Using L-Carnitine

Individuals taking adefovir dipivoxil (brand name Preveon) also need to take a nutritional supplement known as L-carnitine.

The reason is that dipivoxil, the molecule attached to the active part of adefovir dipivoxil and needed for absorption of the drug, combines with a significant percentage of carnitine is lost through urination. Carnitine is critically important in the production of energy from fat in the heart and skeletal muscles. One of the deficiency symptoms of carnitine is progressive muscle weakness.

Carnitine is a natural substance found in food and made from the essential amino acids, lysine and methionine. Carnitine can be absorbed quickly in the small intestines. Carnitine can also be made in the liver and the kidneys and where vitamin C, niacin, vitamin B6 and the mineral iron, are required for that process. Only the L-carnitine form should be used as a supplement.

Triglycerides

The majority of dietary and body fats are made up of triglycerides: 95 percent in the diet and 90 percent in the body. Triglycerides also circulate in the blood.

"Triglycerides" is a term for molecules that have three fatty acids attached to glycerol, which acts as a "backbone" to the triglyceride molecule. There are many types of fatty acids and which three fatty acids are attached to that glycerol backbone determines what that fat looks like and what kind of properties it has. For example, olive oil looks, tastes and acts differently in cooking and in our bodies than, say, the fat found in ground meat.

The fatty acid may be of different lengths. It may be a short-, medium- or long-chain fatty acid. It is the length of the fatty acid that determines the melting point of the fat, and implications for food processing and absorption.

Carnitine works mostly in the muscle cells of the body. In the muscle cell, carnitine is the molecule that transports long-chain-fatty acids across the membrane of the mitochondria. The mitochondria, the structure where energy is produced, is often called the "powerhouse of the cell." Medium-chain-fatty acids do not require carnitine to enter the mitochondria, however, carnitine is needed to stimulate its energy production.

Heart and skeletal muscles depend upon fatty acids as a major source of energy. If fatty acids are not available, other sources of stored energy for the body must be used. These sources of energy are the protein found mostly as muscle and organ tissue, and glucose, found as glycogen stored in limited amounts.

How much is enough?

No recommendations have been established for a daily dietary allowance for carnitine.

Most healthy adults with adequate intake of a good variety of food seem to be able to make enough carnitine. Some people who do not have a dietary intake of carnitine for an extended period of time -including those with muscle disease, cardiac disease, liver disease and kidney disease- may be at risk for carnitine deficiencies.

Some groups of people with HIV may be at higher risk for carnitine deficiencies resulting from "nutritional deficiencies, gastrointestinal disturbances, renal losses or shifts in metabolic pathways." The effect of some drugs, especially AZT, on carnitine has been considered a "major etiology concern," according to a report in the Journal of Child Neurology. In addition, there has been some indication that carnitine supplementation may be helpful in the reduction of elevated triglycerides, a growing problem for many on combination therapies.

Usual intakes of carnitine for non-vegetarian persons average 100-300 mg a day. Greatest quantities of carnitine are found in animal products. According to Recommended Dietary Allowances, published by the National Research Council, the redder the meat, the higher the carnitine concentration. It is the whey portion that contains the main amount of carnitine in dairy products.

Side effects

No significant toxicities are associated with pharmaceutical grade L-carnitine (purity in over-the-counter L-carnitine may vary because nutritional supplements are not regulated adequately). Carnitine oral supplements have been known to cause nausea and diarrhea, especially at the beginning of usage. Reducing the dose to relieve the symptoms and then gradually increasing it to desired levels is reported to be helpful.

Nausea and diarrhea have been observed in clinical trials of adefovir dipivoxil. Whether it was actually the drug or carnitine that caused the GI upset is not known, however, taking the drug and carnitine together with a meal helped reduce these symptoms. Bioavailability of the drug is a little better when taken with a meal (40 percent) than when taken without food (30 percent). D,L-carnitine, another form of carnitine, has been found to cause symptoms of muscle fatigue and should not be used.

The expanded access program for adefovir dipivoxil supplies 500 mg of L-carnitine with the drug, which is approximately three times the amount of carnitine that was found lost due to taking the drug. The L-carnitine supplied with adefovir dipivoxil is an over-the-counter product. Company representatives of Gilead Sciences, Inc. feel confident about its quality and stressed that it is from a single supplier which has been evaluated for its good manufacturing practices. It is anticipated that L-carnitine will continue to be required with adefovir dipivoxil and supplied to all patients.

Ernie Rodriguez is a treatment advocate in AIDS Project Los Angeles' Treatment Education Program and may be reached at erodriguez@apla.org.

Marcy Fenton, M.S., R.D., is AIDS Project Los Angeles' HIV nutrition advocate and may be contacted by e-mail at mfenton@apla.org.