Alpha-Lipoic Acid

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Alpha-Lipoic Acid

Common Names

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

For Patients & Caregivers

How It Works

Alpha-lipoic acid is an antioxidant. Although there is some evidence it may help treat conditions related to diabetes, confirming studies are needed.

Alpha lipoic acid (ALA) is a compound naturally produced by the body that acts as a cofactor in the production of energy. It is often referred to and marketed as a universal antioxidant. Lab studies show that ALA and its metabolite, dihydrolipoic acid (DHLA), have chelating, scavenging, and protective properties. In addition, DHLA is able to repair oxidative damage and regenerate antioxidants such as vitamin C, vitamin E, and glutathione.

Some studies in humans suggest that ALA may help improve liver function, blood sugar levels, and reduce nerve damage caused by diabetes. However, additional studies are needed to confirm safety and effectiveness.

Purported Uses
  • To prevent and treat cancer
    ALA is an antioxidant, but there is no evidence that it can be used to treat cancer.
  • To relieve conditions related to diabetes, such as diabetic neuropathy
    Data from some studies suggest efficacy, but confirming studies are needed.
  • To treat liver disease
    A few studies show that ALA may help improve liver function, but more research is needed.
Patient Warnings
  • Taking high doses of ALA should be avoided as it could cause serious conditions.
Side Effects
  • Nausea, vomiting
  • May lower blood sugar levels

Case reports

Convulsions and other serious conditions have been reported with high doses.

Special Point

Taking ALA appears to be relatively safe, but high doses could cause serious conditions and more evidence of safety and effectiveness are needed. Diabetic patients should consult their physicians before using ALA.

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For Healthcare Professionals

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

Alpha lipoic acid (ALA) is an endogenous cofactor found in cells that can also be obtained in the diet. It is sometimes referred to as a “universal antioxidant” because it is both water- and fat-soluble and can neutralize reactive oxygen species (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. 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 (23) in overweight or obese subjects. It also improved wound healing and scarring in women undergoing cesarean section (35), and reduced postsurgical 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, similar effects were not found with a combination of coenzyme Q, vitamin C, vitamin E, and ALA (20). Topical application with creams containing ALA may help prevent photoaging of facial skin (12).

High doses of ALA can cause hypoglycemic symptoms (4), as well as other serious conditions. In addition, because of its antioxidant effects, ALA may antagonize the effects of chemotherapy and radiation therapy.

Food Sources

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

Purported Uses
  • Cancer
  • 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 reactive oxygen species (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 an autoimmune hypoglycemia in genetically predisposed individuals, particularly those with HLADRB1*04:03 or HLADRB1*04:06 alleles (38) (39).

Adverse Reactions

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

Case Reports
Insulin autoimmune syndrome: 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).
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.

Herb-Drug Interactions

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

Dosage (OneMSK Only)
References
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  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.
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  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.
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  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).
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  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.
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  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.
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