In recent years, increasing attention has been paid to the group of vitamins, minerals, and enzymes known as antioxidants. Some of the better known antioxidants are vitamins A, C and E, beta-carotene, selenium, and melatonin. Antioxidants play an important role in preventing aging-related degenerative conditions through their actions in fighting free radicals. Free radicals are wastes generated by the regular metabolic processes in the cells. Free radicals are normally present in the body and actually serve useful purposes, such as aiding in the production of hormones and activating enzymes. However, when there is an excess of free radicals in the body, they become destructive.

In addition to being by-products of normal metabolic processes, free radicals also can result from exposure to radiation, toxic chemicals (such as those contained in cigarette smoke, automobile exhaust, and other environmental pollutants), and from overexposure to the sun's rays. Free radicals are atoms or molecules that contain unpaired electrons. They tend to bind to other molecules, causing chemical reactions that can be destructive to the body. They can damage cells, interfere with the immune system, and contribute to degenerative diseases such as cancer and cardiovascular disease. In fact, free radical damage may be the basis for the aging process. Antioxidants bind with these reactive molecules to counteract their harmful effect.

The antioxidant alpha-lipoic acid (also called thioctic acid) is made by the body and directly supports detoxifying abilities of the liver. It enhances the antioxidant functions of vitamins C and E and glutathione. Alpha-lipoic acid has growth-stimulating properties, prevents cell damage, regulates blood sugar, and chelates toxic metals out of the blood. In animal studies, it has been shown to enhance cognitive function as well. It is also involved in the production of muscular energy and directs calories toward energy production. Because it is both water- and fat-soluble, alpha-lipoic acid is able to function in almost any part of the body, including the brain.

Dietary sources of alpha-lipoic acid include the following:

• Spinach
• Broccoli
• Beef
• Yeast
• Kidney
• Heart

Alpha-lipoic acid, along with glutathione, is one of the thiol antioxidants. It is a carboxy acid with two sulfur atoms in its molecule, and occurs as an amide in plant and animal tissues.

Alpha-lipoic acid is available commercially in capsule form.

Because alpha-lipoic acid relieves stress on the liver and directly supports its detoxifying functions, it has been used in the treatment of chronic hepatitis and Amanita (a particularly toxic mushroom) poisoning. It is able to bind to toxic metals and is used for heavy metal detoxification. Alpha-lipoic acid can help eliminate toxic effects of anesthesia, analgesics, or other drugs used in the course of surgery, and to ease subsequent pain. A recommended dose is two 100-mg capsules tid one week before surgery and two weeks postoperatively.

The thiols are central to antioxidant defense in the brain. Alpha-lipoic acid has a low molecular weight; it is readily absorbed from nutritional sources and crosses the blood-brain barrier. Current research indicates that alpha-lipoic acid and its metabolite dihydrolipoate have protective effects on brain and neural tissue. Preliminary human studies support conclusions of animal and in vitro studies showing a role for alpha-lipoic acid in the treatment of stroke and other brain disorders involving free radical damage. In an animal study, treatment with alpha-lipoic acid was associated with a four-fold increase in stroke survival.

Alpha-lipoic acid has shown great promise in the treatment of nerve dysfunction in diabetics. Diabetes mellitus is associated with free radicals; studies with diabetics have revealed oxidative stress loads. In more than one study, treatment with alpha-lipoic acid has significantly reduced the pain, burning, paresthesia, and numbness associated with diabetic neuropathy. Alpha-lipoic acid has also been shown to increase glucose transport in diabetics, and to lead to improved heart rate variability.

Currently, no recommended dosages have been established for alpha-lipoic acid. Alpha-lipoic acid manufacturers suggest one or two 50-mg capsules daily as a dietary supplement.

Studies investigating the effects of alpha-lipoic acid on nerve damage related to diabetes found no side effects at the dosage levels they were testing.

Diabetics should take ALA with caution as it can cause hypoglycemia.

Supplementation with alpha-lipoic acid (100 mg/kg/day) in rats treated with amikacin significantly reduced cochlear damage caused by ototoxic doses of this drug (Conlon et al. 1999). Treatment with alpha-lipoic acid (25 mg/kg/day) also ameliorated the oxidative stress caused by gentamicin (100 mg/kg/day) in rats (Sandhya and Varalakshmi 1997). Gentamicin-induced oxidative stress is thought to underlie the potentially serious renal side effects associated with this drug.

A study comparing alpha-lipoic acid at several different doses (25 to 100 mg/kg), with and without cisplatin, concluded that the alpha-lipoic acid conferred significant protection against cisplatin ototoxicity at all dose levels in rats (Rybak et al. 1999). This effect was associated with improvements in glutathione metabolic markers and reduced oxidative stress.

Preclinical evidence suggests that alpha-lipoic acid may protect against the cytotoxic effects induced by cyclophosphamide (Faust et al. 1994). Supplementation with alpha-lipoic acid significantly reduced the incidence of cyclophosphamide-induced diabetes in mice.

In rats, alpha-lipoic acid (7.5 mg/100 g/day) inhibited enzymatic conversion of triiodothyronine (T₃) to thyroxine (T₄) (Segermann et al. 1991). Alpha-lipoic acid supplementation with T₄ also had an apparent synergistic effect on serum cholesterol, producing significantly greater depression than T₄ alone. Blood hormone levels and thyroid function tests should be monitored for this potential interaction.

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