Introduction
Emmanuel Opara in NUTRITION and DIABETES, 2005
In experimental animals, a wide variety of antioxidants, including vitamin E (95), probucol (21), α-lipoic acid (76), butylated hydroxytoluene (22), carvedilol (29), glutathione (19), desferroxamine (30), and N-acetylcysteine (83), slow the progression of neuropathy. Vitamin E (53) and a combination of vitamin E and N-acetyl-cysteine (58) protect the pancreas from the effects of chronic hyperglycemia in experimental animals. The vast majority of human studies have involved α-lipoic acid. This interesting and versatile antioxidant is well-tolerated clinically and has been extensively studied, as discussed by Russell and Kamisnsky in chapter 21. α-Lipoic acid is reduced in vivo to dihydrolipoate, which is able to regenerate multiple other antioxidants, including reduced glutathione, vitamin C, and vitamin E (76). This enhances nitric-oxide bioavailability, suppresses peroxynitrite-induced endothelial damage, and dramatically improves peripheral-nerve function in diabetic rats (28). Clinical trials, however, have revealed that α-lipoic acid leads to only a modest improvement in symptoms (100), and the benefits are marginal unless the drug is given intravenously (93). The drug leads to only minor improvements in objective measures of somatosensory (93, 100) and autonomic function (101). These disappointing results may stem from the fact that the trials have been performed in patients with long-standing diabetes who have irreversible nerve damage. Alternatively, it is possible that oxidative stress is less important clinically than it is in experimental animals.
Cardiovascular Disease and Oxidative Stress
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
Experimental therapeutic agents in pre-clinical drug development focus on a broad spectrum with transition-state inhibitors, stabilizing agents and targeted drugs against various diseases. There are experimental therapeutics focused towards CVD and associated causes of oxidative stress and one experimental therapeutic group of compounds constantly being studied and tested are antioxidants. Yet, there are limitations on experimental therapeutic agents because the pathophysiology for specific CVDs are not addressed and analyzed (Sovari and Dudley, 2012), such as ion channel blockage of sodium channels and limitations on the catheter ablation that is used for tissue destruction for blocking focal activity (Xiao, 2011). Several experimental drugs are being tested as therapeutic agents to lessen the effect of oxidative stress species in various experimental cell-based and animal models of cardiovascular disease (Table 7.6) and their potential preclinical use assessed in many clinical trials (Table 7.7). Currently there are three sources of experimental therapeutic drugs that have been approved in combating oxidative stress species in CVD. Quercetin is a polyphenolic flavonoid found originally in plants. It is a dietary antioxidant that comes from fruits, vegetables, leaves and grains. Rhein is an anthraquinone that is obtained from the rhubarb plant and considered to be one of many medicinal plants. Lipoic acid is an organosulphur compound that is naturally produced within the body and essential for metabolism, though it can be administered from an external source as well.
Alpha-lipoic acid (ALA)
Linda M. Castell, Samantha J. Stear (Nottingham), Louise M. Burke in Nutritional Supplements in Sport, Exercise and Health, 2015
Alpha-lipoic acid, not to be confused with alpha-linoleic acid, is a mitochondrial fatty acid that acts as an antioxidant and is also involved in a range of cellular actions as a metal chelator and mediator of cell signalling pathways. It is produced endogenously in small amounts and is also supplied via the diet by foods including red meat (specifically organ meat) and some fruits and vegetables (Shay et al., 2009). Supplementation of alpha-lipoic acid has been shown to reduce symptoms in patients with diabetic neuropathy, but more human trials are needed to determine potential benefits for neurological disorders, weight loss and other chronic inflammatory conditions (Golbidi et al., 2011).
Effect of Curcumin and α-Lipoic Acid in Attenuating Weight Gain and Adiposity
Published in Journal of the American College of Nutrition, 2019
Evgeniy Panzhinskiy, Raza Bashir, Debasis Bagchi, Sreejayan Nair
α-lipoic acid (thioctic acid, 5-(1,2-dithiolan-3-yl) pentanoic acid) is a naturally occurring antioxidant that also serves as a cofactor for mitochondrial respiration in vivo (9, 13). Several studies in rodents have demonstrated that supplementation with α-lipoic acid promotes weight loss and reduces body fat mass (9, 13–18). A recent systematic review of 12 placebo-controlled clinical trials showed that supplementation with α-lipoic acid slightly but significantly decreased body weight and body mass index compared to placebo (19, 20).
Targeting oxidative stress through antioxidants in diabetes mellitus
Published in Journal of Drug Targeting, 2018
Parul Thakur, Ashwini Kumar, Awanish Kumar
α-Lipoic acid is a hydrophilic antioxidant and can exert beneficial effects in both aqueous and lipid environments. α-Lipoic acid is reduced to another active compound dihydrolipoate. Dihydrolipoate is able to regenerate other antioxidants such as vitamin C, vitamin E and reduced glutathione through redox cycling [46]. Although α-lipoic acid functions as a cofactor for some mitochondrial dehydrogenases, it also acts as a metal chelator and antioxidant [47].
Effect of d -chiro-inositol and alpha-lipoic acid combination on COH outcomes in overweight/obese PCOS women
Published in Gynecological Endocrinology, 2020
Paolo Giovanni Artini, Maria Elena Rosa Obino, Elisabetta Micelli, Elisa Malacarne, Chiara Vacca, Francesca Papini, Vito Cela
Oxidative stress is reported to be increased in PCOS [16] and it is related to central obesity, age, blood pressure, serum glucose, insulin and triglyceride levels and IR [17,18]. Alpha-lipoic acid (ALA) is a powerful antioxidant, and the controlled release of ALA has been reported to improve glucose control in type 2 diabetes patients [16], and in PCOS, to improve insulin sensitivity and metabolic disorders [19].
Related Knowledge Centers
- Antioxidant
- Caprylic Acid
- Cellular Respiration
- Cofactor
- Dietary Supplement
- Disulfide
- Enantiomer
- Organosulfur Chemistry
- Medication
- Conjugate