Alpha Lipoic Acid: Supplement of the Month

Alpha lipoic Acid – Supplement of the Month – Updated from our December Series on Sanctuary’s favorite supplements.

            Alpha lipoic acid is another supplement with multiple benefits.  It begins as an anti-oxidant which can lower lipid peroxides, continues as a metal detoxifier, acts as a mitochondrial enhancer, and serves to recycle glutathione.  Update:  Alpha lipoic acid also may improve insulin sensitivity and thus could improve glucose balance in diabetes.  In diabetic patients, evidence indicates it reduces symptoms of peripheral neuropathy (nerve damage).  In the 2018 study by Akbari in Metabolism alpha lipoic acid also lowered triglycerides, LDL (bad cholesterol), and insulin levels. In other studies the chemical is being investigated for use in other diseases associated with oxidative stress such as multiple sclerosis.  A study in 2015 suggested that alpha lipoic acid with or without the Omega 3 EPA could help lower weight in dieting individuals.

            Anti-oxidant:  Alpha lipoic acid serves to recycle other anti-oxidants like Vitamin E and Vitamin C.  Whereas the latter work in either fatty membranes or the watery portions respectively, alpha lipoic acid operates in both.  With its anti-oxidant ability, it can lower lipid peroxides, the oxidized forms of fatty acids which lead to cellular aging and chronic disease.

            Metals Detoxification:  By chelating metals, alpha lipoic acid prevents these toxins from producing oxidative stress upon other cellular materials.  Manganese, copper, lead, zinc, mercury, and iron are included in those chelated.

            Mitochondrial:  Whether due to aging or primary mitochondrial disorders, alpha lipoic acid offers benefits. For aging and neurodegenerative disorders like Alzheimer’s, it can slow or reverse mitochondrial dysfunction.

            Glutathione recycling:  As a specific extension of its anti-oxidative properties, alpha lipoic acid serves to recycle glutathione (the key intra-cellular anti-oxidant).  Alpha lipoic acid reduces oxidized glutathione so that the glutathione is able to continue its important work.

            Diabetes control:  Some preliminary research indicates that besides lower oxidative stress in diabetic patients, the supplement may lower A1c, insulin levels (a marker of insulin resistance), and fasting glucose levels.  While not ready for a full replacement of diabetic medications, the dual benefits of lowering oxidative stress and glucose makes it an intriguing tool.

            Diabetic Neuropathy:  Numerous studies show that a total dose of 600mg to 1200mg of alpha lipoic acid per day in divided doses (2 to 3 times per day) reduces symptoms of nerve damage which often occurs with diabetes. 

            Cholesterol Lowering:  Mild lowering of triglycerides and low density lipoproteins (LDL) occurred in at least one study and did not worsen HDL levels (the good cholesterol). 

            Diseases of oxidative stress:  Various studies are looking at whether alpha lipoic acid may benefit patients who are experiencing diseases of excess oxidative stress. These include multiple sclerosis and alzheimers.  We look forward to more results from such studies.

            Weight Loss:  Alpha lipic appears to assist low calorie diets in lowering weight.  Researchers theorize that the supplement helps metabolism burn more fatty acids and decrease the formation of new fat cells.  Another study in animals suggested that alpha lipoic acid may increase energy expenditure in lab mice.  Human studies have shown smaller but real effects on weight. 

Dosing options:

            The mixed version with R and S forms can be found much less expensive than the biologically active R form.  No study has shown clear benefit of R over the combined R and S at this time so a definitive answer of which form is best can be given.  For patients with amalgams there is the potential for molecular extraction of mercury from the amalgam filling so lower doses are recommended. 

Cautions:

                        One study suggested that alpha lipoic acid may lower the conversion of administered T4 into T3 which is more biologically active.  This deserves more study. 

            Alpha Lipoic acid is generally well tolerated, with studies showing safety up to 2400mg per day.  Few studies have been performed in pregnant or lactating women, so caution or avoidance of higher doses is advised until a physician has a valid reason otherwise.

            Given the sulfur content of alpha lipoic acid, patients who are sulfur sensitive should monitor their total intake of sulfur containing supplements.  In some patients with excess body acid, this may add to that load and trigger gastric irritation and bladder irritation in our experience.  Cessation of the supplement generally results in resolution of these symptoms in 24 to 72 hours. 

Diabetes Glucose Control

    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.     Akbari, Maryam et al.      Metabolism – Clinical and Experimental , Volume 87 , 56 – 69.  https://www.metabolismjournal.com/article/S0026-0495(18)30153-7/fulltext

Diabetic Neuropathy:

Int J Endocrinol. 2012;2012:456279. doi: 10.1155/2012/456279. Epub 2012 Jan 26.

Alpha lipoic Acid for symptomatic peripheral neuropathy in patients with diabetes: a meta-analysis of randomized controlled trials.

Mijnhout GS1, Kollen BJ, Alkhalaf A, Kleefstra N, Bilo HJ.

Gomes, Marilia Brito and Carlos Antonio Negrato. “Alpha-lipoic acid as a pleiotropic compound with potential therapeutic use in diabetes and other chronic diseases” Diabetology & metabolic syndrome vol. 6,1 80. 28 Jul. 2014, doi:10.1186/1758-5996-6-80

Ziegler D, Hanefeld M, Ruhnau KJ, Meissner HP, Lobisch M, Schütte K, Gries FA. Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant alpha-lipoic acid. A 3-week multicentre randomized controlled trial (ALADIN Study) Diabetologia. 1995;38(12):1425–1433. doi: 10.1007/BF00400603.

Reljanovic M, Reichel G, Rett K, Lobisch M, Schuette K, Möller W, Tritschler HJ, Mehnert H. 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;31(3):171–179. doi: 10.1080/10715769900300721.

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):1296–1301. doi: 10.2337/diacare.22.8.1296.

Ruhnau KJ, Meissner HP, Finn JR, Reljanovic M, Lobisch M, Schütte K, Nehrdich D, Tritschler HJ, Mehnert H, Ziegler D. Effects of 3-week oral treatment with the antioxidant thioctic acid (alpha-lipoic acid) in symptomatic diabetic polyneuropathy. Diabet Med. 1999;16(12):1040–1043. doi: 10.1046/j.1464-5491.1999.00190.x.

Ametov AS, Barinov A, Dyck PJ, Hermann R, Kozlova N, Litchy WJ, Low PA, Nehrdich D, Novosadova M, O’Brien PC, Reljanovic M, Samigullin R, Schuette K, Strokov I, Tritschler HJ, Wessel K, Yakhno N, Ziegler D, SYDNEY Trial Study Group The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: the SYDNEY trial. Diabetes Care. 2003;26(3):770–776. doi: 10.2337/diacare.26.3.770.

Ziegler D, Ametov A, Barinov A, Dyck PJ, Gurieva I, Low PA, Munzel U, Yakhno N, Raz I, Novosadova M, Maus J, Samigullin R. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Care. 2006;29(11):2365–2370. doi: 10.2337/dc06-1216.

Ziegler D, Low PA, Litchy WJ, Boulton AJ, Vinik AI, Freeman R, Samigullin R, Tritschler H, Munzel U, Maus J, Schütte K, Dyck PJ. Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care. 2011;34(9):2054–2060. doi: 10.2337/dc11-0503.

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(2):114–121. doi: 10.1111/j.1464-5491.2004.01109.x.

Antixodant:

Kempaiah RK, Srinivasan K. Ann Nutr Metab 2004;48:314-320.

Gomes, Marilia Brito and Carlos Antonio Negrato. “Alpha-lipoic acid as a pleiotropic compound with potential therapeutic use in diabetes and other chronic diseases” Diabetology & metabolic syndrome vol. 6,1 80. 28 Jul. 2014, doi:10.1186/1758-5996-6-80

Metals Detoxification:

Altern Med Rev. 2002 Dec;7(6):456-71.

Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Patrick L.

(This article is a repository of numerous other related articles)

Gomes, Marilia Brito and Carlos Antonio Negrato. “Alpha-lipoic acid as a pleiotropic compound with potential therapeutic use in diabetes and other chronic diseases” Diabetology & metabolic syndrome vol. 6,1 80. 28 Jul. 2014, doi:10.1186/1758-5996-6-80

Mitochondrial:

Neurobiol Aging. 2013, pii: S0197-4580(13)00525-3

Mech Ageing Dev. 2010 Jul-Aug;131(7-8):473-9

Neurochem Res. 2008 Jan;33(1):194-203. Epub 2007 Jun 29.

The effects and mechanisms of mitochondrial nutrient alpha-lipoic acid on improving age-associated mitochondrial and cognitive dysfunction: an overview.

Liu J1.

Neurochem Res. 2007 Sep;32(9):1552-8. Epub 2007 May 3.

Mitochondrial ageing and the beneficial role of alpha-lipoic acid.

Palaniappan AR1, Dai A.

Barbiroli B, Medori R, Tritschler HJ, Klopstock T, Seibel P, Reichmann H, et al. Lipoic (thioctic) acid increases brain energy availability and skeletal muscle performance as shown by in vivo 31P-MRS in a patient with mitochondrial cytopathy. J Neurol 1995;242:472-7.

Glutathione recycling:

Free Radic Biol Med. 1997;22(1-2):359-78. Neuroprotection by the metabolic antioxidant alpha-lipoic acid.  Packer L1, Tritschler HJ, Wessel K.

Novel Approaches for other diseases:

Multiple Sclerosis:  Lipoic Acid: A Novel Therapeutic Approach for Multiple Sclerosis and Other Chronic Inflammatory Diseases of the CNS.  Author(s): Sonemany Salinthone, Vijayshree Yadav, Dennis N. Bourdette, Daniel W. Carr.  Journal Name: Endocrine, Metabolic & Immune Disorders – Drug Targets.  Volume 8 , Issue 2 , 2008.  DOI : 10.2174/187153008784534303

Weight Loss:

Effects of α-lipoic acid and eicosapentaenoic acid in overweight and obese women during weight loss. Huerta AE, Navas-Carretero S, Prieto-Hontoria PL, Martínez JA, Moreno-Aliaga MJ. Obesity (Silver Spring). 2015 Feb;23(2):313-21. doi: 10.1002/oby.20966. Epub 2014 Dec 31. PMID:     25594166

Wang, Yi et al. “alpha-Lipoic acid increases energy expenditure by enhancing adenosine monophosphate-activated protein kinase-peroxisome proliferator-activated receptor-gamma coactivator-1alpha signaling in the skeletal muscle of aged mice.” Metabolism: clinical and experimental vol. 59,7 (2009): 967-76. doi:10.1016/j.metabol.2009.10.018

Kucukgoncu, S et al. “Alpha-lipoic acid (ALA) as a supplementation for weight loss: results from a meta-analysis of randomized controlled trials.” Obesity reviews : an official journal of the International Association for the Study of Obesity vol. 18,5 (2017): 594-601. doi:10.1111/obr.12528


Thyroid Effects:

Arzneimittelforschung. 1991 Dec;41(12):1294-8.  Effect of alpha-lipoic acid on the peripheral conversion of thyroxine to triiodothyronine and on serum lipid-, protein- and glucose levels.  Segermann J, Hotze A, Ulrich H, Rao GS.  

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