Alpha lipoic acid


Alpha-lipoic acid (also known as thioctic acid and ALA) is the supplemental form of lipoic acid, a vitamin-like antioxidant found in living organisms as well as foods such as liver, kidney, yeast, spinach, and broccoli. Alpha-lipoic acid was first discovered as an essential co-factor for energy production (the conversion of pyruvate to acetyl-CoA). It has since been learned that ALA also plays a role as an antioxidant and a recycler of other cellular antioxidants (such as vitamin C and glutathione).[i] Alpha-lipoic acid also chelates metal ions, including zinc, copper, and heavy metals. Resent research suggests ALA may have insulin-like properties (insulin mimetic); it also stimulates glucose uptake in many different cells, and may modulate insulin signaling.[ii] Natural biosynthesis of alpha-lipoic acid decreases with age. [iii]

History of Use

Because of its many roles in the body (antioxidant, energy, insulin-like), alpha-lipoic acid may be potentially useful in a number of conditions including chronic fatigue syndrome, cancer, diabetes, neuropathy, liver disease, heart disease, Lyme disease, cataracts, glaucoma, weight loss and others. The most studied of these conditions is diabetic neuropathy, where it excels when intravenously injected and recent studies suggest that oral dosing may be just as effective.


Supplemental (oral) alpha-lipoic acid (ALA) is best absorbed on an empty stomach; taking ALA with food decreases peak plasma concentration by around 30 percent when compared to fasting.[iv] Plasma concentrations of ALA following oral administration peak at one hour and then decline rapidly indicating only transient activity in the body.[v]


Oral alpha-lipoic acid appears to be well tolerated in doses up to 600 milligrams a day; a more typical dose is in the 200-300 milligram range for diabetic neuropathy, or 10-40 milligram range when used as a general antioxidant.

Research Review

Diabetic Neuropathy: Intravenous alpha-lipoic acid has been researched for diabetic neuropathy and seems to make meaningful reductions in symptoms.[vi] Oral alpha-lipoic acid, in the range of 600 milligrams a day may also be successful, although it may take as long as 4-7 months of treatment to see results.[vii] Investigations for other types of neuropathies (chemotherapy induced) has not been successful.[viii]

  • A meta-analysis of fifteen randomly controlled trials involving the administration of 300-600 milligram of ALA intravenously per day demonstrated an overall effect of significantly increased nerve conduction velocities in the groups receiving ALA.[ix]
  • Twenty patients with diabetic neuropathy were treated with intravenous dose of 600 milligrams of Alpha-lipoic Acid (ALA) for 21 days, followed by 600 milligrams orally for three months. The patients showed decreases in paresthesia, night pain, and muscular atrophy. Patients that had better glycemic control showed better results.[x]
  • To test the oral efficacy of alpha-lipoic acid, 24 patients with diabetic neuropathy were supplemented with 1,800 milligrams a day for three weeks and when compared to a placebo group showed improvement.[xi]
  • A randomized, double-blind study involving 181 patients with diabetic neuropath found that lower dosing of 600 milligrams, was just as effective as higher doses (1,200 and 1,800 milligrams a day) at improving symptoms of diabetic neuropathy.[xii]
  • Diabetic neuropathy patients (N=299) taking either 600 milligrams or 1,200 milligrams of alpha-lipoic acid were followed for two years. Only 65 patients completed the full study. Both the 600 milligram and 1,200 milligram groups showed similar improvement in electrophysiological tests of nerve conduction compared to those who took placebo.[xiii]
  • In the largest, longest trial, 421 patients with diabetic neuropathy were assigned to either ALA or placebo for four years. No difference was shown between groups for primary endpoint (a composite score assessing neuropathic impairment and nerve conduction).[xiv]

Diabetes: Considering the high oxidative damage that is a common in diabetes, alpha-lipoic acid makes sense to take as an antioxidant and a recycler of other antioxidants. Recent studies have suggested that alpha-lipoic acid may act like insulin itself (insulin mimetic) and may help insulin efficacy. These uses of alpha-lipoic acid and just beginning to be investigated and some research inconsistencies exist.

  • Alpha-lipoic acid was tested in diabetics (n=57); half were randomized to placebo and the other half to 300 milligrams ALA for eight weeks. Improvements in both fasting blood glucose and insulin resistance were noted in the supplemented groups when compared to placebo.[xv]
  • A trail of 72 patients with type 2 diabetes supplemented with oral 600, 1,200, and 1800 milligrams improved insulin sensitivity by 25 percent following four weeks of treatment. No significant differences between the groups taking differing doses.[xvi]

BRAIN: Alpha-lipoic acid has been investigated for use in Alzheimer’s and multiple sclerosis,[xvii] but these studies are non-placebo, non-randomized and, while they do show a trend, are not significant enough to suggest supplementation.

  • 600 milligrams of ALA were supplemented to nine patients with Alzheimer’s disease who were also receiving standard treatment with acetylcholinesterase inhibitors in an open study. They were observed over an average of 337 days. The patients demonstrated stabilized and constant scores in two neuropsychological tests (mini-mental state examination: MMSE and AD assessment scale, cognitive subscale: ADAScog) over the study period.[xviii]
  • 43 patients with mild dementia were supplemented with 600mg alpha-lipoic acid and were assessed over four years. Alpha-lipoic acid appeared to slow the rate of decline when compared to the normal progression of untreated populous. [xix]
  • Diabetes: Because alpha-lipoic acid has the potential to alter blood sugar, caution should be used whenever combining ALA and medications for diabetes.



[i] Jones W, Li X, Qu ZC, Perriott L, Whitesell RR, May JM. Uptake, recycling, and antioxidant actions of alpha-lipoic acid in endothelial cells. Free Radic Biol Med. 2002 Jul 1;33(1):83-93. PMID: 12086686.

[ii] Salinthone S, Yadav V, Bourdette DN, Carr DW. Lipoic acid: a novel therapeutic approach for multiple sclerosis and other chronic inflammatory diseases of the CNS. Endocr Metab Immune Disord Drug Targets. 2008 Jun;8(2):132-42. PMID: 18537699.

[iii] Singh U, Jialal I. Alpha-lipoic acid supplementation and diabetes. Nutr Rev. 2008 Nov;66(11):646-57. PubMed PMID: 19019027.

[iv] Gleiter CH, Schug BS, Hermann R, Elze M, Blume HH, Gundert-Remy U. Influence of food intake on the bioavailability of thioctic acid enantiomers. Eur J Clin Pharmacol. 1996;50(6):513-4. PMID: 8858282.

[v] Evans JL, Heymann CJ, Goldfine ID, Gavin LA. Pharmacokinetics, tolerability, and fructosamine-lowering effect of a novel, controlled-release formulation of alpha-lipoic acid. Endocr Pract. 2002 Jan-Feb;8(1):29-35. PMID: 11951812.

[vi] 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 Feb;21(2):114-21. PMID: 14984445.

[vii] Ziegler D. Thioctic acid for patients with symptomatic diabeticpolyneuropathy: a critical review. Treat Endocrinol. 2004;3(3):173-89. PMID: 16026113.

[viii] Guo Y, Jones D, Palmer JL, et al. Oral alpha-lipoic acid to prevent chemotherapy-induced peripheral neuropathy: a randomized, double-blind, placebo-controlled trial. Support Care Cancer. 2014 May;22(5):1223-31. PMID: 24362907.

[ix] Han T, Bai J, Liu W, Hu Y. A systematic review and meta-analysis of α-lipoic acid in the treatment of diabetic peripheral neuropathy. Eur J Endocrinol. 2012 Oct;167(4):465-71. PMID: 22837391.

[x] Ibrahimpasic K. Alpha lipoic acid and glycaemic control in diabetic neuropathies at type 2 diabetes treatment. Med Arch. 2013;67(1):7-9. PMID: 23678828.

[xi] Ruhnau KJ, Meissner HP, Finn JR, 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. PMID: 10656234.

[xii] Ziegler D, Ametov A, Barinov A, et al. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Care. 2006 Nov;29(11):2365-70. PMID: 17065669.

[xiii] Reljanovic M, Reichel G, Rett K, et al. Treatment 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;31(3):171-9. PMID: 10499773.

[xiv] Ziegler D, Low PA, Litchy WJ, et al. Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care. 2011 Sep;34(9):2054-60. PMID: 21775755.

[xv] Ansar H, Mazloom Z, Kazemi F, Hejazi N. Effect of alpha-lipoic acid on blood glucose, insulin resistance and glutathione peroxidase of type 2 diabetic patients. Saudi Med J. 2011 Jun;32(6):584-8. PMID: 21666939.

[xvi] Jacob S, Rett K, Henriksen EJ, Häring HU. Thioctic acid–effects on insulin sensitivity and glucose-metabolism. Biofactors. 1999;10(2-3):169-74. PMID: 10609878.

[xvii] Salinthone S, Yadav V, Bourdette DN, Carr DW. Lipoic acid: a novel therapeutic approach for multiple sclerosis and other chronic inflammatory diseases of the CNS. Endocr Metab Immune Disord Drug Targets. 2008 Jun;8(2):132-42. PMID: 18537699.

[xviii] Hager K, Marahrens A, Kenklies M, Riederer P, Münch G. Alpha-lipoic acid as a new treatment option for Alzheimer [corrected] type dementia. Arch Gerontol Geriatr. 2001 Jun;32(3):275-82. Erratum in: Arch Gerontol Geriatr. 2010 Jul-Aug;51(1):110. PMID: 11395173.

[xix] Hager K, Kenklies M, McAfoose J, Engel J, Münch G. Alpha-lipoic acid as a new treatment option for Alzheimer’s disease–a 48 months follow-up analysis. J Neural Transm Suppl. 2007;(72):189-93. PMID: 17982894.