23.
Sano M, Bell K, Cote L, et al. Double-blind parallel design pilot study of acetyl levocarnitine in patients with Alzheimer’s disease. Arch Neurol 1992; 49: 1137–1141.
Spagnoli A, Lucca U, Menasce G, et al. Long term acetyl-L-carnitine treatment in Alzheimer’s disease. Neurology 1991; 41: 1726–1732.
Montgomery SA, Thal LJ, Amrein R. 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.
Hudson S, Tabet N. Acetyl-L-carnitine for dementia. Cochrane database, issue 2, 2003. London: Macmillan.
Mingrone G, Greco AV, Capristo E. L-carnitine improves glucose disposal in type 2 diabetic patients. J Am Coll Nutr 1999; 18: 77–82.
De Grandis D, Minardi C. Acetyl-L-carnitine in the treatment of diabetic neuropathy. A long-term, randomised, double-blind, placebo-controlled study. Drugs R D 2002; 3: 223–231.
Sima AA, Calvani M, Mehra M, et al. Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic dia-betic neuropathy: an analysis of two randomized placebo-controlled trials. Diabetes Care 2005; 1: 89–94.
Shuper A, Gutman A, Mimoumi M. Intractable epilepsy. Lancet 1999; 353: 1238.
Moretti S, Alesse E, Di Marzio L. Effect of L-carnitine on human immunodeficiency virus-1 infection-associated apoptosis: a pilot study. Blood 1998; 91: 3817–3824.
De Simone C, Tzantzoglou S, Famularo G. High dose L-carnitine improves immunologic and metabolic parameters in AIDS patients. Immunopharmacol Immunotoxicol 1993; 15: 1–12.