Oral tranexamic acid does lighten melasma for many people while they take it. In a placebo-controlled trial, three months of 250 mg twice daily cut the modified MASI (Melasma Area and Severity Index) score by 49%, against 18% with placebo. The catch is what happens after stopping: three months later, the same group was back to a 26% reduction, against 19% in the placebo group, a gap of only seven points. We found no placebo-controlled trial showing that oral vitamin C on its own fades melasma.

You have been taking the pills religiously. Tranexamic acid, 250 mg twice a day. Vitamin C, 1000 mg every morning. Maybe glutathione capsules too, because someone on a skincare forum swore by them. You protect your skin from the sun. You follow all the advice.

And yet, six months later, the patches on your cheeks are still there. Perhaps slightly lighter, perhaps unchanged.

You are probably not doing anything wrong. Oral tranexamic acid holds melasma down while you take it, but it does not change what keeps producing the pigment, and some of what it held back tends to return once you stop. Vitamin C and most other "skin" supplements have far weaker evidence than people expect. This article goes through what the trials actually show.

Table of Contents

The Appeal of Oral Melasma Medications

The popularity of oral treatments for melasma is easy to understand. They are simple to take, require no clinic visits, carry no risk of procedural complications, and feel like a gentle approach. For patients who have been burned by aggressive laser treatments or irritated by strong creams, treating the problem from the inside is appealing.

Oral tranexamic acid has earned its place with placebo-controlled trials. In Del Rosario 2018 (double-blind, 44 patients enrolled), 250 mg twice daily for three months reduced the mMASI score by 49%, compared with 18% in the placebo group, with everyone using sunscreen. In Colferai 2019 (37 patients completing 12 weeks), 50% of the treated group improved based on the four evaluation methods, against 5.9% on placebo. That second number also means half of the treated patients did not reach that bar.

Vitamin C (ascorbic acid), glutathione, and other antioxidant supplements have a much thinner evidence base. They are widely used because of their known roles in melanin chemistry: vitamin C inhibits tyrosinase in the lab, and glutathione shifts melanin production from darker eumelanin toward lighter pheomelanin. Whether swallowing them changes melasma is a separate question, covered below.

Tranexamic Acid: What It Can and Cannot Do

Tranexamic acid is a synthetic lysine analog that blocks the conversion of plasminogen to plasmin. In melasma, the proposed mechanism is that plasmin in sun-exposed skin prompts keratinocytes to release arachidonic acid and prostaglandins, which push melanocytes to make more pigment. Blocking plasmin interrupts that signal. Tranexamic acid also has anti-angiogenic effects that may help with the increased blood vessels seen in melasma skin.

Taken by mouth, roughly a third to a half of the dose is absorbed: 34% in Pilbrant 1981 and 46% in a pooled analysis of 114 volunteers (Grassin-Delyle 2019). That is enough to produce the trial results above.

What it cannot do is change the drivers that keep melasma active: ultraviolet and visible light, heat, and hormones. It suppresses pigment production while it is in your system. When the medication is stopped, the suppression goes with it, which is why relapse is the real limitation of oral treatment (next section).

Most people who respond see a change within about two months; in the 561-patient review by Lee 2016, response was seen within two months of starting. A network meta-analysis of dosing (Wang 2023) found 250 mg three times daily for 12 weeks to be the optimal dose, with twice daily an acceptable option for people who struggle to take a third dose.

What Happens When You Stop, and How Long You Can Take It

Relapse after stopping is common. How common depends on the study:

  • Del Rosario 2018: the 49% reduction on treatment had fallen back to 26% three months after stopping, against 19% in the placebo group. Most of the difference from placebo was gone.
  • Kumaran 2021: among patients who had failed topical treatment and were switched to oral tranexamic acid, most relapsed within six weeks of stopping.
  • Reported relapse rates vary widely, for example 9.5% in Wu 2012 (74 patients followed beyond six months) and 27.2% in Lee 2016. Follow-up length and patient selection differ, so there is no single figure to quote.

How long to take it depends on who is supervising. An Indian expert consensus (Godse 2023) states that tranexamic acid may be given for up to six months. A case series of 26 patients treated beyond six months (Lam 2024) found the effect was maintained for up to 28 months with no thromboembolic events. All 26 were also using topical treatment, the series only included people who chose to continue past six months, and only 14 could be assessed at one year and six at two years. In Japan, where tranexamic acid for melasma is sold over the counter, the package insert limits use to two months at a time with at least two months off before restarting. The manufacturer's stated reason is that there is not enough efficacy and safety data beyond two months; it does not cite loss of effect. Patients often ask about fixed cycles such as three months on and one month off; we found no study comparing on-and-off schedules like that, so the cycle length is a decision to make with your doctor based on your response and clotting risk.

If melasma comes back, another course is an accepted option: the Pigmentary Disorders Society Delphi consensus (Sarkar 2023) notes that repeated dosing may be required for patients who relapse.

Side Effects and Who Should Not Take It

At melasma doses (usually 500 to 750 mg a day), most side effects are mild. In Wu 2012, gastrointestinal discomfort occurred in 5.4% and lighter periods in 8.1%.

The concern that matters is blood clots, because tranexamic acid slows the breakdown of clots.

  • In Lee 2016 (561 patients), one patient developed deep vein thrombosis and was later diagnosed with familial protein S deficiency.
  • In a propensity-matched electronic health record study (Hernandez 2026, 682 matched pairs of patients prescribed 650 mg tablets versus untreated patients), there was no difference in venous thromboembolism over 120 days. That study excluded people with coagulation disorders, hormone or estrogen-modulator use, pregnancy, nicotine dependence, or prior clots, so it says nothing about those groups.

People who should avoid it, according to the Indian expert consensus (Godse 2023): anyone with a history of, risk of, or active thromboembolic disease; women using combined hormonal contraception; and anyone allergic to the drug. The Japanese over-the-counter label adds hormone replacement therapy and age 55 or over as reasons to consult a doctor first, and lists dialysis as a reason not to take it. Smoking is not listed as a contraindication in these documents, but it is a clotting risk factor worth telling your prescriber about.

On testing, the Sarkar 2023 consensus recommends a baseline coagulation profile for everyone before starting, and more extensive tests (complete blood count, liver function, protein C and S) for people at high risk of clots.

Vitamin C and Antioxidants: The Bioavailability Problem

The absorption ceiling is real for vitamin C. In a pharmacokinetic study of healthy volunteers (Levine 1996), a single 200 mg dose was completely absorbed. At single doses of 500 mg and higher, absorption declined and the extra was excreted in urine. Plasma was fully saturated at 1000 mg a day, and the authors concluded that daily doses above 400 mg have no evident value.

More importantly, we found no placebo-controlled trial of oral vitamin C alone for melasma. The one old trial that included a vitamin-C-only group (Hayakawa 1981) used it as a comparison arm: vitamins E and C together did better than vitamin C alone, and there was no placebo group.

Glutathione has a similar problem. Oral glutathione is broken down extensively in the gut before absorption, and evidence for melasma specifically is limited. Intravenous glutathione bypasses the gut but also lacks evidence of lasting benefit in melasma.

Best Oral Vitamins and Supplements for Melasma: What the Evidence Shows

If the question is which oral option has the best evidence for melasma, the answer is tranexamic acid, which is a prescription medicine in most countries rather than a vitamin. Among supplements, the evidence is thin:

Oral optionBest evidence foundWhat it showed
Tranexamic acidSeveral double-blind placebo-controlled trials49% vs 18% mMASI reduction at 3 months (Del Rosario 2018); gains fade after stopping
Procyanidin with vitamins A, C, EOne 8-week placebo-controlled trial, 60 women (Handog 2009)Safe and effective for epidermal melasma; the main ingredient is procyanidin, so the result cannot be credited to vitamin C
Vitamins E and C togetherOne 1981 trial without a placebo group (Hayakawa 1981)Better than vitamin C alone
Vitamin C aloneNo placebo-controlled melasma trial foundAbsorption saturates at about 1000 mg a day; the authors saw no evident value above 400 mg a day
Oral glutathioneLimited melasma-specific evidenceDegraded in the gut; not established for melasma
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Can Tranexamic Acid and Vitamin C Be Taken Together?

Yes. The Japanese over-the-counter melasma product Transino EX combines tranexamic acid (750 mg a day) and vitamin C (300 mg a day) in the same tablet.

What is missing is a controlled trial comparing tranexamic acid plus vitamin C against tranexamic acid alone, so there is no evidence that adding vitamin C lightens melasma further. If you are choosing one for melasma, tranexamic acid is the one with placebo-controlled evidence. Vitamin C is fine as general nutrition, and there is no reason to take large doses. Taking them at the same time of day is fine; we found no study showing that timing changes the result.

The Pharmacological Gap: Systemic Delivery vs. Local Need

The argument for local delivery goes like this: melasma sits in a few square centimeters of facial skin, while an oral drug circulates through the whole body. Putting the drug into the affected skin should, in theory, do more with less.

The head-to-head trials of tranexamic acid do not bear that out as a large difference:

  • Sharma 2017 compared oral tranexamic acid (250 mg twice daily) with local microinjections every four weeks for 12 weeks and found both equally effective.
  • El Hadidi 2021 compared oral treatment with two strengths of intradermal microinjection for 8 weeks and found no significant difference.
  • Meta-analyses disagree. A network meta-analysis (Liang 2024) found oral better in the short term and no difference by route in the long term; a meta-analysis of randomized trials (Chen 2025) found injection and microneedling more effective, while patient satisfaction was higher with oral treatment.

So for tranexamic acid on its own, the route matters less than the theory suggests. What local treatment does allow is limiting the drug to the affected area and combining it with other agents chosen for that skin.

Dr. Liu's approach: At Liusmed Clinic, the melasma injection (a hand-injected skin booster) is meant to calm the pigment cells whose turnover has gone wrong, as gently as possible, and to repair the local environment around them. Tranexamic acid and PRP (platelet-rich plasma, a concentrate from your own blood that carries repair factors) are placed directly within the dermis, around the junction with the epidermis. Injecting by hand in small deposits, the total amount that enters the skin is roughly five times what a machine delivers, in Dr. Liu's experience. With oral tranexamic acid alone, Dr. Liu usually sees it take one to two months to show, and the effect is real but modest, which is why the clinic generally pairs it with the hand-injected treatment. With the injection, many patients at the clinic can see the melasma lightening within the first month. That is the clinic's observation, not a trial result against oral treatment, and results vary from person to person.

Oral Medications vs. Targeted Local Delivery: A Comparison

FactorOral tranexamic acidLocal injection (tranexamic acid, with or without other agents)
How it is givenDaily tablets, absorbed into the whole bodyPeriodic clinic sessions, placed into the affected skin
Head-to-head trial results (tranexamic acid alone)Similar to injection in randomized trialsSimilar to oral in randomized trials; meta-analyses disagree on which is better
Main safety checksClotting risk screening; GI upset and lighter periods reportedNeedle discomfort at the treated area; clotting safety of injected tranexamic acid has not been studied separately, so the same history is checked beforehand
After stoppingRelapse is commonMelasma is chronic and can return after any treatment
Can combine other agents in the same stepNoYes (for example, PRP)
EffortDaily medicationClinic visits
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When Oral Medications Have a Role and When They Do Not

Where oral tranexamic acid is reasonable: For people without clotting risk factors who want a well-studied, simple option, as part of a plan that includes strict sun protection. It works best when you and your doctor agree in advance how long to take it and what to do if melasma returns.

Where it is a poor fit: In anyone with a history of clots, clotting risk, or combined hormonal contraception. As a lifelong, unsupervised habit. When the "melasma" is actually a different kind of pigment, such as solar lentigines, which the melasma trials did not study.

Where vitamin C and antioxidant supplements fit: General nutrition and overall skin health. Not as a treatment expected to fade established melasma patches on their own.

If you have been taking oral medication without the result you hoped for, the first step is to confirm the diagnosis and look at what is still driving the pigment: sun and visible light, heat, hormones, or stopping and restarting the pills. A Melasma Injection Treatment consultation is one option for building a local plan around that.

Frequently Asked Questions

Q1: Should I stop taking oral tranexamic acid if I start injection treatment?

This depends on your individual plan and should be decided with your treating physician. Oral tranexamic acid can be continued alongside injections for people without clotting risk factors, and Liusmed Clinic often combines the two. Whether and when to taper it depends on your response. The goal is to use no more medication than needed.

Q2: I have been taking tranexamic acid for a year. Is it safe to continue indefinitely?

Long-term data are limited. Expert consensus supports courses of up to about six months (Godse 2023). A small case series (Lam 2024) followed patients for up to 28 months without clotting events, but only six were still being assessed at two years. If you have been on it for a year, review your clotting risk factors with your prescriber (smoking, hormonal contraception or hormone therapy, personal or family history of clots, recent surgery or immobility) and agree on a plan rather than continuing indefinitely by default.

Q3: Are higher doses of vitamin C more effective for melasma?

No. In Levine 1996, plasma vitamin C was fully saturated at 1000 mg a day, absorption dropped at single doses of 500 mg or more, and the authors found no evident value above 400 mg a day. Taking more mainly increases what you excrete.

Q4: My melasma improved initially on tranexamic acid but has plateaued. Does this mean it stopped working?

Probably not. We found no study showing that tranexamic acid loses its effect over time, and the Lam 2024 case series saw the effect maintained for up to 28 months. A plateau usually means the drug has suppressed what it can. If things are getting worse, look at what else is changing: summer sun, heat, hormonal changes such as pregnancy or the pill, missed doses, or pigment that is not melasma at all.

Q5: Are there newer oral medications for melasma that work better than tranexamic acid?

Research continues into agents such as Polypodium leucotomos extract, melatonin, and procyanidin combinations. Some show promise in small studies, but we are not aware of any that has been shown to clearly outperform tranexamic acid.

Q6: Can injection therapy work for someone who did not respond to oral medications?

It can be worth trying, but set expectations with the evidence in mind. In head-to-head trials, injected and oral tranexamic acid performed similarly, so switching the route of the same drug may not change the result by itself. What changes with a local approach is the ability to combine agents such as PRP and to focus on the affected skin. A Melasma Injection Treatment consultation should start with confirming that the pigment is melasma.

References

  1. Del Rosario E, Florez-Pollack S, Zapata L Jr, et al. Randomized, placebo-controlled, double-blind study of oral tranexamic acid in the treatment of moderate-to-severe melasma. J Am Acad Dermatol. 2018;78(2):363-369. PMID 28987494 / DOI 10.1016/j.jaad.2017.09.053
  2. Colferai MMT, Miquelin GM, Steiner D. Evaluation of oral tranexamic acid in the treatment of melasma. J Cosmet Dermatol. 2019;18(5):1495-1501. PMID 30536592 / DOI 10.1111/jocd.12830
  3. Lee HC, Thng TG, Goh CL. Oral tranexamic acid (TA) in the treatment of melasma: A retrospective analysis. J Am Acad Dermatol. 2016;75(2):385-392. PMID 27206758 / DOI 10.1016/j.jaad.2016.03.001
  4. Wu S, Shi H, Wu H, et al. Treatment of melasma with oral administration of tranexamic acid. Aesthetic Plast Surg. 2012;36(4):964-970. PMID 22552446 / DOI 10.1007/s00266-012-9899-9
  5. Wang WJ, Wu TY, Tu YK, et al. The optimal dose of oral tranexamic acid in melasma: A network meta-analysis. Indian J Dermatol Venereol Leprol. 2023;89(2):189-194. PMID 36332095 / DOI 10.25259/IJDVL_530_2021
  6. Godse K, Sarkar R, Mysore V, et al. Oral Tranexamic Acid for the Treatment of Melasma: Evidence and Experience-Based Consensus Statement from Indian Experts. Indian J Dermatol. 2023;68(2):178-185. PMID 37275826 / DOI 10.4103/ijd.ijd_266_22
  7. Sarkar R, Narayan RV, Vinay K, et al. Prescribing practices of tranexamic acid for melasma: Delphi consensus from the Pigmentary Disorders Society. Indian J Dermatol Venereol Leprol. 2023;90(1):41-45. PMID 37609738 / DOI 10.25259/IJDVL_1157_2022
  8. Lam K, Mansour D, Sutton A. Oral tranexamic acid treatment beyond 6 months for melasma patients - A retrospective case series. JAAD Int. 2024;15:195-196. PMID 38707929 / DOI 10.1016/j.jdin.2024.03.006
  9. Kumaran MS, Narayan RV, Kaushik A, et al. Clinico-epidemiological profile and long term follow up in melasma. Dermatol Ther. 2021;34(6):e15143. PMID 34549495 / DOI 10.1111/dth.15143
  10. Hernandez T, Penny K, Culotta N. Oral tranexamic acid use for melasma is not associated with thromboembolism: Findings from a multicenter propensity score-matched electronic health record cohort. JAAD Int. 2026;24:64-66. PMID 41256337 / DOI 10.1016/j.jdin.2025.09.005
  11. Sharma R, Mahajan VK, Mehta KS, et al. Therapeutic efficacy and safety of oral tranexamic acid and that of tranexamic acid local infiltration with microinjections in patients with melasma: a comparative study. Clin Exp Dermatol. 2017;42(7):728-734. PMID 28649780 / DOI 10.1111/ced.13164
  12. El Hadidi H, Mosaad R, Ragab N. The efficacy of oral vs different dilutions of intradermal tranexamic acid microinjections in melasma - A randomized clinical trial. Dermatol Ther. 2021;34(3):e14924. PMID 33651442 / DOI 10.1111/dth.14924
  13. Liang R, Luo H, Pan W, et al. Comparative efficacy and safety of tranexamic acid for melasma by different administration methods: A systematic review and network meta-analysis. J Cosmet Dermatol. 2024;23(4):1150-1164. PMID 38059683 / DOI 10.1111/jocd.16104
  14. Chen LY, Kang YN, Hoang KD, et al. Intradermal Injection of Tranexamic Acid for the Treatment of Adult Melasma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Facial Plast Surg Aesthet Med. 2025;27(4):305-312. PMID 39574359 / DOI 10.1089/fpsam.2024.0187
  15. Handog EB, Galang DA, de Leon-Godinez MA, et al. A randomized, double-blind, placebo-controlled trial of oral procyanidin with vitamins A, C, E for melasma among Filipino women. Int J Dermatol. 2009;48(8):896-901. PMID 19659873 / DOI 10.1111/j.1365-4632.2009.04130.x
  16. Hayakawa R, Ueda H, Nozaki T, et al. Effects of combination treatment with vitamins E and C on chloasma and pigmented contact dermatitis. A double blind controlled clinical trial. Acta Vitaminol Enzymol. 1981;3(1):31-38. PMID 7027767
  17. Levine M, Conry-Cantilena C, Wang Y, et al. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc Natl Acad Sci U S A. 1996;93(8):3704-3709. PMID 8623000 / DOI 10.1073/pnas.93.8.3704
  18. Pilbrant A, Schannong M, Vessman J. Pharmacokinetics and bioavailability of tranexamic acid. Eur J Clin Pharmacol. 1981;20(1):65-72. PMID 7308275 / DOI 10.1007/BF00554669
  19. Grassin-Delyle S, Semeraro M, Foissac F, et al. Tranexamic acid through intravenous, intramuscular and oral routes: an individual participant data meta-analysis of pharmacokinetic studies in healthy volunteers. Fundam Clin Pharmacol. 2019;33(6):670-678. PMID 31013357 / DOI 10.1111/fcp.12474
  20. Transino EX package insert (Daiichi Sankyo Healthcare, Japan; listed in JAPIC / KEGG MEDICUS) and the manufacturer's FAQ on the dosing period and drug holiday.

About the Author

Dr. Ta-Ju Liu

  • Current Position: Director, Liusmed Clinic
  • Experience:
    • Board-certified dermatologist in Taiwan
    • 15+ years of clinical minimal incision surgery experience
  • Approach to melasma: Being straight with patients about how far oral treatment can hold melasma down and what happens when it stops, then, for those who want to work on the local skin environment, adding hand-injected tranexamic acid and PRP.

Disclaimer

This article is provided for educational and informational purposes only and does not constitute medical advice. Do not alter your prescribed medication regimen without consulting your treating physician. Individual skin conditions vary significantly, and treatment outcomes depend on numerous patient-specific factors. Always consult a qualified dermatologist or medical professional before making decisions about melasma treatment. The information presented here reflects current medical understanding as of the last review date and may be updated as new research becomes available.