Carnitine

Carnitine, derived from an amino acid, is found in nearly all cells of the body. Its name is derived from the Latin carnus or flesh, as the compound was isolated from meat. Carnitine is the generic term for a number of compounds that include L-carnitine, acetyl-L-carnitine, and propionyl-L-carnitine. Children and adults can make carnitine in their kidneys from the amino acids lysine and methionine.

Carnitine plays a critical role in energy production. It transports long-chain fatty acids into the mitochondria, which are organelles in the cytoplasm of cells. The mitochondria produce energy for cellular processes by “burning” (oxidizing) the fatty acids. Some byproducts of energy production are toxic, and carnitine removes these compounds to prevent their accumulation in the mitochondria. Given these key functions, carnitine is concentrated in tissues like skeletal and cardiac muscle that utilize fatty acids as a dietary fuel.

Sources

Animal products, such as beef, are among the best sources of carnitine. Source: WikiMedia Commons

The body makes sufficient carnitine to meet the needs of most people. For genetic or medical reasons, some individuals (such as preterm infants), cannot make enough. Supplementation is necessary in these individuals.

Animal products like meat, fish, poultry, and milk are the best sources of carnitine. In general, the carnitine content is higher in redder meats. Dairy products contain carnitine primarily in the whey fraction. The carnitine content of several foods is listed in Table 1.

Table 1: Selected food sources of carnitine

Carnitine occurs in two forms, called D and L, that are mirror images (enantiomers) of each other. Only L-carnitine is active in the body and is the form found in food.

Recommended Daily Intakes

Healthy children and adults do not need to consume carnitine from food or supplements, as the liver and kidneys produce sufficient amounts from the amino acids lysine and methionine to meet daily needs. The Food and Nutrition Board (FNB) of the National Academy of Sciences reviewed studies on the functions of carnitine in 1989 and concluded it was not an essential nutrient. Essential nutrients need to be acquired from the diet because the body does not make them. Non-essential nutrients, like carnitine, are made in the body. The FNB has not established Dietary Reference Intakes (DRIs)—including a recommended dietary allowance (RDA)—for carnitine.

Supplemental sources of carnitine

L-carnitine, acetyl-L-carnitine, and propionyl-L-carnitine are available over-the-counter as dietary supplements. Carnitine is often promoted as an aid for weight loss, to improve exercise performance, and to enhance a sense of well-being. It is also approved by the Food and Drug Administration to treat primary and certain secondary carnitine-deficiency syndromes.

Absorption and metabolism

Adults eating mixed diets that include red meat and other animal products obtain about 60–180 mg (milligrams) of carnitine per day. Vegans get considerably less (about 10–12 mg) since they avoid animal-derived foods. Most (54%–86%) of dietary carnitine is absorbed in the small intestine and enters the bloodstream.

The kidneys efficiently conserve carnitine, so even carnitine-poor diets have little impact on the body's total carnitine content. Rather than being metabolized, excess carnitine is excreted in the urine as needed.^[1]

Carnitine Deficiency

Two types of carnitine deficiency states exist. Primary carnitine deficiency is a genetic disorder of the cellular carnitine-transporter system. It usually manifests by five years of age with symptoms of heart damage, skeletal-muscle weakness, and low blood sugar (hypoglycemia).^[2] Secondary carnitine deficiencies are often caused by certain disorders (such as chronic renal failure) or under particular conditions (e.g., use of certain antibiotics) that reduce carnitine absorption or increase its excretion. There is scientific agreement on carnitine's value as a prescription product for treating carnitine deficiency.^[3]

Too Much Carnitine

At doses of approximately 3 g/day, carnitine supplements may cause nausea, vomiting, abdominal cramps, diarrhea, and a "fishy" body odor. More rare side effects include muscle weakness in uremic patients and seizures in those with seizure disorders.

Carnitine and medication interactions

Carnitine interacts with certain antibiotics, such as pivampicillin that are used in the long-term prevention of urinary tract infections. Chronic administration of these antibiotics can lead to carnitine depletion.^[4] However, while tissue carnitine levels may become low enough to limit fatty acid oxidation, no cases of illness due to deficiency have been described. Blood concentrations of carnitine may be reduced in children treated for convulsions with phenobarbital, valproic acid (Depakene), phenytoin (Dilantin), or carbamazepine (Tegretol), but no clinical consequences have been shown. Carnitine supplementation may be appropriate to avoid toxic effects of valproic acid.^[5]

Research

Carnitine has been studied extensively because it is important to energy production and is a well-tolerated and generally safe therapeutic agent. Researchers prefer to use acetyl-L-carnitine in studies because it is better absorbed from the small intestine than L-carnitine and crosses the blood-brain barrier more efficiently (i.e., gets into brain tissue).

Athletic performance
Some athletes take carnitine to improve performance. However, twenty years of research has found no consistent evidence that carnitine supplements improve exercise or physical performance in healthy subjects when taken at doses of 2–6 g (grams)/day for 1 to 28 days. The total body content of carnitine is about 20 g in a man weighing 155 pounds, almost all of it in the skeletal muscle. For example, carnitine supplements do not appear to increase the body's use of oxygen or improve metabolic status when exercising, nor do they necessarily increase the amount of carnitine in muscle.^[6]

Aging
A decline in mitochondrial function is thought to contribute to the aging process. Mitochondria are membrane-enclosed structures that provide cells of the body with energy. Carnitine may be involved in the aging process because its concentration in tissues declines with age.^[7] This decline may contribute to the degeneration of mitochondrial membranes. Research in aged rats found supplementation with high doses of acetyl-L-carnitine and alpha-lipoic acid (an antioxidant) to reduce mitochondrial decay. Mice treated with these supplements also moved about more and had improved performance on tests of memory. At present there are no equivalent studies of this kind in humans. However, an analysis of double-blind, placebo-controlled studies suggested that supplements of acetyl-L-carnitine improve mental function and reduce deterioration in older adults with mild cognitive impairment and Alzheimer disease.^[8]

Cardiovascular and peripheral-arterial disease
Several studies have examined supplemental carnitine in the management of cardiac ischemia (restriction of blood flow to the heart) and peripheral arterial disease (of which the most important symptom is poor circulation in the legs, known as intermittent claudication). Because levels of carnitine are low in the failing heart muscle, supplemental amounts might be beneficial to the organ by counteracting the toxic effects of free fatty acids and improving carbohydrate metabolism. In short-term studies, carnitine has demonstrated anti-ischemic properties when given orally and by injection. A double-blind, placebo-controlled, multicenter clinical trial in Italy with patients who had suffered a first heart attack found that supplemental carnitine (given intravenously for five days, then 6 g/day orally for one year) reduced heart failure and overall mortality.^[9] The results were not conclusive, but they were promising enough to justify a larger study that has yet to be completed.

Cancer
Fatigue resulting from chemotherapy, radiation treatment, and poor nutritional status is common in cancer patients. These patients may also be deficient in carnitine. In one study, treatment with carnitine supplements (4 g/day for one week) ameliorated fatigue in most chemotherapy-treated subjects and restored normal blood levels of carnitine. In another trial, terminal cancer patients supplemented with carnitine (doses ranged from 250 mg to 3 g/day) experienced less fatigue and improved mood and quality of sleep. In both studies, most subjects were carnitine deficient before taking the supplements. A more recent randomized controlled trial, however, failed to reproduce these findings.^[10]

Type 2 diabetes
Insulin resistance, which plays an important role in the development of type 2 diabetes, may be associated with a defect in fatty-acid oxidation in muscle. This raises the question as to whether mitochondrial dysfunction might be a factor in the development of the disease. Increased storage of fat in lean tissues has become a marker for insulin resistance. Early research suggests that supplementation with L-carnitine intravenously may improve insulin sensitivity in diabetics by decreasing fat levels in muscle and may lower glucose levels in the blood by more promptly increasing its oxidation in cells. A recent analysis of two multicenter clinical trials of subjects with either type 1 or type 2 diabetes found that treatment with acetyl-L-carnitine (3 g/day orally) for one year provided significant relief of nerve pain and improved vibration perception in those with diabetic neuropathy. The treatment was most effective in subjects with type 2 diabetes of short duration.^[11]

HIV and AIDS
The human immunodeficiency virus (HIV) causes a decline in the number of lymphocytes (one type of white blood cell), resulting in acquired immunodeficiency syndrome (AIDS). HIV-infected individuals often accumulate fat in some areas of the body, lose fat in other areas, and develop high levels of blood fats (hyperlipidemia) and insulin resistance, which together constitute the lipodystrophy syndrome. This syndrome may represent mitochondrial toxicity brought about by the HIV infection and the antiretroviral drugs used to treat it. This syndrome can induce a carnitine deficiency that limits mitochondrial fat metabolism. The molecular mechanisms by which this occurs are poorly understood. Preliminary research provides conflicting findings but suggests that supplementation with carnitine both intravenously and orally (at doses of 2–6 g/day for weeks or months) in HIV-infected individuals may slow the death of lymphocytes (which in turn may slow HIV progression), reduce neuropathy,^[12] and favorably affect blood lipid levels.

End-stage renal disease and hemodialysis
Carnitine homeostasis (balance within the body) among individuals with renal diseases can be substantially impaired by several factors. Two particularly important factors are reduced carnitine synthesis, increased elimination of the compound by the kidneys, and reduced intake from food due to poor appetite and consumption of fewer animal products. Many patients with end-stage renal disease, particularly those on hemodialysis, become carnitine insufficient.^[13] Anemia, muscle weakness, fatigue, altered levels of blood fats, and heart disorders may develop when carnitine blood levels and muscle stores are low. Numerous studies suggest that high doses of supplemental carnitine (often injected) in patients on maintenance hemodialysis can correct some or all of these symptoms, though most involve small numbers of patients and are not double-blinded trials. A recent analysis of these studies concludes that carnitine supplements may aid anemia management but not blood-lipid profiles, and that their effects on exercise capacity or heart stability are inconclusive.

Male infertility
The carnitine content of seminal fluid is directly related to sperm count and motility, suggesting that the compound might be of value in treating male infertility. Several studies indicate that carnitine supplementation (2–3 g/day for 3–4 months) may improve sperm quality, and one double-blind trial found that 2 g/day of carnitine taken for 2 months by 100 infertile men increased the concentration and both total and forward motility of their sperm. The reported benefits may relate to increased mitochondrial fatty-acid oxidation (providing more energy for sperm) and reduced cell death in the testes. However, a recent trial with 21 infertile men found that 3 g/day of carnitine taken for 24 weeks did not significantly increase sperm motility or total motile sperm count as compared to placebo. Larger and more carefully designed studies are needed to evaluate carnitine's potential value as an infertility therapy.^[14]

References

1. ↑ Mitchell ME. Carnitine metabolism in human subjects. I. Normal metabolism. Am J Clin Nutr. 1978 Feb;31(2):293-306. Abstract | PDF
2. ↑ Longo N, Amat di San Filippo C, Pasquali M. Disorders of carnitine transport and the carnitine cycle. Am J Med Genet C Semin Med Genet. 2006 May 15;142C(2):77-85. Abstract | Full Text | PDF
3. ↑ Winter SC. Treatment of carnitine deficiency. J Inherit Metab Dis. 2003;26(2-3):171-80. Abstract
4. ↑ Rose SJ, Stokes TC, Patel S, Cooper MB, Betteridge DJ, Payne JE. Carnitine deficiency associated with long-term pivampicillin treatment: the effect of a replacement therapy regime. Postgrad Med J. 1992 Nov;68(805):932-4. Abstract | PDF
5. ↑ Lheureux PE, Penaloza A, Zahir S, Gris M. Science review: carnitine in the treatment of valproic acid-induced toxicity - what is the evidence? Crit Care. 2005 Oct 5;9(5):431-40. Abstract | PDF
6. ↑ Brass EP. Supplemental carnitine and exercise. Am J Clin Nutr. 2000 Aug;72(2 Suppl):618S-23S. Abstract | Full Text | PDF
7. ↑ Ames BN, Liu J. Delaying the mitochondrial decay of aging with acetylcarnitine. Ann N Y Acad Sci. 2004 Nov;1033:108-16. Abstract
8. ↑ Kidd PM. Alzheimer's disease, amnestic mild cognitive impairment, and age-associated memory impairment: current understanding and progress toward integrative prevention. Altern Med Rev. 2008 Jun;13(2):85-115. Abstract | PDF
9. ↑ Tarantini G, Scrutinio D, Bruzzi P, Boni L, Rizzon P, Iliceto S. Metabolic treatment with L-carnitine in acute anterior ST segment elevation myocardial infarction. A randomized controlled trial. Cardiology. 2006;106(4):215-23. Abstract
10. ↑ Cruciani RA, Dvorkin E, Homel P, et al. l-Carnitine Supplementation in Patients with Advanced Cancer and Carnitine Deficiency: A Double-Blind, Placebo-Controlled Study. J Pain Symptom Manage. 2008 Sep 20. Abstract
11. ↑ Sima AA. Acetyl-L-carnitine in diabetic polyneuropathy: experimental and clinical data. CNS Drugs. 2007;21 Suppl 1:13-23 Abstract
12. ↑ Chiechio S, Copani A, Gereau RW 4th, Nicoletti F. Acetyl-L-carnitine in neuropathic pain: experimental data. CNS Drugs. 2007;21 Suppl 1:31-8 Abstract
13. ↑ Hedayati SS. Dialysis-related carnitine disorder. Semin Dial. 2006 Jul-Aug;19(4):323-8. Abstract
14. ↑ Zhou X, Liu F, Zhai S. 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. Abstract

External Links

Dietary Guidelines for Americans

U.S. Department of Agriculture's food guidance system