Alpha-Lipoic Acid

What is alpha-lipoic acid?

Alpha-lipoic acid, also known as lipoic acid or thiotic acid, is a naturally occurring compound that is produced in small amounts by both plants and animals, including humans (R, R). There are 2 optical isomers of alpha-lipoic acid, but only the R-isomer is synthesised endogenously. It is this R-isomer that is found in food, bound covalently to the amino acid lysine to form lipoyllysine. The liver, heart and kidney tissues of animals contain the highest amount of lipoyllysine (R, R), while vegetables rich in lipoyllysine include broccoli and spinach (R).

Functionally, alpha lipoic acid is an essential cofactor for several mitochondrial multienzyme complexes and plays a fundamental role in the breakdown of various alpha keto-acids and amino acids (R, R). It also has antioxidant properties, being able to chelate metals and scavenge reactive oxygen species, and its reduced form has the ability to regenerate endogenous antioxidants (R).

Is alpha-lipoic acid stable?

The distorted five-membered ring of alpha-lipoic acid makes it quite vulnerable to UV radiation (R, R). Upon exposure to UV light, alpha-lipoic acid is easily decomposed (R, R) and its degradation products possess an unpleasant odour (R), which complicates the preparation of cosmetic formulations suitable for topical use (R).

Studies indicate that the presence of retinyl palmitate, ascorbyl palmitate or butylhydroxytoluene favours the chemical stability of alpha-lipoic acid, but that tocopheryl acetate does not protect alpha lipoic acid from degradation (R, R). The amino acid homocysteine has also been shown to protect against the degradation of alpha-lipoic acid slightly and more importantly, to regenerate alpha-lipoic acid after UV irradiation (R).

Nanoencapsulation also increases the stability of alpha lipoic acid (R, R).

Does alpha-lipoic acid get absorbed?

Alpha-lipoic acid is lipophilic and has a low molecular weight, characteristics that enable it to readily penetrate the stratum corneum. In a study on mice, the maximum concentration of alpha-lipoic acid in the skin was reached 2 hours after application, with 95% in the stratum corneum, 1% in the epidermis and 4% in the dermis and subcutaneous layers (R). 30% to 80% of alpha-lipoic acid was also demonstrated to successfully penetrate pig skin in vitro, with formulations of water/oil emulsions and penetration enhancers such as phytantriol aiding permeation (R).

A study on cutaneous delivery using microemulsions found that they did not affect the penetration of alpha-lipoic acid despite disrupting the skin barrier (R). However, the amount of alpha-lipoic acid distributed to the skin increased when it was loaded in lipid nanocapsules (R).

What happens after alpha-lipoic acid is absorbed?

After its delivery into the skin, a proportion of alpha-lipoic acid is reduced to dihydrolipoic acid (R).