Alpha-Lipoic Acid

Share
Share
Alpha-Lipoic Acid

Common Names

  • Thioctic acid
  • Lipoate
  • Lipoic acid
  • ALA
  • Thioctan

For Patients & Caregivers

Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.


What is it?

Alpha-lipoic acid is a chemical your body makes. It’s also found in foods such as red meat, spinach, broccoli, tomatoes, peas, Brussel sprouts, and rice bran.

You can take alpha-lipoic acid as a dietary supplement. It comes as tablets or capsules.

What are the potential uses and benefits?

Your body uses alpha-lipoic acid to make energy. Alpha-lipoic acid is also used to:

  • Treat nerve pain due to diabetes
  • Treat liver disease

Alpha-lipoic acid has other uses, but doctors haven’t studied them to see if they work.

It’s generally safe to eat foods that have alpha-lipoic acid. Talk with your healthcare providers before taking alpha-lipoic acid supplements. Supplements are stronger than compounds that are naturally found in foods. They can also interact with some medications and affect how they work. For more information, read the “What else do I need to know?” section below.

What are the side effects?

Side effects of using alpha-lipoic acid may include:

  • Nausea (feeling like you’re going to throw up)
  • Vomiting (throwing up)
  • Low blood sugar level
What else do I need to know?
  • Talk with your healthcare provider if you take drugs that lower your blood sugar level. If you do, alpha-lipoic acid may be harmful because it also lowers your blood sugar level.
Back to top

For Healthcare Professionals

Scientific Name
1,2-dithiolane-3-pentanoic acid
Clinical Summary

Alpha lipoic acid (ALA) is an endogenous cofactor found in cells. It can be obtained from a variety of foods in the diet. ALA is sometimes referred to as a “universal antioxidant” because it is both water- and fat-soluble and can neutralize free radicals (26). It is marketed as a dietary supplement for this reason, and is also used as adjuvant therapy for neuropathy and to improve glycemic control. Preclinical studies show that ALA plays a crucial role in energy production, and exerts antioxidant and apoptotic effects (1) (2) (3).

Studies on ALA in humans have been conducted across various populations. Preliminary data suggest long-term supplementation may help preserve walking ability in patients with secondary progressive multiple sclerosis, especially those with less disability at baseline (27). Studies of intravenous and oral forms suggest improved insulin sensitivity, vasodilation, and neuropathy symptoms in diabetic patients (5) (6) (7) (21) (28), although earlier studies to determine its role in reversing neuropathies (8) (9) and liver disease (10) (11) produced mixed results. Data from a double-blind RCT suggest short-term ALA supplementation can be beneficial for idiopathic pain without altering glycemia in patients with normal levels (45), but another trial did not find it helpful for fibromyalgia (46).

In women with gestational diabetes, oral ALA may improve liver function and glucose metabolism (29). Meta-analyses also suggest ALA supplementation may reduce inflammatory mediators such as CRP, IL-6, TNF-α, and improve some glucose and lipid parameters (30) (31) (32) (33) (34), but confirming studies are needed. In other preliminary studies, ALA induced mild weight loss and waist circumference reduction in overweight or obese subjects (23). Long-term use of R-ALA, which has increased bioavailability, produced modest weight loss in overweight/obese adults without significant reductions in triglyceride levels (47).

In postoperative settings, ALA helped improve wound healing and scarring in women undergoing cesarean section (35), and reduced pain after carpal tunnel decompression (24). In patients with atrial fibrillation, it reduced serum markers of inflammation but not AF recurrence after ablative treatment (25).

Although current data suggest protective effects of antioxidants against Alzheimer’s disease, such effects were not found with a combination of coenzyme Q, vitamin C, vitamin E, and ALA (20). And even though preclinical studies of ALA demonstrate antioxidant properties with efficacy in neurodegenerative models, oral ALA was ineffective in patients with geographic atrophy from advanced macular degeneration (48).

High doses of ALA can cause hypoglycemic symptoms (4) and other serious conditions. ALA may also antagonize the effects of chemotherapy and radiation therapy because of its antioxidant properties.

Food Sources

Organ meats, spinach, broccoli, tomato, peas, Brussels sprouts, rice bran

Purported uses and benefits
  • Diabetes
  • Liver disease
Mechanism of Action

ALA acts as a lipophilic free radical scavenger. Dihydrolipoic acid (DHLA), a reduced form of ALA, has more antioxidant effects. It can assist in repairing oxidative damage and regenerate endogenous antioxidants such as vitamin C, vitamin E, and glutathione. Both DHLA and ALA also have metal-chelating capacities. As a lipoamide, ALA functions as a cofactor in various multienzyme systems involved in the decarboxylation of alpha-keto acids such as pyruvate (13) (14) (15).

ALA produced cell cycle arrest in G0/G1 phases in FaDu and Jurkat human tumor cell lines (1). It also scavenged ROS in MCF-7 breast cancer cells, followed by cell growth arrest and apoptosis (16). In another study, ALA induced cell death in colorectal cancer cells independent of their p53 status, and enhanced cytotoxicity of 5-fluorouracil (22).

In healthy controls and secondary progressive multiple sclerosis patients, ALA appears to stimulate cAMP production (36). In critically ill patients, ALA reduced oxidative stress and improved insulin resistance (37).

Warnings

Clinicians should be aware that ALA is often used for its antioxidant properties, and may trigger autoimmune hypoglycemia or insulin autoimmune syndrome (IAS) in genetically predisposed individuals, particularly those with HLA DRB1 expression (38) (39) (49).

Adverse Reactions

Hypoglycemia (4) (13); nausea, vomiting, dyspepsia (28) (48)

Case Reports
Insulin autoimmune syndrome (IAS): Spontaneous hypoglycemia in a woman who began ALA supplementation for joint pain (38). This syndrome has been associated with some HLA alleles, one of which was identified in this patient. Overall about 27 such cases have been reported, mostly in Japan with additional reports from Italy (39).

IAS misdiagnosed as an insulinoma: In a 71-year-old female who had a pancreatic cystic lesion, but was also prescribed ALA 600 mg/day for osteoarthritis, about 1 week before the appearance of symptoms (50).

Recurrent hypoglycemia from IAS: In a 36-year-old Indian male with dizziness and feeling of hunger with sweating, related to ALA supplement use and requiring steroid therapy (51).

Multiple organ failure: In a 70-year-old woman, due in part to a prescribing error that led to an inappropriately high dose of ALA (40).

Pediatric convulsions: Caused by accidental access by a toddler to alpha lipoic acid (41). Adults may view ALA as just a supplement, but inadvertent access by children leading to accidental ingestion can cause intoxication, convulsions, and other serious conditions.

Peditriatric intoxication, poisoning: Several cases, including one case in a teenage girl who presented with seizures and coagulopathy after low-dose ALA of about 30 mg/kg (52).

Herb-Drug Interactions

Hypoglycemic agents: ALA may produce synergetic effects (7).

Dosage (OneMSK Only)
References
  1. van de MK, Chen JS, Steliou K, Perrine SP, Faller DV. Alpha-lipoic acid induces p27Kip-dependent cell cycle arrest in non-transformed cell lines and apoptosis in tumor cell lines. J Cell Physiol 2003;194:325-40.
  2. Simbula G, Columbano A, Ledda-Columbano GM, et al. Increased ROS generation and p53 activation in alpha-lipoic acid-induced apoptosis of hepatoma cells. Apoptosis 2007 Jan;12(1):113-23.
  3. Shi DY, Liu HL, Stern JS, et al. Alpha-lipoic acid induces apoptosis in hepatoma cells via the PTEN/Akt pathway. FEBS Lett. 2008 May 28;582(12):1667-71.
  4. Jacob S, 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;27:309-14.
  5. Gu XM, Zhang SS, Wu JC, et al. Efficacy and safety of high-dose á-lipoic acid in the treatment of diabetic polyneuropathy. Zhonghua Yi Xue Za Zhi. 2010 Sep;90(35):2473-2476.
  6. Heinisch BB, Francesconi M, Mittermayer F, et al. Alpha-lipoic acid improves vascular endothelial function in patients with type 2 diabetes: a placebo-controlled randomized trial. Eur J Clin Invest. 2010 Feb;40(2):148-54.
  7. Ziegler D, Nowak H, Kempler P, Vargha P, Low PA. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a meta-analysis. Diabet.Med 2004;21:114-21.
  8. Ziegler D, 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 Aug;22(8):1296-301.
  9. Ruhnau k, et al. Effects of 3-week oral treatment with the antioxidant thioctic acid (alpha-lipoic acid) in symptomatic diabetic polyneuropathy. Diabet Med. 1999 Dec;16(12):1040-3.
  10. Marshall AW, et al. Treatment of alcohol-related liver disease with thioctic acid: a six month randomized double-blind trial. Gut 1982;23:1088-93.
  11. Park KG, Min AK, Koh EH, et al. Alpha-lipoic acid decreases hepatic lipogenesis through adenosine monophosphate- activated protein kinase (AMPK)-dependent and AMPK-independent pathways. Hepatology 2008 Nov;48(5):1477-86.
  12. 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;149:841-9.
  13. Biewenga GP, Haenen GR, Bast A. The pharmacology of the antioxidant lipoic acid. Gen Pharmacol 1997;29:315-31.
  14. Packer L. alpha-Lipoic acid: a metabolic antioxidant which regulates NF-kB signal transduction and protects against oxidative injury. Drug Metab Rev 1998;30:245-75.
  15. Schupke H, et al. New metabolic pathways of a-lipoic acid. Drug Metab Disp 2001;29:855-62.
  16. Dozio E, Ruscica M, Passafaro L, et al. The natural antioxidant alpha-lipoic acid induces p27(Kip1)-dependent cell cycle arrest and apoptosis in MCF-7 human breast cancer cells Eur J Pharmacol. 2010 Sep 1;641(1):29-34.
  17. Sen CK, Packer L. Thiol homeostasis and supplements in physical exercise. Am J Clin Nutr 2000;72(suppl):653S-69S.
  18. Teichert J, et al. Investigations on the pharmacokinetics of alpha-lipoic acid in healthy volunteers. Int J Clin Pharmacol Ther 1998;36:625-8.
  19. Breithaupt-Grogler K, et al. Dose-proportionality of oral thioctic acid - coincidence of assessments via pooled plasma and individual data. Eur J Pharm Sci 1999;8:57-65.
  20. Galasko DR, Peskind E, Clark CM, et al; for the Alzheimer’s Disease Cooperative Study. Antioxidants for Alzheimer Disease: A Randomized Clinical Trial With Cerebrospinal Fluid Biomarker Measures. Arch Neurol. 2012 Jul;69(7):836-41.
  21. Papanas N, Ziegler D. Efficacy of α-lipoic acid in diabetic neuropathy. Expert Opin Pharmacother. 2014 Dec;15(18):2721-31.
  22. Dörsam B, Göder A, Seiwert N, Kaina B, Fahrer J. Lipoic acid induces p53-independent cell death in colorectal cancer cells and potentiates the cytotoxicity of 5-fluorouracil. Arch Toxicol. 2015 Oct;89(10):1829-46.
  23. Li N, Yan W, Hu X, et al. Effects of oral alpha-lipoic acid administration on body weight in overweight or obese subjects: a crossover randomized, double-blind, placebo-controlled trial. Clin Endocrinol (Oxf). May 2017;86(5):680-687.
  24. Boriani F, Granchi D, Roatti G, et al. Alpha-lipoic Acid After Median Nerve Decompression at the Carpal Tunnel: A Randomized Controlled Trial. J Hand Surg Am. Apr 2017;42(4):236-242.
  25. Sardu C, Santulli G, Santamaria M, et al. Effects of Alpha Lipoic Acid on Multiple Cytokines and Biomarkers and Recurrence of Atrial Fibrillation Within 1 Year of Catheter Ablation. Am J Cardiol. May 1 2017;119(9):1382-1386.
  26. Salehi B, Berkay Yılmaz Y, Antika G, et al. Insights on the Use of α-Lipoic Acid for Therapeutic Purposes. Biomolecules. Aug 9 2019;9(8).
  27. Loy BD, Fling BW, Horak FB, et al. Effects of lipoic acid on walking performance, gait, and balance in secondary progressive multiple sclerosis. Complement Ther Med. Dec 2018;41:169-174.
  28. Ziegler D, Ametov A, Barinov A, et al. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Care. Nov 2006;29(11):2365-2370.
  29. Aslfalah H, Jamilian M, Rafiei F, et al. Reduction in maternal serum values of glucose and gamma-glutamyltransferase after supplementation with alpha-lipoic acid in women with gestational diabetes mellitus. J Obstet Gynaecol Res. Feb 2019;45(2):313-317.
  30. Saboori S, Falahi E, Eslampour E, et al. Effects of alpha-lipoic acid supplementation on C-reactive protein level: A systematic review and meta-analysis of randomized controlled clinical trials. Nutr Metab Cardiovasc Dis. Aug 2018;28(8):779-786.
  31. Haghighatdoost F, Hariri M. The effect of alpha-lipoic acid on inflammatory mediators: a systematic review and meta-analysis on randomized clinical trials. Eur J Pharmacol. Apr 15 2019;849:115-123.
  32. Haghighatdoost F, Hariri M. Does alpha-lipoic acid affect lipid profile? A meta-analysis and systematic review on randomized controlled trials. Eur J Pharmacol. Mar 15 2019;847:1-10.
  33. Akbari M, Ostadmohammadi V, Lankarani KB, et al. The effects of alpha-lipoic acid supplementation on glucose control and lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials. Metabolism. Oct 2018;87:56-69.
  34. Mousavi SM, Shab-Bidar S, Kord-Varkaneh H, et al. Effect of alpha-lipoic acid supplementation on lipid profile: A systematic review and meta-analysis of controlled clinical trials. Nutrition. Mar 2019;59:121-130.
  35. Sammour H, Elkholy A, Rasheedy R, et al. The effect of alpha lipoic acid on uterine wound healing after primary cesarean section: a triple-blind placebo-controlled parallel-group randomized clinical trial. Arch Gynecol Obstet. Mar 2019;299(3):665-673.
  36. Fiedler SE, Yadav V, Kerns AR, et al. Lipoic Acid Stimulates cAMP Production in Healthy Control and Secondary Progressive MS Subjects. Mol Neurobiol. Jul 2018;55(7):6037-6049.
  37. Hejazi N, Mazloom Z, Zand F, et al. The Beneficial Effects of α-Lipoic Acid in Critically Ill Patients: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial. Asian J Anesthesiol. Jun 2018;56(2):45-55.
  38. Izzo V, Greco C, Corradini D, et al. Insulin autoimmune syndrome in an Argentine woman taking α-lipoic acid: A case report and review of the literature. SAGE Open Med Case Rep. 2018;6:2050313x18819601.
  39. Moffa S, Improta I, Rocchetti S, et al. Potential cause-effect relationship between insulin autoimmune syndrome and alpha lipoic acid: Two case reports. Nutrition. Jan 2019;57:1-4.
  40. Moretti R, Angeletti C, Minora S. Multiple organ failure and shock following acute alpha lipoic acid (ALA) intoxication. Clin Toxicol (Phila). Aug 2019;57(8):749-751.
  41. Tolunay O, Çelik T, Kömür M, et al. A rare cause of status epilepticus; alpha lipoic acid intoxication, case report and review of the literature. Eur J Paediatr Neurol. Nov 2015;19(6):730-732.
  42. Emir DF, Ozturan IU, Yilmaz S. Alpha lipoic acid intoxicatıon: An adult. Am J Emerg Med. Jun 2018;36(6):1125.e1123-1125.e1125.
  43. Gulen M, Simsek Y, Oner E, et al. First description of the alpha lipoic acid intoxication in an adult patient worldwide following oral administration. Am J Emerg Med. Jun 2018;36(6):1126.e1125-1126.e1126.
  44. Hadzik B, Grass H, Mayatepek E, et al. Fatal non-accidental alpha-lipoic acid intoxication in an adolescent girl. Klin Padiatr. Sep 2014;226(5):292-294.
  45. Esposito C, Ugo Garzarella E, Santarcangelo C, et al. Safety and efficacy of alpha-lipoic acid oral supplementation in the reduction of pain with unknown etiology: A monocentric, randomized, double-blind, placebo-controlled clinical trial. Biomed Pharmacother. Dec 2021;144:112308.
  46. Gilron I, Robb S, Tu D, et al. Double-blind, randomized, placebo-controlled crossover trial of alpha-lipoic acid for the treatment of fibromyalgia pain: the IMPALA trial. Pain. Feb 1 2021;162(2):561-568.
  47. Bobe G, Michels AJ, Zhang WJ, et al. A Randomized Controlled Trial of Long-Term (R)-α-Lipoic Acid Supplementation Promotes Weight Loss in Overweight or Obese Adults without Altering Baseline Elevated Plasma Triglyceride Concentrations. J Nutr. Sep 1 2020;150(9):2336-2345.
  48. Kim BJ, Hunter A, Brucker AJ, et al. Orally Administered Alpha Lipoic Acid as a Treatment for Geographic Atrophy: A Randomized Clinical Trial. Ophthalmol Retina. Sep 2020;4(9):889-898.
  49. Cappellani D, Macchia E, Falorni A, et al. Insulin Autoimmune Syndrome (Hirata Disease): A Comprehensive Review Fifty Years After Its First Description. Diabetes Metab Syndr Obes. 2020;13:963-978.
  50. Gullo D, Magliozzo M, Strano A, et al. Insulin autoimmune syndrome misdiagnosed as an insulinoma in a woman presenting with a pancreatic cystic lesion and taking alpha lipoic acid: a lesson to be learned. Hormones (Athens). Sep 2021;20(3):593-595.
  51. Maheshwari TM, Sharma A, Maheshwari BB. Insulin autoimmune syndrome: A rare cause of hypoglycemia. J Family Med Prim Care. Sep 2020;9(9):5046-5048.
  52. Polat S, Kılıçaslan Ö, Sönmez FT. Alpha-lipoic acid intoxication in an adolescent girl: Case report and review of the literature. Turk Pediatri Ars. 2020;55(3):328-330.
Back to top
Back to top
Email your questions and comments to [email protected].

Last Updated