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Carnitine

Carnitine, also known as L-carnitine is an amino acid responsible for transport of fatty acids into a cell's mitochondria. It is often sold as a nutritional supplement. more...

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Like all other proteinogenic amino acids natural carnitine is the L-stereoisomer. It can be synthesised within the body from the amino acids lysine or methionine. Vitamin C (ascorbic acid) is essential to the synthesis of carnitine. It has been speculated that during growth or pregnancy the requirement of carnitine could exceed its natural production.

Role in fatty acid metabolism

Fatty acids must be activated before they can be carried into the mitochondria, where fatty acid oxidation occurs. This process occurs in two steps:

The formula for the above is:
RCOO- + CoA + ATP + H2O → RCO-CoA + AMP + PPi + 2H+
This reaction is reversible and its equilibrium lies near 1. However, pyrophosphate is hydrolized by a pyrophosphatase, which drives the reaction forward, and to completion.

Once activated, the acyl CoA is transported into the mitochondrial matrix. This occurs via a series of similar steps:

  1. Acyl CoA is conjugated to carnitine by carnitine acyltransferase I located on the outer mitochondrial membrane
  2. Acyl carnitine is shuttled inside by a translocase
  3. Acyl carnitine is converted to acyl CoA by carnitine acyltransferase II located on the inner mitochondrial membrane

It is important to note that carnitine acyltransferase I undergoes allosteric inhibition as a result of malonyl CoA, an intermediate in fatty acid biosynthesis.

Natural sources

The best source of natural carnitine is in red meat and dairy products. Other natural sources of Carnitine include nuts and seeds (e.g pumpkin, sunflower, sesame), legumes or pulses (beans, peas, lentils, peanuts), vegetables (artichokes, asparagus, beet greens, broccoli, brussels sprouts, collard greens, garlic, mustard greens, okra, parsley), fruits (apricots, bananas), cereals (buckwheat, corn, millet, oatmeal, rice bran, rye, whole wheat, wheat bran, wheat germ) and other 'health' foods (bee pollen, brewer's yeast, carob, kale).

Acetyl-L-carnitine

section references:

Acetyl-L-carnitine or ALCAR, is an acetylated form of L-carnitine. ALCAR is far superior to normal L-carnitine in terms of bioavailability in that it is absorbed by the gastrointestinal tract, enters cells and crosses the blood-brain barrier more readily than unacetylated carnitine.

ALCAR has a broad range of uses including combination with alpha lipoic acid to comprise a patented formulation that has been evidenced to "rejuvenate" the mitochondria of aging mice in studies conducted by Bruce Ames and others. Accordingly, acetyl-L-carnitine has potential as a life extension supplement probably capable of improving the quality and possibily also extending the average life-span of humans. Other attributed uses for ALCAR include using it as a treatment for depression (250 mg per day for several weeks) and for clearing plaque/fatty deposits out of the veins and arteries.

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Carnitine
From Gale Encyclopedia of Alternative Medicine, 4/6/01 by Judith Turner

Description

Carnitine is an amino acid that is essential for babies and nonessential for others. In this context, essential means it must be obtained in the diet. Nonessential types of amino acids can be synthesized to some extent within the body. The kidney is able to form carnitine from the amino acids lysine and methionine, in addition to iron and vitamins B6, niacin, and C. The function of carnitine is to mobilize long-chain fatty acids into the powerhouse of the cell, where they are used for energy. Carnitine is necessary for infants to grow and develop normally.

General use

The strongest indication for supplemental carnitine is a genetic defect that causes a deficiency. It may also be inadequately manufactured by babies, particularly those who are premature or have a low birth weight.

Abnormally low levels of carnitine are most commonly associated with a few rare genetic diseases. Symptoms of inadequate carnitine can include confusion, heart pain, muscle weakness, and obesity. Poor consumption of the nutrients required in order to synthesize carnitine also sometimes results in deficiency. These nutrients include lysine, methionine, vitamin C , iron, niacin, and vitamin B6 (pyridoxine). Anyone with a protein deficient diet may have inadequate levels of the building blocks for carnitine. Lysine and methionine are likely to be lacking in a strict vegan diet, although some fortified grains are available. Those who are under severe or chronic health stress are also at higher risk. People who have had surgery, severe burns, or wasting illnesses require higher protein levels, and might benefit from a supplement. The use of supplements containing D-carnitine has the potential to cause L-carnitine deficiency.

The heart is the most carnitine-rich organ in the body, and there are several heart or circulatory conditions that may benefit from more carnitine than is normally in the diet. Carnitine appears to help the heart, a muscle that requires a lot of energy, function better. One of the primary heart problems that can be helped by carnitine supplementation is angina (heart pain due to decreased oxygen because of coronary artery disease). Two studies using L-carnitine, and one using L-propionyl-carnitine, have demonstrated a reduction in symptoms of this condition. When carnitine is added to the treatment plan, it can potentially reduce some of the other medications used to control angina. However, reducing medication for angina patients should be supervised and guided by a healthcare provider.

Intermittent claudication is a condition that develops in some people with severe atherosclerosis. Walking becomes painful as a result of decreased blood flow to the legs. Most studies have shown significant improvement in the distance walked without pain when a supplement of L-propionyl-carnitine was used. The dose used in one study was 0.07 oz (2 g) per day.

When used along with traditionally prescribed medications, carnitine may improve survival rates after a heart attack . Other benefits, including lowering the heart rate, blood pressure, and lipid levels occurred in treated groups. The dose and type used in one study was 0.14 oz (4 g) per day of L-carnitine.

Most studies of carnitine used to improve athletic performance have not shown any benefit. Supplementation may have some minimal effects on Alzheimer's patients; some study groups had slightly slower rates of deterioration. These results remain questionable and further study is needed.

There is some evidence that the use of supplemental L-carnitine, at a dose of approximately 500-1000 mg three times per day, may help to lower levels of serum cholesterol. However, this regimen would be expensive, and there are other effective and less expensive supplements available. These include garlic, red yeast rice, niacin, high fiber diets, and soy proteins.

A condition known as chronic fatigue syndrome (CFS) causes a number of potentially debilitating symptoms, including severe fatigue, muscle pain, and depression. Carnitine may prove helpful in alleviating the symptoms of CFS, perhaps by increasing the efficiency of energy production. One small study used a dose of 0.1 oz (3 g) of L-carnitine per day.

Undocumented claims for the health benefits of carnitine include treatment of Down's syndrome, muscular dystrophy, some forms of male infertility, chronic obstructive pulmonary disease (COPD), and alcoholic fatty liver disease. Carnitine has also been said to reduce the toxicity of AZT, a medication for AIDS.

Preparations

Carnitine is found primarily in meats, but may also be found in avocados, breast milk, dairy products, and tempeh. In the body, it can be synthesized in the kidney from lysine and methionine. Supplements are available in capsules, but are generally quite expensive.

Several forms of oral carnitine are available, including L-carnitine, D-carnitine, and DL-carnitine. The latter two forms are often found in over-the-counter nutritional products and supplements. They are associated with more adverse effects. Products containing D-carnitine and DL-carnitine should be avoided. L-acetyl-carnitine and L-propionyl-carnitine are acceptable alternative formulations that may be recommended for specific conditions.

Precautions

Women who are pregnant or may become pregnant should not take carnitine supplements. Breastfeeding mothers should also avoid them, since they may not be safe for infants in this situation. Babies requiring a supplement due to low birth weight or pre-term conditions should have it prescribed and monitored by a healthcare provider. Those with food allergies to proteins are at risk of adverse reactions to carnitine. People who have chronic liver disease are at risk of having high carnitine levels due to their illness and should not take carnitine supplements.

Side effects

L-carnitine taken by mouth has been known to cause gastrointestinal symptoms, including nausea, vomiting, cramps, and diarrhea. DL-carnitine is sometimes associated with a syndrome of severe weakness and wasting of muscle, particularly in patients with kidney disease who have been on long-term hemodialysis.

Interactions

Valproic acid, a drug sometimes used to treat seizures, is more likely to cause toxicity if the patient under treatment has a carnitine deficiency. The drug may cause decreased carnitine levels. A healthcare provider should be consulted regarding the advisability of taking supplemental carnitine under those circumstances. Supplements of carnitine may increase the effects of the anticoagulant medication warfarin.

Key Terms

Amino acids
Building block units that compose proteins.
Anticoagulant
Substance that inhibits blood clotting, used therapeutically for such things as stroke prevention in susceptible people.
Atherosclerosis
Deposition of fatty plaque on the inner wall of arteries, hindering blood flow.
Vegan
A person who doesn't eat any meat or animal products, including dairy and eggs.

Further Reading

For Your Information

Books

  • Balch, James, and Phyllis Balch. Prescription for Nutritional Healing. New York: Avery Publishing Group, 1997.
  • Bratman, Steven, and David Kroll. Natural Health Bible. Prima Publishing, 1999.
  • Griffith, H. Winter. Vitamins, Herbs, Minerals & Supplements: The complete guide. Arizona: Fisher Books, 1998.
  • Jellin, Jeff, Forrest Batz, and Kathy Hitchens. Pharmacist's Letter/Prescriber's Letter Natural Medicines Comprehensive Database. California: Therapeutic Research Faculty, 1999.
  • Pressman, Alan H., and Sheila Buff. The Complete Idiot's Guide to Vitamins and Minerals. New York: Alpha books, 1997.

Gale Encyclopedia of Alternative Medicine. Gale Group, 2001.

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