How does tranexamic acid act on the skin?

Discovered in the 1950s, tranexamic acid is a structurally similar derivative of the amino acid lysine. It is a molecule composed of a carboxylic acid function and an aminomethyl function, both branched on a cyclohexane (C8H15NO2). It was initially used in the medical field for its ability to inhibit fibrinolysis, a physiological mechanism of blood clot dissolution. Taken orally, it can regulate excessive bleeding induced by events such as severe trauma, surgical procedures, postpartum haemorrhages, and heavy menstruation. This use is based on its coagulating abilities, which help to reduce blood loss.

It is noteworthy that tranexamic acid is listed on the World Health Organisation's (WHO) list of essential medicines. However, it was only recently, in 2009, that it was authorised and incorporated into cosmetic product formulations by the Cosmetology Commission. Thanks to its depigmenting action, this acid has the notable ability to reduce the appearance of various forms of skin hyperpigmentation, such as melasma, post-inflammatory hyperpigmented marks and sun spots.

By acting in this way, it promotes a clearer complexion by limiting the production of melanin. Studies have even suggested that the effectiveness of tranexamic acid could be comparable to that of thehydroquinone, an active ingredient widely used in this context. Furthermore, this acid is also sought after for its anti-inflammatory properties.

When applied topically in skincare products, tranexamic acid is generally well tolerated and does not cause major side effects However, in rare cases, it could cause temporary reactions, such as redness or itching. For this reason, it is recommended to perform a patch test by applying the product to a small area of the body upon first use.

Tranexamic acid possesses properties to combat hyperpigmentation by acting on two levels: on tyrosinase and on plasminogen.

By what molecular mechanism does tranexamic acid act on hyperpigmentation?

The effectiveness of the anti-brown spot activity of tranexamic acid through topical application is partly attributable to its mechanism of action, whereby the activation of melanocytes is inhibited by the anti-plasmin action of tranexamic acid in the skin.

The Urokinase-type plasminogen activator (uPA), which plays a role in the transformation of plasminogen into plasmin, is a naturally occurring double-strand enzyme in human epidermal keratinocytes. These cells produce pro-uPA, a single-strand precursor of uPA without enzymatic activity. Given that cultured human melanocytes generate a limited or even non-existent amount of pro-uPA, research indicates that these melanocytes are stimulated by the action of uPA from the epidermal keratinocytes and plasminogen from the dermal vascular system.

This process occurs at the level of the basal layer of the epidermis. Hyperpigmented regions reveal a co-expression of tyrosinase mRNA and pro-uPA, suggesting an involvement of the uPA/plasminogen system at the basal layer of the epidermis in the hyperpigmentation mechanism. Tranexamic acid is capable of forming a reversible and highly specific complex with the lysine binding sites of plasminogen and plasminogen activator, thus inhibiting their binding to the cell membrane. This allows for the inhibition of the conversion of plasminogen into plasmin, inhibiting the production of pro-uPA and thus the stimulation of melanocytes.

Tranexamic acid can also interact with tyrosinase, an enzyme that catalyses the oxidation of tyrosine to produce melanin. The structure of tyrosinase varies across different species, but it includes a central domain composed of six histidine residues. Its structure is similar to that of tranexamic acid, which can competitively bind to its receptor and act as an antagonist of the enzyme.

Tranexamic acid can thus block the activity of tyrosinase by acting as an antagonist, but it can also halt its activity through the inhibition of the plasminogen/plasmin system, which results in the blocking of interactions between melanocytes and keratinocytes. Therefore, tranexamic acid has a anti-plasmin effect, an anti-tyrosinase activity which can be beneficial in reducing sensitivity to hyperpigmentation.