FM/CFS/ME RESOURCES - Drug Database

Current Issues & Controversies

Carnitine has been studied extensively because it is important to energy production and is a well-tolerated and generally safe therapeutic agent. Researchers prefer to use acetyl-L-carnitine in research studies because it is better absorbed from the small intestine than L-carnitine and more efficiently crosses the blood-brain barrier (i.e., gets into brain tissue).

Athletic Performance
Some athletes take carnitine to improve performance. However, twenty years of research finds no consistent evidence that carnitine supplements can improve exercise or physical performance in healthy subjects—at doses ranging from 2-6 grams/day administered for 1 to 28 days. (The total body content of carnitine is about 20 grams in a man weighing 155 pounds, almost all of it in the skeletal muscle.) For example, carnitine supplements do not appear to increase the body's use of oxygen or improve metabolic status when exercising, nor do they necessarily increase the amount of carnitine in muscle.

Aging
A decline in mitochondrial function is thought to contribute to the aging process. Carnitine may be involved because its concentration in tissues declines with age and thereby reduces the integrity of the mitochondrial membrane. Research in aged rats found supplementation with high doses of acetyl-L-carnitine and alpha-lipoic acid (an antioxidant) to reduce mitochondrial decay. The animals also moved about more and improved their performance on memory-requiring tasks. At present there are no equivalent studies of this kind in humans. However, a meta-analysis of double-blind, placebo-controlled studies suggests that supplements of acetyl-L-carnitine may improve mental function and reduce deterioration in older adults with mild cognitive impairment and Alzheimer's disease. In these studies, subjects took 1.5-3.0 grams/day of acetyl-L-carnitine for 3-12 months.

Cardiovascular and Peripheral-Arterial Disease
Several studies have examined supplemental carnitine in the management of cardiac ischemia (restriction of blood flow to the heart) and peripheral arterial disease (of which the most important symptom is poor circulation in the legs, known as intermittent claudication). Because levels of carnitine are low in the failing heart muscle, supplemental amounts might be beneficial to the organ by counteracting the toxic effects of free fatty acids and improving carbohydrate metabolism. In short-term studies, carnitine has demonstrated anti-ischemic properties when given orally and by injection. A double-blind, placebo-controlled, multicenter clinical trial in Italy with patients who had suffered a first heart attack found that supplemental carnitine (given intravenously for five days, then 6 grams/day orally for one year) reduced heart failure and overall mortality. The results were not conclusive but promising enough to justify a larger study whose results have not yet been reported.

Claudication results from an inadequate supply of oxygen-rich blood to the legs and leads to an accumulation of acetylcarnitine in muscle due to its incomplete utilization. Patients with peripheral arterial disease who develop claudication have significant impairments in exercise performance and find it difficult to walk even short distances at a slow speed. Two published randomized, controlled trials raise the possibility that carnitine may improve the performance of skeletal muscles in the leg. In one European multicenter clinical trial, subjects with moderate to severe claudication who were supplemented with L-carnitine (in the form of propionyl-L-carnitine at 2 grams/day for 12 months) significantly improved their maximal walking distance and perceived quality of life as compared to subjects receiving the placebo. A similar multicenter trial in the United States and Russia found the same daily dose and form of carnitine administered for 6 months in patients with disabling claudication to significantly improve walking distance and speed, reduce bodily pain, enhance physical function, and improve perceived health state as compared to controls.

Cancer
Fatigue resulting from chemotherapy, radiation treatment, and poor nutritional status is common in cancer patients. They may also be deficient in carnitine. In one study, treatment with carnitine supplements (4 grams/day for one week) ameliorated fatigue in most chemotherapy-treated subjects and restored normal blood levels of carnitine. In another trial, terminal cancer patients supplemented with carnitine (doses ranged from 250 milligrams to 3 grams/day) experienced less fatigue and improved mood and quality of sleep. In both studies, most subjects were carnitine deficient before taking the supplements.

Type 2 diabetes
Insulin resistance, which plays an important role in the development of type 2 diabetes, may be associated with a defect in fatty-acid oxidation in muscle. This raises the question as to whether mitochondrial dysfunction might be a factor in the development of the disease. Increased storage of fat in lean tissues has become a marker for insulin resistance. Early research suggests that supplementation with L-carnitine intravenously may improve insulin sensitivity in diabetics by decreasing fat levels in muscle and may lower glucose levels in the blood by more promptly increasing its oxidation in cells. A recent analysis of two multicenter clinical trials of subjects with either type 1 or type 2 diabetes found that treatment with acetyl-L-carnitine (3 grams/day orally) for one year provided significant relief of nerve pain and improved vibration perception in those with diabetic neuropathy. The treatment was most effective in subjects with type 2 diabetes of short duration.

HIV and AIDS
The human immunodeficiency virus (HIV) causes a decline in the number of lymphocytes (one type of white blood cell), resulting in acquired immunodeficiency syndrome (AIDS). HIV-infected individuals often accumulate fat in some areas of the body and lose fat in others and develop high levels of blood fats (hyperlipidemia) and insulin resistance, which together constitute the lipodystrophy syndrome. This syndrome may represent mitochondrial toxicity brought about by the HIV infection and the antiretroviral drugs used to treat it, and can induce a carnitine deficiency that limits mitochondrial fat metabolism. The molecular mechanisms by which this occurs are poorly understood. Preliminary research provides conflicting findings but suggests that supplementation with carnitine both intravenously and orally (at doses of 2-6 grams/day for weeks or months) in HIV-infected individuals may slow the death of lymphocytes (which in turn may slow HIV progression), reduce neuropathy, and favorably affect blood lipid levels.