Alpha-Lipoic Acid (ALA)

Overview

Alpha-lipoic acid is one of the most powerful antioxidants ever discovered. It is a vitamin-like sulfur-containing compound that is synthesized naturally in the human body. Sometimes it is referred to as alpha-lipoate, thioctic acid, or just lipoic acid. One of its most important characteristics is that it is both fat-soluble and water-soluble. This enables it to provide antioxidant protection in a much wider range of physiological environments throughout the body, which has resulted in some scientists referring to alpha-lipoic acid as the “universal” antioxidant.

In the body, alpha-lipoic acid is converted to dihydrolipoic acid (DHLA), which also functions as a strong antioxidant. Lipoic acid is part of two enzyme systems: PDH (pyruvate dehydrogenase) and alpha-ketoglutarate dehydrogenase. These enzymes are part of the Krebs cycle and are essential in the production of energy.

Dosage Info

Dosage Range

20-600mg daily.

Most Common Dosage

25-50mg, 2 times a day.

Dosage Forms

Capsules and tablets.

Adult RDI

None established

Adult ODA

None established

RDA

  • General RDA: None established

Active Forms

Alpha-lipoic acid.

Absorption

Because of its small size and the fact that it is both fat and water-soluble, alpha-lipoic acid is easily absorbed from the gastrointestinal tract.

Toxicities & Precautions

General

There are no known toxicities associated with alpha-lipoic acid.

Side Effects

Occasional skin rashes have been reported.

Functions in the Body

Universal Antioxidant

Because it is able to function in both fat- and water-soluble environments throughout the human body, lipoic acid has been called the "universal" antioxidant. (1) , (2)

Energy Production

Functions as a co-enzyme cofactor in the pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase mitochondrial enzyme complexes in the production of energy. (3)

Regulation of Blood Glucose

Increases glucose uptake into muscle cells. (4)

Recycling of other Antioxidants

Able to recycle antioxidants such as vitamin C, vitamin E, glutathione, and coenzyme Q10. (5) , (6) , (7) , (8)

Heavy Metal Detoxification

Lipoic acid reduces the toxicity from toxic metals such as mercury, (9) cadmium, (10) and lead. (11) It is also able to form stable complexes with copper, manganese, and zinc ions. (12)

Clinical Applications

Memory Enhancement

Memory enhancement has also been demonstrated in animal studies, with possible mechanisms identified. Two studies were completed in rats evaluating the use and impact of acetyl-L-carnitine (ALC) and/or (R) – lipoic acid (LA). One study evaluated the association of brain mitochondrial decay and RNA/DNA oxidation to memory loss. The test group taking the combination of the two products experienced improved memory in both spatial memory and temporal memory. The results suggest that feeding ALC and/or LA to old rats improved memory performance by lowering oxidative damage to nucleic acids and improving mitochondrial function by reversing age-associated structural decay. (13) The second study indicated improved mitochondrial-supported cellular metabolism and lowered oxidative stress. (14) Both studies showed that the combination of ALC and LA were more effective than either supplement alone.

Glaucoma

Over 50 percent of patients with stage II open angle glaucoma exhibited significant improvement when given 150mg of alpha-lipoic acid for a period of 2 months. (15)

Peripheral Neuropathy

Diabetic individuals treated with alpha-lipoic acid experienced significant improvement in nerve conduction and nerve blood flow. (16)

Cataracts

Studies have shown that alpha-lipoic acid’s antioxidant activity and its ability to regenerate glutathione help to prevent the type of damage in eyes that leads to the development of cataracts. (17)

Amanita mushroom poisoning

Lipoic acid has been used successfully alone and in combination with other agents in patients with amanita mushroom posioning. (18) , (19) , (20)

Aids

Alpha-lipoic acid blocks the activation of a substance called NF-kappa B, which is necessary for the transcription of the HIV virus. Thus, alpha-lipoic acid may play an important therapeutic role for HIV-infected individuals. (21) In a study with HIV-infected patients, supplementation with alpha-lipoic acid provided a variety of benefits related to antioxidant status, T-helper lymphocytes, and the T-helper/ suppressor cell ratio. (22)

Diabetes

Alpha-lipoic acid increases glucose uptake into muscle cells and increases insulin sensitivity in individuals with Type 2 diabetes. (23) , (24) Also, alpha-lipoic acid’s antioxidant activity helps protect against many of the health risks associated with diabetes. (25) , (26)

Diabetic Neuropathy

In experimental diabetic neuropathy, alpha-lipoic acid provided increased nerve blood flow, reduced oxidative stress, and improved distal nerve conduction. (27) In humans, it has been demonstrated that oral administration of 600 mg/day of lipoic acid can prevent or improve diabetic neuropathy, which may be due to a lowering of lipid peroxidation. (28)

Alzheimer's Disease

The authors of a small study in Germany reported that lipoic acid may be a successful 'neuroprotective' agent in the treatment of Alzheimer’s disease and related dementias. Nine patients were administered 600 mg/day of alpha-lipoic acid in conjunction with their standard treatment with acetylcholinesterase inhibitor drugs over a period ranging from approximately 8.5 to 14 months. This treatment lead to a stabilization of cognitive function as evidenced by constant scores in two standard neuropsychological tests commonly used to assess AD patients. (29)

Hepatitis C

It has been reported that alpha-lipoic acid in combination with selenium and silymarin is an effective and far less expensive treatment for hepatitis C compared to conventional therapy. Three closely monitored cases involved cirrhosis, portal hypertension and esophageal varicies secondary to hepatitis C. Each patient received the antioxidant combination and had their hepatitis C complication resolve. The patients returned to work, resumed their normal daily activities and reported feeling healthy, avoiding liver transplantation. Whereas liver transplantation is estimated to cost more than $300,000 a year, the annual cost of this triple antioxidant therapy is approximately $2,000. (30)

Cardiovascular Disease

Oxidative stress plays a major role in the aging of the cardiovascular system. The administered lipoic acid to aged rats significantly reduced the level of oxidant production in cardiac myocytes, down to the level found in young non-supplemented rats. Lipoic acid also restored myocardial vitamin C levels and reduced oxidative damage to DNA. This animal study suggests that the aging of the heart in the elderly is at least in part due to oxidative stress in mitochondria of cardiac myocytes, and that lipoic acid may provide significant protection against this process. (31)

Symptoms and Causes of Deficiency

Since alpha-lipoic acid can be synthesized in the human body, it is not classified as an essential nutrient and there is no deficiency condition associated with it.

Dietary Sources

Red meat is the best dietary source of alpha-lipoic acid. Smaller amounts occur in the leaves of some plants and in potatoes, carrots, yams, and sweet potatoes.

References

  1. View Abstract: Kagan VE, Shvedova A, Serbinova E, et al. Dihydrolipoic acid--a universal antioxidant both in the membrane and in the aqueous phase. Reduction of peroxyl, ascorbyl and chromanoxyl radicals. Biochem Pharmacol. Oct1992;44(8):1637-49.
  2. Monograph:Alpha-Lipoic Acid. Altern Med Rev. Aug1998;3(4):308-11.
  3. View Abstract: Evans JL, Goldfine ID. Alpha-lipoic acid: a multifunctional antioxidant that improves insulin sensitivity in patients with type 2 diabetes. Diabetes Technol Ther. Sep2000;2(3):401-13.
  4. View Abstract: Estrada DE, Ewart HS, Tsakiridis T, et al. Stimulation of glucose uptake by the natural coenzyme alpha-lipoic acid/thioctic acid: participation of elements of the insulin signaling pathway. Diabetes. 1996;45:1798-1804.
  5. View Abstract: Packer L, Witt EH, Tritschler HJ. alpha-Lipoic acid as a biological antioxidant. Free Radic Biol Med. Aug1995;19(2):227-50.
  6. View Abstract: Stoyanovsky DA, Goldman R, Darrow RM, et al. Endogenous ascorbate regenerates vitamin E in the retina directly and in combination with exogenous dihydrolipoic acid. Curr Eye Res. Mar1995;14(3):181-9.
  7. View Abstract: Busse E, Zimmer G, Schopohl B, et al. Influence of alpha-lipoic acid on intracellular glutathione in vitro and in vivo. Arzneimittel-Forschung. 1992;42:829-831.
  8. View Abstract: Kagan V, Serbinova E, Packer L. Antioxidant effects of ubiquinones in microsomes and mitochondria are mediated by tocopherol recycling. Biochem Biophys Res Comm. 1990;169:851-857.
  9. View Abstract: Anuradha B, Varalakshmi P. Protective role of DL-alpha-lipoic acid against mercury-induced neural lipid peroxidation. Pharmacol Res. Jan1999;39(1):67-80.
  10. View Abstract: Sumathi R, Baskaran G, Varalakshmi P. Relationship between glutathione and DL alpha-lipoic acid against cadmium-induced hepatotoxicity. Jpn J Med Sci Biol. Apr1996;49(2):39-48.
  11. View Abstract: Gurer H, Ozgunes H, Oztezcan S, Ercal N. Antioxidant role of alpha-lipoic acid in lead toxicity. Free Radic Biol Med. Jul1999;27(1-2):75-81.
  12. Sigel H, Prijs B, McCormick DB, Shih JCH. Stability and structure of binary and ternary complexes of a-lipoate and lipoate derivatives with Mn2+, Cu2+, and Zn2+ in solution. Arch Biochem Biophys. 1978;187:208-214.
  13. View Abstract: Liu J, Head E, Gharib AM, Yuan W, Ingersoll RT, Hagen TM, et al. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: Partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid. Proc Natl Acad Sci U S A. Feb2002;99(4):2356-2361.
  14. View Abstract: Hagen TM, Liu J, Lykkesfeldt J, Wehr CM, Ingersoll RT, Vinarsky V, et al. Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proc Natl Acad Sci U S A. Feb2002;99(4):1870-1875.
  15. View Abstract: Filina AA, et al. Lipoic Acid as a Means of Metabolic Therapy of Open-angle Glaucoma. Vestn Oftalmol. Dec1995;111(4):6-8.
  16. View Abstract: Low PA, et al. The Roles of Oxidative Stress and Antioxidant Treatment in Experimental Diabetic Neuropathy. Diabetes. Sep1997;46(Suppl 2):S38-42.
  17. View Abstract: Kilic F, et al. Modelling Cortical Cataractogenesis XX. In Vitro Effect of Alpha-lipoic Acid on Glutathione Concentrations in Lens in Model Diabetic Cataractogenesis. Biochem Mol Biol Int. Oct1998;46(3):585-95.
  18. Berkson BM. Thioctic acid in treatment of hepatotoxic mushroom (Phalloides) poisoning. N Engl J Med. Feb1979;300(7):371.
  19. View Abstract: Plotzker R, Jensen DM, Payne JA. Case report. Amanita virosa acute hepatic necrosis: treatment with thioctic acid. Am J Med Sci. Mar1982;283(2):79-82.
  20. View Abstract: Parish RC, Doering PL. Treatment of Amanita mushroom poisoning: a review. Vet Hum Toxicol. Aug1986;28(4):318-22.
  21. View Abstract: Merin JP, et al. Alpha-lipoic Acid Blocks HIV-1 LTR-dependent Expression of Hygromycin Resistance in THP-1 Stable Transformants. FEBS Lett. Sep1996;394(1):9-13.
  22. View Abstract: Fuchs J, et al. Studies on Lipoate Effects on Blood Redox State in Human Immunodeficiency Virus Infected Patients. Arzneim Forsch. 1993;43:1359-362.
  23. View Abstract: Jacob S, et al. Enhancement of Glucose Disposal in Patients with Type 2 Diabetes by Alpha-lipoic Acid. Arzneimittelforschung. Aug1995;45(8):872-74.
  24. View Abstract: Evans JL, Goldfine ID. Alpha-lipoic acid: a multifunctional antioxidant that improves insulin sensitivity in patients with type 2 diabetes. Diabetes Technol Ther. Sep2000;2(3):401-13.
  25. Packer L. Antioxidant Properties of Lipoic Acid and Its Therapeutic Effects in Prevention of Diabetes Complications and Cataracts. Ann N Y Acad Sci. Nov1994;738:257-64.
  26. View Abstract: Midaoui AE, Elimadi A, Wu L, Haddad PS, de Champlain J. Lipoic acid prevents hypertension, hyperglycemia, and the increase in heart mitochondrial superoxide production. Am J Hypertens. Mar2003;16(3):173-9.
  27. View Abstract: Nagamatsu M, et al. Lipoic acid improves nerve blood flow, reduces oxidative stress, and improves distal nerve conduction in experimental diabetic neuropathy. Diabetes Care. 1995;18:1160-167.
  28. View Abstract: Androne L, Gavan NA, Veresiu IA, Orasan R. In vivo effect of lipoic acid on lipid peroxidation in patients with diabetic neuropathy. In Vivo. Mar2000;14(2):327-30.
  29. View Abstract: Hager K, Marahrens A, Kenklies M, et al. Alpha-lipoic acid as a new treatment option for Azheimer type dementia. Arch Gerontol Geriatr. Jun2001;32(3):275-282.
  30. View Abstract: Berkson BM. A conservative triple antioxidant approach to the treatment of hepatitis C. Combination of alpha lipoic acid (thioctic acid), silymarin, and selenium: three case histories. Med Klin. Oct1999;94(Suppl 3):84-9.
  31. View Abstract: Suh JH, Shigeno ET, Morrow JD, et al. Oxidative stress in the aging rat heart is reversed by dietary supplementation with (R)-(alpha)-lipoic acid. FASEB J. Mar2001;15(3):700-6.