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Alpha-Lipoic Acid

Nutrient Name: Alpha-lipoic acid.
Synonyms: Alpha lipoic acid, ALA, acetate replacing factor, biletan, lipoic acid, lipoicin, thioctacid, thioctan, thioctic acid.
Related Substance: Alpha-dihydrolipoic acid (DHLA); dihydrolipate.

Summary Table
nutrient description

Chemistry and Forms

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.

Physiology and Function

Known by many names, alpha-lipoic acid (ALA) is a naturally occurring, fat-soluble and water-soluble, vitamin-like antioxidant and enzyme cofactor. It is involved in antioxidant protection and cell damage prevention, energy production and blood sugar regulation, growth stimulation and regulation of gene transcription, detoxification, and toxic metal chelation. Although the enzyme pathway for its de novo synthesis has not been fully elucidated, cysteine appears to be the source of sulfur, and octanoate serves as the intermediate precursor for the 8-carbon fatty acid. ALA is readily converted into dihydrolipoic acid (DHLA), its reduced form, in many tissues of the body. ALA is not required in the diet and therefore is not considered a true vitamin, because it can be synthesized by humans, as well as plants and other animals.

Lipoic acid was first isolated in 1951 by Reed and co-workers, in the course of research on “potato growth factor” in lactic acid bacteria, as a catalytic agent associated with pyruvate dehydrogenase; it serves as a coenzyme in the Krebs cycle and functions in the same manner as many B-complex vitamins. Lipoamide, the protein-bound form of the naturally occurring isomer R-alpha-lipoic acid, where it is covalently attached through the carboxylic acid to lysine residues, is a required cofactor for several multienzyme complexes that catalyze energy metabolism reactions within mitochondria. The pyruvate dehydrogenase complex and the alpha-ketoglutarate dehydrogenase complex both catalyze reactions within the citric acid cycle. The alpha-ketoacid dehydrogenase complex catalyzes the metabolism of leucine, isoleucine, and valine, the three branched-chain amino acids. ALA also increases glucose transport and improves heart rate variability. Biliary excretion, electrochemically inactive degradation products, and complete utilization of ALA appear to be the primary substrate in the endogenous metabolism. Urinary excretion of ALA and its main metabolites does not play a significant role in ALA elimination.

Alpha-lipoic acid is a carboxy acid with two sulfur atoms that can be oxidized or reduced and thus, along with glutathione, is one of the thiol antioxidants. Lester Packer, PhD, of the University of California–Berkeley, and others demonstrated the potent antioxidant activity of ALA and described it as the “universal,” “ideal,” and “metabolic” antioxidant because of its unique ability to neutralize free radicals in both lipophilic and hydrophilic environments and operate effectively throughout all tissues, including the brain. The low molecular weight and lipophilicity of ALA also enables it to cross the blood-brain barrier and may contribute to its protective effects on brain and neural tissue. ALA directly supports the liver in its detoxifying functions and plays an important role enhancing the activity of the body’s systemic “antioxidant network.” ALA and dihydrolipoic acid (DHLA), also known as dihydrolipoate, both act as powerful antioxidants, protecting against oxidative damage by interacting with potentially damaging reactive oxygen and nitrogen species. In particular, the two forms work together to quench peroxynitrite radicals, an especially destructive class of free radicals consisting of both oxygen and nitrogen, which are known to play a role in the pathophysiology of chronic inflammation, atherosclerosis, lung disease, and neurological disorders. DHLA also enhances the uptake of cysteine by cells to enable increased glutathione synthesis and support intracellular glutathione levels. Furthermore, ALA and DHLA facilitate the synergistic relationship among antioxidants by regenerating ascorbic acid from dehydroascorbic acid, indirectly regenerating vitamin E, and reducing the oxidized forms of vitamin C, glutathione, and coenzyme Q10 to extend their metabolic life spans. Both ALA and DHLA may also chelate free metal ions, such as iron, copper, and arsenic, and prevent them from generating highly reactive free radicals that induce oxidative damage. Lastly, ALA (and DHLA) may play a role in repair of oxidative damage.

Alpha-lipoic acid also regulates signal transduction of nuclear factor kappa B (NF-κB), a transcription factor protein that binds to DNA and affects the rate of transcription of certain genes, with NF-κB-binding sites. By inhibiting the activation of NF-κB, ALA may influence a wide range of pathological processes, including inflammation, atherosclerosis, diabetes, hypertension, glaucoma, cancer, and acquired immunodeficiency syndrome (AIDS).

nutrient in clinical practice

Known or Potential Therapeutic Uses

Alpha-lipoic acid has been used clinically to protect against oxidative stress, to enhance mitochondrial function, to support healthy liver and neurological function, and to reduce the cellular effects of aging. In a clinical trial investigating in vivo antioxidant activity of ALA in healthy humans, Marangon et al. 1 found that a 4-month course of 600 mg/day significantly decreased several biomarkers of oxidative stress compared to baseline. Pharmacokinetic studies of oral ALA suggest that it might be most effectively administered in divided doses throughout the day, rather than in a single daily dose, because it is rapidly absorbed, rapidly metabolized, and rapidly cleared from plasma and tissues.

Historical/Ethnomedicine Precedent

Alpha-lipoic acid has not been used historically as an isolated nutrient.

Possible Uses

Age-related macular degeneration, Alzheimer’s disease (dementia), Amanita poisoning, antioxidant support, cancer, cataracts, cellular oxidative damage, diabetic polyneuropathy, glaucoma, hepatitis C, human immunodeficiency virus and acquired immunodeficiency syndrome (HIV/AIDS) support, insulin resistance, ischemia-reperfusion injury, metal chelation, neuralgias, surgical recovery, type 2 diabetes mellitus.

Deficiency Symptoms

De novo synthesis generally prevents ALA deficiency, which has not been described per se. Nevertheless, the destruction of its cofactor form may play an important role in numerous pathophysiological processes. For example, individuals with primary biliary cirrhosis may have circulating antibodies to lipoamide-containing enzyme subunits. 2 Likewise, arsenic can render ALA inactive in arsenic toxicity by forming a complex with ALA in dehydrogenase enzymes. 3

Dietary Sources

Limited quantitative information is available regarding ALA content in various food sources, and research into the relationship of dietary sources to circulating free ALA is in preliminary stages. Most dietary ALA is derived from lipoamide-containing enzymes and delivered as lipoyllysine (i.e., bound to lysine), which digestive enzymes may not effectively cleave. 3

Foods that contain mitochondria, especially red meat, are believed to provide the highest levels of alpha-lipoic acid. Other animal sources include heart, liver, kidney, and skeletal muscle (i.e., red meat). Broccoli, spinach, tomatoes, and potatoes are rich plant sources of lipoyllysine, with yeast, peas, brussels sprouts, and rice bran having lower amounts. 4

Nutrient Preparations Available

The R-isomer of alpha-lipoic acid is the form synthesized naturally and is the only form that functions as a cofactor for mitochondrial enzymes; it is currently commercially available. Previously, ALA was exclusively available as a 50/50 racemic mixture of the two optical isomers, R-alpha-lipoic acid and S-alpha-lipoic acid, as rendered by conventional chemical synthesis. R-ALA has greater bioavailability than S-ALA when administered orally and is reduced within the mitochondria to DHLA 28 times more rapidly, hypothetically providing significantly greater antioxidant activity. 5

Dosage Forms Available

Capsule.

Dosage Range

Adult

Dietary: Alpha-lipoic acid is created in the human body and thus is not an essential nutrient. Consequently, humans are usually not deficient in ALA.

Supplemental/Maintenance: 20 to 50 mg/day.

Pharmacological/Therapeutic: 50 to 400 mg/day.

The amount of ALA used in research has ranged from 150 to 600 mg per day, with 600 mg/day being used to treat diabetic neuropathies and 150 mg/day for glaucoma.

Toxic: No upper limit (UL) dose has been established.

safety profile

Overview

Alpha-lipoic acid has been well tolerated and is considered to be extremely safe in the dosages typically used in clinical settings (e.g., 600 mg/day). When administered under medical supervision to patients with diabetic neuropathy, oral doses as high as 1200 mg/day (600 mg twice daily) for 2 years and 1800 mg/day (600 mg three times daily) for 3 weeks produced no adverse effects. No cases of toxicity from ALA overdose in humans have been published or otherwise reported. Nevertheless, no long-term studies have yet systematically evaluated the safety of ALA in healthy adults.

Nutrient Adverse Effects

General Adverse Effects

Skin rash (occasional).

Pregnancy and Nursing

There are no reports of adverse reactions. However, because no studies have confirmed the safety or documented any dangers of using ALA during pregnancy, nutraceutical intake should be avoided by pregnant or lactating women until safety has been demonstrated.

Contraindications

Use of ALA and other antioxidants is controversial during radiation therapy and some forms of chemotherapy.

Precautions and Warnings

Theoretically, as discussed later, orally administered ALA might enhance the effects of insulin and oral hypoglycemic agents and induce hypoglycemia.

interactions review

Strategic Considerations

Although research into the biological activity of alpha-lipoic acid has been underway for more than 40 years, scientific knowledge of its potential role in clinical medicine has only recently begun emerging in a comprehensive and cohesive picture. The significant antioxidant activity of ALA and alpha-dihydrolipoic acid (DHLA), as well as other modes of biological activity, presents numerous apparent, and many as-yet undiscovered, opportunities for concomitant use with conventional medications, in both the prevention and the reduction of drug adverse effects, as well as through collaborative implementation of integrative strategies and by invoking beneficial or supportive interactions within the context of professional management. Even though R-ALA is the naturally occurring form and has superior pharmacokinetic characteristics, almost all human clinical trials of ALA administration have been performed using racemic ALA. 6 Furthermore, continued research into ALA’s relative role in antioxidant networks will undoubtedly reveal deeper implications for its physiological functions and clinical applications. Thus, more refined research design is warranted to enable advancement of clinical knowledge concerning the therapeutic use and efficacy of alpha-lipoic acid.

nutrient-drug interactions
Cisplatin and Related Platinum Chemotherapy Compounds
Research
Gentamicin, Amikacin, and Related Aminoglycoside Antibiotics
Haloperidol
Haloperidol (Haldol).
Prevention or Reduction of Drug Adverse Effect
Beneficial or Supportive Interaction, with Professional Management

Probability: 3. Possible
Evidence Base: Preliminary

Effect and Mechanism of Action

Haloperidol, a widely used neuroleptic, acts through blockade of dopamine receptors, leading to increased turnover of dopamine. Excessive production of hydrogen peroxide and thus generation of oxidative stress are predictable outcomes from such increased turnover of dopamine. The antioxidant activity of alpha-lipoic acid, as well as that of glutathione, may protect against and reverse free-radical damage.

Research

Using a rat model, Shivakumar and Ravindranath 15 demonstrated that chronic administration of haloperidol induced significant oxidative stress and thiol modification in brain tissue, particularly after the first month. However, after 6 months of haloperidol administration, the glutathione-protein thiol homeostasis was largely restored, and the concentration of lipid peroxidation products decreased. Subsequently, Balijepalli et al. 16 examined the effects of a variety of classic and atypical neuroleptic drugs and found that haloperidol was the most potent inhibitor of mitochondrial NADH ubiquinone oxido-reductase (complex I) activity. They found that in vitro treatment of mouse brain slices with haloperidol resulted in a loss of glutathione, and that pretreatment of slices with glutathione and ALA abolished haloperidol-induced loss of complex I activity.

Nutritional Therapeutics, Clinical Concerns, and Adaptations

Preliminary evidence indicates that coadministration of ALA (and/or glutathione) could potentially reduce depletion of naturally occurring glutathione and other adverse side effects caused by use of haloperidol. No definitive advice or dosage recommendations can be offered given the lack of clinical trials. Physicians prescribing haloperidol, and possibly related antiemetics and antipsychotics, are advised to work in close collaboration with health care professionals trained and experienced in nutritional therapeutics and closely monitor patients choosing to use ALA (and/or glutathione) during and after haloperidol therapy. ALA, typically at dosages of 20 to 50 mg per day, is frequently prescribed for general antioxidant protection, whereas 800 mg/day ALA and 150 mg/day glutathione are often administered in the treatment of other neurological conditions involving free-radical damage. ALA has no known toxic effects at such dosages and has never been shown to inhibit the therapeutic efficacy of haloperidol.

Irbesartan and Related Angiotensin II Receptor Antagonists
Oral Hypoglycemic Agents and Insulin
theoretical, speculative, and preliminary interactions research, including overstated interactions claims
Anesthesia, General
Cyclophosphamide and Vincristine
Doxorubicin and Related Anthracycline Chemotherapy
Levothyroxine, Thyroid
herb-nutrient interactions
Acetyl- SMALLCAPS L END_SMALLCAPS -Carnitine
Biotin
Coenzyme Q10
Copper
Omega-3 Fatty Acids (Fish Oil)
Iron
Selenium and Milk Thistle (Silybum marianum)
Vitamin B 1 (Thiamine)
Vitamin E
Vitamin K
Citations and Reference Literature
  • 1.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 Radic Biol Med 1999;27:1114-1121.View Abstract
  • 2.Yeaman SJ, Kirby JA, Jones DE. Autoreactive responses to pyruvate dehydrogenase complex in the pathogenesis of primary biliary cirrhosis. Immunol Rev 2000;174:238-249.View Abstract
  • 3.Biewenga GP, Haenen GR, Bast A. The pharmacology of the antioxidant lipoic acid. Gen Pharmacol 1997;29:315-331.View Abstract
  • 4.Lodge JK, Youn HD, Handelman GJ et al. Natural sources of lipoic acid: determination of lipoyllysine released from protease-digested tissues by high performance liquid chromatography incorporating electrochemical detection. J Appl Nutr 1997;49:3-11.
  • 5.Hermann R, Niebch G, Borbe HO et al. Enantioselective pharmacokinetics and bioavailability of different racemic α-lipoic acid formulations in healthy volunteers. Eur J Pharm Sci 1996;4:167-174.
  • 6.Hagen TM. Alpha-Lipoic Acid. Accessed October 31, 2003, at www.lpi.oregonstate.edu/infocenter/othernuts/la/index.html. View Abstract
  • 7.Rybak LP, Husain K, Whitworth C, Somani SM. Dose dependent protection by lipoic acid against cisplatin-induced ototoxicity in rats: antioxidant defense system. Toxicol Sci 1999;47:195-202.View Abstract
  • 8.Somani SM, Husain K, Whitworth C et al. Dose-dependent protection by lipoic acid against cisplatin-induced nephrotoxicity in rats: antioxidant defense system. Pharmacol Toxicol 2000;86:234-241.View Abstract
  • 9.Gedlicka C, Kornek GV, Schmid K, Scheithauer W. Amelioration of docetaxel/cisplatin induced polyneuropathy by alpha-lipoic acid. Ann Oncol 2003;14:339-340.View Abstract
  • 10.Culy CR, Clemett D, Wiseman LR. Oxaliplatin: a review of its pharmacological properties and clinical efficacy in metastatic colorectal cancer and its potential in other malignancies. Drugs 2000;60:895-924.View Abstract
  • 11.Gedlicka C, Scheithauer W, Schull B, Kornek GV. Effective treatment of oxaliplatin-induced cumulative polyneuropathy with alpha-lipoic acid. J Clin Oncol 2002;20:3359-3361.View Abstract
  • 12.Tran Ba Huy P, Deffrennes D. Aminoglycoside ototoxicity: influence of dosage regimen on drug uptake and correlation between membrane binding and some clinical features. Acta Otolaryngol 1988;105:511-515.
  • 13.Sandhya P, Varalakshmi P. Effect of lipoic acid administration on gentamicin-induced lipid peroxidation in rats. J Appl Toxicol 1997;17:405-408.View Abstract
  • 14.Conlon BJ, Aran JM, Erre JP, Smith DW. Attenuation of aminoglycoside-induced cochlear damage with the metabolic antioxidant alpha-lipoic acid. Hear Res 1999;128:40-44.View Abstract
  • 15.Shivakumar BR, Ravindranath V. Oxidative stress and thiol modification induced by chronic administration of haloperidol. J Pharmacol Exp Ther 1993;265:1137-1141.View Abstract
  • 16.Balijepalli S, Boyd MR, Ravindranath V. Inhibition of mitochondrial complex I by haloperidol: the role of thiol oxidation. Neuropharmacology 1999;38:567-577.View Abstract
  • 17.Sola S, Mir MQ, Cheema FA et al. Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: results of the Irbesartan and Lipoic Acid in Endothelial Dysfunction (ISLAND) Study. Circulation 2005;111:343-348.View Abstract
  • 18.Melhem MF, Craven PA, Liachenko J, DeRubertis FR. Alpha-lipoic acid attenuates hyperglycemia and prevents glomerular mesangial matrix expansion in diabetes. J Am Soc Nephrol 2002;13:108-116.View Abstract
  • 19.El Midaoui A, de Champlain J. Prevention of hypertension, insulin resistance, and oxidative stress by alpha-lipoic acid. Hypertension 2002;39:303-307.View Abstract
  • 20.Gleiter CH, Schreeb KH, Freudenthaler S et al. Lack of interaction between thioctic acid, glibenclamide and acarbose. Br J Clin Pharmacol 1999;48:819-825.
  • 21.Berger M, Habs M, Schmahl D. [Effect of thioctic acid (alpha-lipoic acid) on the chemotherapeutic efficacy of cyclophosphamide and vincristine sulfate]. Arzneimittelforschung 1983;33:1286-1288.
  • 22.Faust A, Burkart V, Ulrich H et al. Effect of lipoic acid on cyclophosphamide-induced diabetes and insulitis in non-obese diabetic mice. Int J Immunopharmacol 1994;16:61-66.View Abstract
  • 23.Brouwer CA, Gietema JA, van den Berg MP et al. Long-term cardiac follow-up in survivors of a malignant bone tumour. Ann Oncol 2006;17:1586-1591.View Abstract
  • 24.Al-Majed AA, Gdo AM, Al-Shabanah OA, Mansour MA. Alpha-lipoic acid ameliorates myocardial toxicity induced by doxorubicin. Pharmacol Res 2002;46:499-503.View Abstract
  • 25.Balachandar AV, Malarkodi KP, Varalakshmi P. Protective role of dlalpha-lipoic acid against Adriamycin-induced cardiac lipid peroxidation. Hum Exp Toxicol 2003;22:249-254.View Abstract
  • 26.Malarkodi KP, Balachandar AV, Sivaprasad R, Varalakshmi P. Prophylactic effect of lipoic acid against Adriamycin-induced peroxidative damages in rat kidney. Ren Fail 2003;25:367-377.View Abstract
  • 27.Malarkodi KP, Balachandar AV, Varalakshmi P. Protective effect of lipoic acid on Adriamycin-induced lipid peroxidation in rat kidney. Mol Cell Biochem 2003;247:9-13.View Abstract
  • 28.Malarkodi KP, Balachandar AV, Varalakshmi P. The influence of lipoic acid on Adriamycin-induced nephrotoxicity in rats. Mol Cell Biochem 2003;247:15-22.View Abstract
  • 29.Malarkodi KP, Balachandar AV, Varlakshmi P. The influence of lipoic acid on Adriamycin-induced hyperlipidemic nephrotoxicity in rats. Mol Cell Biochem 2003;247:139-145.View Abstract
  • 30.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. Arzneimittelforschung 1991;41:1294-1298.View Abstract
  • 31.Hagen TM, Liu J, Lykkesfeldt J 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 2002;99:1870-1875.
  • 32.Liu J, Head E, Gharib AM 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 2002;99:2356-2361.View Abstract
  • 33.Reche PA. Lipoylating and biotinylating enzymes contain a homologous catalytic module. Protein Sci 2000;9:1922-1929.View Abstract
  • 34.Marquet A, Bui BT, Florentin D. Biosynthesis of biotin and lipoic acid. Vitam Horm 2001;61:51-101.View Abstract
  • 35.Grafe F, Wohlrab W, Neubert RH, Brandsch M. Transport of biotin in human keratinocytes. J Invest Dermatol 2003;120:428-433.View Abstract
  • 36.Zempleni J, Trusty TA, Mock DM. Lipoic acid reduces the activities of biotin-dependent carboxylases in rat liver. J Nutr 1997;127:1776-1781.View Abstract
  • 37.Kozlov AV, Gille L, Staniek K, Nohl H. Dihydrolipoic acid maintains ubiquinone in the antioxidant active form by two-electron reduction of ubiquinone and one-electron reduction of ubisemiquinone. Arch Biochem Biophys 1999;363:148-154.View Abstract
  • 38.Da Costa S, da Silva J. [Alpha-lipoic acid and the metabolism of copper and iron]. Sangre (Barc) 1962;7:367-385.View Abstract
  • 39.Gaetke LM, Chow CK. Copper toxicity, oxidative stress, and antioxidant nutrients. Toxicology 2003;189:147-163.View Abstract
  • 40.Sheline CT, Choi EH, Kim-Han JS et al. Cofactors of mitochondrial enzymes attenuate copper-induced death in vitro and in vivo. Ann Neurol 2002;52:195-204.View Abstract
  • 41.Lenin M, Latha LM, Nagaraj M, Varalakshmi P. Mitigation of free radical toxicity in hyperoxaluric condition by a novel derivative eicosapentaenoate-lipoate. Hum Exp Toxicol 2002;21:153-158.View Abstract
  • 42.Da Costa SF, da Silva JA. [Metabolic significance of alpha-lipoic acid. 3. Alpha-lipoic acid and iron metabolism (preliminary note)]. J Soc Cienc Med Lisb 1963;127:15-52.View Abstract
  • 43.Da Costa S, da Silva J, Correia JA, Maldonado FE. [Metabolic significance of alpha-lipoic acid. V. Comparative action of alpha-lipoic acid, vitamin B 12 and cocarboxylase on metabolism of copper and iron and on aminoacidurias (further observations)]. Arq Patol 1963;35:91-97.View Abstract
  • 44.Da Costa S, da Silva J, Maldonado FE. [Metabolic significance of alpha-lipoic acid. IV. Action of alpha-lipoic acid on ceruloplasmin and transferrin in different pathological conditions (preliminary report)]. Arq Patol 1963;35:3-19.View Abstract
  • 45.Scott BC, Aruoma OI, Evans PJ et al. Lipoic and dihydrolipoic acids as antioxidants: a critical evaluation. Free Radic Res 1994;20:119-133.View Abstract
  • 46.Packer L, Witt EH, Tritschler HJ. Alpha-lipoic acid as a biological antioxidant. Free Radic Biol Med 1995;19:227-250.View Abstract
  • 47.Lovell MA, Xie C, Xiong S, Markesbery WR. Protection against amyloid beta peptide and iron/hydrogen peroxide toxicity by alpha lipoic acid. J Alzheimers Dis 2003;5:229-239.View Abstract
  • 48.Ames BN. The metabolic tune-up: metabolic harmony and disease prevention. J Nutr 2003;133:1544S-1548S.View Abstract
  • 49.Persson HL, Yu Z, Tirosh O et al. Prevention of oxidant-induced cell death by lysosomotropic iron chelators. Free Radic Biol Med 2003;34:1295-1305.View Abstract
  • 50.Dudchenko NO, Mykhailik OM, Lubianova IP. [Effect of alpha-lipoic acid preparations on bilirubin and transferrin levels and ferritin iron and transferrin iron content]. Ukr Biokhim Zh 2001;73:102-105.View Abstract
  • 51.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 (Munich) 1999;94 Suppl 3:84-89.View Abstract
  • 52.Gal EM. Reversal of selective toxicity of (–)-alpha-lipoic acid by thiamine in thiamine-deficient rats. Nature 1965;207:535.View Abstract
  • 53.Bast A, Haenen GR. Regulation of lipid peroxidation by glutathione and lipoic acid: involvement of liver microsomal vitamin E free radical reductase. Adv Exp Med Biol 1990;264:111-116.View Abstract
  • 54.Kagan VE, Serbinova EA, Forte T et al. Recycling of vitamin E in human low density lipoproteins. J Lipid Res 1992;33:385-397.View Abstract
  • 55.Stoyanovsky DA, Goldman R, Claycamp HG, Kagan VE. Phenoxyl radical-induced thiol-dependent generation of reactive oxygen species: implications for benzene toxicity. Arch Biochem Biophys 1995;317:315-323.View Abstract
  • 56.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 1995;14:181-189.View Abstract
  • 57.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.View Abstract
  • 58.Bast A, Haenen GR. Lipoic acid: a multifunctional antioxidant. Biofactors 2003;17:207-213.View Abstract
  • 59.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.View Abstract
  • 60.Thijssen HH, Janssen YP, Vervoort LT. Microsomal lipoamide reductase provides vitamin K epoxide reductase with reducing equivalents. Biochem J 1994;297(Pt 2):277-280.View Abstract
  • 61.Marriage B, Clandinin MT, Glerum DM. Nutritional cofactor treatment in mitochondrial disorders. J Am Diet Assoc 2003;103:1029-1038.View Abstract
  • .[No author listed.] [Alpha-lipoic acid in diabetic neuropathy: action mechanism and therapy: clinical picture and pathogenesis of diabetic neuropathy.] Internist (Berl) 1994;35(6 Alpha-liponsa):1-4. [German]
  • .[No author listed.] Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33): UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352(9131):837-853.
  • .[No author listed.] Monograph: alpha-lipoic acid. Altern Med Rev 1998;3(4):308-310.
  • .[No author listed.] The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus: the Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329(14):977-986.
  • .Aguirre N, Barrionuevo M, Ramirez MJ, et al. Alpha-lipoic acid prevents 3,4-methylenedioxy-methamphetamine (MDMA)-induced neurotoxicity. Neuroreport 1999;10(17):3675-3680.
  • .Ames BN. The metabolic tune-up: metabolic harmony and disease prevention. J Nutr 2003;133(5 Suppl 1):1544S-1548S.
  • .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(3):770-776.
  • .Androne L, Gavan NA, Veresiu IA, et al. In vivo effect of lipoic acid on lipid peroxidation in patients with diabetic neuropathy. In Vivo 2000;14(2):327-330.
  • .Anuradha B, Varalakshmi P. Protective role of DL-alpha-lipoic acid against mercury-induced neural lipid peroxidation. Pharmacol Res 1999;39(1):67-80.
  • .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.
  • .Atamna H, Ames BN, Liu J. Delaying aging with mitochondrial micronutrients and antioxidants. Sci World J 2001;1(1 Suppl 3):81-82.
  • .Baker H, Deangelis B, Baker ER, et al. A practical assay of lipoate in biologic fluids and liver in health and disease. Free Radic Biol Med 1998;25(4-5):473-479.
  • .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.
  • .Bassendine MF, Jones DE, Yeaman SJ. Biochemistry and autoimmune response to the 2-oxoacid dehydrogenase complexes in primary biliary cirrhosis. Semin Liver Dis 1997;17(1):49-60. (Review)
  • .Bast A, Haenen GR. Lipoic acid: a multifunctional antioxidant. Biofactors 2003;17(1-4):207-213. (Review)
  • .Baur A, Harrer T, Peukert M, et al. Alpha-lipoic acid is an effective inhibitor of human immuno-deficiency virus (HIV-1) replication. Klin Wochenschr 1991;69(15):722-724.
  • .Beckman KB, Ames BN. Mitochondrial aging: open questions. Ann N Y Acad Sci. 1998;854:118-127.
  • .Beitner H. Randomized, placebo-controlled, double blind study on the clinical efficacy of a cream containing 5% alpha-lipoic acid related to photoageing of facial skin. Br J Dermatol 2003;149(4):841-849.
  • .Berkson BM. Thioctic acid in treatment of hepatotoxic mushroom (Phalloides) poisoning. N Engl J Med 1979;300(7):371.
  • .Biewenga GP, Haenen GR, Bast A. The pharmacology of the antioxidant lipoic acid. Gen Pharmacol 1997;29(3):315-331.
  • .Biewenga G, Haenen GR, Bast A. The role of lipoic acid in the treatment of diabetic polyneuropathy. Drug Metab Rev 1997;29(4):1025-1054.
  • .Biewenga GP, Veening-Griffioen DH, Nicastia AJ, et al. Effects of dihydrolipoic acid on peptide methionine sulfoxide reductase: implications for antioxidant drugs. Arzneimittelforschung 1998;48(2):144-148.
  • .Borcea V, Nourooz-Zadeh J, Wolff SP, et al. alpha-Lipoic acid decreases oxidative stress even in diabetic patients with poor glycemic control and albuminuria. Free Radic Biol Med 1999;26(11-12):1495-1500.
  • .Breithaupt-Grogler K, Niebch G, Schneider E, et al. Dose-proportionality of oral thioctic acid: coincidence of assessments via pooled plasma and individual data. Eur J Pharm Sci 1999;8(1):57-65.
  • .Busse E, Zimmer G, Schopohl B, et al. Influence of alpha-lipoic acid on intracellular glutathione in vitro and in vivo. Arzneimittelforschung 1992;42(6):829-831.
  • .Bustamante J, Lodge JK, Marcocci L, et al. Alpha-lipoic acid in liver metabolism and disease. Free Radic Biol Med 1998;24(6):1023-1039. (Review)
  • .Byrd DJ, Krohn HP, Winkler L, et al. Neonatal pyruvate dehydrogenase deficiency with lipoate responsive lactic acidaemia and hyperammonaemia. Eur J Pediatr 1989;148:543-547.
  • .Cao X, Phillis JW. The free radical scavenger, alpha-lipoic acid, protects against cerebral ischemia-reperfusion injury in gerbils. Free Radic Res 1995;23(4):365-370. Erratum in Free Radic Res 1995;23(6):629.
  • .Carreau JP. Biosynthesis of lipoic acid via unsaturated fatty acids. Meth Enzmol 1979;62:152-158.
  • .Ceriello A. New insights on oxidative stress and diabetic complications may lead to a "Causal" antioxidant therapy. Diabetes Care 2003;26(5):1589-1596.
  • .Chaudiere J, Ferrari-Iliou R. Intracellular antioxidants: from chemical to biochemical mechanisms. Food Chem Toxicol 1999;37(9-10):949-962.
  • .Chidlow G, Schmidt KG, Wood JP, et al. Alpha-lipoic acid protects the retina against ischemia-reperfusion. Neuropharmacology 2002;43(6):1015-1025.
  • .Constantinescu A, Tritschler H, Packer L. alpha-Lipoic acid protects against hemolysis of human erythrocytes induced by peroxyl radicals. Biochem Mol Biol Int 1994;33(4):669-679.
  • .Devasagayam TP, Subramanian M, Pradhan DS, et al. Prevention of singlet oxygen induced DNA damage by lipoate. Chem Biol Interact 1993;86:79-92.
  • .Eremeeva ME, Silverman DJ. Effects of the antioxidant alpha-lipoic acid on human umbilical vein endothelial cells infected with Rickettsia rickettsii. Infect Immun 1998;66(5):2290-2299.
  • .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(12):1798-1804.
  • .Evans JL, Goldfine ID. Alpha-lipoic acid: a multifunctional antioxidant that improves insulin sensitivity in patients with type 2 diabetes. Diabetes Technol Ther 2000;2(3):401-413.
  • .Evans JL, Goldfine ID, Maddux BA, et al. Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev 2002;23(5):599-622. (Review)
  • .Evans JL, Heymann CJ, Goldfine ID, et al. Pharmacokinetics, tolerability, and fructosamine-lowering effect of a novel, controlled-release formulation of alpha-lipoic acid. Endocr Pract 2002;8(1):29-35.
  • .Femiano F. Burning mouth syndrome (BMS): an open trial of comparative efficacy of alpha-lipoic acid (thioctic acid) with other therapies. Minerva Stomatol 2002;51(9):405-409.
  • .Filina AA, Davydova NG, Endrikhovskii SN, et al. [Lipoic acid as a means of metabolic therapy of open-angle glaucoma.] Vestn Oftalmol 1995;111(4):6-8. [Russian]
  • .Gleiter CH, Schug BS, Hermann R, et al. Influence of food intake on the bioavailability of thioctic acid enantiomers. Eur J Clin Pharmacol 1996;50(6):513-514.
  • .Goralska M, Dackor R, Holley B, et al. Alpha lipoic acid changes iron uptake and storage in lens epithelial cells. Exp Eye Res 2003;76(2):241-248.
  • .Greene DA, Stevens MJ, Obrosova I, et al. Glucose-induced oxidative stress and programmed cell death in diabetic neuropathy. Eur J Pharmacol 1999;375(1-3):217-223.
  • .Gregus Z, Stein AF, Varga F. Effect of lipoic acid on biliary excretion of glutathione and metals. Toxicol Appl Pharmacol 1992;114:88-96.
  • .Grothey A. Oxaliplatin-safety profile: neurotoxicity. Semin Oncol 2003;30(4 Suppl 15):5-13.
  • .Grunert RR. The effect of DL-alpha-lipoic acid on heavy-metal intoxication in mice and dogs. Arch Biochem Biophys 1960;86:190-194.
  • .Gualandri W, Gualandri L, Demartini G, et al. 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.
  • .Gurer H, Ozgunes H, Oztezcan S, et al. Antioxidant role of alpha-lipoic acid in lead toxicity. Free Radic Biol Med 1999;27(1-2):75-81.
  • .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(3):168-174.
  • .Hagen TM, Liu J, Lykkesfeldt J, 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 2002;99(4):1870-1875.
  • .Hagen TM. Alpha-lipoic acid. Available at www.lpi.oregonstate.edu/infocenter/othernuts/la/index.html. Accessed October 31, 2003. (Review)
  • .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(2):411-418.
  • .Hagen TM, Vinarsky V, Wehr CM, et al. (R)-alpha-lipoic acid reverses the age-associated increase in susceptibility of hepatocytes to tert-butylhydroperoxide both in vitro and in vivo. Antioxid Redox Signal 2000;2(3):473-483.
  • .Hager K, Marahrens A, Kenklies M, et al. Alpha-lipoic acid as a new treatment option for Alzheimer type dementia. Arch Gerontol Geriatr 2001;32(3):275-282.
  • .Halat KM, Dennehy CE. Botanicals and dietary supplements in diabetic peripheral neuropathy. J Am Board Fam Pract 2003;16(1):47-57. (Review)
  • .Han D, Handelman G, Marcocci L, et al. Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. Biofactors 1997;6(3):321-338.
  • .Handelman GJ, Han D, Tritschler H, et al. Alpha-lipoic acid reduction by mammalian cells to the dithiol form, and release into the culture medium. Biochem Pharmacol 1994;47(10):1725-1730.
  • .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.
  • .Henriksen EJ, Saengsirisuwan V. Exercise training and antioxidants: relief from oxidative stress and insulin resistance. Exerc Sport Sci Rev 2003;31(2):79-84. (Review)
  • .Heitzer T, Finckh B, Albers S, et al. Beneficial effects of alpha-lipoic acid and ascorbic acid on endothelium-dependent, nitric oxide-mediated vasodilation in diabetic patients: relation to parameters of oxidative stress. Free Radic Biol Med 2001;31(1):53-61.
  • .Hermann R, Niebch G, Borbe HO, et al. Enantioselective pharmacokinetics and bioavailability of different racemic α-lipoic acid formulations in healthy volunteers. Eur J Pharm Sci 1996;4:167-174.
  • .Hofmann MA, Schiekofer S, Isermann B, et al. Peripheral blood mononuclear cells isolated from patients with diabetic nephropathy show increased activation of the oxidative-stress sensitive transcription factor NF-kappaB. Diabetologia 1999;42(2):222-232.
  • .Hofmann MA, Schiekofer S, Kanitz M, et al. Insufficient glycemic control increases nuclear factor-kappa B binding activity in peripheral blood mononuclear cells isolated from patients with type 1 diabetes. Diabetes Care 1998;21(8):1310-1316.
  • .Hong YS, Kerr DS, Liu TC, et al. Deficiency of dihydrolipoamide dehydrogenase due to two mutant alleles (E340K and G101del): analysis of a family and prenatal testing. Biochim Biophys Acta 1997;1362:160-168.
  • .Hounsom L, Horrobin DF, Tritschler H, et al. A lipoic acid-gamma linolenic acid conjugate is effective against multiple indices of experimental diabetic neuropathy. Diabetologia 1998;41(7):839-843.
  • .Jacob S, Henriksen EJ, Schiemann AL, et al. Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid. Arzneimittelforschung 1995;45(8):872-874.
  • .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(3):284-288.
  • .Jacob S, Rett K, Henriksen EJ, et al. Thioctic acid: effects on insulin sensitivity and glucose-metabolism. Biofactors 1999;10(2-3):169-174.
  • .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(3-4):309-314.
  • .Jones W, Li X, Qu ZC, et al. Uptake, recycling, and antioxidant actions of alpha-lipoic acid in endothelial cells. Free Radic Biol Med 2002;33(1):83-93.
  • .Kagan V, Khan S, Swanson C, et al. Antioxidant action of thioctic acid and dihydrolipoic acid. Free Radic Biol Med 1990;9S:15.
  • .Kagan V, Serbinova E, Packer L. Antioxidant effects of ubiquinones in microsomes and mitochondria are mediated by tocopherol recycling. Biochem Biophys Res Commun 1990;169(3):851-857.
  • .Kagan VE, Serbinova EA, Forte T, et al. Recycling of vitamin E in human low density lipoproteins. J Lipid Res 1992;33(3):385-397.
  • .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 1992;44(8):1637-1649.
  • .Kagan V, Witt E, Goldman R, et al. Ultraviolet light-induced generation of vitamin E radicals and their recycling: a possible photosensitizing effect of vitamin E in skin. Free Radic Res Commun 1992;16(1):51-64.
  • .Kawabata T, Packer L. Alpha-lipoate can protect against glycation of serum albumin, but not low density lipoprotein. Biochem Biophys Res Commun 1994;203:99-104.
  • .Kehler W, Kuklinski B, Ruhlmann C, et al. 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.
  • .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(1-3):67-75.
  • .Khamaisi M, Potashnik R, Tirosh A, et al. Lipoic acid reduces glycemia and increases muscle GLUT4 content in streptozotocin-diabetic rats. Metabolism 1997;46(7):763-768.
  • .Khanna S, Atalay M, Lodge JK, et al. Skeletal muscle and liver lipoyllysine content in response to exercise, training and dietary alpha-lipoic acid supplementation. Biochem Mol Biol Int 1998;46(2):297-306.
  • .Kilic F, Handelman GJ, Traber K, 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 1998;46(3):585-595.
  • .Kishi Y, Schmelzer JD, Yao JK, et al. Alpha-lipoic acid: effect on glucose uptake, sorbitol pathway, and energy metabolism in experimental diabetic neuropathy. Diabetes 1999;48(10):2045-2051.
  • .Kobberling J, Hompesch M. alpha-Lipoic acid in NIDDM patients with cardiac autonomic neuropathy. Diabetes Care 1997;20(12):1918-1920. (Letter)
  • .Konrad D, Somwar R, Sweeney G, et al. The antihyperglycemic drug alpha-lipoic acid stimulates glucose uptake via both GLUT4 translocation and GLUT4 activation: potential role of p38 mitogen-activated protein kinase in GLUT4 activation. Diabetes 2001;50(6):1464-1471.
  • .Konrad T, Vicini P, Kusterer K, et al. 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;22(2):280-287.
  • .Kozlov AV, Gille L, Staniek K, et al. Dihydrolipoic acid maintains ubiquinone in the antioxidant active form by two-electron reduction of ubiquinone and one-electron reduction of ubisemiquinone. Arch Biochem Biophys 1999;363(1):148-154.
  • .Kramer K, Packer L. R-alpha-lipoic acid. In: Kramer K, Hoppe P, Packer L, eds. Nutraceuticals in health and disease prevention. New York: Marcel Dekker, Inc; 2001:129-164.
  • .Liu J, Head E, Gharib AM, 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 2002;99(4):2356-2361.
  • .Lockhart B, Jones C, Cuisinier C, et al. Inhibition of L-homocysteic acid and buthionine sulphoximine-mediated neurotoxicity in rat embryonic neuronal cultures with alpha-lipoic acid enantiomers. Brain Res 2000;855(2):292-297.
  • .Loffelhardt S, Bonaventura C, Locher M, et al. Interaction of alpha-lipoic acid enantiomers and homologues with the enzyme components of the mammalian pyruvate dehydrogenase complex. Biochem Pharmacol 1995;50(5):637-646.
  • .Lovell MA, Xie C, Xiong S, et al. Protection against amyloid beta peptide and iron/hydrogen peroxide toxicity by alpha lipoic acid. J Alzheimers Dis 2003;5(3):229-239.
  • .Low PA, Nickander KK, Tritschler HJ. The roles of oxidative stress and antioxidant treatment in experimental diabetic neuropathy. Diabetes 1997;46(Suppl 2):S38-542.
  • .Lykkesfeldt J, Hagen TM, Vinarsky V, et al. Age-associated decline in ascorbic acid concentration, recycling, and biosynthesis in rat hepatocytes: reversal with (R)-alpha-lipoic acid supplementation. FASEB J 1998;12(12):1183-1189.
  • .Maitra I, Serbinova E, Tritschler HJ, et al. Stereospecific effects of R-lipoic acid on buthionine sulfoximine-induced cataract formation in newborn rats. Biochem Biophys Res Commun 1996;221(2):422-429.
  • .Mantovani G, Maccio A, Madeddu C, et al. A phase II study with antioxidants, both in the diet and supplemented, pharmaconutritional support, progestagen, and anti-cyclooxygenase-2 showing efficacy and safety in patients with cancer-related anorexia/cachexia and oxidative stress. Cancer Epidemiol Biomarkers Prev 2006;15(5):1030-1034.
  • .Mantovani G, Maccio A, Madeddu C, et al. Reactive oxygen species, antioxidant mechanisms, and serum cytokine levels in cancer patients: impact of an antioxidant treatment. J Environ Pathol Toxicol Oncol 2003;22(1):17-28.
  • .Mantovani G, Maccio A, Madeddu C, et al. Reactive oxygen species, antioxidant mechanisms and serum cytokine levels in cancer patients: impact of an antioxidant treatment. J Cell Mol Med 2002;6(4):570-582.
  • .Mantovani G, Maccio A, Melis G, et al. Restoration of functional defects in peripheral blood mononuclear cells isolated from cancer patients by thiol antioxidants alpha-lipoic acid and N-acetyl cysteine. Int J Cancer 2000;86(6):842-847.
  • .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 Radic Biol Med 1999;27(9-10):1114-1121.
  • .Marquet A, Bui BT, Florentin D. Biosynthesis of biotin and lipoic acid. Vitam Horm 2001;61:51-101. (Review)
  • .Marriage B, Clandinin MT, Glerum DM. Nutritional cofactor treatment in mitochondrial disorders. J Am Diet Assoc 2003;103(8):1029-1038. (Review)
  • .Matalon R, Stumpf DA, Michals K, et al. Lipoamide dehydrogenase deficiency with primary lactic acidosis: favorable response to treatment with oral lipoic acid. J Pediatr 1984;104:65-69.
  • .McGahon BM, Martin DS, Horrobin DF, et al. Age-related changes in LTP and antioxidant defenses are reversed by an alpha-lipoic acid-enriched diet. Neurobiol Aging 1999;20(6):655-664.
  • .Melhem MF, Craven PA, Liachenko J, et al. Alpha-lipoic acid attenuates hyperglycemia and prevents glomerular mesangial matrix expansion in diabetes. J Am Soc Nephrol 2002;13(1):108-116.
  • .Merin JP, Matsuyama M, Kira T, et al. Alpha-lipoic acid blocks HIV-1 LTR-dependent expression of hygromycin resistance in THP-1 stable transformants. FEBS Lett 1996;394(1):9-13.
  • .Mervaala E, Finckenberg P, Lapatto R, et al. Lipoic acid supplementation prevents angiotensin II-induced renal injury. Kidney Int 2003;64(2):501-508.
  • .Midaoui AE, Elimadi A, Wu L, et al. Lipoic acid prevents hypertension, hyperglycemia, and the increase in heart mitochondrial superoxide production. Am J Hypertens 2003;16(3):173-179.
  • .Mizuno M, Packer L. Effects of alpha-lipoic acid and dihydrolipoic acid on expression of proto-oncogene c-fos. Biochem Biophys Res Commun 1994;200(2):1136-1142.
  • .Moini H, Packer L, Saris NE. Antioxidant and prooxidant activities of alpha-lipoic acid and dihydrolipoic acid. Toxicol Appl Pharmacol 2002;182(1):84-90. (Review)
  • .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(3):175-183.
  • .Mythili Y, Sudharsan PT, Sudhahar V, et al. Protective effect of DL-alpha-lipoic acid on cyclophosphamide induced hyperlipidemic cardiomyopathy. Eur J Pharmacol 2006;543(1-3):92-96.
  • .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(8):1160-1167.
  • .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.
  • .Nichols TW Jr. Alpha-lipoic acid: biological effects and clinical implications. Altern Med Rev 1997;2:177-183. (Review)
  • .Nickander KK, McPhee BR, Low PA, et al. Alpha-lipoic acid: antioxidant potency against lipid peroxidation of neural tissues in vitro and implications for diabetic neuropathy. Free Radic Biol Med 1996;21:631-639.
  • .Orzechowski A. Justification for antioxidant preconditioning (or how to protect insulin-mediated actions under oxidative stress). J Biosci 2003;28(1):39-49.
  • .Ou P, Nourooz-Zadeh J, Tritschler HJ, et al. 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.
  • .Ou P, Tritschler HJ, Wolff SP. Thioctic (lipoic) acid: a therapeutic metal-chelating antioxidant? Biochem Pharmacol 1995;50:123-126.
  • .Packer L. alpha-Lipoic acid: a metabolic antioxidant which regulates NF-kappa B signal transduction and protects against oxidative injury. Drug Metab Rev 1998;30(2):245-275.
  • .Packer L. Antioxidant properties of lipoic acid and its therapeutic effects in prevention of diabetes complications and cataracts. Ann N Y Acad Sci 1994;738:257-264.
  • .Packer L. Oxidants, antioxidant nutrients and the athlete. J Sports Sci 1997;15(3):353-363.
  • .Packer L, Kraemer K, Rimbach G. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 2001;17(10):888-895.
  • .Packer L, Roy S, Sen CK. Alpha-lipoic acid: a metabolic antioxidant and potential redox modulator of transcription. Adv Pharmacol 1997;38:79-101. (Review)
  • .Packer L, Tritschler HJ, Wessel K. Neuroprotection by the metabolic antioxidant alpha-lipoic acids. Free Radic Biol Med 1997;22:359-378. (Review)
  • .Packer L, Witt EH, Tritschler HJ. alpha-Lipoic acid as a biological antioxidant. Free Radic Biol Med 1995;19(2):227-250. (Review)
  • .Parish RC, Doering PL. Treatment of Amanita mushroom poisoning: a review. Vet Hum Toxicol 1986;28(4):318-322.
  • .Patrick L. Mercury toxicity and antioxidants: part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Altern Med Rev 2002;7(6):456-471. (Review)
  • .Plotzker R, Jensen DM, Payne JA. Case report: Amanita virosa acute hepatic necrosis: treatment with thioctic acid. Am J Med Sci 1982;283(2):79-82.
  • .Podda M, Tritschler HJ, Ulrich H, et al. Alpha-lipoic acid supplementation prevents symptoms of vitamin E deficiency. Biochem Biophys Res Commun 1994;204(1):98-104.
  • .Prehn JH, Karkoutly C, Nuglisch J, et al. Dihydrolipoate reduces neuronal injury after cerebral ischemia. J Cereb Blood Flow Metab 1992;12:78-87.
  • .Rabinovic AD, Hastings TG. Role of endogenous glutathione in the oxidation of dopamine. J Neurochem 1998;71(5):2071-2078.
  • .Reed LJ, DeBusk BG, Gunsalus IC, et al. Crystalline alpha-lipoic acid: a catalytic agent associated with pyruvate dehydrogenase. Science 1951;114:93-94.
  • .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(3):171-179.
  • .Rett K, Wicklmayr E, Maerker P, et al. Effect of acute infusion of thioctic acid on oxidative and non-oxidative metabolism in obese subjects with NIDDM. Diabetologia 1995;38:A41.
  • .Rodriguez-Budelli M, Kark P. Kinetic evidence for a structural abnormality of lipoamide dehydrogenase in two patients with Friedreich ataxia. Neurology 1978;28:1283-1286. (Abstract)
  • .Rosenburg HR, Culik R. Effects of alpha-lipoic acid on vitamin C and vitamin E deficiencies. Arch Biochem Biophys 1959;80:86-93.
  • .Roy S, Sen CK, Tritschler HJ, et al. Modulation of cellular reducing equivalent homeostasis by alpha-lipoic acid: mechanisms and implications for diabetes and ischemic injury. Biochem Pharmacol 1997;53(3):393-399.
  • .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(12):1040-1043.
  • .Sastrasinh M, Weinberg JM, Humes HD. The effect of gentamicin on calcium uptake by renal mitochondria. Life Sci 1982;30(26):2309-2315.
  • .Scholich H, Murphy ME, Sies H. Antioxidant activity of dihydrolipoate against microsomal lipid peroxidation and its dependence on alpha-tocopherol. Biochim Biophys Acta 1989;1001(3):256-261.
  • .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(2-3):335-342.
  • .Schupke H, Hempel R, Peter G, et al. New metabolic pathways of alpha-lipoic acid. Drug Metab Dispos 2001;29(6):855-862.
  • .Scott BC, Arouma OI, Evans PJ, et al. Lipoic and dihydrolipoic acid as antioxidants: a critical evaluation. Free Radic Res 1994;20:119-133.
  • .Selvakumar E, Prahalathan C, Sudharsan PT, et al. Protective effect of lipoic acid on micronuclei induction by cyclophosphamide. Arch Toxicol 2006;80(2):115-119.
  • .Sen CK, Roy S, Han D, et al. Regulation of cellular thiols in human lymphocytes by alpha-lipoic acid: a flow cytometric analysis. Free Radic Biol Med 1997;22(7):1241-1257.
  • .Sigel H, Prijs B, McCormick DB, et al. 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.
  • .Streeper RS, Henriksen EJ, Jacob S, et al. Differential effects of lipoic acid stereoisomers on glucose metabolism in insulin-resistant skeletal muscle. Am J Physiol 1997;273(1 Pt 1):E185-191.
  • .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.
  • .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 2001;15(3):700-706.
  • .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.
  • .Sumathi R, Devi VK, Varalakshmi P. DL alpha-lipoic acid protection against cadmium-induced tissue lipid peroxidation. Med Sci Res 1994;22:23-25.
  • .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(3):1709-1715.
  • .Suzuki YJ, Tsuchiya M, Packer L. Thiotic acid and dihydrolipoic acid are novel antioxidants which interact with reactive oxygen species. Free Rad Res Commun 1991;15:255-263.
  • .Teichert J, Kern J, Tritschler HJ, et al. Investigations on the pharmacokinetics of alpha-lipoic acid in healthy volunteers. Int J Clin Pharmacol Ther 1998;36(12):625-628.
  • .Teichert J, Hermann R, Ruus P, et al. Plasma kinetics, metabolism, and urinary excretion of alpha-lipoic acid following oral administration in healthy volunteers. J Clin Pharmacol 2003;43(11):1257-1267.
  • .Tirosh O, Sen CK, Roy S, et al. Neuroprotective effects of alpha-lipoic acid and its positively charged amide analogue. Free Radic Biol Med 1999;26(11-12):1418-1426.
  • .Tirosh O, Shilo S, Aronis A, et al. Redox regulation of mitochondrial permeability transition: effects of uncoupler, lipoic acid and its positively charged analog LA-plus and selenium. Biofactors 2003;17(1-4):297-306.
  • .Varalakshmi P, Sandhya S, Malarkodi KP. Evaluation of the effect of lipoic acid administered along with gentamicin in rats rendered bacteremic. Mol Cell Biochem 2003;248(1-2):35-40.
  • .Visioli F, Smith A, Zhang W, et al. Lipoic acid and vitamin C potentiate nitric oxide synthesis in human aortic endothelial cells independently of cellular glutathione status. Redox Rep 2002;7(4):223-227.
  • .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(1):74-76.
  • .Wollin SD, Jones PJ. Alpha-lipoic acid and cardiovascular disease. J Nutr 2003;133(11):3327-3330.
  • .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.
  • .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.
  • .Yaworsky K, Somwar R, Ramlal T, et al. Engagement of the insulin-sensitive pathway in the stimulation of glucose transport by alpha-lipoic acid in 3T3-L1 adipocytes. Diabetologia 2000;43(3):294-303.
  • .Yeaman SJ, Kirby JA, Jones DE. Autoreactive responses to pyruvate dehydrogenase complex in the pathogenesis of primary biliary cirrhosis. Immunol Rev 2000;174:238-249.
  • .Zhang WJ, Frei B. Alpha-lipoic acid inhibits TNF-alpha-induced NF-kappaB activation and adhesion molecule expression in human aortic endothelial cells. FASEB J 2001;15(13):2423-2432.
  • .Ziegler D, Ametov A, Barinov A, et al. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Care 2006;29(11):2365-2370.
  • .Ziegler D, Gries FA. Alpha-lipoic acid in the treatment of diabetic peripheral and cardiac autonomic neuropathy. Diabetes 1997;46(Suppl 2):S62-66.
  • .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(8):1296-1301.
  • .Ziegler D, Hanefeld M, Ruhnau KJ, et al. Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant alpha-lipoic acid: a 3-week multicentre randomized controlled trial (ALADIN Study). Diabetologia 1995;38(12):1425-1433.
  • .Ziegler D, Reljanovic M, Mehnert H, et al. Alpha-lipoic acid in the treatment of diabetic polyneuropathy in Germany: current evidence from clinical trials. Exp Clin Endocrinol Diabetes 1999;107(7):421-430. (Review)
  • .Ziegler D, Schatz H, Conrad F, et al. 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): Deutsche Kardiale Autonome Neuropathie. Diabetes Care 1997;20(3):369-373.