Acid Alpha Lipoic Acid – The Science

Acid Alpha Lipoic Acid Molecular Structure

Updated on 11th August 2008 by Dr Charles Tweed

Intro
Alpha Lipoic Acid is an organic acid that occurs naturally in the body and has multiple functions. Primarily it is used as a co-enzyme and mitochondrial reactions and most work on the subject has been directed towards this action, but it has other functions – as listed here:
A potent co-enzyme in the metabolic pathway (helps the cells produce energy).
Free radical scavenger/anti-oxidant – it has the remarkable property of being able to do this directly and also by regenerating other anti-oxidants such as glutathione and vitamin C and E.
Improves glucose utilisation:
Cellular uptake of glucose is improved.
This effect, along with the free radical scavenging, is probably the reason it is effective in managing diabetic neuropathy (see below).
Improves the redox balance – this decreases inflammation at a cellular level, which is the root cause of diabetes, cardiovascular disease, arthritis and some cancers.
Chelates metals that may be implicated in disease promotion through the creation of particularly aggressive free-radicals.
It has been used for many years in clinical studies and is an increasingly popular supplement. It is primarily used in conjunction with Acetyl L-Carnitine (ALCAR) with which it has a synergistic effect. It has been used either on its own or conjunction with Acetyl L-Carnitine in the following areas:

Acetyl Carnitine for Cognitive Health
Neurodegenerative disorders
Alzheimers [1, 2, 3, 4]
Age related Cognitive decline [5, 6, 7, 8, 9]
Parkinsons disease [10, 11, 12]
Multiple sclerosis [13, 14, 15]
Diabetic neuropathy [16, 17, 18, 19, 20]
Diabetes [21, 22, 23]
Liver disease [24, 25, 26, 27, 28]
Arthritis [29, 30, 31]
Vascular disorders [32, 33, 34, 35]

Please see the Google Scholar links below for dynamic, constantly updating data of recent studies so that you can research Alpha Lipoic Acid’s benefits for yourself.

Google Scholar
Alzheimers
Age-related cognitive decline
Parkinsons disease
Multiple sclerosis
Diabetic neuropathy
Diabetes
Liver Disease
Arthritis
Vascular disorders

The science
The story so far is extremely encouraging. The best studies to date have been conducted in the neurodegenerative disorders. There is startling laboratory evidence that alpha lipoic acid alone and in combination with Acetyl L-Carnitine, can attenuate and even reverse the changes at a cellular level of many of the neurodegenerative disorders. Observation studies show the rate of progression is massively slowed compared to the usual course observed in Alzheimer’s [1] and multiple sclerosis [13]. Clinical trials are generally very encouraging, but as yet not robust enough to say without fear of contradiction that the case is settled, except in diabetic peripheral neuropathy, where the data are incontrovertible. Many of you may be familiar with the ground breaking work by Prof. Bruce Ames et al. They have shown how age related cognitive decline can be prevented in the rat and dog model. This gives us all great hope that as humans we can all benefit from the combination of Alpha Lipoic Acid and Acetyl L-Carnitine to ward off the gradual decline in mental ability that affects everyone as they age. [6, 7, 8] There have been a wave of publications that have been built on these promising results, looking at conditions as diverse as diabetes, cardiovascular disease and arthritis. Currently these are at an early stage ie only laboratory and animal models. Having said that, there is enough preliminary optimism, based on these, to hope that alpha lipoic acid has remarkable properties in most degenerative disorders, particularly in relation to mitochondrial dysfunction. There is also discussion over which isomer is superior. The body only produces the R-enantiomer. Most supplements are sold in the racemic form (equal mixture of R and S). There is debate as to how effectively the different forms are absorbed and how they interact once within the body, but data to date suggests only the R enantiomer is biologically active. Almost all the studies have been with the racemic form, however half of the dose you pay for could be wasted. Most studies use 200-600mg daily orally which would be our recommendation, until further studies clarify this area.

Safety
Reported side effects are rare. In the intravenous form, patients have suffered allergic reactions but in the oral form this is vanishingly uncommon. As with almost all supplements, there are no data of safety during pregnancy and breastfeeding – so avoid it under these conditions.

aging-management.com Buyer’s Guide and Recommendation
Take 400-600mg daily on empty stomach in combination with Acetyl L-Carnitine for neuro-degenerative disorders, to prevent cognitive decline and for cardiovascular health. Take 400-600mg daily on empty stomach for improved insulin control, liver disorders and arthritis.

References:
(Back) J Neural Transm Suppl. 2007;(72):189-93. Alpha-lipoic acid as a new treatment option for Alzheimer’s disease–a 48 months follow-up analysis. Hager K, Kenklies M, McAfoose J, Engel J, Münch G. Department of Medical Rehabilitation and Geriatrics, Henriettenstiftung, Hannover, Germany.
(Back) Free Radic Biol Med. 2007 Feb 1;42(3):371-84. Epub 2006 Nov 10. Involvement of PI3K/PKG/ERK1/2 signaling pathways in cortical neurons to trigger protection by cotreatment of acetyl-L-carnitine and alpha-lipoic acid against HNEmediated oxidative stress and neurotoxicity: implications for Alzheimer’s disease. Abdul HM, Butterfield DA. Department of Chemistry, Center of Membrane Sciences, University of Kentucky, Lexington, KY 40506-0055, USA.
(Back) Pharmacol Ther. 2007 Jan;113(1):154-64. Epub 2006 Sep 20. Lipoic acid as a novel treatment for Alzheimer’s disease and related dementias. Holmquist L, Stuchbury G, Berbaum K, Muscat S, Young S, Hager K, Engel J, Münch G. Department of Biochemistry and Molecular Biology and Comparative Genomics Centre, School of Pharmacy and Molecular Sciences, James Cook University, Townsville, Australia.
(Back) J Alzheimers Dis. 2003 Jun;5(3):229-39. Protection against amyloid beta peptide and iron/hydrogen peroxide toxicity by alpha lipoic acid. Lovell MA, Xie C, Xiong S, Markesbery WR. Sanders-Brown Center on Aging, University of Kentucky, 800 S. Limestone St., Lexington, KY 40536-0230, USA. malove2@pop.uky.edu
(Back) Neurobiol Aging. 2007 Feb;28(2):213-25. Epub 2006 Jan 31. Chronic dietary alpha-lipoic acid reduces deficits in hippocampal memory of aged Tg2576 mice. Quinn JF, Bussiere JR, Hammond RS, Montine TJ, Henson E, Jones RE, Stackman RW Jr. Portland Veterans Affairs Medical Center, P3 R&D; Portland, OR, United States.
(Back) 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 J. Institute for Brain Aging and Dementia, University of California, 1261 Gillespie Neuroscience Research Facility, Irvine, CA, 92697, USA, j.liu@uci.edu.
(Back) FASEB J. 2007 Nov;21(13):3756-62. Epub 2007 Jul 10. Acetyl-L-carnitine and alpha-lipoic acid supplementation of aged beagle dogs improves learning in two landmark discrimination tests. Milgram NW, Araujo JA, Hagen TM, Treadwell BV, Ames BN. University of Toronto, Division of Life Sciences, Scarborough, Ontario, Canada. milgram@psych.utoronto.ca
(Back) Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2356-61. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid. Liu J, Head E, Gharib AM, Yuan W, Ingersoll RT, Hagen TM, Cotman CW, Ames BN. Division of Biochemistry and Molecular Biology, University of California, Berkeley, CA 94720, USA.
(Back) Ann N Y Acad Sci. 2002 Apr;959:133-66. Delaying brain mitochondrial decay and aging with mitochondrial antioxidants and metabolites. Liu J, Atamna H, Kuratsune H, Ames BN. Division of Biochemistry and Molecular Biology, University of California, Berkeley, California 94720, USA.
(Back) FASEB J. 2007 Jul;21(9):2226-36. Epub 2007 Mar 16. Activation of apoptosis signal regulating kinase 1 (ASK1) and translocation of deathassociated protein, Daxx, in substantia nigra pars compacta in a mouse model of Parkinson’s disease: protection by alpha-lipoic acid. Karunakaran S, Diwakar L, Saeed U, Agarwal V, Ramakrishnan S, Iyengar S, Ravindranath V. Divisions of Molecular and Cellular Neuroscience, National Brain Research Centre, Nainwal Mode, Manesar, 122050, India.
(Back) Neurotoxicology. 2002 Oct;23(4-5):479-86. Pre-treatment with R-lipoic acid alleviates the effects of GSH depletion in PC12 cells: implications for Parkinson’s disease therapy. Bharat S, Cochran BC, Hsu M, Liu J, Ames BN, Andersen JK. Buck Institute for Age Research, Novato, CA 94945, USA. bsrinivas@buckinstitute.org
(Back) Biochem Biophys Res Commun. 2007 Mar 2;354(1):259-64. Epub 2007 Jan 3. Lipoic acid stimulates cAMP production in T lymphocytes and NK cells. Schillace RV, Pisenti N, Pattamanuch N, Galligan S, Marracci GH, Bourdette DN, Carr DW. Portland Veterans Affairs Medical Center and Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA.
(Back) J Immunol. 2006 Aug 15;177(4):2630-7. Lipoic acid affects cellular migration into the central nervous system and stabilizes blood-brain barrier integrity. Schreibelt G, Musters RJ, Reijerkerk A, de Groot LR, van der Pol SM, Hendrikx EM, Döpp ED, Dijkstra CD, Drukarch B, de Vries HE. Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.
(Back) Mult Scler. 2005 Apr;11(2):159-65. Lipoic acid in multiple sclerosis: a pilot study. Yadav V, Marracci G, Lovera J, Woodward W, Bogardus K, Marquardt W, Shinto L, Morris C, Bourdette D. Department of Veterans Affairs Medical Center, Portland, OR, USA.
(Back) J Neuroimmunol. 2004 Mar;148(1-2):146-53. Alpha-lipoic acid is effective in prevention and treatment of experimental autoimmune encephalomyelitis. Morini M, Roccatagliata L, Dell’Eva R, Pedemonte E, Furlan R, Minghelli S, Giunti D, Pfeffer U, Marchese M, Noonan D, Mancardi G, Albini A, Uccelli A. Molecular Oncology Laboratory, National Cancer Research Institute, Genoa, Italy.
(Back) Zhonghua Yi Xue Za Zhi. 2007 Oct 16;87(38):2706-9. [Curative effect of alpha-lipoic acid on peripheral neuropathy in type 2 diabetes: a clinical study] Liu F, Zhang Y, Yang M, Liu B, Shen YD, Jia WP, Xiang KS. Zhonghua Yi Xue Za Zhi. 2007 Oct 16;87(38):2706-9. [Curative effect of alpha-lipoic acid on peripheral neuropathy in type 2 diabetes: a clinical study] Liu F, Zhang Y, Yang M, Liu B, Shen YD, Jia WP, Xiang KS. (PubMed)
(Back) Diabet Med. 2007 Sep;24(9):1034-8. Epub 2007 May 8. read Links The effect of alpha-lipoic acid on symptoms and skin blood flow in diabetic neuropathy. Jin HY, Joung SJ, Park JH, Baek HS, Park TS. Division of Endocrinology and Metabolism, Department of Internal Medicine, Chonbuk National University, Medical School, Jeon-ju, South Korea.
(Back) Diabetes Educ. 2007 Jan-Feb;33(1):111-7. Efficacy and safety of alpha-lipoic acid supplementation in the treatment of symptomatic diabetic neuropathy. Foster TS. University of Medicine and Dentistry of New Jersey, Graduate Program in Clinical Nutrition, Department of Primary Care, Newark, NJ, USA. tlsteww@hotmail.com
(Back) Ann N Y Acad Sci. 2006 Nov;1084:250-66. Treatment of diabetic polyneuropathy: Update 2006. Ziegler D. German Diabetes Clinic, German Diabetes Center, Leibniz Institute at the Heinrich Heine University, WHO Collaborating Center in Diabetes, European Training Center in Endocrinology and Metabolism, Düsseldorf, Germany. dan.ziegler@ddz.uniduesseldorf.de
(Back) Diabetes Care. 2006 Nov;29(11):2365-70. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Ziegler D, Ametov A, Barinov A, Dyck PJ, Gurieva I, Low PA, Munzel U, Yakhno N, Raz I, Novosadova M, Maus J, Samigullin R. FRCPE, Deutsche Diabetes-Klinik, Deutsches Diabetes-Zentrum, Leibniz-Institut an der Heinrich-Heine-Universität, Auf#39;m Hennekamp 65, 40225 Düsseldorf, Germany. dan.ziegler@ddz.uni-duesseldorf.de
(Back) Br J Pharmacol. 2007 Oct 1 Effects of alpha-lipoic acid on endothelial function in aged diabetic and high-fat fed rats. Sena CM, Nunes E, Louro T, Proença T, Fernandes R, Boarder MR, Seiça RM. Institute of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal [2] 2Center for Neurosciences and Cell Biology of Coimbra, University of Coimbra, Coimbra, Portugal.
(Back) Am J Nephrol. 2007;27(1):70-4. Epub 2007 Jan 26. Effects of alpha-lipoic acid on the plasma levels of asymmetric dimethylarginine in diabetic end-stage renal disease patients on hemodialysis: a pilot study. Chang JW, Lee EK, Kim TH, Min WK, Chun S, Lee KU, Kim SB, Park JS. Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
(Back) Diabetes. 2006 Aug;55(8):2238-44. alpha-Lipoic acid prevents the increase in atherosclerosis induced by diabetes in apolipoprotein E-deficient mice fed high-fat/low-cholesterol diet. Yi X, Maeda N. Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, 701 Brinkhous-Bullitt Bldg., 27599-7525, USA.
(Back) Eur Surg Res. 2007;39(6):325-31. Epub 2007 Jul 2. Hepatocellular injury of nonischemic liver tissue after selective clamping in rats– protective action by pharmacological pretreatment with lipoic acid. Duenschede F, Westermann S, Miesner I, Albrecht-Schöck S, Kneist W, Korenkov M, Schad A, Dutkowski P, Kiemer AK, Junginger T. Department of General and Abdominal Surgery, University Hospital Mainz, Mainz, Germany. duenschede@ach.klinik.uni-mainz.de
(Back) Mol Cell Biochem. 2005 Apr;272(1-2):179-85. Mitigation of oxidative stress in cyclophosphamide-challenged hepatic tissue by DLalpha- lipoic acid. Selvakumar E, Prahalathan C, Mythili Y, Varalakshmi P. Department of Medical Biochemistry, Dr A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, India.
(Back) Toxicology. 2006 Jan 5;217(1):71-8. Epub 2005 Oct 3. Chemoprotective effect of lipoic acid against cyclophosphamide-induced changes in the rat sperm. Selvakumar E, Prahalathan C, Sudharsan PT, Varalakshmi P. Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, Tamil Nadu, India.
(Back) Pharmacol Res. 2003 Dec;48(6):585-91. Prophylaxis against lipopolysaccharide-induced liver injuries by lipoic acid in rats. Suntres ZE. Health Hazards Group, Operational Medicine Section, Defence Research and Development Canada-Toronto, 1133 Sheppard Avenue West, Toronto, Ont, Canada M3M 3B9. Zach.Suntres@drdc-rddc.gc.ca
(Back) Free Radic Biol Med. 1998 Apr;24(6):1023-39. Alpha-lipoic acid in liver metabolism and disease. Bustamante J, Lodge JK, Marcocci L, Tritschler HJ, Packer L, Rihn BH. Department of Molecular and Cell Biology, University of California, Berkeley 94720- 3200, USA.
(Back) Int Immunopharmacol. 2008 Feb;8(2):362-70. Epub 2007 Nov 29. Alpha-lipoic acid inhibits TNF-alpha induced NF-kappaB activation through blocking of MEKK1-MKK4-IKK signaling cascades. Lee CK, Lee EY, Kim YG, Mun SH, Moon HB, Yoo B. Division of Allergy and Rheumatology, Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea.
(Back) Int Immunopharmacol. 2008 Feb;8(2):362-70. Epub 2007 Nov 29. Alpha-lipoic acid inhibits TNF-alpha induced NF-kappaB activation through blocking of MEKK1-MKK4-IKK signaling cascades. Lee CK, Lee EY, Kim YG, Mun SH, Moon HB, Yoo B. Division of Allergy and Rheumatology, Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea.
(Back) Rheumatol Int. 2007 Jan;27(3):225-33. Epub 2006 Aug 31. Alpha-lipoic acid suppresses the development of collagen-induced arthritis and protects against bone destruction in mice. Lee EY, Lee CK, Lee KU, Park JY, Cho KJ, Cho YS, Lee HR, Moon SH, Moon HB, Yoo B. Division of Allergy and Rheumatology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 138-736, Republic of Korea.
(Back) Br J Pharmacol. 2007 Oct 1 Effects of alpha-lipoic acid on endothelial function in aged diabetic and high-fat fed rats. Sena CM, Nunes E, Louro T, Proença T, Fernandes R, Boarder MR, Seiça RM. Institute of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal [2] 2Center for Neurosciences and Cell Biology of Coimbra, University of Coimbra, Coimbra, Portugal.
(Back) Rev Port Cardiol. 2007 Jun;26(6):609-19. Endothelial dysfunction in type 2 diabetes: effect of antioxidants. Sena CM, Nunes E, Louro T, Proença T, Seiça RM. Instituto de Fisiologia, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal.
(Back) J Altern Complement Med. 2007 Jun;13(5):577-84. Effects of alpha-lipoic acid supplementation in peripheral arterial disease: a pilot study. Vincent HK, Bourguignon CM, Vincent KR, Taylor AG. Center for the Study of Complementary and Alternative Therapies, University of Virginia Health System, Charlottesville, VA, USA. vincehk@ortho.ufl.edu
(Back) J Clin Hypertens (Greenwich). 2007 Apr;9(4):249-55. Effect of combined treatment with alpha-Lipoic acid and acetyl-L-carnitine on vascular function and blood pressure in patients with coronary artery disease. McMackin CJ, Widlansky ME, Hamburg NM, Huang AL, Weller S, Holbrook M, Gokce N, Hagen TM, Keaney JF Jr, Vita JA. Evans Department of Medicine and Whitaker Cardovascular Institute, Boston University School of Medicine, Boston, MA, USA.

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