Alpha Lipoic Acid:
The Universal Antioxidant

This section is compiled by Frank M. Painter, D.C.
Send all comments or additions to:    Frankp@chiro.org

From The October 2000 Issue of Nutrition Science News

by David Wolfson, N.D.

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Move over vitamins C and E, there is another antioxidant in town said to provide a far wider range of benefits. Lipoic acid, which is the priority name according to the American Society of Biological Chemistry, is also known as alpha-lipoic acid and thioctic acid. Like other antioxidants, lipoic acid has the ability to scavenge the body for disease-causing free radicals; however, that appears to only scratch the surface of this supplement's benefits. Antioxidants are substances that inhibit oxidation of cells by neutralizing free radicals. Free radicals are highly reactive molecules that contain one or more unpaired electrons and cause damage by "stealing" electrons from other molecules such as DNA, fats and proteins. Antioxidants prevent this damage by donating electrons to the radical, preempting its need to "steal" and thus neutralizing the radical's reactivity.

Antioxidants typically come in two varieties: water soluble and fat soluble. A few, such as lipoic acid, are both. This dual nature allows lipoic acid to function in both fatty and aqueous regions of the body, an ability that is the reason why lipoic acid is often termed "universal antioxidant."

In the 1950s, lipoic acid was first identified as a component of several human enzyme systems involved in the conversion of carbohydrates and fats into energy. As such, it became known as a co-factor for energy production, similar in function to many of the B vitamins. Unlike the Bs, however, lipoic acid was not classified as a vitamin because small amounts of it can be synthesized by the body. Although it is now known that certain vitamins such as A, D and K are indeed synthesized in the body, their designation has not changed.

Scientific interest in lipoic acid shifted during the 1960s from its physiological role to its potential for therapeutic applications. After noticing lower serum levels of lipoic acid in individuals suffering from diabetes, liver cirrhosis and other diseases, a group of German physicians began administering lipoic acid to patients in order to help them overcome the deficiency. In doing so, the physicians found that orally administered lipoic acid is both well absorbed from the gastrointestinal tract and widely distributed throughout the body. Further studies revealed that oral lipoic acid exhibits significant antioxidant activity, leading researchers to consider its potential for preventing and treating disease. [1] Several decades of research on lipoic acid have enabled researchers to identify four main areas of this supplement's antioxidant function as well as numerous functions specific to particular illnesses.

Free radical scavenging:   Lipoic acid is one of the most versatile antioxidants known. Aside from its ability to function in both aqueous and lipid media, lipoic acid is capable of neutralizing a wide variety of free radicals: singlet oxygen, superoxides, peroxyl and hydroxyl radicals, hypochlorite, and peroxynitrite. [2] These types of radicals are believed to play a significant role in disease processes such as hardening of the arteries (atherosclerosis), cancer, cataract formation and diabetes.

Metal chelation:   In vitro tests show that lipoic acid, like other antioxidants, forms insoluble complexes with toxic metals such as arsenic, cadmium, lead and mercury. In other words, by binding to these substances, it pulls them out of circulation and facilitates their excretion, thereby preventing damage to body tissue. While human trials have yet to be performed, animal studies have demonstrated that lipoic acid can effectively prevent intoxication by these metals. For instance, a rat study conducted by R. Sumathi and colleagues at the University of Madras in India showed that pretreatment with lipoic acid significantly decreased liver damage and overall toxicity after exposure to cadmium as compared to controls. [3]

Antioxidant regeneration:   Once an antioxidant neutralizes a free radical it usually loses its antioxidant ability. In living systems, however, antioxidants can be regenerated, often with the help of other antioxidants. Glutathione, for example, can regenerate vitamin C. Vitamin C can in turn regenerate vitamin E. True to its versatile nature, lipoic acid has, in lab studies, regenerated a variety of antioxidants including glutathione, vitamins C and E, and the mitochondrial antioxidant coenzyme Q10. [4]

Damaged molecule repair:   Free radical activity causes damage to physiological structures such as DNA, lipids and proteins. Living organisms have developed a number of mechanisms to repair some of this damage. Studies show that by donating electrons to certain key enzyme systems, lipoic acid plays a role in the repair of oxidatively damaged molecules. [5]

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Specific Applications

Lipoic acid's broad range of antioxidant effects makes it an excellent candidate for therapeutic applications. Results of both animal and human studies suggest a number of clinical uses. Following are some examples.

Atherosclerosis protection:   In animal models of atherosclerosis, characterized by buildup of plaque in the arteries, lipoic acid has been shown to have a protective effect. In one such study, conducted by the Department of Poultry Science, North Carolina State University in Raleigh, atherosclerotic lesions were induced in two groups of Japanese quail that had been fed an atherogenic diet. One of the groups also received lipoic acid and exhibited 75 percent fewer atherogenic lesions than the control group. The researchers concluded that lipoic acid may guard against atherosclerosis by preventing oxidation of LDL cholesterol and/or by recycling vitamin E. [6]

Cataract protection:   Additional animal studies have demonstrated that lipoic acid might also be protective against cataract formation. Cataracts are associated with reduced antioxidant activity in the lens of the eye, and lipoic acid is known to regenerate several important lens antioxidants, including glutathione. Results of one rat study conducted by I. Maitra and colleagues at the University of California, Berkeley, showed a lipoic acid dose of 25 mg/kg body weight protected 60 percent of
the animals from cataract formation. [7] Although further testing is needed to confirm these benefits in humans, the results to date seem promising.

Protection against irradiation:   In one very interesting Russian study involving Chernobyl radiation victims, lipoic acid was shown to reduce free radical damage caused by radiation exposure. One group of 16 children given 400 mg of lipoic acid daily for 28 days showed significant reductions in both white blood cell free radical activity and urinary excretion of radioactive isotopes compared to a control group of 12 children.

A second group of 14 children given 400 mg lipoic acid plus 200 mg vitamin E daily for 28 days showed an even greater reduction in urinary excretion as compared to both the lipoic acid and control groups. [8]

HIV treatment:   Based in its antioxidant regenerative properties, lipoic acid has been shown to improve the antioxidant status in a group of 11 HIV-infected patients. In a study conducted in Germany, researchers administered 450 mg lipoic acid per day for 14 days and found significant increases in plasma vitamin C and glutathione in a majority of the patients. These observations coincided with a decrease in blood peroxidation products and improvements in white blood cell counts. [9]

Diabetes therapy:   Perhaps the most widely noted clinical application of lipoic acid is in the treatment of diabetes and its complications. Diabetics frequently suffer from peripheral neuropathy, a degenerative nerve condition that involves numbness, tingling and sometimes burning pain in the extremities. Studies indicate lipoic acid can help reduce these nerve dysfunction symptoms.

The exact mechanism behind this pain relief is not clear; however, it is believed that lipoic acid prevents free radical damage within nerve cells. In one randomized, double-blind, placebo-controlled, multicenter study conducted in Germany, 82.5 percent of a group of 63 non-insulin-dependent (Type II) diabetics with peripheral neuropathy experienced a significant reduction in their symptoms after three weeks of daily intravenous infusions of 600 mg of lipoic acid. The lipoic acid group reported fewer adverse effects than the plecebo group. [10] Considering lipoic acid is well absorbed from the gastrointestinal tract, similar results may be expected from an oral dose.

Besides relieving neuropathy, lipoic acid offers diabetics the additional benefit of reducing insulin resistance, the inability of insulin receptors to effectively uptake glucose at the cellular level. Insulin resistance appears to be the underlying problem for many people with Type II diabetes. To compensate, the pancreas secretes large amounts of insulin, resulting in hyperinsulinemia. Individuals whose bodies compensate in this way may be at increased risk for developing heart disease and hypertension as a result of their hyperinsulinemic condition.

Studies indicate that lipoic acid can reduce hyperglycemia and may be a safer alternative to oral hypoglycemic agents. [11, 12] In one recent multicenter, placebo-controlled trial performed in Germany, 74 Type II diabetic patients received either 600, 1,200 or 1,800 mg lipoic acid daily or a placebo. After four weeks, all treatment groups showed an improvement in glucose disposal compared to placebo, with no significant differences between the lipoic acid groups. The combined results of the treated groups vs. the placebo group showed a 27 percent increase in insulin-stimulated glucose uptake. Furthermore, no serious side effects were noted in any of the treatment groups. [13 ](Type I diabetics should consult with their physician before using lipoic acid as it may necessitate a change in their insulin dosage.)

A mere 1 g of lipoic acid has been shown to exert numerous therapeutic applications, and it has proven to be virtually free of side effects. [2] Furthermore lipoic acid is capable of chelating heavy metals, regenerating other antioxidants, repairing damaged molecules and mitigating the oxidative damage caused by free radicals.

In his book on lipoic acid, The Antioxidant Miracle (John Wiley & Sons, 1999), Lester Packer, Ph.D., one of the foremost experts on antioxidants, recommends regular daily supplementation with 100 mg of lipoic acid. [14 ]People with established health problems may wish to increase their daily dose to the 400 to 600 mg range, or work with their health care practitioner to achieve the optimal dose for their particular condition.

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David Wolfson, N.D., is a naturopathic physician, nutrition educator and writer, as well as a consultant to the natural products industry.

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References

1. Fuchs J, et al., editors.
Lipoic acid in health and disease.
New York: Marcel Dekker Inc.; 1997.

2. Biewanga G, et al.
The pharmacology of the antioxidant lipoic acid.
Gen Pharmac 1997;29(3):315-31.

3. Sumathi R, et al.
Relationship between glutathione and DL alpha-lipoic acid against cadmium-induced hepatotoxicity.
Jpn J Med Sci Biol 1996;49(2):39-48.

4. Packer L, et al.
Alpha-lipoic acid as a biological antioxidant.
Free Rad Biol Med 1995;19(2):227-50.

5. Spector A, et al.
Thioredoxin fragment 31-36 is reduced by dihydrolipoamide and reduces oxidized protein.
Biochem Biophys Res Commun 1988;150:156-62.

6. Shih JCH.
Atherosclerosis in Japanese quail and the effect of lipoic acid.
Fed Proc 1983;42:2494-7.

7. Maitra I, et al.
Alpha-lipoic acid prevents buthionine sulfoximine-induced cataract formation in newborn rats.
Free Rad Biol Med 1995;18:823-9.

8. Korkina L, et al.
Antioxidant therapy in children affected by irradiation from the Chernobyl nuclear accident.
Biochem Soc Trans 1993;21:314S.

9. Fuchs J, et al.
Studies on lipoate effects on blood redox state in human immunodeficiency virus infected patients.
Arzneim-Forsh 1993;43(2):1359-62.

10. Ziegler D, et al.
Treatment of symptomatic diabetic peripheral neuropathy with the antioxidant alpha-lipoic acid:
a 3-week multicentre randomized controlled trial (ALADIN study).
Diabetologia 1995;38:1425-33.

11. Jacob S, et al.
Improvement of insulin-stimulated glucose disposal in type 2 diabetes after repeated
parenteral administration of thioctic acid.
Exp Clin Endocrinol Diabetes, 1996;104:284-8.

12. Konrad T, et al.
Alpha lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves
glucose effectiveness in lean and obese patients with type 2 diabetes.
Diab Care 1999;22:280-7.

13. Jacob S, et al.
Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2
diabetes mellitus: aplacebo-controlled pilot trial.
Free Rad Biol Med 1999;27(3/4):309-14.

14. Packer L, Colman R.
The antioxidant miracle.
New York (NY):John Wiley & Sons Inc.; 1999. p 32

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