Alpha-Lipoic Acid: Not the Average Antionidant
Today’s Dietitian
By Leslie K. Kay, MS, RD
Vol. 6 No. 4 p. 56

Alpha-lipoic acid (ALA) is a unique enzyme present in the mitochondria and a dietary supplement ingredient promoted to treat diabetes, retinopathy, cataracts, HIV/AIDS, cancer, and lactic acidosis caused by inborn errors of metabolism and liver disease.

As an enzyme in the body, ALA is involved in cellular energy production; however, its chief role as a dietary supplement may be as a powerful antioxidant that works synergistically with other antioxidants such as vitamins C and E. ALA has been shown to combat oxidative stress by quenching a variety of reactive oxygen species (free radicals).

The body appears to be able to manufacture enough ALA for its metabolic functions (as a cofactor for a number of enzymes involved in converting fat and sugar to energy), but the excess levels provided by supplements allow ALA to circulate in a “free” state. In this state, ALA functions as both a water- and fat-soluble antioxidant. This unique ability of ALA to be active in water and lipid compartments of the body is important because most antioxidants, such as vitamins C and E, are effective in only one area or the other. Vitamin C is usually restricted to the interior compartment of cells and the watery portion of blood, while vitamin E embeds itself in the fatty portion of cell membranes.

Adding to the potential importance of ALA is its role in the production of glutathione, one of the chief antioxidants produced directly by the body. ALA has been shown to be involved in the recycling of other antioxidants in the body, including vitamins C and E and glutathione.

SUPPORTIVE CLAIMS FOR ALA
ALA prevents cellular damage (from free radicals), reduces oxidative stress, lowers blood sugar, and increases energy levels.

ALA may be helpful in patients with diabetes in a number of ways. ALA is frequently prescribed in Europe as a treatment for diabetic peripheral neuropathy, a common complication of diabetes that can cause significant morbidity and mortality. Some 30% of hospitalized and 20% of community-dwelling diabetes patients have peripheral neuropathy; the annual incidence rate is approximately 2%. The primary risk factor is hyperglycemia. A number of studies supplementing with ALA demonstrated an improvement in insulin sensitivity by possibly promoting the production of energy from fat and sugar in the mitochondria. Patients who took 600 to 1,800 milligrams daily of ALA had significant improvement in insulin resistance and glucose effectiveness after four weeks.1 ALA doesn’t seem to lower glycosylated hemoglobin levels in patients with type 2 diabetes.

Giving ALA seems to reduce symptoms of peripheral neuropathy in diabetes patients, such as burning, pain, numbness, and prickling of the feet and legs. It also seems to improve objective measures such as ratings of neurological deficit and disability. Onset of symptom improvement occurs within three to five weeks; however, lower doses have not been shown to be effective.2,3

ALA has been used in Germany for more than 30 years. The American Diabetes Association has also suggested that ALA plus vitamin E may be helpful in combating some of the other health complications associated with diabetes, including heart disease, vision problems, nerve damage, and kidney disease. ALA has also been implicated in helping protect the brain from damage following a stroke.

Clinical trials support the effectiveness of ALA in the treatment of diabetes and peripheral neuropathy; however, research is lacking to support its use in treating alcohol-related disease and HIV dementia. People with alcohol-related liver disease taking ALA orally 300 milligrams per day for six months did not demonstrate significant improvement compared with placebo. The antioxidant effects of ALA might be beneficial in liver diseases in which oxidative stress is a factor. ALA has shown promise in experimental models to prevent heavy metal (lead, arsenic, cadmium, mercury) and chemical (hexachlorobenzene, hexane) poisoning. Children treated with ALA, alone or in combination with vitamin E, showed normalized organ function and lessened indices of oxidative damage following radiation exposure in the Chernobyl accident.

Preliminary data suggests that ALA can inhibit replication of the HIV by inhibiting reverse transcriptase. ALA might increase the T helper/suppressor ratio in patients infected with HIV. In a small trial comparing ALA alone or in combination with selegiline (Deprenyl) and placebo, taking ALA orally had no effect on HIV-associated cognitive impairment.

Preliminary data suggest that antioxidant effects of ALA might provide protection in cerebral ischemia, excitotoxic amino acid brain injury, mitochondrial dysfunction, and other causes of damage to brain or neural tissue. Preliminary evidence suggests that ALA and vitamin E might prevent oxidative stress in cardiac ischemia injury. Case reports indicate that it may be helpful in various inborn errors of metabolism that result in lactic acidosis.4

SIDE EFFECTS and ADVERSE REACTIONS
Therapeutic amounts of ALA appear to be safe; however, skin rash has been reported after dietary supplement use. Laboratory studies suggest that very large doses of ALA can cause fatal toxicity in thiamin-deficient animals. For people taking high doses of ALA and who are at risk for thiamin deficiency (eg, alcoholics), thiamin supplementation may be warranted.

INTERACTIONS WITH HERBS AND/OR DRUGS
Theoretically, herbs that increase blood glucose levels might antagonize the antidiabetic effects of ALA. Herbs with hyperglycemic potential include ephedra, ginger, gotu kola, and the above-ground parts of the stinging nettle.

Theoretically, ALA might have additive effects with herbs that decrease blood glucose levels. Herbs with hypoglycemic potential include devil’s claw, fenugreek, garlic, guar gum, horse chestnut seed, Panax ginseng, psyllium, and Siberian ginseng.

Theoretically, ALA and hypoglycemic agents might cause additive hypoglycemic effects.

PRACTICAL TIPS
Taking ALA with food decreases bioavailability; therefore, ALA should ideally be taken on an empty stomach. In addition, ALA is approximately 30% absorbed from dietary or supplemental sources; hence, many of the research studies used an intravenous form of ALA. Since most dietary supplements include only roughly 50 milligrams of ALA per tablet, it would be very difficult to achieve therapeutic doses (600 to 1,200 milligrams daily) used in clinical studies.

— Leslie K. Kay, MS, RD, is a speaker on the topic of dietary supplements.

References for this article are available upon request by e-mailing TDeditor@gvpub.com.

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