L-carnitine

 

L-Carnitine Introduction

Also referenced as: Carnitine and carnitor.

L-carnitine should not be confused with Acetyl-L-Carnitine or Propionyl-L Carnitine; as they are completely different substances.

L-carnitine is a key nutrient in the body’s production of cellular energy. It is necessary for the body to utilize a chief energy source, fatty acids. L-carnitine also allows for fatty acids to undergo beta-oxidation in the mitochondria of the cells. In order for a fatty acid (which are typically very long molecules) to enter the cell, it must be bound to a specific enzyme (coenzyme A) to form a complex known as fatty acyl-Coenzyme A. L-carnitine serves as a “gatekeeper,” and is responsible for moving the fatty acyl-Coenzyme A molecule into the cell for utilization in the energy processes. [1]

Carnitine has many applications in the areas of health and well-being. However, carnitine has been marketed for many other purposes that while not fully validated, do have interesting theoretical applications based on the actions of this nutrient in the body.

L-Carnitine Food Sources

L-carnitine is, technically, an amino acid. It is found in the highest quantities in protein-based food sources (e.g. meats), with less in dairy products and comparatively little or none found in fruits, vegetables, or cereals (as evidenced by their low overall protein content). [2] Carnitine is synthesized in the body from two primary amino acids: methionine and lysine; both of which are available components of most protein sources. The kidney plays a role in maintaining levels of carnitine in the body by preventing its loss through urination. Typically, the large majority of carnitine is reabsorbed in the kidneys rather than lost. Reabsorbtion of carnitine becomes even more efficient if the body is low in this amino acid. [3]

L-Carnitine Uses

Because of the widespread implication of carnitine’s mechanism of action within the body, there are several applications for its use. Primarily, L-carnitine is used to supplement people suffering from specific genetic conditions or ‘inborn errors of metabolism’; in which they are unable to synthesis or retain this amino acid. L-carnitine is also widely employed as an adjunctive nutritional nutrient for those undergoing hemodialysis (artificial blood filtration due to kidney damage). Supplementation with L-carnitine in this circumstance has been shown to augment red blood cell and hemoglobin numbers. [4] Additionally, the use of L-carnitine in end stage renal disease (and subsequent hemodialysis) is sanctioned by the Food and Drug Administration. [5]

L-carnitine can also be used to treat overdose of valproate (an anticonvulsant drug) and muscle diseases resulting as a side effect from the administration of zidovudine and isotretinoin. L-carnitine is especially useful in strict vegetarians, as their levels of this amino (as well as levels of L-carnitine precursor amino acids) may be suboptimal.

Other uses of L-carnitine include; supplementation following heart attack, stable angina, and congestive heart failure. L-carnitine is also commonly utilized in premature infants. It may also be supplemented in those with chronic fatigue syndrome, leg ulcers, and persons wishing to enhance exercise performance. The intravenous administration of L-carnitine has been used to bolster CD-4 cell levels in people with HIV/AIDS and in patients receiving TPN (total parenteral nutrition).

L-Carnitine Dosages

Typically, L-carnitine is dosed at one to two grams, twice per day. Higher end doses have been reported and may reach up to 6 grams per day. [6]

L-Carnitine Deficiencies and Toxicities

L-Carnitine Deficiencies

Frank deficiency of L-carnitine is relatively rare, with the exception of those born with metabolic errors in which carnitine becomes deficient. L-carnitine deficiency may occur at some level in long-term vegetarians, vegans, or those on protein-restrictive diets. As mentioned earlier, a deficiency of L-carnitine will occur in those with kidney failure who are undergoing hemodialysis; as this artificial blood filtration mechanism cannot retain L-carnitine as efficiently as the kidneys. Deficiency may also arise from taking certain pharmaceutical drugs such as zidovudine (for treatment of HIV) and isotretinoin (for severe acne and other skin conditions).

L-Carnitine Toxicities

Side effects reported when taking L-carnitine (either orally or intravenously) include; nausea, vomiting, diarrhea, seizures, heartburn, body odor, and gastrointestinal (GI) distress. [7] Some people may have the presence of an L-carnitine metabolite that may lead to foul smelling urine, breath, and sweat. [8] A certain mixture of L-carnitine and its isomer D-carnitine have been administered together with negative results. This included symptoms of muscle wasting, weakness, and discolored urine (due to myoglobinuria). The compound, DL-carnitine is thought to allow D-carnitine to competitively inhibit the action of L-carnitine in the body, leading to a L-carnitine deficiency state. [9]

L-Carnitine Interactions:

  • Herbs/Supplements: D-carnitine may interfere with L-carnitine in the body; high doses may lead to L-carnitine deficiency symptoms. [9, 10]
  • Laboratory tests: L-carnitine may elevate CD4 and CD8 cell counts in people with HIV/AIDS. [11, 12] L-carnitine may elevate HDL cholesterol and decrease triglyceride levels in children with type IV hyperlipoproteinemia. [13]
  • Disease conditions: L-carnitine may negatively affect thyroid hormone activity in some susceptible people; it should be avoided in people with hypothryoidism. [14] Some people with a medical history of seizures may experience an increase in number or severity of seizures when taking L-carnitine; the mechanism of this is action remains unknown.
  • Drugs: Several pharmaceutical medications can lower endogenous levels of carnitine; supplementing with carnitine may be considered when taking these drugs: Carbamazepine, cefditoren pivoxil pivampicillin, phenobarbital, phenytoin, valproic acid, and zidovudine. [15, 19]

References

1. Lenzi A, Sgro P, Salacone P, 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.

2. Krajcovicova-Kudlackova M, Simoncic R, Bederova A, Babinska K, Beder I. Correlation of carnitine levels to methionine and lysine intake. Physiol Res. 2000;49(3):399-402.

3. Rebouche CJ. Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-L-carnitine metabolism. Ann N Y Acad Sci 2004;1033:30-41.

4. Hurot JM, Cucherat M, Haugh M, Fouque D. Effects of L-carnitine supplementation in maintenance hemodialysis patients: a systematic review. J Am Soc Nephrol 2002;13:708-14.

5. Online document at: http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/101840.shtml

6. Iliceto S, Scrutinio D, Bruzzi P, et al. Effects of L-carnitine administration on left ventricular remodeling after acute anterior myocardial infarction: the L-Carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) Trial. J Am Coll Cardiol 1995;26:380-7.

7. Anonymous. Carnitor (levocarnitine) package insert. Sigma-Tau Pharmaceuticals Inc, Gaithersburg, MD. December 1999.

8. Evans AM, Fornasini G. Pharmacokinetics of L-carnitine. Clin Pharmacokinet 2003;42:941-67..

9. Tsoko M, Beauseigneur F, Gresti J, et al. Enhancement of activities relative to fatty acid oxidation in the liver of rats depleted of L-carnitine by D-carnitine and a gamma- butyrobetaine hydroxylase inhibitor. Biochem Pharmacol 1995;49:1403-10. 9 Ibid

10. Wu X, Huang W, Prasad PD, et al. Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter. J Pharmacol Exp Ther 1999;290:1482-92.

11. Famularo G, De Simone C, Cifone G. Carnitine stands on its own in HIV infection treatment. Arch Intern Med 1999;159:1143-4.

12. Moretti S. Effect of L-carnitine on human immunodeficiency virus-1 infection-associated apoptosis: a pilot study. Blood 1998;91:3817-24.

13. Young DS. Effects of Drugs on Clinical Laboratory Tests 4th ed. Washington: AACC Press, 1995.

14. Benvenga S, Amato A, Calvani M, Trimarchi F. Effects of carnitine on thyroid hormone action. Ann N Y Acad Sci 2004;1033:158-67.

15. Hug G, McGraw CA, Bates SR, et al. Reduction of serum carnitine concentrations during anticonvulsant therapy with phenobarbital, valproic acid, phenytoin, and carbamazepine in children. J Pediatr 1991;119:799-802.

16. Brass EP. Pivalate-generating prodrugs and carnitine homeostasis in man. Pharmacol Rev 2002;54:589-98. 16 Ibid

17. Castro-Gago M, Eiris-Punal J, Novo-Rodriguez MI, 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. 17 Ibid

18. De Vivo DC, Bohan TP, Coulter DL, et al. L-carnitine supplementation in childhood epilepsy: Current perspectives. Epilepsia 1998;39:1216-25.

19. Georges B, Galland S, Rigault C, et al. Beneficial effects of L-carnitine in myoblastic C2C12 cells. Interaction with zidovudine. Biochem Pharmacol 2003;65:1483-8.