Alpha Lipoic Acid
Scientific Name(s):1,2-dithiolane-3-pentanoic acid; 1,2-dithiolane-3-valeric acid; 6,8-thioctic acid; alpha-lipoic acid; 5-(1,2-dithiolan-3-yl) valeric acid
Common Name(s): Alpha-lipoic acid , lipoic acid , thioctic acid , acetate replacing factor , biletan , lipoicin , thioctacid , thioctan
Clinical Overview
Uses of Alpha Lipoic Acid
Alpha lipoic acid has been used as an antioxidant for the treatment of diabetes and HIV. It also has been used for cancer, liver ailments, and various other conditions.
Alpha Lipoic Acid Dosing
Oral dosage of alpha lipoic acid given in numerous clinical studies ranges from 300 to 1800 mg daily. It also is given intravenously at similar daily dosages.
Contraindications
Contraindications have not yet been determined.
Pregnancy/Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking.
Alpha Lipoic Acid Interactions
None well documented.
Alpha Lipoic Acid Adverse Reactions
No adverse effects have been reported.
Toxicology
No data.
Lipoic acid is a fat-soluble, sulfur-containing, vitamin-like antioxidant. It is not a true vitamin because it can be synthesized in the body and is not necessary in the diet of animals. Lipoic acid functions in the same manner as many B-complex vitamins. Good sources of lipoic acid are yeast and liver. 1 , 2 Other sources include spinach, broccoli, potatoes, kidney, heart, and skeletal muscle. 3
History
In the 1930s, it was found that a certain “potato growth factor” was necessary for growth of certain bacteria. 3 In 1951, a fat-soluble coenzyme factor was discovered from work done on lactic acid bacteria. Reed et al, isolated this naturally occurring d-form and found it to be an important growth factor for many bacteria and protozoa. This compound was isolated and identified as “alpha lipoic acid.” 4
Chemistry
Alpha lipoic acid is a molecule with 2 sulfur high-energy bonds. It functions as a coenzyme with pyrophosphatase in carbohydrate metabolism to convert pyruvic acid to acetyl-coenzyme A (Krebs cycle) to produce energy. 1
Alpha Lipoic Acid Uses and Pharmacology
Pharmacokinetics and bioavailability of different enantiomers of alpha lipoic acid (ALA) have been performed in 12 subjects. 5 Pharmacology of ALA has been studied in the areas of oxidation, diabetes, AIDS, cancer, and liver ailments.
OxidationMechanism of action
ALA's antioxidant properties have been demonstrated. It has the ability to chelate metals and to scavenge free radicals. 6
ALA is easily absorbed and transported across cell membranes; thus, free radical protection occurs both inside and outside of cells. It is also water- and fat-soluble, which makes it effective against a broader range of free radicals than vitamin C (water-soluble) and vitamin E (fat-soluble) alone. 2 ALA administration also increases intracellular levels of glutathione, an important antioxidant. 7
Animal dataALA regenerates or recycles antioxidant vitamins C and E 3 but in one report, had no effect on vitamin E tissue concentration in animals, contradicting this effect. 8
The body routinely converts ALA to dihydrolipoic acid, an even more powerful antioxidant. Both forms “quench” the dangerous peroxynitrite radicals, which are responsible in part for heart, lung, and neurological disease and inflammation as well. 9 In oxidative stress models such as ischemia, reperfusion injury, and radiation inury, ALA has been shown to be beneficial. 10 , 11
Clinical dataResearch reveals no clinical data regarding the use of alpha lipoic acid as an antioxidant.
DiabetesALA has been shown to be beneficial in type 1 and type 2 diabetes. ALA has prevented various pathologies associated with this disease, such as reperfusion injury, macular degeneration, cataracts, and neuropathy. 2 , 3 , 10 , 12
Animal dataALA reduced diabetic neuropathy in rats, which was improved in a dose-dependent manner. In part, the mechanism was suggested to be caused by reduction of the effects of oxidative stress. 12 ALA is approved in Germany to treat diabetic neuropathy. High doses (600 mg/day) improve this condition. 2
ALA also improves the diabetic condition by improving blood sugar metabolism. It facilitates better conversion of sugar into energy. 2
Clinical dataIn 13 noninsulin-dependent diabetes mellitus patients, ALA increased insulin-stimulated glucose disposal. Metabolic clearance rate for glucose rose by 50% compared with the control group. 13
ALA improves blood flow to peripheral nerves and stimulates regeneration of nerve fibers. 2 A German study evaluating 800 mg/day ALA in diabetics with damaged autonomic nervous systems was compared against placebo. After 4 months, sympathetic systems showed improvement and autonomic nerve disorder decreased in the ALA group. 14
Antioxidants in general may lead to regression of diabetic complications. When ALA was compared with antioxidant vitamin E, results failed to justify the higher cost of ALA over less-expensive and equally effective nutritional antioxidants. 2
AIDSPatients with HIV have a compromised antioxidant defense system, which may benefit from ALA's role as an effective antioxidant. 2
Animal dataResearch reveals no animal data regarding the use of alpha lipoic acid as an antioxidant in HIV illnesses.
ALA significantly inhibits replication of HIV by reducing the activity of reverse transcriptase, the enzyme which makes virus from DNA of lymphocytes. 2 In another report, ALA was found to also inhibit activation of “nuclear factor kappa-B,” which is involved in AIDS progression. 15
Clinical dataA small pilot study was conducted administering 150 mg ALA 3 times daily to HIV patients. It increased glutathione in all 10 patients and increased vitamin C in most patients as well. In addition, it improved the T-helper lymphocyte to T-helper suppressor cell ratio in 6 of 10 patients. 2
CancerThere is limited information available concerning ALA's role in cancer. Its mechanism of action and anticarcinogenic and cytoprotective effects have been addressed. 16
Animal dataALA administration, in conjunction with cyclophosphamide, lowered the toxic effects of this anticancer drug when tested in animals. 17
Clinical dataResearch reveals no clinical data regarding the use of alpha lipoic acid in cancer treatment.
Other usesVarious reports on ALA pharmacology include the following: Suppression of T-4 metabolism, exerting a lipid-lowering effect in rats, 18 treatment in Wilson disease, 4 and cardiovascular disease. 3
ALA has been used as an antidote to Amanita mushroom poisoning. 4 A review on mushroom intoxications employing ALA and other antidotes is available. 19
Dosage
Oral dosage of alpha-lipoic acid given in numerous clinical studies ranges from 300 to 1800 mg daily. It also is given intravenously at similar daily dosages. 14
Pregnancy/Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking.
Interactions
None well documented.
Adverse Reactions
No adverse effects from ALA supplementation have been reported in either animal or human studies, even with large doses or extended use. 2 Its use in diabetes may warrant a reduction in dose of insulin or other oral diabetic medications. Close monitoring of blood sugar levels must be performed. In addition, ALA use may spare vitamins C and E, as well as other antioxidants. 2
Toxicology
Research reveals little or no information regarding toxicology with the use of this product.
Bibliography
1. Ensminger AH, Ensminger ME, Konlande JE, Robson JRK. Foods and Nutrition Encyclopedia . 2nd ed. Boca Raton, FL: CRC Press Inc; 1994:1318-1319.2. Murray M. Encyclopedia of Nutritional Supplements . Rocklin, CA: Prima Publishing; 1996;343-346.
3. Ley BM. The Potato Antioxidant: Alpha Lipoic Acid: A Health Learning Handbook . Aliso Viejo, CA: BL Publications; 1996.
4. Budavari S, ed. The Merck Index . 11th ed. Rahway, NJ: Merck and Co.; 1989.
5. Hermann R, et al. Eur J Pharm Sci . 1996;4:167-174.
6. Nichols T. Altern Med Rev . 1997;2:177-183.
7. Busse E, Zimmer G, Schopohl B, Kornhuber B. Influence of alpha-lipoic acid on intracellular glutathione in vitro and in vivo. Arzneimittel-Forschung . 1992;42:829-831.
8. Podda M, Tritschler HJ, Ulrich H, Packer L. Alpha-lipoic acid supplementation prevents symptoms of vitamin E deficiency. Biochem Biophys Res Commun . 1994;204:98-104.
9. Whiteman M, Tritschler H, Halliwell B. Protection against peroxynitrite-dependent tyrosine nitration and alpha 1-antiproteinase inactivation by oxidized and reduced lipoic acid. FEBS Lett . 1996;379:74-76.
10. Schonheit K, Gille L, Nohl H. Effect of alpha-lipoic acid and dihydrolipoic acid on ischemia/reperfusion injury of the heart and heart mitochondria. Biochim Biophys Acta . 1995;1271:335-342.
11. Cao X, Phillis JW. The free radical scavenger, alpha-lipoic acid, protects against cerebral ischemia-reperfusion injury in gerbils. Free Radic Res . 1995;23:365-370.
12. Nagamatsu M, Nickander KK, Schmelzer JD, et al. Lipoic acid improves nerve blood flow, reduces oxidative stress, and improves distal nerve conduction in experimental diabetic neuropathy. Diabetes Care . 1995;18:1160-1167.
13. Jacob S, Henriksen EJ, Schiemann AL, et al. Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid. Arzneimittel-Forschung . 1995;45:872-874.
14. Ziegler D, Schatz H, Conrad F, Gries FA, Ulrich H, Reichel G. Effects of treatment with the antioxidant alpha-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. A 4-month randomized controlled multicenter trial (DEKAN Study). Diabetes Care . 1997;20:369-373.
15. Suzuki YJ, Aggarwal BB, Packer L. Alpha-lipoic acid is a potent inhibitor of NF-kappa B activation in human T cells. Biochem Biophys Res Commun . 1992;189:1709-1715.
16. Dovinova I. Alpha-lipoic acid—a natural disulfide cofactor and antioxidant with anticarcinogenic effects [in Slovak]. Ceska Slov Farm . 1996;45:237-241.
17. Berger M, Habs M, Schmahl D. Effect of thioctic acid (alpha-limpoic acid) on the chemotherapeutic efficacy of cyclophosphamide and vincristine sulfate [in German]. Arzneimittel-Forschung . 1983;33:1286-1288.
18. Segermann J, Hotze A, Ulrich H, Rao GS. Effect of alpha-lipoic acid on the peripheral conversion of thyroxine to triiodothyronine and on serum lipid-, protein- and glucose levels. Arzneimittel-Forschung . 1991;41:1294-1298.
19. Lampe KF. Current concepts of therapy in mushroom intoxication. Clin Toxicol . 1974;7:115-121.
20. Ametov AS, Barinov A, Dyck PJ, et al. The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: the SYDNEY trial. Diabetes Care . 2003;26:770-776.
21. Hummel T, Heilmann S, Huttenbriuk KB. Lipoic acid in the treatment of smell dysfunction following viral infection of the upper respiratory tract. Laryngoscope . 2002;112:2076-2080.
22. Morcos M, Borcea V, Isermann B, et al. 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;52:175-183.
23. Haak E, Usadel KH, Kusterer K, et al. Effects of alpha-lipoic acid on microcirculation in patients with peripheral diabetic neuropathy. Exp Clin Endocrinol Diabetes . 2000;108:168-174.
24. Ruhnau KJ, Meissner HP, Finn JR, et al. Effects of 3-week oral treatment with the antioxidant thioctic acid (alpha-lipoic acid) in symptomatic diabetic polyneuropathy. Diabet Med . 1999;16:1040-1043.
25. Reljanovic M, Reichel G, Rett K, et al. Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (alpha-lipoic acid): a two year multicenter randomized double-blind placebo-controlled trial (ALADIN II). Alpha Lipoic Acid in Diabetic Neuropathy. Free Radic Res . 1999;31:171-179.
26. Ziegler D, Hanefeld M, Ruhnau KJ, et al. 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;22:1296-1301.
27. Jacob S, Ruus P, Hermann R, et al. 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;27:309-314.
28. Ziegler D, Gries FA. Alpha-lipoic acid in the treatment of diabetic peripheral and cardiac autonomic neuropathy. Diabetes . 1997;46(Suppl 2):S62-S66.
29. Marshall AW, Graul RS, Morgan MY, Sherlock S. Treatment of alcohol-related liver disease with thioctic acid: a six month randomised double-blind trial. Gut . 1982;23:1088-1093.
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