ALA and Atherosclerosis-Heart Disease, Strokes, Blood Vessel Health
Oxidative stress is considered to be the primary cause in many cardiovascular diseases, including atherosclerosis.42 As we age, oxidative stress increases through an increase in the production of reactive oxygen species and/or a decrease in the body’s antioxidant defenses. This increase in oxidative stress is paralleled by an increase in cardiovascular conditions like atherosclerosis. Research demonstrates that antioxidants help to decrease the incidence of atherosclerosis. ALA exerts potent antioxidant effects on the body and has been studied in experimental models for its ability to prevent and reverse atherosclerosis.
In one study, Watanabe heritable hyperlipidemic rabbits were fed with high cholesterol chow for 6 weeks and then randomized to receive either high cholesterol diet alone or high cholesterol diet combined with 20 mg/kg/day of ALA for 12 weeks.43 At the end of the 12 weeks, researchers found that ALA decreased body weight by 15 ± 5% without alterations in lipid parameters and reduced atherosclerotic plaque in the abdominal aorta with morphological analysis revealing reduced lipid and inflammatory cell content. Furthermore, ALA improved vascular reactivity (as revealed by decreased constriction to angiotensin II and increased relaxation to acetylcholine and insulin), inhibited NF-κB activation, and decreased oxidative stress and expression of key adhesion molecules in the vasculature.
An unrelated study demonstrated the cardioprotective effects of ALA. Eighteen adult male New Zealand White rabbits were randomly assigned to three groups for 10 weeks. One group was fed with normal chow (control group), one was fed with a 1% high cholesterol diet to induce hypercholesterolemia, and the third group was fed a 1% high cholesterol diet plus 4.2 mg/body weight of ALA. At the end of the study, blood total cholesterol (TCHOL) and lowdensity lipoprotein (LDL) levels were found to be significantly lower in the ALA group compared to that of the group that consumed a high cholesterol diet alone. The ALA group also had less atherosclerotic plaque in their aortas than the group that consumed a high cholesterol diet alone, leading researchers to conclude that, apart from its antioxidant activity, ALA may also exert a lipid-lowering effect on TCHOL and LDL levels and may reduce atherosclerosis formation in rabbits fed a high cholesterol diet.
A similarly designed study conducted on streptozotocin-induced diabetic mice models revealed that ALA completely prevented the increase in TCHOL, atherosclerotic lesions, and the general decline in health typically observed with diabetes, suggesting that ALA is a promising protective agent for reducing cardiovascular complications of diabetes.44
1. Paolisso G, D’Amore A, Volpe C, Balbi V, Saccomanno F, Galzerano D, Giugliano D, Varricchio M, D’Onofrio F. Evidence for a relationship between oxidative stress and insulin action in non-insulin-dependent (type II) diabetic patients. Metabolism. 1994;43:1426–9.
2. Rochette L, Ghibu S, Muresan A, Vergely C. Alpha-lipoic acid: molecular mechanisms and therapeutic potential in diabetes. Can J Physiol Pharmacol. 2015;93(12):1021-7.
3. Akbari M., Ostadmohammadi V., Tabrizi R., et al. The effects of alpha-lipoic acid supplementation on inflammatory markers among patients with metabolic syndrome and related disorders: a systematic review and meta-analysis of randomized controlled trials. Nutrition and Metabolism. 2018;15(1).
4. Konrad T, Vicini P, Kusterer K, Hoflich A, Assadkhani A, Bohles HJ, Sewell A, Tritschler HJ, Cobelli C, Usadel KH. Alpha-lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with type 2 diabetes. Diabetes Care. 1999;22: 280–7.
5. Ziegler D, Gries FA. Alpha-lipoic acid in the treatment of diabetic peripheral and cardiac autonomic neuropathy. Diabetes. 1997;46 Suppl 2:S62-6.
6. Jacob S, Henriksen EJ, Schiemann AL, Simon I, Clancy DE, Tritschler HJ, Jung WI, Augustin HJ, Dietze GJ. Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid. Arzneimittel-Forschung. 1995;45:872–874.
7. Jacob S, Henriksen EJ, Tritschler HJ, Augustin HJ, Dietze GJ. Improvement of insulinstimulated glucose-disposal in type 2 diabetes after repeated parenteral administration of thioctic acid. Exp Clin Endocrinol Diabetes. 1996;104:284–288.
8. Jacob S, Ruus P, Hermann R, Tritschler HJ, Maerker E, Renn W, Augustin HJ, Dietze GJ, Rett K. Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial. Free Rad Biol Med. 1999;27:309–14.
9. Evans JL, Goldfine ID. Alpha-lipoic acid: a multifunctional antioxidant that improves insulin sensitivity in patients with type 2 diabetes. Diabetes Technol Ther. 2000;2(3):401- 13.
10. Palacios-Sánchez B, Moreno-López LA, Cerero-Lapiedra R, Llamas-Martínez S, Esparza-Gómez G. Alpha lipoic acid efficacy in burning mouth syndrome. A controlled clinical trial. Med Oral Patol Oral Cir Bucal. 2015;20(4):e435–e440.
11. Femiano F, Scully C. Burning mouth syndrome (BMS): double blind controlled study of alpha-lipoic acid (thioctic acid) therapy. J Oral Pathol Med. 2002;31(5):267-9.
12. Carbone M, Pentenero M, Carrozzo M, Ippolito A, Gandolfo S. Lack of efficacy of alpha-lipoic acid in burning mouth syndrome: a double-blind, randomized, placebocontrolled study. Eur J Pain. 2009;13(5):492-6.
13. López-Jornet P, Camacho-Alonso F, Leon-Espinosa S. Efficacy of alpha lipoic acid in burning mouth syndrome: a randomized, placebo-treatment study. J Oral Rehabil. 2009;36(1):52-7.
14. Femiano F, Gombos F, Scully C, Busciolano M, De Luca P. Burning mouth syndrome (BMS): controlled open trial of the efficacy of alpha-lipoic acid (thioctic acid) on symptomatology. Oral Dis. 2000;6(5):274-7.
15. Steele JC, Bruce AJ, Drage LA, Rogers RS 3rd. Alpha-lipoic acid treatment of 31 patients with sore, burning mouth. Oral Dis. 2008;14(6):529-32.
16. Femiano F, Gombos F, Scully C. Burning mouth syndrome: the efficacy of lipoic acid on subgroups. J Eur Acad Dermatol Venereol. 2004;18(6):676-8.
17. Fatima G, Das SK, Mahdi AA. Some oxidative and antioxidative parameters and their relationship with clinical symptoms in women with fibromyalgia syndrome. Int J Rheum Dis. 2017 Jan;20(1):39-45.
18. Coskun Benlidayi I. Role of inflammation in the pathogenesis and treatment of fibromyalgia. Rheumatol Int. 2019;39(5):781-91.
19. Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta. 2009;1790(10):1149–1160.
20. Yoshida K, Hirokawa J, Tagami S, Kawakami Y, Urata Y, Kondo T. Weakened cellular scavenging activity against oxidative stress in diabetes mellitus: regulation of glutathione synthesis and efflux. Diabetologia. 1995;38(2):201–210.
21. Wong A, Dukic-Stefanovic S, Gasic-Milenkovic J, Schinzel R, Wiesinger H, Riederer P, et al. Anti-inflammatory antioxidants attenuate the expression of inducible nitric oxide synthase mediated by advanced glycation endproducts in murine microglia. Eur J Neurosci. 2001;14:1961–1967.
22. Bierhaus A, Chevion S, Chevion M, Hofmann M, Quehenberger P, Illmer T, et al. Advanced glycation end product-induced activation of NF-kappaB is suppressed by alpha-lipoic acid in cultured endothelial cells. Diabetes. 1997;46:1481–1490.
23. Gilron I, Tu D, Holden R, et al. Innovations in the Management of Musculoskeletal Pain With Alpha-Lipoic Acid (IMPALA Trial): Study protocol for a Double-Blind, Randomized, Placebo-Controlled Crossover Trial of Alpha-Lipoic Acid for the Treatment of Fibromyalgia Pain. JMIR Res Protoc. 2017;6(3):e41.
24. Lee JS, Kim HG, Lee DS, Son CG. Oxidative Stress is a Convincing Contributor to Idiopathic Chronic Fatigue. Sci Rep. 2018;8(1):12890.
25. Morris G, Maes M. Oxidative and Nitrosative Stress and Immune-Inflammatory Pathways in Patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS). Curr Neuropharmacol. 2014;12(2):168–85.
26. Maes M. A new case definition of Neuro-Inflammatory and Oxidative Fatigue (NIOF), a neuroprogressive disorder, formerly known as chronic fatigue syndrome or Myalgic Encephalomyelitis: results of multivariate pattern recognition methods and external validation by neuro-immune biomarkers. Neuro Endocrinol Lett. 2015;36(4):320-9.
27. Myhill S, Booth NE, McLaren-Howard J. Chronic fatigue syndrome and mitochondrial dysfunction. Int J Clin Exp Med. 2009;2(1):1–16.
28. Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta. 2009;1790(10):1149–1160.
29. Solmonson A, DeBerardinis RJ. Lipoic acid metabolism and mitochondrial redox regulation. J Biol Chem. 2018;293(20):7522–30.
30. Vallianou N, Evangelopoulos A, Koutalas P. Alpha-lipoic Acid and diabetic neuropathy. Rev Diabet Stud. 2009;6(4):230–236.
31. Papazafeiropoulou A, Xourgia E, Papantoniou S, Trikkalinou A, Melidonis A. Effect of 3-month α-lipoic acid treatment on sural nerve conduction velocity and amplitude in patients with diabetic neuropathy: a pilot study. Arch Med Sci Atheroscler Dis. 2019;4:e141–e143.
32. 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):2365-70.
33. Agathos E, Tentolouris A, Eleftheriadou I, et al. Effect of α-lipoic acid on symptoms and quality of life in patients with painful diabetic neuropathy. J Int Med Res. 2018;46(5):1779–1790.
34. Mijnhout GS, Kollen BJ, Alkhalaf A, Kleefstra N, Bilo HJ. Alpha lipoic Acid for symptomatic peripheral neuropathy in patients with diabetes: a meta-analysis of randomized controlled trials. Int J Endocrinol. 2012;2012:456279.
35. Mijnhout GS, Alkhalaf A, Kleefstra N, Bilo HJ. Alpha lipoic acid: a new treatment for neuropathic pain in patients with diabetes? Neth J Med. 2010;68(4):158-62.
36. Nguyen N, Takemoto JK. A Case for Alpha-Lipoic Acid as an Alternative Treatment for Diabetic Polyneuropathy. J Pharm Pharm Sci. 2018;21(1s):177s-191s.
37. Feuerecker B, Pirsig S, Seidl C, et al. Lipoic acid inhibits cell proliferation of tumor cells in vitro and in vivo. Cancer Biol Ther. 2012;13(14):1425–35.
38. Na MH, Seo EY, Kim WK. Effects of alpha-lipoic acid on cell proliferation and apoptosis in MDA-MB-231 human breast cells. Nutr Res Pract. 2009;3(4):265–271.
39. Tripathy J, Tripathy A, Thangaraju M, Suar M, Elangovan S. α-Lipoic acid inhibits the migration and invasion of breast cancer cells through inhibition of TGFβ signaling. Life Sci. 2018;207:15-22.
40. Wenzel U, Nickel A, Daniel H. alpha-Lipoic acid induces apoptosis in human colon cancer cells by increasing mitochondrial respiration with a concomitant O2-*-generation. Apoptosis. 2005 Mar;10(2):359-68.
41. Yang L, Wen Y, Lv G, Lin Y, Tang J, Lu J, Zhang M, Liu W, Sun X. α-Lipoic acid inhibits human lung cancer cell proliferation through Grb2-mediated EGFR downregulation. Biochem Biophys Res Commun. 2017;494(1-2):325-31.
42. Skibska B, Goraca A. The Protective Effect of Lipoic Acid on Selected Cardiovascular Diseases Caused by Age-Related Oxidative Stress. Oxid Med Cell Longev. 2015;2015:313021.
43. Ying Z, Kherada N, Farrar B, et al. Lipoic acid effects on established atherosclerosis. Life Sci. 2010;86(3-4):95–102.
44. Yi X, Maeda N. alpha-Lipoic acid prevents the increase in atherosclerosis induced by diabetes in apolipoprotein E-deficient mice fed high-fat/low-cholesterol diet. Diabetes. 2006;55(8):2238-44.
45. Couch RC, Vigil M., Thomas MA, Sibert G. A dose escalation toxicity study of DL-6-8 thioctic acid (lipoic acid) in Rhesus monkeys. Annual Meeting of Toxicology; Cincinnati, Ohio; March12, 1997.
46. Vigil M, Berkson BM, Garcia AP. Adverse effects of high doses of intravenous alpha lipoic Acid on liver mitochondria. Glob Adv Health Med. 2014;3(1):25–27. doi:10.7453/gahmj.2013.011
47. Liu F, Zhang Y, Yang M, Liu B, Shen YD, Jia WP, Xiang KS. [Curative effect of alphalipoic acid on peripheral neuropathy in type 2 diabetes: a clinical study]. Zhonghua Yi Xue Za Zhi. 2007;87(38):2706-9.
49. Palacios-Sánchez B, Moreno-López LA, Cerero-Lapiedra R, Llamas-Martínez S, Esparza-Gómez G. Alpha lipoic acid efficacy in burning mouth syndrome. A controlled clinical trial. Med Oral Patol Oral Cir Bucal. 2015 Jul 1;20(4):e435-40. doi: 10.4317/medoral.20410. PMID: 26034927; PMCID: PMC4523256.
50. Sun A, Wu KM, Wang YP, Lin HP, Chen HM, Chiang CP. Burning mouth syndrome: a review and update. J Oral Pathol Med. 2013;42:649–55. [PubMed] [Google Scholar]
51. de Moraes M, do Amaral Bezerra BA, da Rocha Neto PC, de Oliveira Soares AC, Pinto LP, de Lisboa Lopes Costa A. Randomized trials for the treatment of burning mouth syndrome: an evidence-based review of the literature. J Oral Pathol Med. 2012;41:281–7. [PubMed] [Google Scholar]
52. Femiano F, Gombos F, Scully C, Busciolano M, De Luca P. Burning mouth syndrome (BMS): controlled open trial of the efficacy of alpha-lipoic acid (thioctic acid) on symptomatology. Oral Dis. 2000;6:274–7. [PubMed] [Google Scholar]
53. Femiano F, Scully C. Burning mouth syndrome (BMS): double blind controlled study of alpha-lipoic acid (thioctic acid) therapy. J Oral Pathol Med. 2002;31:267–9. [PubMed] [Google Scholar]
54. Femiano F, Gombos F, Esposito V, Nunziata M, Scully C. Burning mouth syndrome (BMS): an open trial of comparative efficacy of alpha-lipoic acid (thioctic acid) with other therapies. Minerva Stomatol. 2002;51:405–9. [PubMed] [Google Scholar]
55. Femiano F, Gombos F, Scully C. Burning mouth syndrome: the efficacy of lipoic acid on subgroups. J Eur Acad Dermatol Venereol. 2004;18:676–8. [PubMed] [Google Scholar]
56. Femiano F, Gombos F, Scully C. Síndrome de boca ardiente. Estudio de la psicoterapia, medicación con ácido alfa-lipoico y combinación de terapias. Med Oral. 2004;9:8–13. [PubMed] [Google Scholar]
57. López-D'alessandro E, Escovich L. Combination of alpha lipoic acid and gabapentin, its efficacy in the treatment of Burning Mouth Syndrome: a randomized, double-blind, placebo controlled trial. Med Oral Patol Oral Cir Bucal. 2011;16:e635–40. [PubMed] [Google Scholar]
58. Carbone M, Pentenero M, Carrozzo M, Ippolito A, Gandolfo S. Lack of efficacy of alpha-lipoic acid in burning mouth syndrome: a double-blind, randomized, placebo-controlled study. Eur J Pain. 2009;13:492–6. [PubMed] [Google Scholar]
59. López-Jornet P, Camacho-Alonso F, Leon-Espinosa S. Efficacy of alpha lipoic acid in burning mouth syndrome: a randomized, placebo-treatment study. J Oral Rehabil. 2009;36:52–7. [PubMed] [Google Scholar]
60. Cavalcanti DR, da Silveira FR. Alpha lipoic acid in burning mouth syndrome--a randomized double-blind placebo-controlled trial. J Oral Pathol Med. 2009;38:254–61. [PubMed] [Google Scholar]
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