Alpha Lipoic Acid (ALA)

ALA: What is it and how does it work in the body?

• Alpha Lipoic acid (ALA), also known as thioctic acid, is a natural short-chain fatty acid.

• It is an essential cofactor of dehydrogenase enzymes and involved in mitochondrial macronutrient metabolism.

• It has largely been used world wide as a dietary supplement. ALA has antioxidant characteristics that unlike most other antioxidants, is both water-and fat-soluble; thus, it can reach easily into tissues composed of fat, such as the nervous system as well as those mainly of water such as the cardiovascular system.

What is it used for and at what dosage?

• As described above, ALA acts within the nervous system in diabetic neuropathy, Alzheimer’s disease, as an analgesic and even improving behavior.

• Effective dosing in studies ranged from 6000 mg daily up to 1800 mg daily (600 mg three times daily).

Evidence for or against its different uses:

• The Alpha Lipoic Acid in Diabetic Neuropathy (ALADIN) trials (I–III) were successful multicenter studies that supported the efficacy of ALA in alleviating diabetic neuropathic pain and safe dosing. Although ineffective in glucose control (Hgb A1c unchanged) the ALADIN trial showed ALA’s benefits in symptomatic relief (total symptom score, neuropathy impairment score, etc.)

  and improvements in electrophysiological nerve measurements

• Postoperative administration of ALA was associated with a reduced incidence of postoperative pillar pain (frequent symptom following carpal tunnel release) compared with placebo. The difference was statistically significant although groups were slightly underpowered.

• Dayong’s animal study showed a potential benefit of ALA in traumatic brain injury simulated by a weight drop injury model in rats. ALA was administered via intraperitoneal injection after TBI-induced neuron cell apoptosis and improved neurobehavioral function.

• ALA was also found to have cardioprotective properties. Supplementation with 1200 mg ALA after 8 weeks resulted in a substantial reduction in the risk of CVD in type 2 diabetic patient via a decrease in biomarkers such as ox-LDL and Lp-PLA2 mass and improvement in Lp-PLA2 distribution between HDL and apoB-containing lipoproteins.

• ALA treatment coincided with a 1.27 kg (confidence interval = 0.25–2.29) greater mean weight loss compared with the placebo group and an overall mean BMI difference of −0.43 kg/m2 (confidence interval = −0.82 to −0.03) was found between the ALA and placebo groups.

• On the contrary, some concerns have been recently raised regarding ALA, after some reports suggesting a direct causal link between its use and insulin autoimmune syndrome (IAS, Hirata’s disease) due to its sulfhydryl group. About 50% IAS development cases are associated with drugs or dietary supplements containing a sulfur or sulfhydryl group.

Safety concerns, side effects, and precautions:

• ALADIN trials reported side effects such as gastrointestinal distress, headaches, skin irritation, and possible hypoglycemia associated with 1200 mg/ day of parenteral ALA. It may also cause mineral shortages, and iron level should be periodically monitored.

Interactions with medications:

• Co-administering ALA with Valproic Acid (VA) exhibited significant inhibition on the β-oxidation of VA, particularly on the formation of VA-CoA. Separate dosing at least 2 h apart from any medication that chelate such as antiacids 

Key Web Sources

• Mazzali M, Hughes J, Kim YG, Jefferson JA, Kang DH, Gordon KL, Lan HY, Kivlighn S, Johnson RJ. Elevated uric acid increases blood pressure in the rat by a novel crystalline-dependent mechanism. Hypertension. 2001;38:1101–6. https://doi.org/10.1161/hy1101.092839.

• Ziegler D, Hanefeld M, Ruhnau KJ, Hasche H, Lobisch M, Schütte K, Kerum G, Malessa R. 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;22(8):1296–301. https://doi.org/10.2337/diacare.22.8.1296. PMID: 10480774

• Boriani F, Granchi D, Roatti G, Merlini L, Sabattini T, Baldini N. Alpha-lipoic acid after median nerve decompression at the carpal tunnel: a randomized controlled trial. J Hand Surg Am. 2017;42(4):236–42. https://doi.org/10.1016/j.jhsa.2017.01.011. Epub 2017 Feb 28

• Xia D, Zhai X, Wang H, Chen Z, Fu C, Zhu M. Alpha lipoic acid inhibits oxidative stress-induced apoptosis by modulating of Nrf2 signalling pathway after traumatic brain injury. J Cell Mol Med. 2019;23(6):4088–96. https://doi.org/10.1111/jcmm.14296.

• Baziar N, Nasli-Esfahani E, Djafarian K, Qorbani M, Hedayati M, Mishani MA, Faghfoori Z, Ahmaripour N, Hosseini S. The beneficial effects of alpha lipoic acid supplementation on Lp-PLA2 mass and its distribution between HDL and apoB-containing lipoproteins in type 2 diabetic patients: a randomized, double-blind, placebo-controlled trial. Oxid Med Cell Longev. 2020;9(2020):5850865.

• Kucukgoncu S, Zhou E, Lucas KB, Tek C. Alpha-lipoic acid (ALA) as a supplementation for weight loss: results from a meta-analysis of randomized controlled trials. Obes Rev. 2017;18(5):594–601. https://doi.org/10.1111/obr.12528. Epub 2017 Mar 13. PMID: 28295905; PMCID: PMC5523816

• Yukina M, Nuralieva N, Solovyev M, Troshina E, Vasilyev E. Insulin autoimmune syndrome. Endocrinol Diabetes Metab Case Rep. 2020;2020:19–0159. https://doi.org/10.1530/EDM-19-0159.

• Phua LC, New LS, Goh CW, et al. Investigation of the drug–drug interaction between α-lipoic acid and valproate via mitochondrial β-oxidation. Pharm Res. 2008;25:2639–49. [invalid URL removed].