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Alpha‐Lipoic Acid Effects And Combination Therapy With Gamma‐Linolenic Acid
Author(s) -
Cameron Ne,
Cotter Ma
Publication year - 2000
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1046/j.1529-8027.2000.abstracts-4.x
Subject(s) - endocrinology , medicine , diabetes mellitus , gamma linolenic acid , lipoic acid , von willebrand factor , nitric oxide , diabetic neuropathy , chemistry , fatty acid , polyunsaturated fatty acid , platelet , biochemistry , antioxidant
Alpha‐lipoic acid (LPA) has marked effects in experimental diabetic neuropathy. Treatment for 2 weeks after 8 weeks of diabetes in rats corrected motor and sensory conduction velocity and endoneurial perfusion deficits with an ED 50 of approximately 40 mg/kg. There was no difference in efficacy between R‐ and S‐enantiomers of LPA. When combined with the n‐6 essential fatty acid, gamma‐linolenic acid (GLA), either as a drug mixture or joint compound, there was a synergistic effect on neurovascular function, resulting in a 6‐fold increase in treatment efficacy. LPA has wide‐ranging actions on markers of endothelial damage, the coagulation system and lipids that are important risk factors for neuropathy and vascular disease in patients. Thus, 2 months of diabetes in rats caused 2.5‐ to 5.4‐fold elevations of von Willebrand factor, factor VII, triglycerides and LDL cholesterol, which were 41‐64% attenuated by 2 weeks of LPA treatment. Vascular effects are not restricted to endoneurial perfusion. Thus, the time taken for a fixed‐volume tail‐bleed was 4.2‐fold greater with diabetes and this was 79% attenuated by LPA treatment. Nitric oxide and endothelium‐derived hyperpolarizing factor dependent vasodilation were markedly reduced by diabetes in corpus cavernosum and mesenteric vasculature, LPA giving a high degree of protection. The function of small nerve fibres, exemplified by the nitrergic vasodilator innervation to corpus cavernosum, is greatly diminished by diabetes, high‐dose LPA having a protective effect. When LPA was combined with GLA, as for large fibres, there was a marked synergy for both the innervation and the endothelium of corpus cavernosum. Thus LPA alone, and particularly combined with GLA, has a broad spectrum of action highly relevant for the treatment of diabetic neuropathy and micro and macrovascular disease.