Tranexamic Acid: What are the Benefits for the Skin?

In 1979, a dermatologist accidentally discovered that tranexamic acid could have an unusual effect on the skin. He observed that the complexion of one of his patients treated for chronic hives brightened and evened out. This observation paved the way for the study of this ingredient in skin pigmentation disorders.

While its initial use is medical as an anti-fibrinolytic agent to reduce bleeding, tranexamic acid (TXA) is now attracting increasing interest for its targeted action on pigmentary irregularities, whether caused by sun exposure, hormonal changes, or inflammation, for a more radiant and even complexion.

Several studies have confirmed the effectiveness of tranexamic acid in managing hyperpigmentation, particularly when administered orally, showing more pronounced results. However, its topical application, usually between 2 and 5%, offers a significantly more favorable safety profile, as it eliminates the potential thrombosis risks associated with oral use. Research has shown that at these concentrations, no detectable systemic absorption is observed, thereby limiting concerns related to the pro-coagulant properties of the molecule.

The tranexamic acid is regarded as a brightening agent rather than a lightening one. It is intended to reduce unwanted pigmentation spots.

In 2019, it was demonstrated in a double-blind clinical trial published in the Journal of Research in Medical Sciences that the topical application of a 5% tranexamic acid solution is just as effective as a 3% hydroquinonesolution, the absolute benchmark in hyperpigmentation treatment, for reducing the appearance of melasma but with a better safety profile. After 12 weeks of treatment, melasma severity decreased by 27% in the tranexamic acid group, a result comparable to the hydroquinone group, without the adverse effects.

Of course, it's not necessary to have melasma to use tranexamic acid. It may also help to reduce sunspots from UV exposure, which can occur even with diligent sunscreen use, or the appearance of brown marks that can appear after a blemish resolves (post-inflammatory hyperpigmentation).

The tranexamic acid can be used all year round, including in summer. It does not increase skin sensitivity to the sun, although daily application of a sunscreen remains essential to prevent the appearance of new spots.

However, due to its hydrophilic nature and strong affinity for hydrogen bonds, its penetration into the skin is limited. This is why complementary techniques like intradermal injections, microneedling, or optimized formulations are often explored to enhance its effectiveness.

What is the mechanism of action by which tranexamic acid evens skin tone?

The dark spots result from a localized overproduction of melanin. Reducing this synthesis is thus a key lever for unifying the complexion. Unlike AHAs or other well-known skin-brightening agents (such as kojic acid or arbutin), tranexamic acid has a unique mechanism of action by working at multiple complementary levels to unify the complexion:

• When applied topically, tranexamic acid acts as a competitive inhibitor by binding to lysine sites on plasminogen, preventing its conversion into plasmin within keratinocytes—a process triggered primarily by UV exposure or inflammation. This inhibition limits the production of arachidonic acid, an increase of which activates tyrosinase (a key enzyme in melanogenesis) and stimulates melanin synthesis through its metabolite, prostaglandin E2. By curbing these signals, tranexamic acid slows the activation of melanocytes and thus helps mitigate pigmentary disorders.

• By inhibiting the conversion of plasminogen to plasmin, tranexamic acid also reduces the release of basic fibroblast growth factor (bFGF), a potent growth factor for melanocytes.

• Tranexamic acid also blocks the Sc-uPA pathway (Single-chain urokinase Plasminogen Activator), thereby reducing the increase in size and number of dendrites in melanocytes as well as tyrosinase activity.

• Data in vitro have also shown that tranexamic acid inhibits the activation of vascular endothelial growth factor receptors (VEGFR-1 and VEGFR-2) in melanocytes, thereby reducing the subsequent expression of key proteins involved in melanogenesis like tyrosinase. This mechanism also helps to decrease melanin production.

• Due to its structure analogous to tyrosine, tranexamic acid might also directly inhibit tyrosinase activity through a competitive mechanism.

We understand how vital an intact skin barrier is: it limits water loss, protects the skin from external aggressors, and prevents the entry of unwanted agents. However, certain conditions such as rosacea are associated with a compromised barrier, which may contribute to the onset or worsening of symptoms. Interestingly, tranexamic acid, primarily known for its anti-hemorrhagic properties, could also play an unexpected role: supporting the repair of the skin barrier when applied topically.

Studies have shown that when the skin barrier is damaged, it can lead to increased production of pro-inflammatory molecules, infiltration of immune cells, and elevated expression of factors involved in vascularization, all mechanisms frequently observed in rosacea.

A 2015 pilot study (n = 30) highlighted that a topical solution containing 3% tranexamic acid, applied for two weeks, significantly reduced the clinical signs of rosacea compared to the control group. Another study published in 2022 reached similar conclusions in patients with steroid-induced erythematotelangiectatic rosacea. Researchers attributed this improvement to the restoration of the skin's barrier function, although the exact mechanisms of rosacea remain poorly understood.

But how would tranexamic acid work to strengthen the skin barrier?

Available data suggest that tranexamic acid may work by reducing the activity of serine proteases, enzymes involved in inflammation and the breakdown of the skin barrier. This inhibition limits the activation of the PAR-2 receptor, thereby reducing intracellular calcium mobilization in keratinocytes. This cascade slows the secretion of lamellar bodies, which are essential for the formation of epidermal lipids, and promotes the restoration of E-cadherin function, a protein crucial for cell cohesion, thereby helping to restore skin barrier homeostasis.

Furthermore, a study conducted in 2014 by WU P-L. and colleagues demonstrated that tranexamic acid accumulates in the stratum corneum, where it enhances the cohesion between epidermal cells by increasing the expression of occludin, a key protein in tight junctions, speeding up the regeneration of the skin barrier and thereby improving skin appearance and health.

Tranexamic acid is not limited to a depigmenting role: its anti-inflammatory properties also make it an interesting ally to soothe skin prone to redness, particularly in cases of rosacea, inflammatory acne, or skin sensitivity.

A pilot study conducted by KONTOCHRISTOPOULOS et al. (n = 20) evaluated the effectiveness of topical tranexamic acid in erythematotelangiectatic rosacea. Two application methods were compared: a simple damp dressing impregnated with TXA and a combination of microneedling and a tranexamic acid-soaked dressing. After four sessions, all participants showed improvement, with better outcomes observed in the group receiving the combined treatment.

Another study (2023) explored the efficacy of micro-injections of tranexamic acid in treating post-inflammatory erythema in acne-prone skin. Two injections were administered 15 days apart on one side of the face, with the other side serving as a control. At the conclusion of the protocol, a significant reduction in erythema intensity was observed, with no adverse effects reported.

Despite promising results, available studies remain limited and are conducted on small samples. Further research on a larger scale is necessary to establish solid recommendations.

By what mechanisms might tranexamic acid exert its anti-inflammatory and vascular effects?

The anti-inflammatory and vasomodulating properties of tranexamic acid are based on two molecular mechanisms:

• Inhibition of the plasminogen/plasmin pathway.
  Tranexamic acid acts as a competitive inhibitor by binding to the lysine sites of plasminogen, preventing its conversion to plasmin. Plasmin is involved in the release of pro-inflammatory factors such as IL-6 and TNF-α, two key cytokines in skin inflammatory processes.

• Regulation of skin angiogenesis.
  Plasmin also activates the release of VEGF, a key factor in the formation of new blood vessels. Tranexamic acid inhibits this pathway by reducing the activation of VEGF and the expression of its receptor VEGFR-2, and by decreasing the expression of endothelin-1, another pro-angiogenic mediator involved in the persistent vasodilation observed in rosacea.

Although primarily studied for its effects on pigmentation or the skin barrier, tranexamic acid may also be of interest in the management of inflammatory acne. A preliminary randomized, double-blind, placebo-controlled clinical study evaluated the efficacy of a serum containing 10% tranexamic acid in 18 patients with mild to moderate acne. After eight weeks of twice-daily application to one side of the face (with the other side receiving a placebo), a significant reduction in the number of inflammatory lesions was observed on the treated side. The authors suggest that this improvement may be related to tranexamic acid's modulatory effect on the skin's inflammatory response, although the precise mechanisms remain to be clarified. Further studies are needed to confirm this therapeutic potential.

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