Alpha Lipoic Acid

INDICATIONS AND USAGE

Lipoic acid shows evidence of being effective in the treatment of diabetic neuropathy and may be useful in treating some other aspects of diabetes. It may help prevent the oxidation of LDL cholesterol and may be protective, generally, against oxidative stress and, specifically, against atherosclerosis, ischemia-reperfusion injury and various radiologic and chemical toxins. It may also be useful in some inborn metabolic disorders. There is less evidence that it might be helpful in some neurodegenerative conditions. There is preliminary evidence that it might have some immune-modulating effects. It has been suggested that lipoic acid may slow aging of the brain and that it may be an anti-aging substance, in general.

RESEARCH SUMMARY

In a larger, multi-center, double-blind, randomized, placebo-controlled study of 328 patients with type 2 diabetes, significant improvements were recorded in several clinical measures of diabetic polyneuropathy, including pain, numbness, paresthesia and burning sensations. These results were evident after three weeks of intravenous lipoic acid given five times weekly in doses of 600 and 1200 milligrams.

There is evidence, too, that lipoic acid may help prevent or slow the development of the atherosclerosis for which diabetics are at higher risk. It may do this, in part, through a gene-regulatory mechanism that helps prevent endothelial cell activity that has been implicated in the progression of atherosclerosis.

With respect to atherosclerosis, in general, lipoic acid's antioxidant and metabolic effects appear to offer some protection, as demonstrated in various animal models. Recently, researchers demonstrated, in a 16-week randomized trial, that lipoic acid, in oral doses of 600 milligrams daily for eight weeks, significantly inhibits the oxidation of LDL-cholesterol in healthy human subjects. The supplements also significantly reduced levels of F-2 isoprostanes, markers of oxidative stress. In this study, lipoic acid proved to be superior to vitamin E in decreasing levels of plasma protein carbonyls. Protein oxidation and LDL-cholesterol oxidation are implicated in heart disease.

Various animal studies have suggested that lipoic acid can prevent or reduce cell and tissue damage in heart attacks and stroke. There is extensive animal work showing that lipoic acid can exert significant protective effects against ischemia-reperfusion injury.

Animal work is also suggestive of some modest benefit from lipoic acid in the treatment of various neurodegenerative disorders, including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis and Huntington's disease. Results to date, however, remain inconclusive. Clinical studies are needed.

Claims that lipoic acid slows aging of the brain and is an anti-aging substance generally seem to be related to its potent antioxidant properties. Direct proof of anti-aging is lacking, but there is some animal work suggestive of some possible anti-aging effects.

Lipoic acid supplementation was reported to completely reverse age-related declines in hepatocyte ascorbic acid and glutathione levels. There was additional evidence of decreased oxidative damage in the lipoic-acid supplemented aged rats. The researchers concluded: "Little is known about whether lipoic acid may be an effective anti-aging supplement...in humans. Our present findings using rats would suggest that lipoic acid supplementation may be a safe and effective means to improve general metabolic activity and increase antioxidant status, affording increased protection against external oxidative and xenobiotic insults with age." Again, further study is needed.

INTERACTIONS

Supplemental alpha-lipoic acid may lower blood glucose levels. Those with diabetes on antidiabetic medication should have their blood glucose monitored and antidiabetic drug dose appropriately adjusted, if necessary, to avoid possible hypoglycemia.

LITERATURE

Hagen TM, Ingersoll RT, Lykkesfeldt J, et al. (R)-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate. FASEB J. 1999; 13:411-418.

Lykkesfeldt J, Hagen TM, Vinarsky V, Ames BN. Age-associated decline in ascorbic and concentration, recycling and biosynthesis in rat hepatocytes-reversal with (R)-alpha-lipoic acid supplementation. FASEB J. 1998; 12:1183-1189.

Marangon K, Devaraj S, Tirosh O, et al. Comparison of the effect of alpha-lipoic acid and alpha-tocopherol supplementation on measures of oxidative stress. Free Rad Biol Med. 1999; 27:1114-1121.

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Tirosh O, Sen CK, Roy S, et al. Neuroprotective effects of alpha-lipoic acid and its positively charged amide analogue. Free Rad Biol Med. 1999; 26:1418-1426.

Wagh SS, Natraj CV, Menon KKG. Mode of action of lipoic acid in diabetes. J Biosci. 1987; 11:59-74.

Ziegler D, Hanefeld M, Ruhnau KJ, et al. Treatment of symptomatic diabetic peripheral neuropathy with the antioxidant alpha-lipoic acid. A three-week multicentre randomized controlled trial (ALADIN study). Diabetologia. 1995; 38:1425-1433.

Zimmer G, Beikler TK, Schneider M, et al. Dose/response curves of lipoic acid R- and S- forms in the working rat heart during reoxygenation: superiority of the R-entantiomer in the enhancement of aortic flow. J Mol Cell Cardiol. 1995; 27:1895-1903.