Alpha-Lipoic Acid

Overview

Alpha lipoic acid is a sulfur-containing fatty acid compound found in the mitochondria – the energy producing structures found in our cells. As a dietary supplement, alpha-lipoic acid (also known as lipoic acid and thioctic acid) may act as a powerful antioxidant, where it may work in synergy with other nutritional antioxidants like vitamins C and E to help prevent cellular damage from free radicals. Alpha-lipoic acid has also been shown to help control blood sugar levels in patients with diabetes.

Although alpha lipoic acid is involved in cellular energy production, its chief role as a dietary supplement may be as a powerful antioxidant. The body appears to be able to manufacture enough alpha-lipoic acid for its metabolic functions (as a co-factor for a number of enzymes involved in converting fat and sugar to energy), but the excess levels provided by supplements allow alpha-lipoic acid to circulate in a “free” state (outside of the cells where it is usually found). In this state, alpha-lipoic acid has functions as both a water- and fat-soluble antioxidant. This unique ability of alpha-lipoic acid to be active in both 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. For instance vitamin C is usually restricted to the interior compartment of cells and the aqueous (“watery”) portion of blood, while vitamin E embeds itself in the lipid (“fatty”) portion of cell membranes. Adding to the potential importance of alpha-lipoic acid is its role in the production of glutathione, one of the chief cellular antioxidants produced directly by the body.

Comments

If alpha-lipoic acid were just another antioxidant, then its value would be far less. After all, there are dozens of ingredients on the market that have powerful antioxidant functions. The unique qualities possessed by alpha-lipoic acid, functioning as both a water- and fat-soluble antioxidant as well as its role in increasing the overall function of other dietary antioxidants, make it an intriguing supplement worthy of serious consideration – especially for people with diabetes because of its particular benefits in potentially preventing some forms of diabetic peripheral and autonomic neuropathy.

Scientific Support

In animal studies and human trials, alpha-lipoic acid supplementation has been shown to improve several indices of metabolic activity and lower the degree of oxidative stress (Androne et al. 2000, Arivazhagan et al. 2000). Alpha-lipoic acid supplementation may also help to reverse the decline in mitochondrial energy production that is commonly observed during the “normal” aging process (Ames 2003). Physical activity levels in animals can be increased by approximately 3-fold when supplemented with alpha-lipoic acid (Hagen et al. 1999), suggesting a beneficial effect on energy metabolism (Khanna et al. 1998). Levels of other antioxidants, such as glutathione and ascorbic acid, were also elevated in animals consuming alpha-lipoic acid, suggesting that the supplement may help protect and/or recycle these antioxidants and contribute to the overall capacity of the body to neutralize free radical damage (Packer et al. 1997, Packer et al. 1995).

In conjunction with other antioxidants, such as vitamin E, alpha-lipoic acid may be particularly helpful in patients with diabetes. By promoting the production of energy from fat and sugar in the mitochondria, glucose removal from the bloodstream may be enhanced and insulin function improved. Indeed, alpha-lipoic acid has been shown to decrease insulin resistance and is prescribed frequently in Europe as a treatment for peripheral neuropathy (nerve damage) associated with diabetes. In the U.S., the American Diabetes Association has suggested that alpha-lipoic acid plus vitamin E may be helpful in combating some of the health complications associated with diabetes, including heart disease, vision problems, nerve damage and kidney disease. Alpha-lipoic acid has also been implicated in helping to protect the brain from damage following a stroke.

There is a consistent body of evidence that intravenous infusions of alpha-lipoic acid are associated with a reduction in sensory symptoms of diabetic neuropathy (Ametov et al. 2003, Ziegler et al 2004) and that benefits are seen within 8-14 days of treatment on measures of pain, burning, numbness in patients receiving alpha-lipoic acid supplements. In human feeding studies (as opposed to studies of intravenous infusions of lipoic acid where most of the positive results exist for diabetic neuropathy), a handful of studies demonstrate that dietary supplementation with alpha-lipoic acid is able to help prevent hyperglycemia (Kinrad et al. 1999) and improve energetic substrates in muscle cells (Burke et al. 2003).

Safety / Dosage

Although there have been relatively few feeding studies conducted with alpha-lipoic acid in humans, it appears to be safe as a dietary supplement. Intakes of as much as 600mg per day have been used for treatment of diabetic neuropathy, with no serious side effects. General recommendations for antioxidant benefits typically call for 50 – 100mg per day as a general antioxidant, with higher levels of 300-600mg/day for preventing/treating complications of diabetes.

References

1.Ames BN. The metabolic tune-up: metabolic harmony and disease prevention. J Nutr. 2003 May;133(5 Suppl 1):1544S-8S.

2.Ametov AS, Barinov A, Dyck PJ, Hermann R, Kozlova N, Litchy WJ, Low PA, Nehrdich D, Novosadova M, O'Brien PC, Reljanovic M, Samigullin R, Schuette K, Strokov I, Tritschler HJ, Wessel K, Yakhno N, Ziegler D; SYDNEY Trial Study Group. The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: the SYDNEY trial. Diabetes Care. 2003 Mar;26(3):770-6.

3.Androne L, Gavan NA, Veresiu IA, Orasan R. In vivo effect of lipoic acid on lipid peroxidation in patients with diabetic neuropathy. In Vivo. 2000 Mar-Apr;14(2):327-30.

4.Arivazhagan P, Panneerselvam C. Effect of DL - alpha -lipoic acid on neural antioxidants in aged rats. Pharmacol Res. 2000 Sep;42(3):219-22.

5.Gualandri W, Gualandri L, Demartini G, Esposti R, Marthyn P, Volonte S, Stangoni L, Borgonovo M, Fraschini F. Redox balance in patients with Down's syndrome before and after dietary supplementation with alpha-lipoic acid and L-cysteine. Int J Clin Pharmacol Res. 2003;23(1):23-30.

6.Haak E, Usadel KH, Kusterer K, Amini P, Frommeyer R, Tritschler HJ, Haak T. Effects of alpha-lipoic acid on microcirculation in patients with peripheral diabetic neuropathy. Exp Clin Endocrinol Diabetes. 2000;108(3):168-74.

7.Hagen TM, Ingersoll RT, Lykkesfeldt J, Liu J, Wehr CM, Vinarsky V, Bartholomew JC, Ames AB. (R)-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate. FASEB J. 1999 Feb;13(2):411-8.

8.Jacob S, Ruus P, Hermann R, Tritschler HJ, Maerker E, Renn W, Augustin HJ, Dietze GJ, Rett K. Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial. Free Radic Biol Med. 1999 Aug;27(3-4):309-14.

9.Khanna S, Atalay M, Lodge JK, Laaksonen DE, Roy S, Hanninen O, Packer L, Sen CK. Skeletal muscle and liver lipoyllysine content in response to exercise, training and dietary alpha-lipoic acid supplementation. Biochem Mol Biol Int. 1998 Oct;46(2):297-306.

10.Konrad T, Vicini P, Kusterer K, Hoflich A, Assadkhani A, Bohles HJ, Sewell A, Tritschler HJ, Cobelli C, Usadel KH. alpha-Lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with type 2 diabetes. Diabetes Care. 1999 Feb;22(2):280-7.

11.Marriage B, Clandinin MT, Glerum DM. Nutritional cofactor treatment in mitochondrial disorders. J Am Diet Assoc. 2003 Aug;103(8):1029-38.

12.Miquel J. Can antioxidant diet supplementation protect against age-related mitochondrial damage? Ann N Y Acad Sci. 2002 Apr;959:508-16.

13.Morcos M, Borcea V, Isermann B, Gehrke S, Ehret T, Henkels M, Schiekofer S, Hofmann M, Amiral J, Tritschler H, Ziegler R, Wahl P, Nawroth PP. Effect of alpha-lipoic acid on the progression of endothelial cell damage and albuminuria in patients with diabetes mellitus: an exploratory study. Diabetes Res Clin Pract. 2001 Jun;52(3):175-83.

14.Nickander KK, McPhee BR, Low PA, Tritschler H. Alpha-lipoic acid: antioxidant potency against lipid peroxidation of neural tissues in vitro and implications for diabetic neuropathy. Free Radic Biol Med. 1996;21(5):631-9.

15.Packer L, Tritschler HJ, Wessel K. Neuroprotection by the metabolic antioxidant alpha-lipoic acid. Free Radic Biol Med. 1997;22(1-2):359-78.

16.Packer L, Witt EH, Tritschler HJ. alpha-Lipoic acid as a biological antioxidant. Free Radic Biol Med. 1995 Aug;19(2):227-50.

17.Podda M, Tritschler HJ, Ulrich H, Packer L. Alpha-lipoic acid supplementation prevents symptoms of vitamin E deficiency. Biochem Biophys Res Commun. 1994 Oct 14;204(1):98-104.

18.Roy S, Sen CK, Tritschler HJ, Packer L. Modulation of cellular reducing equivalent homeostasis by alpha-lipoic acid. Mechanisms and implications for diabetes and ischemic injury. Biochem Pharmacol. 1997 Feb 7;53(3):393-9.

19.Ruhe RC, McDonald RB. Use of antioxidant nutrients in the prevention and treatment of type 2 diabetes. J Am Coll Nutr. 2001 Oct;20(5 Suppl):363S-369S.

20.Ziegler D, Gries FA. Alpha-lipoic acid in the treatment of diabetic peripheral and cardiac autonomic neuropathy. Diabetes. 1997 Sep;46 Suppl 2:S62-6.

21.Ziegler D, Hanefeld M, Ruhnau KJ, Hasche H, Lobisch M, Schutte K, Kerum G, Malessa R. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy. Diabetes Care. 1999 Aug;22(8):1296-301.

22.Ziegler D, Hanefeld M, Ruhnau KJ, Meissner HP, Lobisch M, Schutte K, Gries FA. Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant alpha-lipoic acid. A 3-week multicentre randomized controlled trial (ALADIN Study). Diabetologia. 1995 Dec;38(12):1425-33.

23.Ziegler D, Nowak H, Kempler P, Vargha P, Low PA. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a meta-analysis. Diabet Med. 2004 Feb;21(2):114-21.

24.Ziegler D, Reljanovic M, Mehnert H, Gries FA. Alpha-lipoic acid in the treatment of diabetic polyneuropathy in Germany: current evidence from clinical trials. Exp Clin Endocrinol Diabetes. 1999;107(7):421-30.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS