CARNITINE

Description
Carnitine is an important amino acid (a protein building-block) the body makes for itself in the liver and kidneys, that is stored in the skeletal muscles, heart, brain and sperm. Carnitine is responsible for the transport of long-chain fatty acids into the mitochondria, or energy-producing centers, of cells throughout the body. In this way carnitine helps the body convert fatty acids into energy that is used primarily for muscular activities throughout the body. It also helps to reverse this process, in which fatty acid chains are transported out of the cells if their concentration becomes excessive or toxic to the cell.

Outright deficiencies of carnitine can occur, but they are not common. Carnitine is found in meat and dairy products in particular, although it is present in lesser levels in other foods. If a deficiency does occur, it is more likely to be due to an inability to properly absorb carnitine from foods. This can occur in a variety of ways: genetic absorption disorders, liver or kidney disease, high-fat diets, medications (anti-seizure drugs such as Depakene and Dilantin), and low dietary intake of the two amino acids that are used to make up carnitine, lysine and methionine. Heart muscle tissue, because of its high energy requirement, is vulnerable to low carnitine levels. For this reason common signs of carnitine deficiency are fatigue, chest pain, muscle pain, weakness, low blood pressure, and/or confusion.

There are three forms of carnitine: L-carnitine, acetyl-L-carnitine and proprionyl-L-carnitine. Acetyl-L-carnitine (ALC) is the principal form used in most research and treatment of Peyronie’s Disease (PD), not the L-carnitine form. This last form, acetyl-L-carnitine, functions in the body as an anti-oxidant, breaking down arachidonic acid and histimine, thus controlling inflammation. Perhaps this is why it is more effective in treating PD. Using the less expensive L-carnitine form is not recommended for this reason.

Adverse Reactions and Side-effects
In 130 patients studied by Spagnoli, et al over one-year, the administration of acetyl-L-carnitine (2000 mgs/day) slowed the progression of Alzheimer’s disease. Patients in the treatment group experienced significant positive effects, as determined by neuropsychological tests. At the 3-month mark, agitation was experienced by 11% of patients taking acetyl-L-carnitine and 6% of patients taking placebo, a difference that was not statistically significant. The incidence of agitation in both groups decreased to 7% by the 6-month follow-up.(1) Adverse reactions occurred in a small study of 36 patients with Alzheimer’s dementia. Eight of the 11 withdrawals from the active group reported nausea/vomiting or agitation/aggression within the first 14 days of the trial. No laboratory abnormalities were noted in the study. Even though these adverse reactions are not statistically significant, it is suggested that administration of the acetyl-L-carnitine follow a meal to minimize symptoms.(2)

Based on clinical and experimental research, it seems prudent to:
Administer ALC with food;
Inform patients that ALC may modify alcohol tolerance;
Inform patients/families of potential agitation, nausea or vomiting.

Warning: Drug interactions
If you are currently being treated with any of the following medications, you should not use carnitine without first talking to your healthcare provider.

AZT - In a laboratory study, L-carnitine supplements protected muscle tissue against toxic side effects from treatment with AZT, a medication used to treat human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). Additional studies are needed to confirm whether L-carnitine would also have this effect in people.

Doxorubicin - Treatment with L-carnitine may protect heart cells against the toxic side effects of doxorubicin, a medication used to treat cancer, without reducing the effectiveness of this chemotherapy agent.

Isotretinoin - Isotretinoin, a strong medication used for severe acne, can cause abnormalities in liver function, measured by a blood test, as well as elevations in cholesterol and muscle pain and weakness. These symptoms are similar to those seen with carnitine deficiency. Researchers in Greece showed that a large group of people who had side effects from isotretinoin got better when taking L-carnitine compared to those who took a placebo.

Valproic Acid - The anticonvulsant medication valproic acid may lower blood levels of carnitine and can cause carnitine deficiency. Taking L-carnitine supplements may prevent deficiency and may also reduce the side effects of valproic acid.

Dosage
Most reports of treatment of PD with acetyly-L-carnitine suggest using 1000 mg (1 gram), twice daily, for a total of 2000 mg (2 grams).

Science
L-Carnitine is synthesized in mammalian liver, kidney and brain tissue with lysine, methionine and vitamin C among the required substrates and co-factors. The main body stores are in skeletal and cardiac muscle. Acetyl-L-Carnitine is one of the esters of carnitine and is found along with free plasma carnitine and other esters.(3)

The formation of ALC originates with cytoplasmic thiokinase which forms acylcoenzyme A from free-fatty acids, ATP and Coenzyme A (CoA). This substance is combined with carnitine to form acylcarnitine via carnitine palmitoyltransferase I. Entry into the mitochondrial matrix occurs through an exchange system of acylcarnitine/carnitine via carnitine-acylcarnitine translocase. For each acylcarnitine molecule traversing the inner mitochondrial membrane, a molecule of carnitine is shuttled out. On the inner mitochondrial membrane, carnitine palmitoyltransferase II converts acylcarnitine to carnitine, liberating acylCoA. Finally, the production of ALC and CoA from carnitine and acetylCoA (obtained via ß oxidation of acylCoA) occurs via carnitine acetyltransferase present in the mitochondrial matrix.(4)

Carnitine and its esters prevent toxic accumulations of fatty acids and acylCoA (in the cytoplasm and mitochondria, respectively) while providing acetylCoA for energy generation in the mitochondria. Acetyl-L-carnitine’s enzymatic formation in the mitochondrial matrix is reversible, providing free Coenzyme A and acetylCoA that can readily be exchanged across membranes, thus providing metabolic energy to intracellular organelles.(5)  Carnitine acetyltransferase is a reversible enzyme system that appears to be linked with choline acetyltransferase (ChAT), thereby supplying intracellular acetylcholine while the opposite reaction liberates acetylCoA.

PD Connection
Perhaps the most important discovery about L-carnitine is that its ester form, acetyl-L-carnitine, can easily cross the blood-brain barrier to improve energy transport and repair mechanisms in nerve tissue. Studies show that HIV infection, emphysema,(6-8) mild Alzheimer’s dementia,(9) depression of the elderly(2,10) and diabetic neuropathies(11) may respond positively to acetyl-L-carnitine administration. Effects of acetyl-L-carnitine on ethyl alcohol (ETOH) metabolism have been observed and hold significant potential in preventing sequelae of habitual ETOH abuse.(12)

There is not much direct association of the above listed conditions with PD. However, there is another medical condition that is similar to PD in an important way that has benefitted by treatment with acetyl-L-carnitine. The condition that has some similarity to PD is intermittent claudication, by way of its association to hardening or scarring of the arteries, or atherosclerosis. As was discussed in the vitamin E section, part of the pathology of atherosclerosis has to do with the cellular infiltration with fibrous tissue resulting in hardening and scarring of the wall of the artery. When this process of atherosclerosis occurs in the blood vessels of the legs, people often have leg pain and difficulty walking due to lack of blood flow to the legs – when these symptoms of leg pain after walking occur it is called intermittent claudication. Severe pain may develop after walking just a few minutes or one-half a block. Although carnitine does not increase blood flow, it appears to improve the leg muscle's ability to function with this reduced blood supply.(13) A 12-month trial of 485 people with intermittent claudication studied the benefits of propionyl-L-carnitine using double-blind placebo-controls.(14) People in the study with more severe intermittent claudication showed a 44% improvement in walking distance, compared to the placebo group. However, those with mild intermittent claudication showed no improvement. A similar second double-blind study of 245 people found similar results.(15) Comparable outcomes have been found in other carnitine studies.

There are two important studies in the literature concerning the effects of using carnitine to treat PD. Both of these studies report that carnitine is helpful in treating PD, and one of the two states that acetyl-L-carnitine is more effective for PD than tamoxifen, the most commonly prescribed medication that is used for treating PD. (16,17) Here is how the findings of this study were reported:

These are very impressive results. No wonder many men are excited about using acetyl-L-carnitine for their PD.

There is probably more good science, and the best research results supporting acetyl-L-carnitine treatment of PD than other therapies that are available. It is difficult to ignore acetyl-L-carnitine as a PD treatment when there is so much research pointing in that direction. However, as will always be seen with PD, even this strong research does not clearly make it a proven treatment for PD.(18) It is necessary for the reader to determine, along with his treating physician, if this is a therapy that should be included in the treatment plan for PD.

Carnitine Product Recommendation
The carnitine product PDI recommends is Acetyl-L-Carnitine in a 500 mg capsule, from Douglas Laboratory. Many PD therapy products we suggest come from Douglas Laboratory because we both want to deal with a dependable and well-known company that has earned a great reputation. Maybe you can get a bottle of acetyl-L-carnitine for a few dollars less (and maybe not because PDI's prices are so competitive, but you cannot find a bottle of this high quality acetyl-L-carnitine from a company with a better reputation or at a better price than we charge.  Please be very skeptical about any carnitine product that can be bought for less than what PDI charges.  There is a strong possibility that product will not be what it is claimed to be.  Buyer beware. When all is said and done, you are also buying the confidence that comes from a highly reputable source of pharmaceutical grade nutritional products.

For ideas and suggestions to put this information about carnitine into a treatment plan, click Create a PD Treatment Plan.

Order Acetyl-L-Carnitine

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1. Spagnoli A, Lucca U, Menasce G, et al. Long-term acetyl-L-carnitine treatment in Alzheimer's disease. Neurology. 1991;41:1726–1732.
2. Garzya G, Corallo D, Fiore A, et al. Evaluation of the effects of L-acetylcarnitine on senile patients suffering from depression. Drugs Exp Clin Res. 1990;16:101–106.
3. Goa KL, Brogden A. 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. Drugs 1987;34:1-24.
4. HarperÍs Review of Biochemistry, 23rd Ed. R.K. Murray,D.K. Granner, P.A. Mayes and V.W. Rodwell; Eds. Appleton-Lange Medical Publications pp 220-223.
5. Calvani M, Carta A. Clues to the mechanism of action of acetyl-L-carnitine in the central nervous system. Dementia 1991;2:1-6.
6. Dal Negro R, Pomari G, Zoccatelli O, et al. L-carnitine and rehabilitative respiratory physiokinesitherapy: metabolic and ventilatory response in chronic respiratory insufficiency. Int J Clin Pharmacol. 1986;24:453–456.
7. Dal Negro R, Turco P, Pomari C, et al. Effects of L-carnitine on physical performance in chronic respiratory insufficiency. Int J Clin Pharmacol. 1988;26:269–272.
8. Dal Negro R, Zoccatelli D, Pomari C, et al. L-carnitine and physiokinesiotherapy in chronic respiratory insufficiency. Preliminary results. Clin Trials J. 1985;22:353–360.
9. 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
10. Bella R, Biondi R, Raffaele R, et al. Effect of acetyl-L-carnitine on geriatric patients suffering from dysthymic disorders. Int J Clin Pharmacol Res. 1990;10:355–360.
11. Turpeinen AK, Kuikka JT, Vanninen E, et al. Long-term effect of acetyl-L-carnitine on myocardial 123I-MIBG uptake in patients with diabetes. Clin Auton Res. 2000;10:13–16.
12. Alt Med Rev 1996;1(2):85-93)
13. Sabba C, Berardi E, Antonica G, et al. Comparison between the effect of L-propionylcarnitine, L-acetylcarnitine and nitroglycerin in chronic peripheral arterial disease: a haemodynamic double blind echo-Doppler study. Eur Heart J. 1994;15:1348–1352.
14. Brevetti G, Diehm C, Lambert D. European multicenter study on propionyl-L-carnitine in intermittent claudication. J Am Coll Cardiol. 1999;34:1618–1624.
15. Brevetti G, Perna S, Sabba C, et al. Propionyl-L-carnitine in intermittent claudication: Double-blind, placebo-controlled, dose titration, multicenter study. J Am Coll Cardiol. 1995;26:1411–1416.
16. Biagiotti G, Cavallini G. Acetyl-L-carnitine vs tamoxifen in the oral therapy of Peyronie’s disease: a preliminary report. BJU Int. 2001;88:63-67.
17. Cavallini G, Biagiotti G, , Koverech A, et al. Oral propionyl-L-carnitine and intraplaque verapamil in the therapy of advanced and resistant Peyronie’s Disease. BJU Int. 2002;89:895-900.
18. Fisman M, Mersky H, Helmes E. Double-blind trial of 2-dimethylaminoethanol in Alzheimer's disease. Am J Psychiaty. 1981;138:970–972.

Peyronie's Disease Institute
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Date last modified:  December 20, 2007

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