Discontinue use if any adverse reactions occur and contact a health care professional. Do not use if seal under cap is broken or missing. Store tightly closed in a cool, dry place. KEEP OUT OF REACH OF CHILDREN.

This product is not intended to diagnose, treat, cure, or prevent any disease. Love this ALA, it is very clean, no worries about the fillers.

Very happy it is in a Glass Bottle. Quality Supplement. Delivery was great, packing was great. At MD Logic Health®, our promise is to supplement your daily nutrition to help you live your best life.

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More details Right. How Can It Benefit Your Health? How is our Alpha-Lipoic Acid different from other products? ALA and its reduced form DHLA have many biological functions in different intracellular systems resulting in a wide range of actions such as antioxidant protection, chelation of metal ions, regeneration of other antioxidant agents such as vitamin C, E and glutathione.

To date, the majority of these actions have been addressed mainly in experimental studies which used a wide range dose of ALA in vitro as well as in vivo. We can also consider that for instance, the used dose was greater than the physiological dose reached with the usual clinically used oral dose of ALA.

It is also to be mentioned that in most of these studies it was not well defined which type of ALA has been used. Finally, the translation of all these pooled experimental data to human studies is a subject for further research.

Currently, there are compelling evidences linking oxidative damage to the majority of chronic diseases with increasing prevalence worldwide such as obesity, DM, CVD and AD. Considering the pleiotropic action of ALA upon different pathways associated with the above mentioned diseases, its use as a potential therapeutical agent seems promising.

So far, although in a limited number, the majority of clinical studies, performed in randomized double-blind and placebo-controlled ways, have been done in diabetic patients with DSPN.

Future clinical studies, also randomized double-blind and placebo-controlled with adequate sample calculation, homogeneity of the studied patients, longer duration and a minimal variability in the established outcomes are needed in order to asses the benefit of ALA upon other diabetes-related chronic complications.

Considering the latter statement it will be an important issue to define the use of ALA as primary or secondary therapeutic intervention. Also, the same aforementioned type of studies with the same criteria must be addressed in other clinical conditions such as obesity, CVD and AD.

Another important question to be answered by these clinical studies is when we are going to start its use according to the natural evolution of each disease in order to reach a benefit.

We need also more experimental studies to evaluate and define if the pro-oxidant action of ALA is dose-dependent. These studies may also give us more information about the use of lipoic acid synthase as a molecular target for increasing the mitochondrial levels of ALA.

Another point to be addressed in these studies is the possibility that hyperglycemia can affect different pathways resulting in a toxicity which could be independent of oxidative stress as recently discussed [ ]. The role of endoplasmic reticulum stress has been pointed out as an important mechanism leading to diabetes-related complications which is independent of oxidative stress.

Finally, although our review had the objective to extended our clinical and biological knowledge about ALA we still need more information about this multifunctional compound to spread its use in routine clinical practice. Golbidi S, Badran M, Laher I: Diabetes and alpha lipoic Acid. Front Pharmacol.

Article PubMed Central PubMed Google Scholar. Reed LJ: From lipoic acid to multi-enzyme complexes. Protein Sci. Article PubMed Central CAS PubMed Google Scholar. Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM: Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential.

Biochim Biophys Acta. Snell EE, Strong FM, Peterson WH: Growth factor for bacteria. VI Fractionation and properties of an accessory factor for lactic acid bacteria. Bichem J.

CAS Google Scholar. Reed LJ, De Busk BG, Gunsalus IC, Hornberger CS: Cristalline alpha-lipoic acid: a catalytic agent associated with pyruvate dehydrogenase. Article CAS PubMed Google Scholar. Bock E, Schneeweiss J: Ein Beitrag zur Therapie der neuropathia diabetic.

Munchner Med Wochenschrift. Google Scholar. McNeilly AM, Davison GW, Murphy MH, Nadeem N, Trinick T, Duly E, Novials A, McEneny J: Effect of α-lipoic acid and exercise training on cardiovascular disease risk in obesity with impaired glucose tolerance.

Lipids Health Dis. Ying Z, Kherada N, Farrar B, Kampfrath T, Chung Y, Simonetti O, Deiuliis J, Desikan R, Khan B, Villamena F, Sun Q, Parthasarathy S, Rajagopalan S: Lipoic acid effects on established atherosclerosis.

Life Sci. Ziegler D, Reljanovic M, Mehnert H, Gries FA: α Lipoic acid in the treatment of diabetic polyneuropathy in Germany: current evidence from clinical trials.

Exp Clin Endocrinol Diabetes. Packer L, Kraemer K, Rimbach G: Molecular aspects of lipoic acid in the prevention of diabetes complications. Vasdev S, Ford CA, Parai S, Longerich L, Gadag V: Dietary alpha-lipoic acid supplementation lowers blood pressure in spontaneously hypertensive rats. J Hypertens.

Moreira PI, Harris PLR, Zhu X, Santos MS, Oliveira CR, Smith MA, Perry G: Lipoic acidi and n-acetyl cysteine decrease mitochondrial-related oxidative stress in Alzheimer disease patient fibroblasts.

J Alzheimers Dis. CAS PubMed Google Scholar. Lott IT, Doran E, Nguyen VQ, Tournay A, Head E, Gillen DL: Down syndrome and dementia: a randomized, controlled trial of antioxidant supplementation. Am J Med Genet A. Article PubMed Central PubMed CAS Google Scholar. Al Abdan M: Alfa-lipoic acid controls tumor growth and modulates hepatic redox state in Ehrlich-ascites-carcinoma-bearing mice.

Scientific World Journal. Szelag M, Mikulski D, Molski M: Quantum-chemical investigation of the structure and the antioxidant properties of α-lipoic acid and its metabolites. J Mol Model. Padmalayam I, Hasham S, Saxena U, Pillarisetti S: Lipoic acid synthase LASY : a novel role in inflammation, mitochondrial function, and insulin resistance.

McLain AL, Cormier PJ, Kinter M, Szweda LI: Glutathionylation of α-ketoglutarate dehydrogenase: the chemical nature and relative susceptibility of the cofactor lipoic acid to modification.

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J Biol Chem. Moini H, Tirosh O, Park YC, Cho KJ, Packer L: R-alpha-lipoic acid action on cell redox status, the insulin receptor, and glucose uptake in 3T3-L1 adipocytes. Arch Biochem Biophys. A-Vadlapudi AD, Vadlapatla RK, Mitra AK: Sodium dependent multivitamin transporter SMVT : a potential target for drug delivery.

Curr Drug Targets. Article Google Scholar. A critical evaluation. Free Radic Res. Packer L, Witt EH, Tritschler HJ: Alpha-lipoic acid as a biological antioxidant. Free Rad Biol Med. Trujillo M, Radi R: Peroxynitrite reaction with the reduced and the oxidized forms of lipoic acid: new insights into the reaction of peroxynitrite with thiols.

Arch of Biochem and Biophys. Vriesman MF, Haenen GR, Westerveld GJ, Paquay JB, Voss HP, Bast A: A method for measuring nitric oxide radical scavenging activity. Scavenging properties of sulfur-containing compounds. Pharm World Sci. Suzuki YJ, Tsuchiya M, Packer L: Thioctic acid and dihydrolipoic acid are novel antioxidants which interact with reactive oxygen species.

Free Radic Res Commun. Suzuki YJ, Tsuchiya M, Packer L: Antioxidant activities of dihydrolipoic acid and its structural homologues. Devasagayam TP, Di Mascio P, Kaiser S, Sies H: Singlet oxygen induced single-strand breaks in plasmid pBR DNA: the enhancing effect of thiols.

Kagan VE, Shvedova A, Serbinova E, Khan S, Swanson C, Powell R, Packer L: Dihydrolipoic acid—a universal antioxidant both in the membrane and in the aqueous phase.

Reduction of peroxyl, ascorbyl and chromanoxyl radicals. Biochem Pharmacol. Haenen GR, Bast A: Scavenging of hypochlorous acid by lipoic acid. Newsholme P, Rebelato E, Abdulkader F, Krause M, Carpinelli A, Curi R: Reactive oxygen and nitrogen species generation, antioxidant defenses, and β-cell function: a critical role for amino acids.

J Endocrinol. Brain Res. Wilking M, Ndiaye M, Mukhtar H, Ahmad N: Circadian rythms connections to oxidative stress: implications for human health. Antioxid Redox Signal.

Dicter N, Madar Z, Tirosh O: Alpha-lipoic acid inhibits glycogen synthesis in rat soleus muscle via its oxidative activity and the uncoupling of mitochondria. J Nutr. Rouchette L, Ghibu S, Richard C, Zeller M, Cottin Y, Vergely C: Direct and indirect antioxidant properties of α -lipoic acid.

Mol Nutr Food Res. Moini H, Packer L, Saris N-E: Antioxidant and prooxidant activities of α-lipoic acid and dihydrolipoic acid.

Toxicol Appl Pharmacol. Zhang DD, Lo S-C, Cross JV, Templeton DJ, Hannink M: keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex.

Mol Cell Biol. Dinkova-kostova AT, Talalay P: Direct and indirect antioxidant properties of inducers of cytoprotective proteins. PubMed Google Scholar.

Frizzell N, Baynes JW: Chelation therapy: overlooked in the treatment and prevention of diabetes complications?. Future Med Chem. Ou P, Tritscheler HJ, Wolff SP: Thioctic lipoic acid : a therapeutical metal-chelating antioxidant?. Bast A, Haenen GR: Lipoic acid: a multifunctional antioxidant.

Smith AR, Shenvi SV, Widlansky M, Suh JH, Hagen TM: Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress.

Curr Med Chem. Yaworsky K, Somwar R, Ramlal T, Tritschler HJ, Klip A: Engagement of the insulin-sensitive pathway in the stimulation of glucose transport by alpha-lipoic acid in 3T3-L1 adipocytes. Henriksen EJ, Jacob S, Streeper RS, Fogt DL, Hokama JY, Tritschler HJ: Stimulation by alpha-lipoic acid of glucose transport activity in skeletal muscle of lean and obese Zucker rats.

Yamamoto Y, Gaynor RB: Therapeutical potential of inhibition of the NFkb pathway in the treatment of inflammation and cancer. J Clin Invest. El-Osta A, Brasacchio D, Yao D, Pocai A, Jones PL, Roeder RG, Cooper ME, Brownlee M: Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia.

J Exp Med. Bierhaus A, Chevion S, Chevion M, Hofmann M, Quehenberger P, Illmer T, Luther T, Berentshtein E, Tritschler H, Müller M, Wahl P, Ziegler R, Nawroth PP: Advanced glycation end product-induced activation of NF-kappaB is suppressed by alpha-lipoic acid in cultured endothelial cells. Ying Z, Kampfrath T, Sun Q, Parthasarathy S, Rajagopalan S: Evidence that α-lipoic acid inhibits NF-κB activation independent of its antioxidant function.

Inflamm Res. Zembron-Lacny A, Gajeswski M, Naczac M, Dziewiecka H, Siatkkowski I: Physical activity and alpha-lipoic acid modulate inflammatory response through changes in thiol redox status. J Physiolo. Sola S, Mir MQ, Cheema FA, Khan-Merchant N, Menon RG, Parthasarathy S, Khan BV: 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.

Steinberg GR, Kemp BE: AMPK in health and disease. Physiol Rev. Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE: Role of AMP-activated protein kinase in mechanism of metformin action.

Am J Physiol Cell Physiol. Wang Y, Li X, Guo Y, Chan L, Guan X: Alpha-Lipoic acid increases energy expenditure by enhancing adenosine monophosphate-activated protein kinase-peroxisome proliferator-activated receptor-gamma coactivator-1alpha signaling in the skeletal muscle of aged mice.

Targonsky ED, Dai F, Koshkin V, Karaman GT, Gyulkhandanyan AV, Zhang Y, Chan CB, Wheeler MB: Alpha-lipoic acid regulates AMP-activated protein kinase and inhibits insulin secretion from beta cells. Koh G, Yang EJ, Kim MK, Lee SA, Lee DH: Alpha-lipoic acid treatment reverses 2-deoxy-D-ribose-induced oxidative damage and suppression of insulin expression in pancreatic β-cells.

Biol Pharm Bull. Ramamurthy S, Ronnet G: AMP-activated protein kinase AMPK and energy sensing in the brain. Exp Neurobiol. Blazquez C, Geelen MJ, Velasco G, Guzmán M: The AMP activated protein kinase prevents ceramide synthesis de novo and astrocytes.

FEBS Lett. Nakatsu Y, Kotake Y, Hino A, Ohta S: Activation of AMO-activated protein kinase by tributyltin induces neuronal cell death. Kim MS, Park JY, Namkoong C, Jang PG, Ryu JW, Song HS, Yun JY, Namgoong IS, Ha J, Park IS, Lee IK, Viollet B, Youn JH, Lee HK, Lee KU: Anti-obesity effects of alpha-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase.

Nat Med. Seo EY, Ha AW, Kim WK: α lipoic acid reduced weight gain and improved lipid profile in rats fed with high fat diet. Nutr Res Pract. Tomassoni D, Amenta F, Amantini C, Farfariello V, Di Cesare ML, Nwankwo IE, Marini C, Tayebati SK: Brain activity of thioctic acid enantiomers: in vitro and in vivo studies in an animal model of cerebrovascular injury.

Int J Mol Sci. Cho KJ, Moon HE, Moini H, Packer L, Yoon DY, Chung AS: Alpha-lipoic acid inhibits adipocyte differentiation by regulating pro-adipogenic transcription factors via mitogen-activated protein kinase pathways.

Wang Y, Dong W, Ding X, Wang F, Wang Y, Chen X, Yu L, Li X, Zhang A, Peng Y: Protective effect of α-lipoic acid on islet cells co-cultured with 3T3L1 adipocytes. Exp Ther Med. PubMed Central CAS PubMed Google Scholar.

Tian YF, He CT, Chen YT, Hsieh PS: Lipoic acid suppresses portal endotoxemia-induced steatohepatitis and pancreatic inflammation in rats. World J Gastroenterol. Ong SL, Vohra H, Zhang Y, Sutton M, Whitworth JA: The effect of alpha-lipoic acid on mitochondrial superoxide and glucocorticoid-induced hypertension.

Oxid Med Cell Longev. Epub Feb Li CJ, Lv L, Li H, Yu D: Cardiac fibrosis and dysfunctionin experimental diabetic cardiomyopathy are amelioreted by alpha-lipoic acid.

Cardiovasc Diabetol. PLoS One. Yi X, Nickeleit V, James LR, Maeda N: α-Lipoic acid protects diabetic apolipoprotein E-deficient mice from nephropathy. J Diabetes Complications.

Inman DM, Lambert WS, Calkins DJ, Horner PJ: α-Lipoic acid antioxidant treatment limits glaucoma-related retinal ganglion cell death and dysfunction.

Jha MK, Jeon S, Suk K: Pyruvate Dehydrogenase Kinases in the nervous system: their principal functions in Neuronal-glial metabolic interaction and Neuro-metabolic disorders. Curr Neuropharmacol. Expert Rev Neurother. J Nutr Health Aging. Adv Drug Deliv Rev. J Neural Transm Suppl.

Int J Mol Med. Prieto-Hontoria PL, Pérez-Matute P, Fernández-Galilea M, Alfredo Martínez J, Moreno-Aliaga MJ: Effects of lipoic acid on AMPK and adiponectin in adipose tissue of low- and high-fat-fed rats.

Eur J Nutr. Deiuliis JA, Kampfrath T, Ying Z, Maiseyeu A, Rajagopalan S: Lipoic acid attenuates innate immune infiltration and activation in the visceral adipose tissue of obese insulin resistant mice.

Lamb RE, Goldstein BJ: Modulating an oxidative-inflmmatory cascade: potential new treatment strategy for improving glucose metabolism, insulin resistance, and vascular function. Int J Clin Pract. Xiao C, Giacca A, Lewis GF: Short-term oral α-lipoic acid does not prevent lipid-induced dysregulation of glucose homeostasis in obese and overweight nondiabetic men.

Am J Physiol Endocrinol Metab. Zhang Y, Han P, Wu N, He B, Lu Y, Li S, Liu Y, Zhao S, Liu L, Li Y: Amelioration of lipid abnormalities by α-lipoic acid through antioxidative and anti-inflammatory effects.

Obesity Silver Spring. Koh EH, Lee WJ, Lee SA, Kim EH, Cho EH, Jeong E, Kim DW, Kim MS, Park JY, Park KG, Lee HJ, Lee IK, Lim S, Jang HC, Lee KH, Lee KU: Effects of alpha-lipoic acid on body weight in obese subjects. Am J Med. Ratliff JC, Palmese LB, Reutenauer EL, Tek C: An open-label pilot trial of alpha-lipoic acid for weight loss in patients with schizophrenia without diabetes.

Clin Schizophr Relat Psychoses. Jose hotmail. Lean MEJ: Sibutramine: a review of clinical efficacy. In J Obes. Lazo M, Clark JM: The epidemiology of nonalcoolic faty liver disease: a global perspective. Semin Liver Dis. Article PubMed Google Scholar. Valdecantos MP, Pérez-Matute P, González-Muniesa P, Prieto-Hontoria PL, Moreno-Aliaga MJ, Martínez JA: Lipoic acid administration prevents nonalcoholic steatosis linked to long-term high-fat feeding by modulating mitochondrial function.

J Nutr Biochem. Jung TS, Kim SK, Shin HJ, Jeon BT, Hahm JR, Roh GS: α-lipoic acid prevents non-alcoholic fatty liver disease in OLETF rats. Liver Int. Valdecantos MP, Pérez-Matute P, González-Muniesa P, Prieto-Hontoria PL, Moreno-Aliaga MJ, Martínez JA: Lipoic acid improves mitochondrial function in nonalcoholic steatosis through the stimulation of sirtuin 1 and sirtuin 3.

Chen WL, Kang CH, Wang SG, Lee HM: α-Lipoic acid regulates lipid metabolism through induction of sirtuin 1 SIRT1 and activation of AMP-activated protein kinase. Chong ZZ, Shang YC, Wang S, Maiesse K: SIRT1: new avenues of discovery for disorders of oxidative stress. Expert Opin Ther Targets.

Gurvits GE, Tan A: Burning mouth syndrome. Cavalcanti DR, da Silveira FR: Alpha lipoic acid in burning mouth syndrome—a randomized double-blind placebo-controlled trial.

J Oral Pathol Med. Femiano F, Lanza A, Buonaiuto C, Gombos F, Nunziata M, Cuccurullo L, Cirillo N: Burning mouth syndrome and burning mouth in hypothyroidism: proposal for a diagnostic and therapeutic protocol.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Femiano F: Burning mouth syndrome BMS : an open trial of comparative efficacy of alpha-lipoic acid thioctic acid with other therapies. Minerva Stomatol. Hu G, Jousilhati P, Qiao Q, Katoh S: Sex differences in cardiovascular and total mortality among diabetic and non-diabetic individuals with or without history of myocardial infarction.

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Durand M, Mach N: Alpha lipoic acid and its antioxidant against cancer and diseases of central sensitization. Nutr Hosp. Michikoshi H, Nakamura T, Sakai K, Suzuki Y, Adachi E, Matsugo S, Matsumoto K: α-Lipoic acid-induced inhibition of proliferation and met phosphorylation in human non-small cell lung cancer cells.

Cancer Lett. Feuerecker B, Pirsig S, Seidl C, Aichler M, Feuchtinger A, Bruchelt G, Senekowitsch-Schmidtke R: Lipoic acid inhibits cell proliferation of tumor cells in vitro and in vivo.

Cancer Biol Ther. Kim JI, Cho SR, Lee CM, Park ES, Kim KN, Kim HC, Lee HY: Induction of ER stress-mediated apoptosis by α-Lipoic Acid in A cell lines.

Korean J Thorac Cardiovasc Surg. Mantovani G, Macciò A, Madeddu C, Mura L, Gramignano G, Lusso MR, Murgia V, Camboni P, Ferreli L: The impact of different antioxidant agents alone or in combination on reactive oxygen species, antioxidant enzymes and cytokines in a series of advanced cancer patients at different sites: correlation with disease progression.

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Polat B, Halici Z, Cadirci E, Albayrak A, Karakus E, Bayir Y, Bilen H, Sahin A, Yuksel TN: The effect of alpha-lipoic acid in ovariectomy and inflammation-mediated osteoporosis on the skeletal status of rat bone.

Eur J Pharmacol. Xiao Y, Cui J, Shi Y, Le G: Lipoic acid increases the expression of genes involved in bone formation in mice fed a high-fat diet. Nutr Res. Skyler J, Oddo C: Diabetes trends in the USA. Diabetes Metab Res Ver. Wild S, Roglic G, Green A, Sicree R, King H: Global prevalences of diabetes, estimates for the year and projections for Diabetes Care.

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Gomes MB, de Mattos Matheus AS, Calliari LE, Luescher JL, Manna TD, Savoldelli RD, Cobas RA, Coelho WS, Tschiedel B, Ramos AJ, Fonseca RM, Araujo NB, Almeida HG, Melo NH, Jezini DL, Negrato CA: Economic status and clinical care in young type 1 diabetes patients: a nationwide multicenter study in Brazil.

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J Pediatr. Evans JL, Goldfine ID, Maddux BA, Grodsky GM: Are oxidative stress-activated signaling pathways mediators of insulin resistance and beta-cell dysfunction?. Chang YC, Chuang LM: The role of oxidative stress in the pathogenesis of type 2 diabetes: from molecular mechanism to clinical implication.

Am J Transl Res. Singh R, Barden A, Mori T, Beilin L: Advanced glycation end- products: a review. Giugliano D, Ceriello A, Paolisso G: Oxidative stress and diabetic vascular complications. Ruderman NB, Williamson JR, Brownlee M: Glucose and diabetic vascular disease.

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References Biochimica et Biophysica Acta BBA -General Subjects. Diabetes Care. Can J Physiol Pharmacol. J Clin Hypertens. J Alzheimers Dis. Eur Rev Med Pharmacol Sci. Int Urol Nephrol. Br J Dermatol. Customer Reviews No reviews yet Write a Review. All-Natural Ingredients.

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J Nutr. Rouchette L, Ghibu S, Richard C, Zeller M, Cottin Y, Vergely C: Direct and indirect antioxidant properties of α -lipoic acid. Mol Nutr Food Res. Moini H, Packer L, Saris N-E: Antioxidant and prooxidant activities of α-lipoic acid and dihydrolipoic acid. Toxicol Appl Pharmacol. Zhang DD, Lo S-C, Cross JV, Templeton DJ, Hannink M: keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex.

Mol Cell Biol. Dinkova-kostova AT, Talalay P: Direct and indirect antioxidant properties of inducers of cytoprotective proteins. PubMed Google Scholar. Frizzell N, Baynes JW: Chelation therapy: overlooked in the treatment and prevention of diabetes complications?.

Future Med Chem. Ou P, Tritscheler HJ, Wolff SP: Thioctic lipoic acid : a therapeutical metal-chelating antioxidant?.

Bast A, Haenen GR: Lipoic acid: a multifunctional antioxidant. Smith AR, Shenvi SV, Widlansky M, Suh JH, Hagen TM: Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress. Curr Med Chem.

Yaworsky K, Somwar R, Ramlal T, Tritschler HJ, Klip A: Engagement of the insulin-sensitive pathway in the stimulation of glucose transport by alpha-lipoic acid in 3T3-L1 adipocytes. Henriksen EJ, Jacob S, Streeper RS, Fogt DL, Hokama JY, Tritschler HJ: Stimulation by alpha-lipoic acid of glucose transport activity in skeletal muscle of lean and obese Zucker rats.

Yamamoto Y, Gaynor RB: Therapeutical potential of inhibition of the NFkb pathway in the treatment of inflammation and cancer. J Clin Invest. El-Osta A, Brasacchio D, Yao D, Pocai A, Jones PL, Roeder RG, Cooper ME, Brownlee M: Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia.

J Exp Med. Bierhaus A, Chevion S, Chevion M, Hofmann M, Quehenberger P, Illmer T, Luther T, Berentshtein E, Tritschler H, Müller M, Wahl P, Ziegler R, Nawroth PP: Advanced glycation end product-induced activation of NF-kappaB is suppressed by alpha-lipoic acid in cultured endothelial cells.

Ying Z, Kampfrath T, Sun Q, Parthasarathy S, Rajagopalan S: Evidence that α-lipoic acid inhibits NF-κB activation independent of its antioxidant function. Inflamm Res. Zembron-Lacny A, Gajeswski M, Naczac M, Dziewiecka H, Siatkkowski I: Physical activity and alpha-lipoic acid modulate inflammatory response through changes in thiol redox status.

J Physiolo. Sola S, Mir MQ, Cheema FA, Khan-Merchant N, Menon RG, Parthasarathy S, Khan BV: 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.

Steinberg GR, Kemp BE: AMPK in health and disease. Physiol Rev. Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE: Role of AMP-activated protein kinase in mechanism of metformin action.

Am J Physiol Cell Physiol. Wang Y, Li X, Guo Y, Chan L, Guan X: Alpha-Lipoic acid increases energy expenditure by enhancing adenosine monophosphate-activated protein kinase-peroxisome proliferator-activated receptor-gamma coactivator-1alpha signaling in the skeletal muscle of aged mice.

Targonsky ED, Dai F, Koshkin V, Karaman GT, Gyulkhandanyan AV, Zhang Y, Chan CB, Wheeler MB: Alpha-lipoic acid regulates AMP-activated protein kinase and inhibits insulin secretion from beta cells. Koh G, Yang EJ, Kim MK, Lee SA, Lee DH: Alpha-lipoic acid treatment reverses 2-deoxy-D-ribose-induced oxidative damage and suppression of insulin expression in pancreatic β-cells.

Biol Pharm Bull. Ramamurthy S, Ronnet G: AMP-activated protein kinase AMPK and energy sensing in the brain. Exp Neurobiol. Blazquez C, Geelen MJ, Velasco G, Guzmán M: The AMP activated protein kinase prevents ceramide synthesis de novo and astrocytes. FEBS Lett. Nakatsu Y, Kotake Y, Hino A, Ohta S: Activation of AMO-activated protein kinase by tributyltin induces neuronal cell death.

Kim MS, Park JY, Namkoong C, Jang PG, Ryu JW, Song HS, Yun JY, Namgoong IS, Ha J, Park IS, Lee IK, Viollet B, Youn JH, Lee HK, Lee KU: Anti-obesity effects of alpha-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase. Nat Med. Seo EY, Ha AW, Kim WK: α lipoic acid reduced weight gain and improved lipid profile in rats fed with high fat diet.

Nutr Res Pract. Tomassoni D, Amenta F, Amantini C, Farfariello V, Di Cesare ML, Nwankwo IE, Marini C, Tayebati SK: Brain activity of thioctic acid enantiomers: in vitro and in vivo studies in an animal model of cerebrovascular injury.

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Download references. Department of Internal Medicine, Diabetes Unit, State University Hospital of Rio de Janeiro, Avenida 28 de Setembro, 77, 3° andar CEP You can also search for this author in PubMed Google Scholar. Correspondence to Marilia Brito Gomes.

MBG and CAN contributed equally analyzing the data and writing the manuscript. Both authors read and approved the final manuscript. This article is published under license to BioMed Central Ltd. Reprints and permissions. Gomes, M. Alpha-lipoic acid as a pleiotropic compound with potential therapeutic use in diabetes and other chronic diseases.

Diabetol Metab Syndr 6 , 80 Download citation. Received : 05 May Accepted : 11 July Published : 28 July Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative.

Skip to main content. Search all BMC articles Search. Download PDF. Introduction Alpha-lipoic acid ALA also known as thioctic acid TA and 1,2 dithiolane pentanoic acid, is a naturally occurring substance, that is essential for the function of different enzymes of oxidative metabolism [ 1 — 3 ].

Synthesis, biochemical properties, absorption and bioavailability ALA is commonly found in dietary components such as vegetables spinach, broccoli, tomato and meats, mainly viscera and also in many dietary supplements. Figure 1. Enantiomers R and S of lipoic acid.

Full size image. Antioxidant properties ALA and its reduced form DHLA, are considered powerful natural antioxidant agents with a scavenging capacity for many reactive oxygen species [ 23 , 24 ].

Figure 2. Table 1 Antioxidant action of ALA and DHLA upon reactive oxygen species and references Full size table. Metal chelator properties Chelation is a powerful function for most living species. Action upon transduction signaling systems Insulin pathway ALA has many actions in the insulin metabolic pathways, glucose uptake and glycogen synthesis with some differences between both isomers.

Nuclear factor kappa B Nuclear factor kappa B NFkB is a transcription factor which is maintained in an inactive form in the cytosol because of its capacity in binding to an inhibitor kinase of NFkB activity, IKK [ 44 ].

Adenosine monophosfatase protein kinase ALA has some important functions in the activity and expression of 5' adenosine monophosphate-activated protein kinase AMPK in peripheral tissues and in brain hypothalamus. Obesity The increasing prevalence of obesity worldwide is an important epidemiological issue because it is occurring in parallel with the increase in the prevalence of DM and cardiovascular disease CVD.

Saris NE, Karjalainen A, Teplova VV, Lindros KO The stimulation of the mitochondrial permeability transition by dihydrolipoate and alpha-lipoate. Biochem Mol Biol Int — Anal Chim Acta — Schupke H, Hempel R, Peter G, Hermann R, Wessel K, Engel J, Kronbach T New metabolic pathways of alpha-lipoic acid.

Drug Metab Dispos — Serbinova E, Khwaja S, Reznick AZ, Packer L Thioctic acid protects against ischemia-reperfusion injury in the isolated perfused Langendorff heart. Free Radic Res Commun — Sicard P, Acar N, Gregoire S, Lauzier B, Bron AM, Creuzot-Garcher C, Bretillon L, Vergely C, Rochette L Influence of rosuvastatin on the NAD P H oxidase activity in the retina and electroretinographic response of spontaneously hypertensive rats.

Br J Pharmacol — Tiganis T Reactive oxygen species and insulin resistance: the good, the bad and the ugly. Touyz RM, Schiffrin EL Signal transduction mechanisms mediating the physiological and pathophysiological actions of angiotensin II in vascular smooth muscle cells.

Pharmacol Rev — Trujillo M, Radi R Peroxynitrite reaction with the reduced and the oxidized forms of lipoic acid: new insights into the reaction of peroxynitrite with thiols. Arch Biochem Biophys — Vasdev S, Gill V, Longerich L, Parai S, Gadag V Salt-induced hypertension in WKY rats: prevention by alpha-lipoic acid supplementation.

Vasdev S, Gill V, Parai S, Gadag V Dietary lipoic acid supplementation attenuates hypertension in Dahl salt sensitive rats. Vergely C, Maupoil V, Benderitter M, Rochette L Influence of the severity of myocardial ischemia on the intensity of ascorbyl free radical release and on post-ischemic recovery during reperfusion.

Vergely C, Perrin C, Laubriet A, Oudot A, Zeller M, Guilland J-C, Rochette L Postischemic recovery and oxidative stress status of vitamin C-deficient rat hearts. Vergely C, Maupoil V, Clermont G, Bril A, Rochette L Identification and quantification of free radicals during myocardial ischemia and reperfusion using electron paramagnetic resonance spectroscopy.

Walker M, Vergely C, Lecour S, Abadie C, Maupoil V, Rochette L Vitamin E analogues reduce the incidence of ventricular fibrillation and scavenge free radicals.

Fundam Clin Pharmacol — Circulation — Ziegler D Thioctic acid for patients with symptomatic diabetic polyneuropathy: a critical review. Treat Endocrinol — Ziegler D, Ametov A, Barinov A, Dyck PJ, Gurieva I, Low PA, Munzel U, Yakhno N, Raz I, Novosadova M, Maus J, Samigullin R Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial.

Diabetes Care — Zoratti M, Szabo I The mitochondrial permeability transition. Download references. You can also search for this author in PubMed Google Scholar.

Correspondence to Luc Rochette. Department of Pharmacology and Therapeutics, University of British Colombia, Vancouver, British Columbia, Canada. Reprints and permissions. Rochette, L. Alpha-Lipoic Acid — an Antioxidant with Protective Actions on Cardiovascular Diseases.

In: Laher, I. eds Systems Biology of Free Radicals and Antioxidants. Springer, Berlin, Heidelberg. Published : 03 May Publisher Name : Springer, Berlin, Heidelberg.

Print ISBN : Online ISBN : eBook Packages : Biomedical and Life Sciences Reference Module Biomedical and Life Sciences. Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative. Policies and ethics. Skip to main content. Abstract Alpha-lipoic acid ALA , either as a dietary supplement or a therapeutic agent, modulates redox potential because of its ability to equilibrate between different subcellular compartments as well as extracellularly.

Keywords Alpha-lipoic acid Antioxidant Cardiovascular diseases Oxidative stress Therapeutic. Buying options Chapter EUR eBook EUR 1, Hardcover Book EUR 2, Tax calculation will be finalised at checkout Purchases are for personal use only Learn about institutional subscriptions. References Al-Majed AA, Gdo AM, Al-Shabanah OA, Mansour MA Alpha-lipoic acid ameliorates myocardial toxicity induced by doxorubicin.

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Am J Physiol Renal Physiol F—F Article CAS PubMed Google Scholar Bonomi F, Cerioli A, Pagani S Molecular aspects of the removal of ferritin-bound iron by DL-dihydrolipoate. Biochim Biophys Acta — Article CAS PubMed Google Scholar Clavreul N, Bachschmid MM, Hou X, Shi C, Idrizovic A, Ido Y, Pimentel D, Cohen RA S-glutathiolation of p21ras by peroxynitrite mediates endothelial insulin resistance caused by oxidized low-density lipoprotein.

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Ann Cardiol Angeiol Paris — Article CAS Google Scholar Delemasure S, Sicard P, Lauzier B, Moreau D, Vergely C, Rochette L Acute administration of Epirubicin induces myocardial depression in isolated rat heart and production of radical species evaluated by electron spin resonance spectroscopy.

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Mol Cell Biochem — Article CAS PubMed Google Scholar Ghibu S, Richard C, Vergely C, Zeller M, Cottin Y, Rochette L b Antioxidant properties of an endogenous thiol: alpha-lipoic acid, useful in the prevention of cardiovascular diseases. J Cardiovasc Pharmacol — Article CAS PubMed Google Scholar Ghibu S, Delemasure S, Richard C, Guilland JC, Martin L, Gambert S, Rochette L, Vergely C General oxidative stress during doxorubicin-induced cardiotoxicity in rats: absence of cardioprotection and low antioxidant efficiency of alpha-lipoic acid.

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Free Radic Biol Med —61 Article CAS PubMed Google Scholar Hercberg S, Galan P, Preziosi P, Bertrais S, Mennen L, Malvy D, Roussel AM, Favier A, Briancon S The SU. By helping to reduce GSSG to GSH, levels of intracellular GSH are maintained, enabling its use as a substrate of GPx to reduce hydrogen peroxide to water Moreover, GPx expression was highly upregulated by ALA.

Emphasizing the important role of GPx in the antioxidant system, a previous study showed that GPx affects the antiapoptotic Bcl-2 expression and its activity. GPx overexpression potently inhibited apoptotic signaling by increasing Bcl-2 expression and decreasing caspase-9 activity in cisplatin-treated H cells, and its antiapoptotic effect was much stronger than that of another antioxidant enzyme, superoxide dismutase Therefore, ALA has a central role in protecting cells from ROS-induced apoptotic cell death through the efficient upregulation of GPx By contrast, increased activity of GR, an enzyme that produces GSH by reducing GSSG, was relatively insignificant in our study, which corresponds with previous ALA studies 36 , In these studies, ALA showed no influence on the activity of GR; however, it remarkably increased GPx activity in rat blood, liver, kidney, and heart.

This study provides direct evidence that ALA plays a specific role in the antioxidant system against oxidative stress, and strongly suggests a therapeutic role of ALA in cisplatin-induced ototoxicity as a GSSG reductant. To our knowledge, this is the first report to demonstrate a therapeutic effect of ALA in cisplatin-induced ototoxicity using both in vitro and in vivo systems.

So far, most ototoxicity studies have only focused on the protective effect of ALA on cisplatin-induced hearing loss, using it as a pretreatment before cisplatin administration. However, because many patients already suffer from hearing damage after cisplatin cancer therapy, it is very important to find effective medications that have a therapeutic effect on existing cisplatin-induced ototoxicity.

It means that ALA can effectively restore mitochondrial redox system resulting in inhibition of cisplatin-induced apoptotic cell death, which emphasize a strong significance of this study that post-treatment with ALA may provide a therapeutic option for patients with existing cisplatin-induced hearing loss.

Furthermore, exploring other effective mitochondria-targeted nutrients that can be coadministrated with ALA will be a highly valuable step to maximize the antioxidative effect of ALA. Coadministration of vitamin E and acetyl- l -carnitine with ALA was reported to produce a synergistic effect 38 , 39 , 40 , 41 , and other antioxidants or mitochondrial enzyme cofactors were also applied with ALA to prevent cell aging in other studies 41 , Thus, identification of an ideal administration partner of ALA will be critical to achieve effective and safe clinical application of ALA to rescue auditory systems damaged by cisplatin.

In summary, this is the first study to report on a strong therapeutic potential of ALA to rescue ototoxic hearing loss caused by cisplatin, and our data provide key evidence that ALA may act as a reducing agent for GSSG to increase GSH levels on behalf of GR. Our results were consistent in cultured cells and an animal model, which improves the clinical value of ALA for therapy of cisplatin-induced ototoxicity.

Further comprehensive research on coadministration of various reagents that affect different intracellular pathways and its effective intracochlear delivery systems will provide us with an important foundation to overcome ototoxic hearing loss.

Male and female mice of the Institute for Cancer Research strain 8 weeks old were purchased from Hyochang Science Daegu, Republic of Korea. All animal procedures were conducted in accordance with the Institutional Animal Care guidelines issued by the Committee of Animal Research at Kyungpook National University.

Mice were divided into five groups: control group, cisplatin group, ALA pretreatment group, ALA post-treatment group, and ALA group. For the groups that received cisplatin, ABR threshold was measured before injections and 4. The control group was treated with 0.

The ALA pretreatment group was injected with ALA for 2 days, followed by cisplatin administration. The ALA post-treatment group was first injected with cisplatin, and then received ALA for the next 2 days.

The ALA group was injected with ALA only for 3 days. To assess auditory function, we performed ABR measurements using an ABR workstation System 3, Tucker Davis Technology, Inc.

All tests were conducted in a soundproof room. Mouse body temperature was monitored using a rectal thermometer. The stimulus signals were generated using a SigGenRP and an RP2.

Stimuli were generated for repetitions in 5-dB decrements, starting from a dB sound pressure level to the acoustic threshold at every frequency. The phase of the stimulus was reversed upon each presentation to reduce the artifacts caused by repetitive stimuli.

Mice were perfused with 1× phosphate-buffered saline PBS , and the inner ears were isolated. The inner ears were dehydrated with a graded ethanol series, permeabilized with xylene, and embedded in paraffin at room temperature.

The paraffin-embedded inner ears were then serially sectioned into 6-μm-thick slices using a microtome Leica RM, Leica Microsystems, Germany and mounted on Superfrost Plus microscope slides Fisher Scientific, Pittsburgh, PA, USA for staining. Nuclei and cytoplasm were stained with hematoxylin and eosin reagent Sigma.

Cell viability was measured using a 3- 4,5-dimethylthiazolyl -2,5-diphenyltetrazolium bromide MTT; Sigma, St. Louis, MO, USA. After the cells were treated with 0. Intracellular ROS levels were measured using the fluorescent dye, DCFH-DA Invitrogen-Molecular Probes, Eugene, OR, USA.

Then, flow cytometry analyses 10, events per sample of DCFH-DA incubated cells were performed using a BD FACS Aria III flow cytometer BD Biosciences, San Diego, CA, USA. The cells were washed twice with 1× PBS and centrifuged.

The centrifuged pellets were resuspended in a solution of RNase A 0. Cell cycle distribution was determined using a BD FACS Aria III flow cytometer BD Biosciences, San Diego, CA, USA. Cell apoptosis was analyzed using an in situ cell death detection kit Roche Biochemicals, Mannheim, Germany based on the terminal TUNEL technique.

Specimens were visualized using fluorescence microscopy Carl Zeiss, Oberkochen, Germany. The suspension was transferred into a pre-cooled 1. The supernatant was aspirated and placed in a fresh tube on ice, and the pellet was discarded.

The separated proteins were electrotransferred to a nitrocellulose membrane. After a series of washes, the membranes were developed using an enhanced chemiluminescent detection system.

Rabbit anti-Bax and anti—caspase-3 antibodies were from Cell Signaling Cell Signaling, Danvers, MA, USA , and rabbit anti-Bcl-2, anti-GR, and anti-GPx antibodies were from Abcam Abcam, Cambridge, MA, UK. Goat anti-rabbit-lgG-HRP was used as the secondary antibody Cell Signaling, Danvers, MA, USA.

Data were analyzed using SPSS statistics software package version 23; SPSS, Chicago, IL, USA. One-way ANOVA was used to analyze the variables among the 5 or 6 groups. Wang, D.

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