In the last issue of the Perspective, we reported on mitochondrial dysfunction as a possible suspect in causing lipodystrophy, the fat redistribution syndrome being experienced by many people with HIV. Since then, additional information has been presented on mitochondrial toxicity by Glaxo-Wellcome as a result of ongoing research it is conducting regarding lipodystrophy. This article will review the basic information that is leading scientists and researchers to suspect mitochondrial toxicity as a factor in lipodystrophy syndrome. Further, proposed therapies for lactic acidosis (lactic acid in the blood) and other mitochondrial toxicities will be explored.

Mitochondria are the energy powerhouses within cells. Each individual cell contains hundreds of mitochondria, and the number of mitochondria in a cell is determined by the specific energy demands of that cell. Healthy mitochondria are important because they play a critical role in the production of energy for the cell. When mitochondria do not function properly, cells fail to get the energy they need to regulate a variety of bodily functions and the result can be serious health complications for the affected person.

Mitochondrial dysfunction occurs when mitochondria with altered DNA replicate. When a majority of a cell's mitochondria (in the range of 70% to 95%) have altered DNA, specific symptoms of mitochondrial disease may occur. These symptoms include increased lactate production, which can lead to lactic acidosis, and possibly lipodystrophy. Suspected causes of mitochondrial dysfunction in people with HIV are:

• Use of protease inhibitors (PIs).

• Use of certain nucleoside analogs, especially Zerit (d4T).

• The duration of time a person has been on antiviral therapy.

• Exposure to the HIV virus and other viruses.

• Combination of the above.

Those of us living with HIV and taking antivirals are familiar with the many side effects that may be attributed to mitochondrial dysfunction. Some of these side effects include fat redistribution syndrome, commonly referred to as lipodystrophy. Lipodystrophy includes increased fat in the neck or stomach; loss of subcutaneous fat from the face, arms, or legs; or enlarged breasts. Additional side effects associated with mitochondrial toxicity are hair loss; numbness and pain in the hands, arms, feet, and legs; muscle disease; heart disease; inflammation of the pancreas; increased acidity of the blood; and kidney irregularities.

Much attention has been given to fat redistribution because of the very visible nature of this side effect. However it is important to be aware of all of the side effects, due to the serious and life-threatening complications they can present. Unfortunately, there are few therapies currently offered that specifically address mitochondrial dysfunction as the underlying cause of these side effects. The following is a review of some proposed therapies and how they might work to reduce mitochondrial toxicity and resulting side effects.

L-Carnitine

L-carnitine is a nutritional supplement that helps the body to burn fat as fuel. It plays a vital role in glycogen storage, which is important for strength and endurance. Glycogen is important as a principal carbohydrate reserve and is necessary for adequate energy supplies for tissues and cells in the body. L-carnitine has many possible benefits in promoting good health, including the following:

• Better use of fat and better fat absorption.

• Improved energy use in cells regulating the heart.

• Improved sugar balance.

• Improved fertility related to certain sperm dysfunctions.

L-carnitine is an amino acid that can be purchased from most health food stores and in some grocery stores; no prescription is needed. By improving the way energy supplies in cells are used, L-carnitine may help people experiencing fat loss and/or gain through better fat processing and storage. Dosing levels between one and three grams per day are believed effective. Additional information on L-carnitine is available through websites or your nutritionist.

Co-Enzyme Q-10

Co-Enzyme Q-10 (a.k.a. "Co-Q-10") is a naturally occurring nutrient found primarily in the heart. Co-Q-10 helps regulate the energy production and energy utilization of the mitochondria, which is vital to good cellular function. Supplementation with Co-Q-10, is believed to help maintain adequate levels of this nutrient in the body, promoting good mitochondrial and cellular function. A possible outcome of this may be a reduction in the symptoms of drug or disease-induced mitochondrial toxicities being experienced by people with HIV.

Co-Q-10 is available without a prescription at most health food stores. All the research on Co-Q-10 strongly recommends the "soft-gel capsules." Absorption using the soft-gel capsules is reported to be in the 60% to 80% range. Powder capsules are also available, but absorption is reported to be much lower, in the 15% to 20% range. No toxicity has ever been reported with Co-Q-10, and famed nutritionist and physician Dr. Andrew Weil reports that he takes 100 milligrams once a day as a general health booster. The cost of Co-Q-10 is relatively high compared to other supplements, but buyers clubs and local discount vitamin and nutrition outlets may be able to offer some savings.

Riboflavin

Also known as vitamin B2, adequate levels of riboflavin are necessary for good red blood cell formation. This vitamin may also help in the production of antibodies to fight off infection, and helps to eliminate abnormal cells and free radicals that place stress on the immune system and may cause mitochondrial dysfunction. Good natural sources of riboflavin are green leafy vegetables and nuts. Riboflavin can also be acquired through supplementation and can be purchased over the counter at any health food store. It is best taken as a part of an overall vitamin supplementation program.

A Few Cautions

Co-Q-10 has been studied in various settings in the United States and Europe as a weight loss supplement. In separate studies at the University of Texas and the University of Antwerp, Co-Q-10 was shown to help obese people lose weight simply by the addition of the nutrient to the diet. These studies help validate the indication of Co-Q-10 supplementation as a possible strategy for treating lipodystrophy. However, if a person is already experiencing weight loss due to HIV or antiretroviral drugs, Co-Q-10 might make the situation worse. If weight loss has been a problem for you, consult your physician before taking Co-Q-10. It is important to remember that in lipodystrophy total body fat is not increased, but rather the distribution of the fat is changed.

The current treatment options for lipodystrophy are extremely limited, and better treatment options will probably not be available until more is known about the specific cause or causes of the syndrome. Mitochondrial toxicity is but one of several "suspects" in the search for a cause of lipodystrophy syndrome. The suggestions for nutritional and supplement therapies presented here are premised on mitochondrial toxicity as causal factors in lipodystrophy syndrome. This is only a hypothesis, and more studies and research on lipodystrophy are required before better therapies can be found to address this growing concern of people living with HIV.