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R Alpha Lipoic AcidWhat is R Alpha Lipoic Acid and Alpha Lipoic Acid?Alpha Lipoic acid is a natural substance found in certain foods and also produced in the human body. Alpha Lipoic acid is a disulfide compound found naturally in mitochondria as the coenzyme for pyruvate dehydrogenase and a-ketoglutarate dehydrogenase. Alpha lipoic acid (ALA) is a unique, vitamin-like antioxidant which exists in two forms, R-alpha-lipoic acid and S-alpha-lipoic acid. These two forms contain the same number and composition of atoms but have different arrangements of the atoms in their respective molecules. Natural lipoic acid is R Alpha lipoic acid. Synthetic lipoic acid contains a 50/50 mixture of the two forms. Studies with the mixture demonstrated beneficial effects in treating a number of diseases and conditions. More recent research has shown that the R Alpha Lipoic acid alone is far more effective than S Alpha Lipoic acid or the mixture. Recently, pure R Alpha Lipoic acid has become available as a nutritional supplement. R Alpha Lipoic Acid as an AntioxidantR Alpha Lipoic acid is regarded by many as the supreme antioxidant. R-Lipoic acid is unique in that it functions as both a fat and water-soluble antioxidant that can easily cross cell membranes. Thus, it can confer free radical protection to both interior and exterior cellular structures. Vitamin E is a potent biological antioxidant that acts to stabilize highly reactive free radicals in lipid (fatty) tissues and cell membranes. In the process of quenching fatty free radicals, vitamin E becomes a free radical itself. The vitamin E radical is then regenerated by vitamin C (ascorbic acid). This process recycles vitamin E from a radical back into an antioxidant again, but results in the formation of a new free radical in the form of unstable vitamin C. Vitamin C is next recycled by glutathione. Up to this point vitamins E, C and glutathione work in concert to control free radicals and prevent cellular damage. But this is also an important stage where the antioxidant regeneration cycle runs into a limiting factor determined by the availability of glutathione. The concentration of these key antioxidants, vitamins E,C and glutathione diminishes with age and the individual becomes more susceptible to oxidative damage and inflammation. Cell membrane integrity, the immune system, organs and DNA integrity all go down hill as antioxidants diminish. Glutathione is an important free-radical deactivator. Cellular glutathione levels are considered by many life extension experts to be the single best predictor of how long an individual will live. Glutathione also plays a vital role in protecting against cataract formation, enhancing immune function, preventing liver damage, slowing the initiation of cancers and eliminating heavy metals. Glutathione is quickly depleted when the body experiences high levels of oxidative stress from causes such as illness, infection, trauma, medication, environmental toxins and surgery. Glutathione deficiency is also associated with low protein intake, diabetes, liver disease, cataracts, HIV infection, respiratory distress syndrome, cancer, and idiopathic pulmonary fibrosis. R-Lipoic acid boosts glutathione levels. Alpha lipoic acid enhances glutathione (GSH) levels. Glutathione is the most important water-soluble antioxidant and is linked to detoxification of xenobiotics, modulation of signal transduction, prostaglandin metabolism, regulation of immune response, control of enzyme activity and peptide hormones, etc. The availability of the amino acid Cysteine is known as the rate-limiting factor in glutathione synthesis. Lipoic acid is taken up rapidly by the cell and reduced to DHLA, which in turn reduces cystine to cysteine and accelerates the biosynthesis of GSH. In summary, R Lipoic Acid acts as a potent anti-oxidant on its own, serves to regenerate other anti-oxidants like vitamin E, Vitamin C and glutathione, and increases the production of glutathione. R Alpha Lipoic acid for Improving Mitocondrial FunctionThe mitochondria are structures inside each individual cell that produce the energy that the cell needs to function. The mitochondria are analagous to an engine, boiler room or furnace. As the cells age, the activity of the mitochondria decreases, resulting in lower energy production, slower metabolism and and increased oxidative stress and damage. Clinical studies with rats have demonstrated that supplementation with R Alpha Lipoic acid improved mitocondrial function, increases metabolic rate and decreases oxidative damage. Ambulatory activity, a measure of general metabolic activity was almost threefold lower in untreated rats compared to treated rats. The decline was reversed in old rats fed R Alpha Lipoic Acid. R Alpha Lipoic Acid as a Chelating AgentStudies with rats and mice have shown that R Alpha Lipoic Acid provided protection against the toxic effects of arsenic, cadmium and mercury. It may also bind to other metals including iron, copper and zinc. The chelating action of R Alpha Lipoic Acid is considered to be relatively weak compared to other chelating agents. Some of the harmful effects of heavy metal poisoning are associated with oxidative damage. In addition, lipoic acid's antioxidant properties reduce the harmful effects of heavy metals. Reduction of Aging from Glycation by R Alpha Lipoic AcidGlycation is the formation of chemical bonds between protein molecules and glucose. This process impairs the physiological function of those proteins and contributes to the effects of aging and many disease processes, especially those associated with diabetes. These sugar-damaged proteins are referred to as advanced glycosylation end products (AGEs). AGEs increase with the length of hyperglycemia and are thought to be responsible for the kidney damage and advanced atherosclerosis seen in diabetes. Researchers have found that noncovalent binding of alpha-lipoic acid to albumin protected proteins against glycation. Thus R Alpha Lipoic Acid acts as an anti-aging nutrient by both its anti-oxidant properties and its anti glycation properties. Clinical Uses for R Alpha Lipoic AcidLarge amounts of free radicals are created in tissue that has been injured by trauma or ischemia. Ischemia is caused by low oxygen levels from blood clots, stroke, etc. Treatment of this type of injury with anti-oxidants could be expected to reduce the effects of the damage. These types of injuries include heart attack, stroke, burns, sprains, strains, contusions, etc. The treatment of some of these entities with alpha lipoic acid have been documented in the literature and some have not. Because alpha lipoic acid helps to conserve and increase production of glutathione, it may be beneficial in treating certain diseases that affect the liver. These include exposure to various toxins, alcoholic liver disease, aminita mushroom poisoning, hepatitis, etc. Alpha lipoic acid is beneficial to individuals with type II diabetes. First, it improved the overall control of blood sugar and reduced blood sugar and insulin levels. Second, its anti-oxidant and anti-glycation effects reduce the damage caused by high blood sugar levels. Perhaps the best use of r alpha lipoic acid is as a life extension nutrient. It acts as an anti-oxidant, anti-glycation agent, blood sugar normalizer, mitochondria activator and glutathione enhancer. All of these effects counter the effects of aging, increase energy and enhance the quality of life. Dosage of R Alpha Lipoic AcidAs a nutritional supplement, doses of 50 to 100 mg. per day are generally recommended. As a Therapeutic agent, higher doses may be used. In Germay, dosages of 600 mg. per day are prescribed for preventing the damaging effects of hyperglycemia in diabetes. Larger doses, 1200 mg. given intravenously, have been used to treat aminita mushroom poisoning. These dosages refer to alpha lipoic acid and alpha lipoic acid contains equal amounts of the R and S version of the molecule. When the R version only is used, only half of the dose is required. R Alpha Lipoic Acid Side Effects and PrecautionsClinical research has shown no evidence of carcinogenic effects with administration of alpha lipoic acid. Serious side effects have not been observed, even at high doses. Minor side effects include skin reactions and gastrointestinal effects, such as nausea and vomiting. However, these effects have only been observed in a small percentage of subjects who received intravenous infusions of 1,200 mg or more of alpha lipoic acid per day. Alpha Lipoic Acid supplementation may reduce glucose and insulin levels in diabetics. Diabetics taking insulin or glucose lowering drugs will have to monitor their sugar levels and adjust medication as needed. Diabetics taking alpha lipoic acid supplements should work with their physician to monitor and and adjust any medication that they may be using. There is a lack of available data regarding use of alpha lipoic acid during pregnancy. During more than three decades of scientific research and clinical usage no serious adverse effects have been reported as a consequence of alpha lipoic acid supplementation. The LD50 is approximately 400-500 mg/kg after oral dosing in dogs. High doses of alpha lipoic acid should be accompanied ty thiamine administration. An experiment done with rats showed that administration of alpha lipoic acid in extremely high doses (20 mg./kg) in the presence of a thiamine deficiency proved fatal. It would probably be beneficial to include a B-complex supplement in a regimen containing alpha lipoic acid. Where to get R Alpha Lipoic AcidFor a high quality source of R Alpha Lipoic Acid and other Health and Life Extension Supplements:
References1. Reed LJ, DeBusk BG, Gunsalus IC, et al. Crystalline alpha-lipoic acid: a catalytic agent associated with pyruvate dehydrogenase. Science 1951;114:93-94. 2. Carreau JP. Biosynthesis of lipoic acid via unsaturated fatty acids. Meth Enzmol 1979;62:152-158. <3. Dupre S, Spoto G, Materese RM, et al. Biosynthesis of alpha-lipoic acid in the rat: Incorporation of S- and C-labeled precursors. Arch Biochem Biophys 1980;202:361-365. 4. Packer L, Witt EH, Tritschler HJ. Alpha-lipoic acid as a biological antioxidant. Free Rad Biol Med 1995;19:227-250. 5. Rosenburg HR, Culik R. Effects of alpha-lipoic acid on vitamin C and vitamin E deficiencies. Arch Biochem Biophys 1959;80:86-93. 6. 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. 7. Xu DP, Wells WW. alpha-lipoic acid dependent regeneration of ascorbic acid from dehydroascorbic acid in rat liver mitochondria. J Bioenerg Biomembr 1996;28:77-85. 8. Scholich H, Murphy ME, Sies H. Antioxidant activity of dihydrolipoate against microsomal lipid peroxidation and its dependence on a-tocopherol. Biochem Biophys Acta 1989;1001:256-261. 9. 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. <10. 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. 11. Passwater RA. Lipoic Acid: The Metabolic Antioxidant. New Canaan, CT: Keats Publishing, Inc; 1995:1-47. 12. Scott BC, Arouma OI, Evans PJ, et al. Lipoic and dihydrolipoic acid as antioxidants: a critical evaluation. Free Rad Res 1994;20:119-133. 13. Suzuki YJ, Tsuchiya M, Packer L. Thiotic acid and dihydrolipoic acid are novel antioxidants which interact with reactive oxygen species. Free Rad Res Comms 1991;15:255-263. 14. Sandhya P, Mohandass S, Varalakshmi P. Role of DL alpha-lipoic acid in gentamicin induced nephrotoxicity. Mol Cell Biochem 1995;145:11-17. 15. Sigel H, Prijs B, McCormick DB, Shih JCH. Stability of binary and ternary complexes of alpha-lipoate and lipoate derivatives with Mn2+, Cu2+, and Zn2+ in solution. Arch Biochem Biophys 1978;187:208-214. 16. Devasagayam TP, Subramanian M, Pradhan DS, Sies H. Prevention of singlet oxygen induced DNA damage by lipoate. Chem-Biol Interations 1993;86:79-92. 17. Bast A, Haenen GR. Interplay between lipoic acid and glutathione in the protection against microsomal lipid peroxidation. Biochem Biophys Acta 1988;963:558-561. 18. Grunert RR. The effect of DL alpha-lipoic acid on heavy-metal intoxication in mice and dogs. Arch Biochem Biophys 1960;86:190-194. 19. Ou P, Tritschler HJ, Wolff SP. Thioctic (lipoic) acid: a therapeutic metal-chelating antioxidant? Biochem Pharmacol 1995;50:123-126. 20. Muller L, Menzel H. Studies on the efficacy of lipoate and dihydrolipoate in the alteration of cadmium toxicity in isolated hepatocytes. Biochem Biophys Acta 1990;1052:386-391. 21. Sumathi R, Baskaran G, Varalakshmi P. Relationship between glutathione and DL alpha-lipoic acid against cadmium-induced hepatotoxicity. Jpn J Med Sci Biol 1996;49:39-48. 22. Sumathi R, Devi VK, Varalakshmi P. DL alpha-lipoic acid protection against cadmium-induced tissue lipid peroxidation. Med Sci Res 1994;22:23-25. 23. Keith RL, Setiarahardjo I, Fernando Q, et al. Utilization of renal slices to evaluate the efficacy of chelating agents for removing mercury from the kidney. Toxicology 1997;116:67-75. 24. Gregus Z, Stein AF, Varga F. Effect of lipoic acid on biliary excretion of glutathione and metals. Toxicol Appl Pharmacol 1992;114:88-96. 25. Strodter D, Lehmann E, Lehmann U, et al. The influence of thioctic acid on metabolism and function of the diabetic heart. Diabetes Res Clin Pract 1995;29:19-26. 26. 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. 27. Faust A, Burkart V, Ulrich H et al. Effect of lipoic acid on cyclophosphamide-induced diabetes and insulitis in nonobese diabetic mice. Int J Immunopharmac 1994;16:61-66. 28. Henricksen EJ, Jacob S, Tritschler HJ, et al. Chronic thioctic treatment increases insulin-stimulated glucose transport activity in skeletal muscle of obese Zucker rats. Diabetes 1994;Supplement 1:122A [abstract]. 29. Kawabata T, Packer L. Alpha-lipoate can protect against glycation of serum albumin, but not low density lipoprotein. Biochem Biophys Res Comms 1994;203:99-104. 30. 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. 31. Jacob S, Henriksen EJ, Tritschler HJ, et al. Improvement of insulin-stimulated glucose-disposal in type 2 diabetes after repeated parenteral administration of thioctic acid. Exp Clin Endocrinol Diabetes 1996;104:284-288. 32. Garrett NE, Malcangio M, Dewhurst M, Tomlinson DR. alpha-lipoic acid corrects neuropeptide deficits in diabetic rats via induction of trophic support. Neurosci Lett 1997;222:191-194. 33. Nagamatsu M, Nickander KK, Schmelzer JD. Lipoic acid improves nerve blood flow, reduces oxidative stress, and improves distal nerve conduction in experimental diabetic neuropathy. Diabetic Care 1995;18:1160-1166. 34. Ziegler D, Hanefield M, Ruhnau KJ, et al. Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant alpha-lipoic acid. A 3-week multicenter randomized controlled trial (ALADIN Study). Diabetologia 1995;38:1425-1433. 35. Kehler W, Kuklinski B, Ruhlmann C, Plotz C. Diabetes mellitus-a free radical associated disease: Effects of adjuvant supplementation of antioxidants. In: Gries FA, Wessel K, eds. The role of antioxidants in diabetes mellitus: Oxygen radicals and anti-oxidants in diabetes. Frankfurt am Maine: pmi. Verl-Gruppe; 1993:33-53. 36. Ou P, Nourooz-Zadeh J, Tritschler HJ, Wolff SP. Activation of aldose reductase in rat lens and metal-ion chelation by aldose reductase inhibitors and lipoic acid. Free Radic Res 1996;25:337-346. 37. Maitra I, Serbinova E, Tritschler HJ, Packer L. Alpha-lipoic acid prevents buthionine sulfoximine-induced cataract formation in newborn rats. Free Radic Biol Med 1995;18:823-829. 38. Maitra I, Serbinova E, Tritschler HJ, Packer L. Stereospecific effects of R-lipoic acid on buthionine sulfoximine-induced cataract formation in newborn rats. Biochem Biophys Res Commun 1996;221:422-429. 39. Filina AA, Davydova NG, Endrikhovskii SN, et al. Lipoic acid as a means of metabolic therapy of open-angle glaucoma. Vestn Oftalmol 1995;111:6-8. 40. Scheer B, Zimmer G. Dihydrolipoic acid prevents hypoxic/reoxygenation and peroxidative damage in rat mitochondria. Arch Biochem Biophys 1993;302:385-390. 41. Assadnazari H, Zimmer G, Freisleben HJ, et al. Cardioprotective efficiency of dihydrolipoic acid in working rat hearts during hypoxia and reoxygenation. P nuclear magnetic resonance investigations. Arzneimittel-Forschung 1993;43:425-432. 42. Prehn JH, Karkoutly C, Nuglisch J, et al. Dihydrolipoate reduces neuronal injury after cerebral ischemia. J Cereb Blood Flow Metab 1992;12:78-87. 43. Wolz P, Krieglstein J. Neuroprotective effects of alpha-lipoic acid and its enantiomers demonstrated in rodent models of focal cerebral ischemia. Neuropharmacology 1996;35:369-375. 44. Panigrahi M, Sadguna Y, Shivakumar BR, et al. alpha-lipoic acid protects against reperfusion injury following cerebral ischemia in rats. Brain Res 1996;717:184-188. 45. Cao X, Phillis JW. The free radical scavenger, alpha-lipoic acid, protects against cerebral ischemia-reperfusion injury in gerbils. Free Rad Res 1995;23:365-70. 46. Haramaki N, Assadnazari H, Zimmer G, et al. The influence of vitamin E and dihydrolipoic acid on cardiac energy and glutathione status under hypoxia-reoxygenation. Biochem Mol Biol Int 1995;37:591-597. 47. Bartter FC, Berkson B, Gallelli J, et al. Thiotic acid in the treatment of poisoning with alpha-amanitin. In: Faulstich H, Kommerell B, Wieland T, eds. Amanita Toxins and Poisoning. Badan-Baden. Verlg Gerhard Witzstrock; 1980:197-202. 48. Nagy I, Pogatsa-Murray G, Zalanyi S Jr, et al. Amanita poisoning during the second trimester of pregnancy. A case report and a review of the literature. Clin Investig 1994;72:794-798. 49. Sabeel AI, Kurkus J, Lindholm T. Intensive hemodialysis and hemoperfusion treatment of Amanita mushroom poisoning. Mycopathologia 1995;131:107-114. 50. Gal EM. Reversal of selective toxicity of (-)-alpha-lipoic acid by thiamine in thiamine-deficient rats. Nature 1965;207:535. 51. Gregus Z, Fekete T, Halaszi E, Klaassen CD. Lipoic acid impairs glycine conjugation of benzoic acid and renal excretion of benzoylglycine. Drug Metab Dispos 1996;24:682-688. 52. Packer L, Tritschler HJ, Wessel K. Neuroprotection by the metabolic antioxidant alpha-lipoic acid. Free Radic Biol Med 1997;22(1-2):359-78. 53. L. Packer, E.H.Witt, H.J. Tritschler, Free Rad Biol and Med 1995; 19: 227-250. 54. Lykkesfeldt J, Hagen TM, Vinarsky V, Ames BN. Age-associated decline in ascorbic acid concentration, recycling, and biosynthesis in rat hepatocytes--reversal with (R)-alpha-lipoic acid supplementation. FASEB J 1998 Sep;12(12):1183-9. 55. Liu J, Atamna H, Kuratsune H, Ames BN. Delaying brain mitochondrial decay and aging with mitochondrial antioxidants and metabolites. Ann N Y Acad Sci 2002 Apr;959:133-66. 56. Liu J, Head E, Gharib AM, Yuan W, Ingersoll RT, Hagen TM, Cotman CW, Ames BN. 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 USA 2002 Feb 19;99(4):2356-61. 57. Hagen TM, Liu J, Lykkesfeldt J, Wehr CM, Ingersoll RT, Vinarsky V, Bartholomew JC, Ames BN. Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proc Natl Acad Sci USA 2002 Feb 19;99(4):1870-5. 58. Hofmann M, Mainka P, Tritschler H, Fuchs J, Zimmer G. Decrease of red cell membrane fluidity and -SH groups due to hyperglycemic conditions is counteracted by alpha-lipoic acid. Arch Biochem Biophys 1995 Dec 1;324(1):85-92. 59. Haramaki N, Assadnazari H, Zimmer G, Schepkin V, Packer L. The influence of vitamin E and dihydrolipoic acid on cardiac energy and glutathione status under hypoxia-reoxygenation. Biochem Mol Biol Int 1995 Oct;37(3):591-7. 9. Zimmer G, Beikler TK, Schneider M, Ibel J, Tritschler H, Ulrich H. Dose/response curves of lipoic acid R-and S-forms in the working rat heart during reoxygenation: superiority of the R-enantiomer in enhancement of aortic flow. J Mol Cell Cardiol 1995 Sep;27(9):1895-903. 60. Haramaki N, Packer L, Assadnazari H, Zimmer G. Cardiac recovery during post-ischemic reperfusion is improved by combination of vitamin E with dihydrolipoic acid. Biochem Biophys Res Commun 1993 Nov 15;196(3):1101-7. 61. Moini, H., Tirosh, O., R-Alpha Lipoic Acid Action on Cell Redox Status, the Insulin Receptor, and Glucose Uptake in 3T3-L1 Adipocytes; Archives of Biochem & BioPhys 397, No2 384-391 (2002). 62. Liu, J. Killilea, D.W. et.al., Age-associated mitochondrial oxidative decay: Improvement of carnitine acetyltransferase substrate binding affinity and activity in brain by feeding old rats acetyl-L-carnitine and/or R-alpha-lipoic acid. Proc Nat Acad Sci 99, 1876-1881 (2002). 63. Hager, K., Marahrens, A.,et.al. Alpha lipoic acid as a new treatment option for Alzheimer type dementia, Arch Geron Geriatr 32 (3): 275-282 (2001). 64. Hermann, R.; Niebch, G.; Enantioselective pharmacokinetics and bioavailability of different racemic alpha lipoic acid formulations in healthy volunteers. Eur J Pharm Sci 4: 167-174 (1996). Disclaimer: The information in this article and on this website is not intended to diagnose, treat, cure or prevent any disease. None of the products mentioned in this article or on this website are intended to diagnose, treat, cure or prevent any disease. The information in this article is not intended to provide personal medical advice, which should be obtained from a medical professional. This information is made available with the understanding that the author and publisher are not providing medical, psychological, or nutritional counseling services on this site. 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