Although often called an amino acid because of its chemical makeup, L-carnitine is actually a vitamin-like nutrient, related in structure to the B vitamins. L-carnitine is the biologically active form of carnitine, and can be synthesized by the human body in the liver and kidneys. It can also be obtained, already formed, from animal foods.
FUNCTIONS AND USES
Energy Production
L-carnitine’s most important function is the transport of fatty acids into the muscles, where they can be burned for energy. Because fatty acids are a major fuel source for working muscles, carnitine deficiency can reduce the amount of energy available to the body.
L-carnitine levels in muscles are increased by physical training. Moreover, supplementation appears to build stamina and endurance, and may therefore enhance exercise performance, particularly in people with low levels of this nutrient. Supplementation appears to be most beneficial in well-conditioned individuals and athletes, whom it helps, resist fatigue. Carnitine is also often prescribed for individuals who suffer from muscle fatigue due to conditions such as fibromyalgia and chronic fatigue syndrome.
Cardiovascular Disease
Just as L-carnitine plays an essential role in transporting fatty acids into other muscles for energy, it is needed to transport these substances into the heart, the most important muscle in the body. Understandably, much of the research concerning L-carnitine has focused on its use in the treatment of heart disease.
Approximately 60 percent of the energy for the heart muscle is supplied by fatty acids. Thus, myocardial (heart muscle) L-carnitine deficiency has been found to be associated with myopathic heart disease, aging, diabetes, diphtheria, and chronic heart failure. L-carnitine supplementation has been shown to help lessen the impairment of heart muscle function associated with these conditions.
L-carnitine supplementation appears to benefit the heart in other ways, as well. Human studies have also shown that carnitine supplementation improves exercise tolerance and heartbeat regularity in patients with angina pectoris; significantly reduces the extent of cardiac necrosis (cell death) in patients hospitalized for heart attack; decreases the incidence of heart failure and reduces the need for pacemaker transplants in patients with heart disorders; and reduces the number of deaths due to myocarditis (inflammation of heart muscle tissue). In addition, carnitine has been used successfully to treat hypertriglyceridemia (elevated blood triglycerides), a risk factor for heart disease. It also increases levels of high-density lipoproteins (HDLs), which have been associated with a reduced risk of heart disease.
The Nervous System
L-Carnitine may also be important for healthy brain function, since it appears to influence the metabolism of several neurotransmitters-chemicals that facilitate the sending of signals from one nerve fiber to another. In a study involving people with Alzheimer’s disease, the progression of the disease was significantly reduced in those receiving 2 grams per day of acetyl-L-carnitine, a particular form of carnitine, orally for one year.
Detoxification
L-carnitine also seems to have some antioxidant properties, as well as the ability to help detoxify certain drugs. For example, it appears to protect the heart muscle from the damage caused by Adriamycin (doxorubicin hydrochloride), a drug used in cancer treatment.
RDIs AND DEFICIENCIES
Vegetarians are at particular risk for low carnitine levels for two reasons. First, L-carnitine can be obtained only from animal foods. Second, certain nutrients-vitamin C, niacin, vitamin B6, iron, and the amino acid L-lysine-are essential for the synthesis of carnitine. Because cereal grains such as corn, wheat, and rice, mainstays of many vegetarian diets are low in L-lysine, a vegetarian’s ability to synthesize carnitine may be compromised. The cooking or toasting of these grains destroys L-lysine entirely.
L-carnitine loss has been documented in patients receiving dialysis. This loss has been related to the complications these patients often face, such as high blood lipids, cardiomyopathy (any disease of the heart muscle), muscle loss, and muscle cramps. Treatment with oral L-carnitine has been shown to replace lost carnitine and improve these complications.
Although as adults we can synthesize L-carnitine, the diet seems to be an infant’s only source of this amino acid. In the case of specific genetic disorders, such as organic aciduria, carnitine supplementation is necessary.
Since L-carnitine can both be found in foods and manufactured in our bodies under normal conditions, there is no RDI for this nutrient.
Food Sources: L-carnitine is found only in animal foods. We can synthesize carnitine provided that we have enough L-lysine, which is predominantly found in animal foods as well as the other nutrients required for its synthesis.
SUPPLEMENTS
The L forms of this nutrient, such as L-carnitine and acetyl-L-carnitine, are the most biologically active forms, and are the only forms found in foods and synthesized by our bodies. When carnitine is chemically synthesized both the L and D forms are produced. Although supplements generally contain the L forms, be sure to avoid ones containing the D form, since they may actually inhibit the action of L-carnitine in metabolic processes.
L-carnitine and acetyl-L-carnitine are available as supplements at this time. Other forms of carnitine are generally used for research purposes, but may eventually find their way into the supplement market.
OPTIMUM DAILY INTAKE
There is no Optimum Daily Intake for carnitine. Studies have generally used 1 to 5 grams of carnitine orally. Higher levels have been used in studies that administered the supplement intravenously.
Remember: If you have a medical condition, please consult your physician before taking supplements.
TOXICITY AND ADVERSE EFFECTS
There is no known toxicity of carnitine, even with very high doses. In studies in which 5 to 6 grams were taken orally, some gastrointestinal side effects, such as bloating and flatulence, were noted. These can be avoided by starting with smaller doses and gradually increasing the dose over time.
CARNITINE (L-carnitine) A nutrient required for fat oxidation and energy production. Carnitine helps transport FATTY ACIDS into mitochondria, the cellular structure specialized for fuel oxidation. Carnitine may be necessary for the oxidation of certain amino acids (VALINE, ISOLEUCINE and LEUCINE) for energy. The daily requirement for L-carnitine for health is unknown. The body synthesizes L-carnitine from two essential amino acids, LYSINE and METHIONINE. The rate may be inadequate for: kidney patients on hemodialysis; patients with liver failure; strict VEGETARIANS; premature and low birth-weight infants; pregnant or lactating women; children with genetic predisposition to carnitine deficiency or who experience infection or malnutrition. Breast milk contains a high level of L-carnitine to nurture the infant, and it may be an essential nutrient for the newborn.
Carnitine deficiency causes muscle weakness, severe confusion, angina, and high blood lipids, including CHOLESTEROL. Carnitine deficiency is also linked to cardiac enlargement and congestive heart failure. Fatty acid oxidation is a major source of energy for the heart muscle, and carnitine deficiency causes extreme metabolic impairment. The normal heart stores carnitine, but if it does not receive adequate oxygen, carnitine levels drop. Supplementation with carnitine raises heart carnitine levels, allowing the heart to use a limited oxygen supply more efficiently. Thus carnitine has been used effectively to treat atherosclerosis, angina and coronary heart disease. Carnitine may reduce blood fat and LOW-DENSITY LIPOPROTEIN (LDL, undesirable cholesterol) and increase HIGH-DENSITY LIPOPROTEIN (HDL, desirable cholesterol). Carnitine also decreases blood fat. It may help patients with angina and CARDIOVASCULAR DISEASE, and with some types of muscle disease. A derivative of carnitine called acetyl L-carnitine appears to be neuroprotective. Supplementing with acetyl L-carnitine may improve cognitive defects associated with forms of senility and age-related depression. Low carnitine levels may be linked to chronic fatigue symptoms.
Good sources of carnitine are red meats and dairy products like milk. Tempeh and avocados contain some carnitine; however, most vegetables, fruits and grains are poor sources. Most soy-based infant formulas are supplemented with carnitine. While the naturally occurring form of carnitine, (L-carnitine) appears to be safe, high doses of synthetic carnitine (D, L-carnitine), a mixture of isomers, for many weeks can cause progressive weakness and atrophy of certain muscles. Symptoms disappear when supplementation with the mixture ceases.
Neuropsychobiology 1997;35(1):16-23
Amantadine and L-carnitine treatment of Chronic Fatigue Syndrome.
Plioplys AV, Plioplys S
Chronic Fatigue Syndrome Center, Department of Research, Mercy Hospital Chicago, Ill 60616, USA.
Carnitine is essential for mitochondrial energy production. Disturbance in mitochondrial function may contribute to or cause the fatigue seen in Chronic Fatigue Syndrome (CFS) patients. Previous investigations have reported decreased carnitine levels in CFS. Orally administered L-carnitine is an effective medicine in treating the fatigue seen in a number of chronic neurologic diseases. Amantadine is one of the most effective medicines for treating the fatigue seen in multiple sclerosis patients. Isolated reports suggest that it may also be effective in treating CFS patients. Formal investigations of the use of L-carnitine and amantadine for treating CFS have not been previously reported. We treated 30 CFS patients in a crossover design
comparing L-carnitine and amantadine. Each medicine was given for 2 months, with a 2-week washout period between medicines. L-Carnitine or amantadine was alternately assigned as fist medicine. Amantadine was poorly tolerated by the CFS patients. Only 15 were able to complete 8 weeks of treatment, the others had to stop taking the medicine due to side effects. In those individuals who completed 8 weeks of treatment, there was no statistically significant difference in any of the clinical parameters that were followed. However, with L-carnitine we found statistically significant clinical improvement in 12 of the 18 studied parameters after 8 weeks of treatment. None of the clinical parameters showed any deterioration. The greatest improvement took place between 4 and 8 weeks of L-carnitine treatment. Only 1 patient was unable to complete 8 weeks of treatment due to diarrhea. L-Carnitine is a safe and very well tolerated supplement which improves the clinical status of CFS patients. In this study we also analyzed clinical and laboratory correlates of CFS symptomatology and improvement parameter
Prev Med 1986 Jul;15(4):373-90
Carnitine: an overview of its role in preventive medicine.
Kendler BS
Carnitine (beta-hydroxy-gamma-N-trimethylaminobutyric acid) is required for transport of long-chain fatty acids into the inner mitochondrial compartment for beta-oxidation. Widely distributed in foods from animal, but not plant, sources, carnitine is also synthesized endogenously from two essential amino acids, lysine and methionine. Human skeletal and cardiac muscles contain relatively high carnitine concentrations which they receive from the plasma, since they are incapable of carnitine biosynthesis themselves. Since the discovery of a primary genetic carnitine deficiency syndrome in 1973, carnitine has become the subject of extensive research. It is now recognized that
carnitine deficiency may also occur secondary to genetic disorders of intermediary metabolism as well as to a variety of clinical disorders, including renal disease treated by hemodialysis, the renal Fanconi syndrome, cirrhosis, untreated diabetes mellitus, malnutrition, Reye’s syndrome, and certain disorders of the endocrine, neuromuscular, and reproductive systems. Administration of the anticonvulsant valproic acid and total parenteral nutrition may also induce hypocarnitinemia. In many instances, the physiological implications of secondary carnitine deficiency have not been
resolved. However, evidence for a specific carnitine requirement for the newborn, especially if preterm, is accumulating. Moreover, carnitine administration may have a favorable effect on some forms of hyperlipoproteinemia. Carnitine, now recognized as a conditionally essential nutrient, is a significant factor in preventive medicine.
Altern Med Rev 1998 Oct;3(5):345-60
L-Carnitine: therapeutic applications of a conditionally-essential amino acid.
Kelly GS
A trimethylated amino acid roughly similar in structure to choline, carnitine 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. Mitochondrial fatty acid oxidation is the primary fuel source in heart and skeletal muscle, pointing to the relative importance of this nutrient for proper function in these tissues. Although L-carnitine deficiency is an infrequent problem in a healthy, well-nourished population consuming adequate protein, many individuals within the population appear to be somewhere along a continuum, characterized by mild deficiency at one extreme, and tissue pathology at the other. Conditions which seem to benefit from exogenous supplementation of L-carnitine include anorexia, chronic fatigue, coronary vascular disease, diphtheria, hypoglycemia, male infertility, muscular myopathies, and Rett syndrome. In addition, pre-term infants, dialysis patients, and HIV+ individuals seem to be prone to a deficiency of L-carnitine, and benefit from supplementation. Although available data on L-carnitine as an ergogenic aid is not compelling, under some experimental conditions pretreatment has favored aerobic processes and resulted in improved endurance performance.
Clin Ther 1991 Jan-Feb;13(1):2-21
The therapeutic potential of carnitine in cardiovascular disorders.
Pepine CJ
Division of Cardiology, University of Florida, Gainesville.
The naturally occurring compound L-carnitine plays an essential role in fatty acid metabolism. It is only by combining with carnitine that the activated long-chain fatty acyl coenzyme A esters in the cytosol are able to be transported to the mitochondrial matrix where beta-oxidation occurs. Carnitine also functions in the removal of compounds that are toxic to metabolic pathways. Clinical evidence indicates that carnitine may have a role in the management of a number of cardiovascular disorders. Supplemental administration of carnitine has been shown to reverse cardiomyopathy in patients with systemic carnitine deficiency. Experimental evidence obtained in laboratory animals and the initial clinical experience in man indicate that carnitine may also have potential in the management of both chronic and acute ischemic syndromes. Peripheral vascular disease, congestive heart failure, cardiac arrhythmias, and anthracycline-induced cardiotoxicity are other cardiovascular conditions that may benefit from carnitine administration, although at this time data on the use of carnitine for these indications are very preliminary.
Basic Res Cardiol 1987;82 Suppl 1:63-73
The role of the carnitine system in myocardial fatty acid oxidation: carnitine deficiency, failing mitochondria and cardiomyopathy.
Scholte HR, Luyt-Houwen IE, Vaandrager-Verduin MH
Department of Biochemistry, Medical Faculty, Erasmus University, Rotterdam, The Netherlands.
The carnitine system functions in the transport of activated acyl groups over the mitochondrial inner membrane, and is needed for oxidation of long-chain fatty acids by all mitochondria. The rate of cardiac fatty acid oxidation is
determined by availability of fatty acids, oxygen and the activity of carnitine palmitoyltransferase I, which is regulated by a variety of factors. It is inhibited by malonyl-CoA, which in rat heart was found to be synthesized by acetyl-CoA carboxylase. It is also inhibited by long-chain acylcarnitine. Linoleoylcarnitine was found to be a better inhibitor than palmitoylcarnitine. The concentration of carnitine in human heart, muscle and other tissues is much higher than is needed for the optimal beta-oxidation rate. In contrast to controls, we found in several myopathic patients that extra carnitine (from 1/2
to 5 mM) caused a considerable increase in beta-oxidation rate of isolated muscle mitochondria. In some of these patients we detected medium-chain acyl-CoA dehydrogenase deficiency. Patients with primary carnitine deficiency
caused by a renal carnitine leak often show cardiomyopathy, which completely disappears under carnitine therapy. Cardiomyopathy may also be the cause of secondary carnitine deficiency resulting from a mitochondrial defect in
acyl-CoA metabolism, or by the mitochondrial defect itself, which may be induced by drugs or viral attack, or be the result of a genetic error. In cardiomyopathic patients with a (subclinical) myopathy, study of isolated mitochondria and homogenate from skeletal muscle may reveal a mitochondrial dysfunction, which, in some patients, is treatable by dietary measures and supplementation with vitamins, CoQ and/or carnitine. When the cause of cardiomyopathy is not known, determination of plasma carnitine and carnitine supplementation of hypocarnitinemic patients is of great therapeutic value.
Drugs 1987 Jul;34(1):1-24
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.
Goa KL, Brogden RN
ADIS Drug Information Services, Auckland.
L-Carnitine occurs naturally as an essential cofactor of fatty acid metabolism which is synthesised endogenously or obtained from dietary sources. In patients with primary carnitine deficiencies, which may be life-threatening, and some secondary deficiencies such as organic acidurias, the exogenously administered compound is clearly beneficial: by abolishing hypotonia, motor skills are improved, as are muscle weakness and wasting. In preliminary clinical trials in patients with ischaemic cardiac disease, therapy with L-carnitine has shown beneficial effects on myocardial function and metabolism and has improved exercise tolerance in patients with angina pectoris-findings which require
further substantiation in larger controlled studies. Moreover, while some interesting evidence suggests that L-carnitine may find potential use in such
diverse conditions as carnitine deficiencies secondary to prolonged total parenteral nutrition supplementation or chronic haemodialysis, hyperlipidaemias and the prevention of toxicity induced by anthracyclines and valproate, such
findings must be regarded as preliminary. Exogenously administered L-carnitine is very well tolerated. Thus, while its role in primary deficiencies is established, with its profile of negligible toxicity L-carnitine is worthy of further investigation to more clearly define its therapeutic applications in a variety of conditions which may be indirectly related to alterations in fatty acid metabolism.
Wiad Lek 1998;51(1-2):71-5
The role of carnitine in human lipid metabolism
Pietrzak I, Opala G
Studium Doktoranckiego Slaskiej Akademii Medycznej w Katowicach.
Carnitine is an important nutrient that is present in diet (particularly in meat and dairy products) and is synthesized from amino acids. Carnitine has two principal functions in the organism. One is to transport long-chain fatty acids
into the mitochondrion. The second function of carnitine is to regulate the intramitochondrial ratio of acylocoenzyme A to free coenzyme A. This function is important because it allows to remove excessive (and potentially toxic) short- and medium-chain fatty acids from the mitochondrion, and because it maintains sufficient free coenzyme A within the mitochondrion to support energy metabolism.
Clin Ter 1993 Aug;143(2):109-13
Treatment of hypertrophic cardiomyopathy with a combination of carnitine and beta blockers. Review of the literature. Description of a clinical case and long-term follow up.
Ferro M, Crivello R, Gianotti A, Conti M
Sezione di Cardiologia e Unita Coronarica, USSL 44, Ospedale E. Agnelli
Pinerolo, TO.
In the past decade, strategies for managing heart failure have changed. The use of beta blockers, although still in the experimental stage, has proved effective in some cases. The protective action of beta-blocking agents against
chronic catecholamine stimulation may be enhanced by the combination with L-carnitine. This substance plays an important and synergistic role 1) as an important source of energy due to fatty acid oxidation, and 2) by avoiding the
accumulation of lipids in the myocardium. The successful follow-up of a case of dilated cardiomyopathy is critically reviewed. Treatment with the L-carnitine-propranolol combination restored cardiac function in a 52-year-old man with dilated cardiomyopathy: a 50% reduction in mitral EPSS (E Point Septal Separation), from 20 to 10 mm was obtained with the above mentioned therapy; as well as a decrease from 60 to 57 mm in diastolic diameter. Our experience suggests promising benefits in adopting beta blockers combined with L-carnitine therapy in myocardial failure secondary to dilated cardiomyopathy.
Biochem Med 1984 Oct;32(2):199-206
Plasma carnitine concentrations in cardiomyopathy patients.
Tripp ME, Shug AL
Carnitine is an essential cofactor for the beta-oxidation of fats. Both hypertrophic and congestive cardiomyopathies have been reported in primary and secondary carnitine deficiency. Conversely in avian cardiomyopathy models abnormally elevated plasma and tissue carnitine concentrations have been described. We measured plasma carnitine concentrations in 25 cardiomyopathy patients. In 14 patients with either hypertrophic or congestive cardiomyopathy plasma carnitine concentrations were abnormally elevated. Patients with
secondary cardiomyopathies tended to have normal carnitine values. One patient with systemic carnitine deficiency was diagnosed. Her cardiac function normalized with L-carnitine replacement. Six of 14 patients with high plasma
carnitine concentrations died. None of the 10 with low or normal plasma carnitine have died. Plasma carnitine determination may be a useful adjunct in the diagnostic evaluation of idiopathic cardiomyopathy.
Cardiologia 1991 Dec;36(12 Suppl 1):373-7
New thoughts of pathophysiology and therapy of ischemic heart disease.
Pepine CJ
Department of Medicine, University of Florida, Gainesville.
L-carnitine has an important role in the metabolism of fatty acids. These molecules are carried to the mitochondrion after binding with L-carnitine. Fatty acids are oxidated in the mitochondrion only after binding with L-carnitine. Clinical experience suggests that this drug may have an important role in the treatment of several cardiovascular disorders. Experimental studies also suggest that there is a rationale for the clinical use of L-carnitine in the treatment of ischemic heart disease. This drug has been tested in patients with acute myocardial infarction, myocardial ischemia (with beneficial effects on symptoms and stress tolerance) and peripheral vascular disease. Preliminary results in patients with cardiac failure suggest that this substance may reduce cardiac arrhythmias and may allow the reduction of digoxin therapy.
Cardiologia 1991 Dec;36(12 Suppl 1):389-92
The role of metabolic therapy in myocardial infarct
Di Biase M, Biasco G, Rizzon P
Istituto di Malattie dell’Apparato Cardiovascolare, Universita degli Studi,
Bari.
During acute myocardial ischemia the metabolism of free fatty acids is impaired. Since the rate of beta-oxidation is reduced, the levels of acil-CoA and long-chain acyl-carnitine increase. The activity of carnitine, which permits the transport of fatty acids into the mitochondria, is reduced both by its transformation in acyl-carnitine and by its release from the cells induced
by acute ischemia. The accumulation of fatty acids induces a deterioration of hemodynamic parameters and some impulse formation and conduction disturbances. Since in experimental studies L-carnitine prevents the occurrence of
hemodynamic and arrhythmic complications, clinical studies with this compound have been performed during acute ischemia in man. In patients with acute myocardial infarction high doses of L-carnitine inducecarnitine esters; a statistically significant reduction of ventricular arrhythmias during the second day after the onset of symptoms; a reduction of the necrotic area as assessed by electrocardiographic and enzymatic methods.
J Card Fail 1997 Sep;3(3):217-24
The propionyl-L-carnitine hypothesis: an alternative approach to treating heart failure.
Ferrari R, De Giuli F
Chair of Cardiology, University of Brescia, Italy.
Propionyl-L-carnitine (PLC) is a naturally occurring compound that has been considered for the treatment of congestive heart failure (CHF). The rationale for its use in this pathology is related to its effects on cardiac and skeletal muscle. Chronic treatment with PLC improves the contraction of isolated and aerobic perfused rabbit hearts. The compound improves energy metabolism and myocardial contractility in different experimental models of heart failure, such as pressure-overloaded rats, infarct model of heart failure, and rabbit with streptozotocin-induced diabetes. In general, the effect of PLC is apparent in situations of high energy demand such as those induced by increased workload. It therefore seems likely that PLC is able to correct some metabolic steps of the process that leads to heart failure. In addition, PLC may be helpful in heart failure because of its specific action on peripheral skeletal muscle. Administration of PLC in patients with CHF improves skeletal muscle metabolism by increasing pyruvate flux into the Krebs cycle and by decreasing lactate production. These effects occur in the absence of major hemodynamic and neuroendocrinologic changes and may underlie the ability of PLC to increase exercise performance in patients with heart failure. In a randomized study of 50 patients with mild CHF, PLC increased the maximal exercise time, reduced lactate production, and improved left ventricular ejection fraction. There have been two large-scale trials on the effects of PLC on both cardiac and peripheral muscle function in CHF. One is ongoing; the other one, which just ended, failed to show an improvement in exercise capacity in the population studied. A benefit was evident only in a subgroup of patients with preserved ejection fraction and impaired baseline exercise duration.
Prog Cardiovasc Dis 1997 Nov-Dec;40(3):265-86
Carnitine and its derivatives in cardiovascular disease.
Arsenian MA
Cape Ann Medical Center, Gloucester, MA 01930, USA.
Carnitine and its derivative propionyl-L-carnitine are endogenous cofactors which enhance carbohydrate metabolism and reduce the intracellular buildup of toxic metabolites in ischemic conditions. The carnitines have been, and are being used in a spectrum of diseases including multiple cardiovascular conditions. These include angina, acute myocardial infarction, postmyocardial infarction, congestive heart failure, peripheral vascular disease, dyslipidemia, and diabetes. Most published data on carnitine, propionyl-L-carnitine, and other carnitine congeners are favorable but the clinical trials have been relatively small. In currently used doses, these substances are virtually devoid of significant side effects.