Acetyl L-Carnitine HCI Products



Acetyl-l-carnitine Alc
 

Acetyl-L-Carnitine Introduction

Acetyl-L-carnitine is a naturally formed derivative of the biochemical compound carnitine, and actively participates in the β-oxidation of fatty acids. The major pathway whereby saturated fatty acids are catabolized occurs in the mitochondria of cells. In order for a saturated fatty acid to be catabolized, it must first enter the cell, get converted to a CoA derivative and then be transported across the inner membrane of the mitochondria. [1] This membrane is, largely, impermeable to bulky polar molecules. This is where carnitine plays an integral role.

Carnitine serves as a specialized carrier in the mitochondrial inner membrane, transporting fatty acids which have undergone a CoA derivative conversion. This transport process is referred to as the “carnitine shuttle.” Once fatty acids are inside the mitochondria, two carbon fragments are removed from the carboxyl end of the fatty acid, thus producing acetyl CoA.

Ultimately, the importance of the carnitine shuttle lies in allowing cells to use long chain fatty acids as a fuel source. Especially in muscle, these fatty acids can be used for energy. By utilizing fatty acids for energy, fatty build up is prevented in organs such as the heart and liver. [2] Assisting the heart with oxygen consumption efficacy, carnitine provides for improved functioning of the cardiac component. This positively affects conditions such as angina, arrhythmias, heart attack recovery, and congestive heart failure. [3]

Carnitine also plays an important role in fat metabolism, which appears to reduce the risk of damage in conditions like diabetes, alcohol-induced fatty liver, and cardiovascular disease. Many specific functions are associated with the carnitine administration, including; decreasing high cholesterol levels, assisting with weight loss, improving muscle strength in musculoskeletal disorders, addressing immune system dysfunction, positively impacting mental function and improving sperm count and motility. Carnitine also protects against oxidative stress, enhances antioxidant activity of some enzymes, and helps to regulate hormonal changes caused by physical stress. [2]

Carnitine is made from the essential amino acids methionine and lysine. Acetyl-L-carnitine, on the other hand, is a derivitave of carnitine (acetic acid is bound to carnitine). Acetyl-L-Carnitine has been widely researched, especially within the treatment of Alzheimer's disease. [4] This form of carnitine structurally resembles acetylcholine, an important neurotransmitter in the brain, and actually mimics some of the actions. It appears that this form of carnitine is more effective in treating conditions of the brain, than carnitine alone. [5, 6]

Acetyl-L-Carnitine Food Sources

The main food source of carnitine is meats, as this compound is highly concentrated in game. Red meat contains the highest amount. As mentioned, carnitine is made from lysine and methionine, therefore consumption of foods high in these two amino acids is important for an adequate supply of carnitine. Vegetarians are a group who are at risk of carnitine deficiency because of the inadequate levels of carnitine, methionine, and lysine in plant proteins. [2] Interestingly, men require more carnitine than women, because of their greater muscle mass.

Acetyl-L-Carnitine Uses

The use of L-carnitine supplementation is not limited to natural medicine practitioners. A review study, published in 1998, documented the use of L-carnitine by pediatric neurologists. [7] A consensus exists regarding the use of intravenous L-carnitine administration for the treatment of valproate-induced hepatotoxicity or overdose (which occurs in patients taking this prescription anti-convulsant medication for seizure disorders, like epilepsy) and other acute metabolic crises associated with a carnitine deficiency.

The treatment of Alzheimer’s disease with acetyl-L-carnitine has received interest in the research community. Controlled trials have been carried out to determine whether supplementation can impact the progression of the disease. [8-10] These studies consistently demonstrated slower rates of deterioration of mental status. One study showed that patients with more severe disease experienced the greatest benefit.

L-carnitine can be used to treat various cardiovascular conditions. Patients with stable angina experienced increased exercise tolerance and improvements were also noted objectively using electrocardiogram recordings. [11, 12] Numerous studies have supported the use of L-carnitine for the treatment of high blood lipids, including cholesterol and triglyceride levels. [13-16] Significant lowering of these lipids was observed.

Another cardiovascular disorder that can be convincingly treated with L-carnitine is peripheral vascular diseases, like intermittent claudication. A double-blind crossover trial demonstrated increased duration of walking without pain when treated with an oral dose of L-carnitine. [17] The mechanism is believed to be related to improved pyruvate utilization and oxidative phosphorylation efficiency in skeletal muscle.

Other conditions for which L-carntine has been found useful include chronic cardiac ischemia, cardiogenic shock, vasospastic syndrome of the upper extremity, Reye’s Syndrome, chronic lung disease, and Acquired Immune Deficiency Syndrome (AIDS). [18-25]

Acetyl-L-Carnitine Dosages

Most studies employ doses of L-carnitine in the range of 1500 - 4000 milligrams daily, taken in divided portions. [3] Generally, patients start with a low dose and progressively take higher amounts over a period of weeks, to adapt to the supplement and minimize any possible side effects. The “D” form of carnitine should not be taken for two reasons: it can create an L-carnitine deficiency in muscle, and it can interfere with the “L” form if one is taking it as a supplement.

Acetyl-L-Carnitine Toxicities and Deficiencies

Acetyl-L-Carnitine Deficiency

Carnitine deficiency has been documented and most frequently is genetically based, due to a defect in carnitine synthase, the enzyme that catalyzes formation of carnitine. Symptoms of the deficiency syndrome include confusion, muscle weakness, obesity, and heart pain. [2] Certain types of muscular dystrophy have been linked to carnitine deficiency. [2]

Adequate levels of iron, vitamin B1, vitamin B6, vitamin C, methionine, and lysine are important for formation of carnitine. If any of these are lacking, deficiency syndrome can manifest.

Acetyl-L-Carnitine Toxicities

Acetyl-L-carnitine (ALC) has relatively low toxicity. Caution should be taken with patients receiving hemodialysis. Supplementation with high doses of L-carnitine can increase triglyceride levels and possibly increase the clotting of blood. Side effects that have been observed with supplementation of ALC include; nausea, vomiting, increased aggression, and confusion.

References

1. Champe PC and Harvey RA. Lippincott’s Illustrated Reviews: Biochemistry. JB Lippincott Company, Philadelphia, PA, 1987:171-172.

2. Balch PA. Prescription for Nutritional Healing: The A-Z Guide to Supplements, 2nd Ed. Penguin Putnam, Inc. New York, NY 2002;104-106.

3. AANP. Nature’s Pharmacy- Your Guide to Healing Foods, Herbs, Supplements and Homeopathic Remedies. Publications International Ltd., Lincolnwood, IL 2001;250-251.

4. Murray M and Pizzorno J. Encyclopedia of Natural Medicine, 2nd Ed. Prima Publishing, Rocklin, CA 1998;391-392.

5. Bowman B. Acetyl-carnitine and Alzheimer’s disease. Nutrition Reviews 1992;50:142-144.

6. Carta A et al. Acetyl-L-Carnitine and Alzheimer’s disease: Pharmacological considerations beyond the cholinergic sphere. Ann NY Acad Sci 1993;695:324-326.

7. De Vico DC et al. L-carnitien supplementation in childhood epilepsy: current perspectives. Epilepsia 1998;39:1216-1225.

8. Spagnoli A et al. Long-term Acetyl-L carnitine treatment in Alzheimer’s disease. Neurology 1991;41:1726-1732.

9. Sano M et al. Double blind parallel design pilot study of acetyl levocarnitine in patients with Alzheimer’s disease. Arch Neurol 1992;49:1137-1141.

10. Pettegrew JW et al. Clinical and neurochemical effects of acetyl-L-carnitine in Alzheiner’s disease. Neurobiol Aging 1995;16:1-4.

11.Kamikawa T et al. Effects of L-carnitine on exercise tolerance in patients with stable angina pectoris. Jpn Heart J 1984;25:587-597.

12. Cherchi A et al. Effects of L-carnitine on exercise tolerance in chronic stable angina: a multi-center, double-blind, randomized, placebo controlled crossover study. Int J Clin Pharm Ther Toxicol 1985;23:569-572.

13. Pola P et al. Carnitine in the therapy of dyslipemic patients. Curr Ther Res 1980;27:208-216.

14. Pola P et al. Statistical evaluation of long-term L-carnitine therapy in hyperlipoproteinaemias. Drugs Exptl Clin Res 1983;9:925-934.

15. Abdel-Aziz MT et al. Effect of carnitine on blood lipid patterns in diabetic patients. Nutr Rep Int 1984;29:1071-1079.

16. Poleszynski DV and Bohmer T. Improved oxygen uptake, blood pressure and triglyceride reduction with oral L-carnitine in healthy women. Int J Biosocial Med Res 1991;13(2):180-191.

17. Brevetti G et al. Increases in walking distance in patients with peripheral vascular disease treated with L-carnitine: a double-blind, cross-over study. Circulation 1988;77:767-773.

18.Orlando G and Rusconi C. Oral L-carnitine in the treatment of chronic cardiac ischaemia in elderly patients. Clin Trials J 1986;23:338-344.

19. Corbucci GG and Loche F et al. L-carnitine in cardiogenci shock therapy: pharmocodynamic aspects and clinical data. Int J Clin Pharm Res 1993;13:87-91.

20. Corbucci GG et al. Cardiogenic shock and L-carnitine; clinical data and therapeutic perspectives. Int J Clin Pharm Res 1991;11:283-294.

21. Pola P et al. Use of a physiological substance, acetyl-carnitine, in the treatment of angiospastic syndromes. Drugs Exptl Clin Res 1984;10:213-217.

22. Anonymous. Oral L-carnitine prevents progression of Reye’s. Med Tribune 1983(Sept 28):3.

23. Dal Negro R et al. L-carnitine and physiokinesiotherapy in chronic respiratory insufficiency. Clin Trials J 1985;22:353.

24. De Simone C et al. High dose L-carnitine improves immunologic and metabolic parameters in AIDS patients. Immunopharmacol Immunotoxicol 1993;15:1-12.

25. De Simone C et al. Carnitine depletion in peripheral blood mononuclear cells from patients with AIDS: Effect of oral L-carnitine. AIDS 1994;8:655-660.