Alpha-Lipoic Acid

Last Updated: December 22 2022

Alpha-lipoic acid (ALA) is a mitochondrial compound involved in energy metabolism. It is commonly taken with L-Carnitine supplements, as they are related in mechanisms. ALA provides a short but potent reduction of oxidation by increasing antioxidant enzymes, and may decrease blood glucose acutely.

Alpha-Lipoic Acid is most often used for

What is alpha-lipoic acid?

Alpha-lipoic acid (ALA), or thioctic acid, is a sulfur-containing antioxidant that is involved in energy production in the mitochondria. It scavenges reactive oxygen species, and is produced in plants, animals, and humans from cysteine and fatty acids.[93][94][95]

What are alpha-lipoic acid’s main benefits?

ALA may have a protective effect on neurons, as it was found that people with multiple sclerosis (MS) supplementing with ALA for 2 years experienced a smaller decrease in brain volume than expected.[96] Furthermore, ALA may reduce disability scores and improve walking performance in people with MS.[94]

ALA has inconsistent benefits for the treatment of complications from type 2 diabetes such as pain from diabetic neuropathy.[97][98][99]

ALA has a small but consistent body of research supporting its ability to improve semen parameters like sperm concentration and sperm motility.[100][101][102] It also appears to be beneficial for female fertility processes like oocyte maturation, fertilization, and embryo development in the context of polycystic ovary syndrome (PCOS).[102]

What are alpha-lipoic acid’s main drawbacks?

ALA is generally found to be safe and tolerable,[96][103][97] though it may cause gastrointestinal upset, headache, rash, and rarely, renal dysfunction.[96][103]

How does alpha-lipoic acid work?

ALA is involved in cellular respiration in the mitochondria by serving as a cofactor of the pyruvate dehydrogenase complex, a key enzyme involved in energy production.[96]

ALA may benefit neurological health by increasing Nf-e2-related factor 2 (Nrf2), which increases phase II detoxification and antioxidant genes, potentially reducing oxidative damage.[104][105] ALA’s role in decreasing oxidative stress and inflammation may benefit vascular health as well.[106] ALA also mildly increases flow-mediated dilation (a measure of vascular function), possibly by increasing endothelium-derived nitric oxide.[107]

What else is Alpha-Lipoic Acid known as?
Note that Alpha-Lipoic Acid is also known as:
  • ALA
  • thioctic acid
  • 1 2-dithiolane-3-pentanoic acid
Alpha-Lipoic Acid should not be confused with:
  • Alpha-Linolenic Acid (omega-3 fatty acid)
Dosage information

Standard dosages of Alpha-Lipoic Acid (ALA) tend to be in the range of 300-600mg, with little differentiation based on whether the racemic mixture of ALA (S- and R- isomers) or Na-R-ALA results in higher blood levels.

ALA appears to be absorbed via transporter-related means, and despite being inherently fat-soluble it does not require dietary fatty acids to be absorbed from the gut. ALA supplementation can be taken in a fasted state.

Join our supplement information course

Examine Database: Alpha-Lipoic Acid
What works and what doesn't?

Unlock the full potential of Examine

Get started

Don't miss out on the latest research

References
2.^Akiba S, Matsugo S, Packer L, Konishi TAssay of protein-bound lipoic acid in tissues by a new enzymatic methodAnal Biochem.(1998 May 1)
3.^Wollin SD, Jones PJAlpha-lipoic acid and cardiovascular diseaseJ Nutr.(2003 Nov)
4.^Moini H, Packer L, Saris NEAntioxidant and prooxidant activities of alpha-lipoic acid and dihydrolipoic acidToxicol Appl Pharmacol.(2002 Jul 1)
7.^Backman-Gullers B, Hannestad U, Nilsson L, Sörbo BStudies on lipoamidase: characterization of the enzyme in human serum and breast milkClin Chim Acta.(1990 Oct 31)
8.^Hiltunen JK, Schonauer MS, Autio KJ, Mittelmeier TM, Kastaniotis AJ, Dieckmann CLMitochondrial fatty acid synthesis type II: more than just fatty acidsJ Biol Chem.(2009 Apr 3)
9.^Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TMAlpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potentialBiochim Biophys Acta.(2009 Oct)
10.^Reed LJFrom lipoic acid to multi-enzyme complexesProtein Sci.(1998 Jan)
11.^Park CH, Youn HR, Lee J, Lee KU, Park JY, Koh EH, Kim HSImproved efficacy of appetite suppression by lipoic acid particles prepared by nanocomminutionDrug Dev Ind Pharm.(2009 Nov)
16.^Jones W, Li X, Qu ZC, Perriott L, Whitesell RR, May JMUptake, recycling, and antioxidant actions of alpha-lipoic acid in endothelial cellsFree Radic Biol Med.(2002 Jul 1)
19.^Takaishi N, Yoshida K, Satsu H, Shimizu MTransepithelial transport of alpha-lipoic acid across human intestinal Caco-2 cell monolayersJ Agric Food Chem.(2007 Jun 27)
20.^Prasad PD, Wang H, Kekuda R, Fujita T, Fei YJ, Devoe LD, Leibach FH, Ganapathy VCloning and functional expression of a cDNA encoding a mammalian sodium-dependent vitamin transporter mediating the uptake of pantothenate, biotin, and lipoateJ Biol Chem.(1998 Mar 27)
21.^Balamurugan K, Vaziri ND, Said HMBiotin uptake by human proximal tubular epithelial cells: cellular and molecular aspectsAm J Physiol Renal Physiol.(2005 Apr)
22.^Teichert J, Kern J, Tritschler HJ, Ulrich H, Preiss RInvestigations on the pharmacokinetics of alpha-lipoic acid in healthy volunteersInt J Clin Pharmacol Ther.(1998 Dec)
24.^Carlson DA, Smith AR, Fischer SJ, Young KL, Packer LThe plasma pharmacokinetics of R-(+)-lipoic acid administered as sodium R-(+)-lipoate to healthy human subjectsAltern Med Rev.(2007 Dec)
25.^Breithaupt-Grögler K, Niebch G, Schneider E, Erb K, Hermann R, Blume HH, Schug BS, Belz GGDose-proportionality of oral thioctic acid--coincidence of assessments via pooled plasma and individual dataEur J Pharm Sci.(1999 Apr)
26.^Harrison EH, McCormick DBThe metabolism of dl-(1,6-14C)lipoic acid in the ratArch Biochem Biophys.(1974 Feb)
27.^Panigrahi M, Sadguna Y, Shivakumar BR, Kolluri SV, Roy S, Packer L, Ravindranath Valpha-Lipoic acid protects against reperfusion injury following cerebral ischemia in ratsBrain Res.(1996 Apr 22)
29.^Mignini F, Capacchietti M, Napolioni V, Reggiardo G, Fasani R, Ferrari PSingle dose bioavailability and pharmacokinetic study of a innovative formulation of α-lipoic acid (ALA600) in healthy volunteersMinerva Med.(2011 Dec)
30.^Schupke H, Hempel R, Peter G, Hermann R, Wessel K, Engel J, Kronbach TNew metabolic pathways of alpha-lipoic acidDrug Metab Dispos.(2001 Jun)
31.^Ou P, Tritschler HJ, Wolff SPThioctic (lipoic) acid: a therapeutic metal-chelating antioxidantBiochem Pharmacol.(1995 Jun 29)
32.^Cakatay U, Kayali R, Kiziler AR, Aydemir BPostmitotic tissue selenium and manganese levels in alpha-lipoic acid-supplemented aged ratsChem Biol Interact.(2008 Feb 15)
36.^Hagen TM, Ingersoll RT, Lykkesfeldt J, Liu J, Wehr CM, Vinarsky V, Bartholomew JC, Ames AB(R)-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rateFASEB J.(1999 Feb)
37.^Liu J, Head E, Gharib AM, Yuan W, Ingersoll RT, Hagen TM, Cotman CW, Ames BNMemory 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 acidProc Natl Acad Sci U S A.(2002 Feb 19)
41.^Arivazhagan P, Ramanathan K, Panneerselvam CEffect of DL-alpha-lipoic acid on mitochondrial enzymes in aged ratsChem Biol Interact.(2001 Nov 28)
42.^Freisleben HJ, Neeb A, Lehr F, Ackermann HInfluence of selegiline and lipoic acid on the life expectancy of immunosuppressed miceArzneimittelforschung.(1997 Jun)
43.^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 KUAnti-obesity effects of alpha-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinaseNat Med.(2004 Jul)
46.^Timmers S, de Vogel-van den Bosch J, Towler MC, Schaart G, Moonen-Kornips E, Mensink RP, Hesselink MK, Hardie DG, Schrauwen PPrevention of high-fat diet-induced muscular lipid accumulation in rats by alpha lipoic acid is not mediated by AMPK activationJ Lipid Res.(2010 Feb)
47.^Fernández-Galilea M, Pérez-Matute P, Prieto-Hontoria P, Martínez JA, Moreno-Aliaga MJEffects of lipoic acid on apelin in 3T3-L1 adipocytes and in high-fat fed ratsJ Physiol Biochem.(2011 Sep)
48.^El Midaoui A, Lungu C, Wang H, Wu L, Robillard C, Deblois D, Couture RImpact of α-lipoic acid on liver peroxisome proliferator-activated receptor-α, vascular remodeling, and oxidative stress in insulin-resistant ratsCan J Physiol Pharmacol.(2011 Oct)
49.^Prieto-Hontoria PL, Pérez-Matute P, Fernández-Galilea M, Barber A, Martínez JA, Moreno-Aliaga MJLipoic acid prevents body weight gain induced by a high fat diet in rats: effects on intestinal sugar transportJ Physiol Biochem.(2009 Mar)
51.^Prieto-Hontoria PL, Pérez-Matute P, Fernández-Galilea M, Martínez JA, Moreno-Aliaga MJLipoic acid inhibits leptin secretion and Sp1 activity in adipocytesMol Nutr Food Res.(2011 Jul)
54.^Prieto-Hontoria PL, Pérez-Matute P, Fernández-Galilea M, Martínez JA, Moreno-Aliaga MJEffects of lipoic acid on AMPK and adiponectin in adipose tissue of low- and high-fat-fed ratsEur J Nutr.(2012 Jun 5)
55.^Valdecantos MP, Pérez-Matute P, González-Muniesa P, Prieto-Hontoria PL, Moreno-Aliaga MJ, Martínez JALipoic acid administration prevents nonalcoholic steatosis linked to long-term high-fat feeding by modulating mitochondrial functionJ Nutr Biochem.(2012 Mar 28)
56.^Valdecantos MP, Pérez-Matute P, González-Muniesa P, Prieto-Hontoria PL, Moreno-Aliaga MJ, Martínez JALipoic Acid Improves Mitochondrial Function in Nonalcoholic Steatosis Through the Stimulation of Sirtuin 1 and Sirtuin 3Obesity (Silver Spring).(2012 Feb 13)
58.^Zhang L, Xing GQ, Barker JL, Chang Y, Maric D, Ma W, Li BS, Rubinow DRAlpha-lipoic acid protects rat cortical neurons against cell death induced by amyloid and hydrogen peroxide through the Akt signalling pathwayNeurosci Lett.(2001 Oct 26)
59.^Poon HF, Farr SA, Thongboonkerd V, Lynn BC, Banks WA, Morley JE, Klein JB, Butterfield DAProteomic analysis of specific brain proteins in aged SAMP8 mice treated with alpha-lipoic acid: implications for aging and age-related neurodegenerative disordersNeurochem Int.(2005 Jan)
60.^Farr SA, Poon HF, Dogrukol-Ak D, Drake J, Banks WA, Eyerman E, Butterfield DA, Morley JEThe antioxidants alpha-lipoic acid and N-acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 miceJ Neurochem.(2003 Mar)
63.^Lee WY, Orestes P, Latham J, Naik AK, Nelson MT, Vitko I, Perez-Reyes E, Jevtovic-Todorovic V, Todorovic SMMolecular mechanisms of lipoic acid modulation of T-type calcium channels in pain pathwayJ Neurosci.(2009 Jul 29)
65.^Kleinkauf-Rocha J, Bobermin LD, Machado Pde M, Gonçalves CA, Gottfried C, Quincozes-Santos ALipoic acid increases glutamate uptake, glutamine synthetase activity and glutathione content in C6 astrocyte cell lineInt J Dev Neurosci.(2013 May)
68.^Han D, Sen CK, Roy S, Kobayashi MS, Tritschler HJ, Packer LProtection against glutamate-induced cytotoxicity in C6 glial cells by thiol antioxidantsAm J Physiol.(1997 Nov)
69.^Tirosh O, Sen CK, Roy S, Kobayashi MS, Packer LNeuroprotective effects of alpha-lipoic acid and its positively charged amide analogueFree Radic Biol Med.(1999 Jun)
72.^Santos PS, Campêlo LM, Freitas RL, Feitosa CM, Saldanha GB, Freitas RMLipoic acid effects on glutamate and taurine concentrations in rat hippocampus after pilocarpine-induced seizuresArq Neuropsiquiatr.(2011)
73.^de Freitas RM, de Oliveira Silva F, Saldanha GB, Jordán JLipoic acid alters amino acid neurotransmitters content in rat hippocampus after pilocarpine-induced seizuresFundam Clin Pharmacol.(2011 Aug)
74.^Patel MN, Ardelt BK, Yim GK, Isom GECyanide induces Ca(2+)-dependent and -independent release of glutamate from mouse brain slicesNeurosci Lett.(1991 Sep 30)
75.^Sun P, Rane SG, Gunasekar PG, Borowitz JL, Isom GEModulation of the NMDA receptor by cyanide: enhancement of receptor-mediated responsesJ Pharmacol Exp Ther.(1997 Mar)
76.^Abdel-Zaher AO, Abdel-Hady RH, Abdel Moneim WM, Salim SYAlpha-lipoic acid protects against potassium cyanide-induced seizures and mortalityExp Toxicol Pathol.(2011 Jan)
77.^Freitas RM, Jordán J, Feng DLipoic acid effects on monoaminergic system after pilocarpine-induced seizuresNeurosci Lett.(2010 Jun 25)
78.^Santos IM, Freitas RL, Saldanha GB, Tomé Ada R, Jordán J, Freitas RMAlterations on monoamines concentration in rat hippocampus produced by lipoic acidArq Neuropsiquiatr.(2010 Jun)
80.^Ranieri M, Sciuscio M, Cortese AM, Santamato A, Di Teo L, Ianieri G, Bellomo RG, Stasi M, Megna MThe use of alpha-lipoic acid (ALA), gamma linolenic acid (GLA) and rehabilitation in the treatment of back pain: effect on health-related quality of lifeInt J Immunopathol Pharmacol.(2009 Jul-Sep)
81.^Di Geronimo G, Caccese AF, Caruso L, Soldati A, Passaretti UTreatment of carpal tunnel syndrome with alpha-lipoic acidEur Rev Med Pharmacol Sci.(2009 Mar-Apr)
83.^Ziegler D, Low PA, Litchy WJ, Boulton AJ, Vinik AI, Freeman R, Samigullin R, Tritschler H, Munzel U, Maus J, Schütte K, Dyck PJEfficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trialDiabetes Care.(2011 Sep)
84.^Zechner R, Kienesberger PC, Haemmerle G, Zimmermann R, Lass AAdipose triglyceride lipase and the lipolytic catabolism of cellular fat storesJ Lipid Res.(2009 Jan)
86.^Park KG, Min AK, Koh EH, Kim HS, Kim MO, Park HS, Kim YD, Yoon TS, Jang BK, Hwang JS, Kim JB, Choi HS, Park JY, Lee IK, Lee KUAlpha-lipoic acid decreases hepatic lipogenesis through adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent pathwaysHepatology.(2008 Nov)
88.^Park KG, Min AK, Koh EH, Kim HS, Kim MO, Park HS, Kim YD, Yoon TS, Jang BK, Hwang JS, Kim JB, Choi HS, Park JY, Lee IK, Lee KUAlpha-lipoic acid decreases hepatic lipogenesis through adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent pathwaysHepatology.(2008 Nov)
89.^Yi X, Pashaj A, Xia M, Moreau RReversal of obesity-induced hypertriglyceridemia by (R)-α-lipoic acid in ZDF (fa/fa) ratsBiochem Biophys Res Commun.(2013 Sep 27)
90.^Alkhouri N, Dixon LJ, Feldstein AELipotoxicity in nonalcoholic fatty liver disease: not all lipids are created equalExpert Rev Gastroenterol Hepatol.(2009 Aug)
91.^Browning JD, Horton JDMolecular mediators of hepatic steatosis and liver injuryJ Clin Invest.(2004 Jul)