Lipoic acid, a thiol, contains sulfur groups in a dithiol ring structure. After reduction by enzymes in the body to its dithiol form known as dihydrolipoic acid (DHLA), which has enhanced antioxidant activity, the source of its extraordinary power as a metabolic antioxidant.

Two general types of antioxidants operate in biological systems: those associated mainly with a lipophilic phase (e.g., membranes or lipoproteins such as vitamin E and ubiquinols) or those which operate in aqueous phase such as ascorbate, glutathione and thioredoxin.

Uniquely, lipoic acid as dihydrolipoate is able to interact with both phases and is a bridge between them.

While new to Americans, lipoic has a long history in Germany of safe use to treat diabetes complications. When present at sufficient concentrations, alpha lipoic acid acts as the anchor of the antioxidant network.

We chose to use alpha lipoic and its reduced form, DHLA, to investigate its action in the redox cycling antioxidant system.

Remarkable results were observed. DHLA readily regenerated vitamin C from its oxidized form in in vitro systems such as suspensions of human Low Density Lipoproteins (LDL), microsomal and mitochondrial membranes, and in tissues such as skin homogenates.

NETWORK ANTIOXIDANTS: THIOLS, VITAMIN C, VITAMIN E INTERACTION The two negative electron reduction potential of dihydrolipoate/a-lipoate couple is -0.32V, much stronger than that of reduced glutathione (GSH)/glutathione disulfide (GSSG) couple (-0.23V). THE ROLE OF LIPOATE IN REGENERATING VITAMIN C AND VITAMIN E

Glutathione is a protein which is easily digested, so glutathione levels cannot be effectively increased by oral supplementation. Pharmaceutical companies have long sought glutathione-boosting drugs, without significant success. Thus, we were delighted to find that a-lipoate boosted cellular glutathione levels. Levels of glutathione, the major cellular antioxidant in the body, decline with age. Low glutathione levels are associated with a higher incidence of diseases in the elderly. Glutathione concentrations are recognized as a predictor of susceptibility to disease, and as a marker of biological age.

1) Dihydrolipoate is able to directly reduce glutathione disulfide.

This increases levels of reduced glutathione which is the antioxidant and biologically active form required for antioxidant action and for glutathione transferase reactions.

2) Dihydrolipoate reduces cystine to cysteine.

Membrane transport of cysteine into the cells is limited when this amino acid is in its oxidized form (as cystine). When a-lipoate is added to cells, it reduces cystine to cysteine in the extracellular space. The cell membrane transport for the uptake of cysteine is about ten times faster than that of cystine, thus accelerating its uptake and increasing the cell's ability to synthesize glutathione.

3) Dihydrolipoate reduces oxidized thioredoxin to reduced thioredoxin, a signaling molecule.

Reduced thioredoxin is important in the binding of transcription factors to DNA and thus is necessary for gene expression

 

Dihydrolipoate acid recycles the major cell antioxidants - Vitamin C, Vitamin E, Glutathione, Thioredoxin and Ubiquinone

Lipoate, in its reduced form, DHLA, is the driving force for maintaining high concentrations of the reduced antioxidant (potent) forms of the major cellular antioxidants such as glutathione, thioredoxin and ascorbic acid in the aqueous phase, and vitamin E and ubiquinol in membranes or lipoproteins. The amount of alpha lipoic acid naturally present in the body may not be adequate to obtain the antioxidant benefits. Increasing the amount of alpha lipoic acid through dietary supplementation can help to perform this vital function. All these attributes make alpha lipoic acid the metabolic antioxidant par excellence.