Alpha-Lipoic Acid

• How It Works

  Alpha-lipoic acid is an antioxidant. There is no evidence to support its use to treat diseases such as diabetes, HIV, liver disease, or cancer.

  Alpha lipoic acid (ALA) is a compound naturally produced by the body that acts as a cofactor in the production of energy. Laboratory studies show that ALA and its metabolite, dihydrolipoic acid (DHLA), have metal-chelating and free radical-scavenging capacities. In addition, DHLA is able to repair oxidative damage and regenerate antioxidants such as vitamin C, vitamin E, and glutathione. However, when taken orally, the amount of ALA delivered to the body varies. Applying a cream containing ALA may help prevent wrinkling of skin due to sun exposure.

• Purported Uses
  • As an antioxidant
    Laboratory studies support this use.
  • 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.
  • To treat HIV and AIDS
    No scientific evidence supports this use.
  • To treat liver disease
    A few studies show that ALA may prevent nonalcoholic liver disease. More research is needed.
• Side Effects

  Alpha-lipoic acid can lower blood sugar levels.

• Special Point

  Taking ALA appears to be relatively safe, but it has yet to be proven beneficial for any of its proposed uses. Diabetic patients should consult their physicians before using ALA.

• Scientific Name

  1,2-dithiolane-3-pentanoic acid

• Clinical Summary

  Alpha lipoic acid, also known as ALA, is an endogenous cofactor found in all eukaryotic and prokaryotic cells that can be obtained in the diet. Patients take it in supplement form to treat and prevent cancer and to treat diabetes, diabetic neuropathies, HIV/AIDS, and liver disease. ALA plays a crucial role in energy production, has antioxidant properties, and exerts apoptotic effects on tumor cells ^{(1) (2) (3)}.

  In overweight or obese subjects, ALA supplementation induced mild weight loss and waist circumference reduction ⁽²³⁾. ALA improved insulin sensitivity, vasodilation, and polyneuropathy in patients with diabetes mellitus ^(5) (6). Analyses of clinical trials using ALA showed significant reductions in neuropathic symptoms in diabetic patients ^(7) (21). Studies to determine its role in reversing neuropathies ^(8) (9) and liver disease ^(10) (11) have produced mixed results. 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⁾.

  Preliminary studies suggests supplementation with ALA after carpal tunnel decompression may reduce postsurgical pain ⁽²⁴⁾. In patients with atrial fibrillation (AF), although ALA supplementation significantly reduced serum markers of inflammation, it did not prevent AF recurrence after ablative treatment ⁽²⁵⁾.

  High doses of ALA can cause hypoglycemic symptoms ⁽⁴⁾. 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 prevention
  • Cancer treatment
  • Diabetes
  • Diabetic neuropathy
  • HIV/AIDS
  • 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⁾.

• Adverse Reactions

  Hypoglycemia ^(4) (13)

• Herb-Drug Interactions

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

• 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.