Alpha-Lipoic Acid

Last Updated: July 25, 2023

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.

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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.[1][2][3]

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.[4] Furthermore, ALA may reduce disability scores and improve walking performance in people with MS.[2]

ALA has inconsistent benefits for the treatment of complications from type 2 diabetes such as pain from diabetic neuropathy.[5][6][7]

ALA has a small but consistent body of research supporting its ability to improve semen parameters like sperm concentration and sperm motility.[8][9][10] 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).[10]

What are alpha-lipoic acid’s main drawbacks?

ALA is generally found to be safe and tolerable,[4][11][5] though it may cause gastrointestinal upset, headache, rash, and rarely, renal dysfunction.[4][11]

Does alpha-lipoic acid cause insulin autoimmune syndrome? (Hirata’s disease)?

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.[4]

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.[12][13] ALA’s role in decreasing oxidative stress and inflammation may benefit vascular health as well.[14] ALA also mildly increases flow-mediated dilation (a measure of vascular function), possibly by increasing endothelium-derived nitric oxide.[15]

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.

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References
  1. ^Christy J, Noorani S, Sy F, Al-Eryani K, Enciso REfficacy of alpha-lipoic acid in patients with burning mouth syndrome compared to that of placebo or other interventions: a systematic review with meta-analyses.J Dent Anesth Pain Med.(2022-Oct)
  2. ^Xie H, Yang X, Cao Y, Long X, Shang H, Jia ZRole of lipoic acid in multiple sclerosis.CNS Neurosci Ther.(2022-Mar)
  3. ^Schreibelt G, Musters RJ, Reijerkerk A, de Groot LR, van der Pol SM, Hendrikx EM, Döpp ED, Dijkstra CD, Drukarch B, de Vries HELipoic acid affects cellular migration into the central nervous system and stabilizes blood-brain barrier integrity.J Immunol.(2006-Aug-15)
  4. ^Spain R, Powers K, Murchison C, Heriza E, Winges K, Yadav V, Cameron M, Kim E, Horak F, Simon J, Bourdette DLipoic acid in secondary progressive MS: A randomized controlled pilot trial.Neurol Neuroimmunol Neuroinflamm.(2017-Sep)
  5. ^Abubaker SA, Alonazy AM, Abdulrahman AEffect of Alpha-Lipoic Acid in the Treatment of Diabetic Neuropathy: A Systematic Review.Cureus.(2022-Jun)
  6. ^Vakali E, Rigopoulos D, Carrillo AE, Flouris AD, Dinas PCEffects of Alpha-lipoic Acid Supplementation on Human Diabetic Nephropathy: A Systematic Review and Meta-analysis.Curr Diabetes Rev.(2022)
  7. ^Jibril AT, Jayedi A, Shab-Bidar SEfficacy and safety of oral alpha-lipoic acid supplementation for type 2 diabetes management: a systematic review and dose-response meta-analysis of randomized trials.Endocr Connect.(2022-Oct-01)
  8. ^Dong L, Yang F, Li J, Li Y, Yu X, Zhang XEffect of oral alpha-lipoic acid (ALA) on sperm parameters: a systematic review and meta-analysis.Basic Clin Androl.(2022-Dec-08)
  9. ^Hodeeb YM, El-Rewiny EM, Gaafar AM, Zayed AN, Hasan MS, Elsaie MLThe effect of alpha lipoic acid supplementation on sperm functions in idiopathic asthenozoospermic patients: a case-controlled study.Hum Fertil (Camb).(2022-Jan-13)
  10. ^Di Tucci C, Galati G, Mattei G, Bonanni V, Capri O, D'Amelio R, Muzii L, Benedetti Panici PThe role of alpha lipoic acid in female and male infertility: a systematic review.Gynecol Endocrinol.(2021-Jun)
  11. ^Reljanovic M, Reichel G, Rett K, Lobisch M, Schuette K, Möller W, Tritschler HJ, Mehnert HTreatment 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-Sep)
  12. ^H J Engels, J C WirthNo ergogenic effects of ginseng (Panax ginseng C.A. Meyer) during graded maximal aerobic exerciseJ Am Diet Assoc.(1997 Oct)
  13. ^The Neuroprotective Antioxidant α-lipoic Acid Induces Detoxication Enzymes in Cultured Astroglial Cells
  14. ^Hajizadeh-Sharafabad F, Sharifi Zahabi ERole of alpha-lipoic acid in vascular function: A systematic review of human intervention studies.Crit Rev Food Sci Nutr.(2022)
  15. ^Jalilpiran Y, Hajishafiee M, Khorshidi M, Rezvani H, Mohammadi-Sartang M, Rahmani J, Mousavi SMThe effect of Alpha-lipoic acid supplementation on endothelial function: A systematic review and meta-analysis.Phytother Res.(2020-Nov-18)
  16. ^Uchigata Y, Hirata YInsulin autoimmune syndrome (IAS, Hirata disease).Ann Med Interne (Paris).(1999-Apr)
  17. ^Wong SL, Priestman A, Holmes DTRecurrent hypoglycemia from insulin autoimmune syndrome.J Gen Intern Med.(2014-Jan)
  18. ^Veltroni A, Zambon G, Cingarlini S, Davì MVAutoimmune hypoglycaemia caused by alpha-lipoic acid: a rare condition in Caucasian patients.Endocrinol Diabetes Metab Case Rep.(2018)
  19. ^Bae SM, Bae MN, Kim EY, Kim IK, Seo MW, Shin JK, Cho SR, Jeong GHRecurrent Insulin Autoimmune Syndrome Caused by α-Lipoic Acid in Type 2 Diabetes.Endocrinol Metab (Seoul).(2013-Dec)
  20. ^Yamada T, Imai J, Ishigaki Y, Hinokio Y, Oka Y, Katagiri HPossible relevance of HLA-DRB1*0403 haplotype in insulin autoimmune syndrome induced by alpha-lipoic acid, used as a dietary supplement.Diabetes Care.(2007-Dec)
  21. ^Gullo D, Evans JL, Sortino G, Goldfine ID, Vigneri RInsulin autoimmune syndrome (Hirata Disease) in European Caucasians taking α-lipoic acid.Clin Endocrinol (Oxf).(2014-Aug)
  22. ^Paiva ES, Pereira AE, Lombardi MT, Nishida SK, Tachibana TT, Ferrer C, Hauache OM, Vieira JG, Reis AFInsulin autoimmune syndrome (Hirata disease) as differential diagnosis in patients with hyperinsulinemic hypoglycemia.Pancreas.(2006-May)
  23. ^Ishida Y, Ohara T, Okuno Y, Ito T, Hirota Y, Furukawa K, Sakaguchi K, Ogawa W, Kasuga MAlpha-lipoic acid and insulin autoimmune syndrome.Diabetes Care.(2007-Sep)
  24. ^Li Z, Su Y, Yi D, Wu C, Fang W, Wang CAnalysis of the clinical characteristics of insulin autoimmune syndrome induced by alpha-lipoic acid.J Clin Pharm Ther.(2021-Oct)
  25. ^Furukawa N, Miyamura N, Nishida K, Motoshima H, Taketa K, Araki EPossible relevance of alpha lipoic acid contained in a health supplement in a case of insulin autoimmune syndrome.Diabetes Res Clin Pract.(2007-Mar)
  26. ^Moffa S, Improta I, Rocchetti S, Mezza T, Giaccari APotential cause-effect relationship between insulin autoimmune syndrome and alpha lipoic acid: Two case reportsNutrition.(2019 Jan)
  27. ^, Turck D, Castenmiller J, de Henauw S, Hirsch-Ernst KI, Kearney J, Knutsen HK, Mangelsdorf I, McArdle HJ, Naska A, Pelaez C, Pentieva K, Siani A, Thies F, Tsabouri S, Vinceti M, Cappellani D, Ijzerman R, Van Loveren H, Titz A, Maciuk AScientific opinion on the relationship between intake of alpha-lipoic acid (thioctic acid) and the risk of insulin autoimmune syndrome.EFSA J.(2021-Jun)
  28. ^Yamada Y, Kitayama K, Oyachi M, Higuchi S, Kawakita R, Kanamori Y, Yorifuji TNationwide survey of endogenous hyperinsulinemic hypoglycemia in Japan (2017-2018): Congenital hyperinsulinism, insulinoma, non-insulinoma pancreatogenous hypoglycemia syndrome and insulin autoimmune syndrome (Hirata's disease).J Diabetes Investig.(2020-May)
Examine Database References
  1. C-Reactive Protein (CRP) - Vincent HK, Bourguignon CM, Vincent KR, Taylor AGEffects of alpha-lipoic acid supplementation in peripheral arterial disease: a pilot studyJ Altern Complement Med.(2007 Jun)
  2. Dementia Symptoms - Lott IT, Doran E, Nguyen VQ, Tournay A, Head E, Gillen DLDown syndrome and dementia: a randomized, controlled trial of antioxidant supplementationAm J Med Genet A.(2011 Aug)
  3. Inflammation - Bae SC, Jung WJ, Lee EJ, Yu R, Sung MKEffects of antioxidant supplements intervention on the level of plasma inflammatory molecules and disease severity of rheumatoid arthritis patientsJ Am Coll Nutr.(2009 Feb)
  4. LDL Oxidation - Andrea M McNeilly, Gareth W Davison, Marie H Murphy, Nida Nadeem, Tom Trinick, Ellie Duly, Anna Novials, Jane McEnenyEffect of α-lipoic acid and exercise training on cardiovascular disease risk in obesity with impaired glucose toleranceLipids Health Dis.(2011 Nov 22)
  5. Weight - M G Carbonelli, L Di Renzo, M Bigioni, N Di Daniele, A De Lorenzo, M A FuscoAlpha-lipoic acid supplementation: a tool for obesity therapy?Curr Pharm Des.(2010)
  6. Weight - 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 KUEffects of alpha-lipoic Acid on body weight in obese subjectsAm J Med.(2011 Jan)
  7. Motion Sickness Symptoms - Baillie JK, Thompson AA, Irving JB, Bates MG, Sutherland AI, Macnee W, Maxwell SR, Webb DJOral antioxidant supplementation does not prevent acute mountain sickness: double blind, randomized placebo-controlled trialQJM.(2009 May)
  8. HbA1c - Coleman MD, Fernandes S, Khanderia LA preliminary evaluation of a novel method to monitor a triple antioxidant combination (vitamins E, C and α-lipoic acid) in diabetic volunteers using in vitro methaemoglobin formationEnviron Toxicol Pharmacol.(2003 Jun)
  9. HbA1c - Porasuphatana S, Suddee S, Nartnampong A, Konsil J, Harnwong B, Santaweesuk AGlycemic and oxidative status of patients with type 2 diabetes mellitus following oral administration of alpha-lipoic acid: a randomized double-blinded placebo-controlled studyAsia Pac J Clin Nutr.(2012)
  10. General Oxidation - P Palacka, J Kucharska, J Murin, K Dostalova, A Okkelova, M Cizova, I Waczulikova, S Moricova, A GvozdjakovaComplementary therapy in diabetic patients with chronic complications: a pilot studyBratisl Lek Listy.(2010)
  11. Glycemic Control - de Oliveira AM, Rondó PH, Luzia LA, D'Abronzo FH, Illison VKThe effects of lipoic acid and α-tocopherol supplementation on the lipid profile and insulin sensitivity of patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trialDiabetes Res Clin Pract.(2011 May)
  12. Anti-Oxidant Enzyme Profile - Martins VD, Manfredini V, Peralba MC, Benfato MSAlpha-lipoic acid modifies oxidative stress parameters in sickle cell trait subjects and sickle cell patientsClin Nutr.(2009 Apr)
  13. Blood Pressure - Sharman JE, Gunaruwan P, Knez WL, Schmitt M, Marsh SA, Wilson GR, Cockcroft JR, Coombes JSAlpha-lipoic acid does not acutely affect resistance and conduit artery function or oxidative stress in healthy menBr J Clin Pharmacol.(2004 Sep)
  14. General Oxidation - Jariwalla RJ, Lalezari J, Cenko D, Mansour SE, Kumar A, Gangapurkar B, Nakamura DRestoration of blood total glutathione status and lymphocyte function following alpha-lipoic acid supplementation in patients with HIV infectionJ Altern Complement Med.(2008 Mar)
  15. C-Reactive Protein (CRP) - Khabbazi T, Mahdavi R, Safa J, Pour-Abdollahi PEffects of Alpha-Lipoic Acid Supplementation on Inflammation, Oxidative Stress, and Serum Lipid Profile Levels in Patients with End-Stage Renal Disease on HemodialysisJ Ren Nutr.(2011 Sep 10)
  16. General Oxidation - G D X, J H P, H L S, L S ZAlpha-lipoic acid improves endothelial dysfunction in patients with subclinical hypothyroidismExp Clin Endocrinol Diabetes.(2010 Oct)
  17. Inflammation - Sola S, Mir MQ, Cheema FA, Khan-Merchant N, Menon RG, Parthasarathy S, Khan BVIrbesartan 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) studyCirculation.(2005 Jan 25)
  18. Blood Pressure - Wray DW, Uberoi A, Lawrenson L, Bailey DM, Richardson RSOral antioxidants and cardiovascular health in the exercise-trained and untrained elderly: a radically different outcomeClin Sci (Lond).(2009 Mar)
  19. Blood Pressure - Weiss C, Bierhaus A, Nawroth PP, Bärtsch PEffects of supplementation with alpha-lipoic acid on exercise-induced activation of coagulationMetabolism.(2005 Jun)
  20. General Oxidation - Zembron-Lacny A, Slowinska-Lisowska M, Szygula Z, Witkowski K, Stefaniak T, Dziubek WAssessment of the antioxidant effectiveness of alpha-lipoic acid in healthy men exposed to muscle-damaging exerciseJ Physiol Pharmacol.(2009 Jun)
  21. Diabetic Neuropathy Symptoms - 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)
  22. Diabetic Neuropathy Symptoms - Foster TSEfficacy and safety of alpha-lipoic acid supplementation in the treatment of symptomatic diabetic neuropathyDiabetes Educ.(2007 Jan-Feb)
  23. Blood Flow - Heinisch BB, Francesconi M, Mittermayer F, Schaller G, Gouya G, Wolzt M, Pleiner JAlpha-lipoic acid improves vascular endothelial function in patients with type 2 diabetes: a placebo-controlled randomized trialEur J Clin Invest.(2010 Feb)
  24. Muscle Creatine Content - Darren G Burke, Philip D Chilibeck, Gianni Parise, Mark A Tarnopolsky, Darren G CandowEffect of alpha-lipoic acid combined with creatine monohydrate on human skeletal muscle creatine and phosphagen concentrationInt J Sport Nutr Exerc Metab.(2003 Sep)
  25. Nerve Repair - 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)