What is Tranexamic acid (TA)? By Dr Jeslin Wong

In the last article, we discussed about hyperpigmentation, more specifically, melasma.

Today, we will deep-dive into the research findings behind tranexamic acid (Trans-4 Aminomethylcyclohexane- carboxylic acid) and its use in melasma.

What is Tranexamic acid (TA)?

Tranexamic acid (TA) is a synthetic derivative of the amino acid, Lysine.

Amino acids are the building blocks of proteins.

How does Tranexamic acid work?

Traditionally, tranexamic acid is used for stopping excessive bleeding from major trauma, surgery, heavy menstrual bleeding etc. due to its blood-clotting properties. It works by blocking the conversion of a protein called plasminogen into plasmin. Plasmin is an enzyme that dissolves blood clots, hence by blocking the formation of plasmin, TA stops bleeding.

Mechanism of Action of Tranexamic Acid (Adapted from Orthobullets[1])

How about Tranexamic acid for the skin?

Tranexamic acid is a relatively new ingredient in the skincare scene. Efficacy of oral tranexamic acid in treating melasma was first reported in 1979 [2] by Nijo Sadako who had used TA for a patient with chronic urticaria, and incidentally found that the patient’s melasma had lightened after 2-3 weeks. This finding prompted further research on TA’s role in improving melasma.

Tranexamic acid [3] blocks the binding of plasminogen to skin cells (keratinocytes), thereby stopping the release of inflammatory mediators (arachidonic acid and prostaglandins) which stimulate pigmentation formation. TA also inhibits UV induced plasmin activity, inflammation and blood vessel growth – all of which stimulate melanin synthesis.

Route of Administration: Oral vs Topical vs Injectable Tranexamic acid?

Tranexamic acid can be given orally, applied to the skin, or injected into the skin (intradermal or  microneedling). [4] Dosing varies, but regimens include 500–1500 mg/day orally for 2–6 months, 250 mg orally twice daily, or 4 mg/mL injected intradermally into the melasma lesion at 1 cm intervals.[5],[6] Multiple studies have documented the efficacy of TA in patients with melasma.

The largest retrospective study of TA treatment was conducted in Singapore[7]. The authors reviewed data from 561 patients with melasma who were treated with TA, and improvement was noted in 90% of patients. Side effects reported in 40 patients (7.1%) were mostly mild. However, one patient developed blood clot in the leg and was later discovered to have underlying clotting disorders. Hence, TA should be avoided in patients with clotting disorders.

Several studies have addressed the efficacy and safety of topical TA [8],[9],[10]

• In a 12-week, split-face, prospective trial which compared the efficacy of a liposomal 5% TA formulation tohydroquinone 4%. Both treatments showed comparable efficacy
• In a separate split-face study, a TA 3% suspension was applied to one side of the face and a suspension with hydroquinone 2%,dexamethasone 01%, and vitamin C to the opposite side. Both formulations showed significant improvement, which suggests similar topical efficacy compared to hydroquinone-based formulations

Side effects with topical TA were less than applying hydroquinone to the skin, especially with concerns of hydroquinone-induced ochronosis (rare bluish discoloration of the skin), limiting its duration of use.

Should I get started on Tranexamic Acid?

TA does not work for all types of dark spots. Current studies support its pigmentation-lightening effect for melasma.

Oral TA can be used to treat melasma that is refractory to other treatments. It is largely safe in short durations, except for those with known clotting problems. It may take up to 8-12 weeks to see improvement, and is given at a low dose of 500mg a day. At present, there are no published studies to show that oral TA is more effective than topical TA. Topical TA at 3-5% concentration have shown comparable efficacy in treating melasma compared to hydroquinone in a few small studies.

Luckily, tranexamic acid works well with other ingredients, so you can combine it with other brighteners like topical retinoids, Kojic Acid, vitamin C or niacinamide for synergistic improvement (refer to the previous article when we discussed about tackling dark spots via different stages of their formation using different pathways).

Tranexamic acid can be combined with in-clinic treatments like Q-switched lasers and chemical peels for faster results.

Lastly, do not forget to protect your skin with sunscreen, to prevent new spots from forming.

References

1. https://www.orthobullets.com/basic-science/9054/anticoagulation-medications
2. Sadako N. Treatment of melasma with tranexamic acid. The Clin Rep 1979; 13: 3129–31 (in Japanese)
3. J. Kim, S.H. Moon, S.H. Cho, J.D. Lee, H. Sung Kim. Efficacy and safety of tranexamic acid in melasma: a meta-analysis and systematic review. Acta Derm Venereol, 97 (6-7) (2017), pp. 776-781
4. Taraz, S. Niknam, A.H. Ehsani. Tranexamic acid in treatment of melasma: A comprehensive review of clinical studies Dermatol Ther (2017), p. 30(3)
5. Kim HJ, Moon S, Cho S, Lee J, Kim H. Efficacy and safety of tranexamic acid in melasma: a meta-analysis and systematic review. Acta Derm Venereol. 2017;97(7):776–781.
6. Lee JH, Park JG, Lim SH, et al. Localized intradermal microinjection of tranexamic acid for treatment of melasma in Asian patients: a preliminary clinical trial. Dermatol Surg. 2006;32(5):626–631
7. C.Lee, T.G. Thng, C.L.Goh. Oral tranexamic acid (TA) in the treatment of melasma: A retrospective analysis. J Am Acad Dermatol, 75 (2) (2016), pp. 385-392
8. Banihashemi, N. Zabolinejad, M.R.Jaafari, M. Salehi, A. Jabari. Comparison of therapeutic effects of liposomal tranexamic acid and conventional hydroquinone on melasma. J Cosmet Dermatol, 14 (3) (2015), pp. 174-177
9. J. Kim, J.Y. Park, T. Shibata, R. Fujiwara, H.Y. Kang. Efficacy and possible mechanisms of topical tranexamic acid in melasma. Clin Exp Dermatol, 41 (5) (2016), pp. 480-485
10. Ebrahimi, F.F. Naeini. Topical tranexamic acid as a promising treatment for melasma. J Res Med Sci, 19 (8) (2014), pp. 753-757

[1] https://www.orthobullets.com/basic-science/9054/anticoagulation-medications

[2] Sadako N. Treatment of melasma with tranexamic acid. The Clin Rep 1979; 13: 3129–31 (in Japanese).

[3] H.J. Kim, S.H. Moon, S.H. Cho, J.D. Lee, H. Sung Kim. Efficacy and safety of tranexamic acid in melasma: a meta-analysis and systematic review. Acta Derm Venereol, 97 (6-7) (2017), pp. 776-781

[4] M. Taraz, S. Niknam, A.H. Ehsani. Tranexamic acid in treatment of melasma: A comprehensive review of clinical studies Dermatol Ther (2017), p. 30(3)

[5] Kim HJ, Moon S, Cho S, Lee J, Kim H. Efficacy and safety of tranexamic acid in melasma: a meta-analysis and systematic review. Acta Derm Venereol. 2017;97(7):776–781.

[6]  Lee JH, Park JG, Lim SH, et al. Localized intradermal microinjection of tranexamic acid for treatment of melasma in Asian patients: a preliminary clinical trial. Dermatol Surg. 2006;32(5):626–631

[7] H.C.Lee, T.G. Thng, C.L.Goh. Oral tranexamic acid (TA) in the treatment of melasma: A retrospective analysis. J Am Acad Dermatol, 75 (2) (2016), pp. 385-392

[8] M. Banihashemi, N. Zabolinejad, M.R.Jaafari, M. Salehi, A. Jabari. Comparison of therapeutic effects of liposomal tranexamic acid and conventional hydroquinone on melasma. J Cosmet Dermatol, 14 (3) (2015), pp. 174-177

[9] S.J. Kim, J.Y. Park, T. Shibata, R. Fujiwara, H.Y. Kang. Efficacy and possible mechanisms of topical tranexamic acid in melasma. Clin Exp Dermatol, 41 (5) (2016), pp. 480-485

[10] B. Ebrahimi, F.F. Naeini. Topical tranexamic acid as a promising treatment for melasma. J Res Med Sci, 19 (8) (2014), pp. 753-757