Does tranexamic acid work? Response to The Beauty Brains

I recently talked about how I don’t think tranexamic acid works in most skincare products I’ve come across, in both a YouTube video and an Instagram post. Perry Romanowski and Valerie George of The Beauty Brains podcast commented on my opinions in Episode 369, “Can Tranexamic Acid Really Reduce Hyperpigmentation?”, published 14 July 2024.

Unfortunately I don’t think they looked at my posts before commenting, because I already addressed a lot of the points they raised.

Relevant expertise

Before we get into tranexamic acid, a bit about my relevant expertise on this topic.

Towards the end of the segment, Perry says I don’t have experience as a cosmetic chemist in industry directly formulating products, so my perspective is that of “an educated consumer”.

Firstly, while the first half is true – this is something I am very upfront about – cosmetic chemistry is still a specialty within chemistry. To say a PhD in chemistry adds little when it comes to understanding cosmetic chemistry is a pretty bizarre claim to me, especially as someone who sees a lot of non-chemists (and sadly, some chemists) talk incorrectly about the chemistry behind cosmetic products.

There’s usually a distinction made between cosmetic chemists and cosmetic formulators, because the extra education allows chemists to understand the underlying chemistry. Last year when some cosmetic chemists were quoted in an Allure article saying that they didn’t need to know much chemistry, many cosmetic chemists protested the idea:

I also never speak on the more practical aspects of formulation without checking the perspectives of cosmetic chemists and other people with relevant expertise. The same goes for any other topic I cover outside of my expertise.

Secondly, dismissing my view as that of “an educated consumer” is strange in the context of tranexamic acid. My opinion is mostly informed by my expertise in medicinal chemistry, the main area of my PhD.

I think they might’ve realised this if they watched the first 10 seconds of my 57 second Instagram reel, where I made it pretty clear:

“This is probably going to be controversial, but I’m not convinced tranexamic acid works in most skincare products. Hi I’m Michelle, my PhD is in medicinal chemistry – let’s talk medicinal chemistry.”

Medicinal chemistry is one of the most relevant expertises when it comes to the analysis and design of biologically active molecules. It’s a core part of what medicinal chemists do.

On the other hand, it’s pretty tangential to the job of a cosmetic chemist, especially ones who mostly specialise in hair like Perry and Valerie. I’m guessing this is why they think working in formulation for a long time is needed – most cosmetic chemists are likely only encountering it by chance, not in a structured, formal manner. 

Medicinal chemistry

A brief summary of what medicinal chemistry involves:

Step 1. Design active molecules to have a particular effect on the body. There are two main parts to this:

1. Pharmacodynamics: The molecule is designed to have a desired action at a biological target (e.g. a receptor or enzyme). This involves understanding how the molecule is meant to work (mechanism of action), then tweaking its structure to better interact with the target. You’re essentially designing different shaped “keys” (molecules) to find the best one for a particular “lock” (target).
2. Pharmacokinetics: It needs to actually get to the target inside your body. This is mostly about designing molecules with the right properties to be “drug-like” for a particular route of administration. Medicinal chemists usually want to make oral drugs which largely obey Lipinski’s rule of 5, but similar principles apply to other routes, including penetration through skin (although the actual properties required for each route can be very different, and delivery systems can expand the properties allowed).

Step 2. Synthesis: Make the active molecules in a high enough quantity and purity for testing. You also need to check they’re actually the molecules you tried to make (characterisation).

Step 3. Testing for properties and activity. Medicinal chemists do some tests (e.g. conformational studies to work out molecular shape), but biological testing is usually someone else’s job, hurray! This includes assays on biomolecules, cells and model systems, and then later, animal and human studies.

Step 4. Analysis of results. Did sticking a ring on the end of the molecule give a larger effect? What about shortening the molecule?

Step 5. Optimisation: Use these insights to go back to Step 1 and design better active ingredients.

Synthesis (step 2) is usually the most time-consuming and technically challenging step, and most medicinal chemists (and organic chemists in general) spend the bulk of their time on this. So you want to ensure the molecules designed in Step 1 have the potential to work before wasting a ton of time and resources making them.

While my PhD was mostly on developing a neat synthetic methodology (making Step 2 more efficient) rather than pumping out molecules and cycling through the steps, I spent a lot of time justifying the molecules I was making. The coursework and seminars were heavy on drug design, and many of my labmates were doing hardcore traditional med chem (most organic chemists get a lot of exposure to medicinal chemistry because it’s one of our standard career pathways). The basics of medicinal chemistry are also often covered in undergraduate courses.

(Note: Active ingredients in cosmetic products aren’t technically medicines/drugs, but this is a legal distinction – your skin can’t tell the difference, they’re all just molecules. All active ingredients, drug or cosmetic, operate on the same pharmacodynamic and pharmacokinetic principles.)

Onto tranexamic acid. There are a few reasons for my doubts…

Pharmacokinetics

The main reason for my skepticism about tranexamic acid is pharmacokinetics (part of Step 1) – it doesn’t have the right properties to penetrate skin. This was the focus of my Instagram reel:

“This is probably going to be controversial, but I’m not convinced tranexamic acid works in most skincare products. Hi I’m Michelle, my PhD is in medicinal chemistry – let’s talk medicinal chemistry.

Here’s what tranexamic acid looks like. It has an acid group here:”

“You might already know that a lot of skincare acids like glycolic acid need to be at a low pH to get into skin. That’s because when the pH is too high, above about 4.5, it’s charged – charged things don’t get into skin easily.

So no problem, let’s make it low pH then… Yes problem! Tranexamic acid also has this basic group here:”

“It’s an amine, and it’s charged when the pH is lower than about 10. So at any pH, tranexamic acid will have at least one charge, maybe two. That means it’s too polar – too water-loving – to get into skin easily.”

“This isn’t a problem when you take it as an oral medication – charged things get through your digestive system all the time. A lot of the hype comes from tranexamic acid as an oral medication. But for skincare, I think it’s really riding off that undeserved hype.”

In my YouTube video, I also added that because tranexamic acid is a small molecule, the charge is quite concentrated, so it’s too polar to get into skin effectively. I also said that a special delivery system could potentially help (hence why I said most skincare products).

The Beauty Brains’ points

(I’ve condensed quotes for brevity, hopefully without misrepresenting anything – the full transcript is at the bottom.)

The topic of tranexamic acid came up in a listener question from Lydia:

“[Michelle] said that because tranexamic acid contains an amine that remains positively charged at any pH under 10, then that makes tranexamic acid molecule nearly impossible to penetrate the skin […] She hypothesized that any dark spot reduction from the tranexamic acid topical treatment is due to other ingredients and not the tranexamic acid. What are your thoughts on her perspective? Did I misunderstand the explanation?”

Valerie: “The pKa that Lab Muffin (Dr Michelle Wong) was talking about relates to the point at which a molecule has a positive, a neutral, or a negative charge. And pKa is only one property that is taken into consideration when we’re talking about skin penetration. There’s other things such as the dimensions – the way the molecule is shaped in 3D – its molecular weight, its hydrophilic/lipophilic propensity to penetrate into the skin, as well as the anatomy and physiology of the skin and what other products it’s formulated with. So to say that just because it has a high pKa and it’s not going to go in – I saw the post, I personally thought it was clickbait to get you to click on it. I think there’s a lot of other factors that go into formulating products.”

Firstly, I don’t actually mention pKa in any of my posts on tranexamic acid – Lydia was pretty good at distilling down the key argument! Tranexamic acid actually has a pretty unremarkable pKa for an acid – all things being equal, acids with higher pKas would actually penetrate skin better, because they don’t need as extreme a pH to be uncharged.

My actual argument is about charge and polarity, which mostly impacts hydrophilicity/lipophilicity, one of the other factors Valerie (correctly) says determines skin penetration. It’s usually the most important factor.

If we look at molecules that we know penetrate skin (retinoids, ascorbic acid, niacinamide, lactic acid etc.), tranexamic acid’s small and usually double-charged (zwitterionic) structure sticks out like a sore thumb. Structurally, it’s quite similar to standard amino acids which also have an amine and an acid group (hence their name) – they’re only really used in skincare as humectant moisturisers that sit at the top of the skin, since it’s widely accepted that they don’t penetrate skin well.

The Beauty Brains mention that there are exceptions to these theoretical predictions of what does and doesn’t penetrate, which is true:

Valerie: “[…] there’s a lot of work focused on the skin delivery aspect. And so to say “well, it doesn’t work” doesn’t mean anything. Salicylic acid works above a neutral pH to do all the things it could do at a low pH. So I totally wouldn’t put a lot of weight in that. It’s really about the product and the way that it has been used.”

Perry: “I will mention that I looked through a study on tranexamic acid and they showed evidence of it working topically. And while Michelle has looked at the chemistry of it, looking at the chemistry and then predicting what’s going to happen in real life when it’s used – those are kind of different things, because sometimes surprising things happen. You know, there are people who say hyaluronic acid can’t penetrate because it’s over 500 Dalton, but then there are some studies that show that it penetrates where, when it shouldn’t […] the power is in the proof, is in the pudding or as they would say. If you do a study where tranexamic acid topically applied, is applied for a few months and you see hyperpigmentation reduction, maybe it’s doing something.”

But unlike these examples, there isn’t anything unusual about tranexamic acid’s relatively simple structure that might help it penetrate skin:

• Salicylic acid becomes charged at neutral pH, but its internal hydrogen bonding reduces the charge concentration
• Hyaluronic acid is highly humectant, so it can act as its own penetration enhancer

Of course, despite these very one-sided pharmacokinetic predictions, it’s possible (though unlikely) that tranexamic acid has some penetration-enhancing feature we don’t know about yet. As Perry says:

“You can look at the molecule and say “oh that shouldn’t work”, but if you have a study that says it works, you know there’s a disconnect there.”

But in science, a claim that contradicts well-established scientific principles requires good evidence. Let’s look at the clinical evidence…

Clinical evidence

The peer-reviewed clinical studies on topical tranexamic acid are really not that convincing. In addition, while I was more optimistic when I first posted about tranexamic acid back in 2020, the longer we go without convincing studies, the more this absence of evidence becomes evidence of absence of any real effect. From my YouTube video:

“How well it works orally also adds to why I don’t think it works well in skincare. Even though there are some clinical trials where the results were statistically significant, you’d expect that to happen even with ingredients that don’t work, if you test them enough.

Tranexamic acid works well orally, it’s cheap, it’s pretty safe and it’s been around for a long time – it is exactly the sort of ingredient you’d expect a lot of researchers to be testing. It is way easier to publish studies where something worked than where something didn’t work. So I am willing to bet there are a whole bunch of unpublished trials where it didn’t work. I’ve personally heard of at least 2 unpublished studies where it didn’t work.

There are products out there with tranexamic acid that have good reviews, but all of the ones I’ve seen have other pigment targeting ingredients in them that have much better evidence.”

(I’ve talked before about some of these meta considerations when it comes to interpreting the literature in the context of retinol.)

The Beauty Brains’ points

Valerie and Perry discuss a number of studies which might seem promising at first glance, but don’t hold up if you look more critically.

As I’ve explained before, peer review isn’t a guarantee of quality, but a rather low barrier:

• Plenty of dodgy studies get published thanks to rushed and biased peer review, and predatory journals may only pretend to do peer review. For example, over a quarter of published medical studies are estimated to be fatally flawed or fradulent (coincidentally, this article discusses studies on tranexamic acid in the context of postpartum bleeding).
• Peer-reviewed papers are written by postgraduate academics for other postgraduate academics, so there’s a lot of assumed knowledge that isn’t explained, which leads to misunderstandings.
• Research that seems more important is more likely to get published, so papers tend to present their research in the best possible light, often to the point of being misleading. 
• Exaggerated claims are especially rife in abstracts, introductions, discussions and conclusions. This isn’t really seen as a big problem, since most scientists working in the field (including the peer reviewers) know to take those sections with a grain of salt – they usually assess the methods and results directly, on their own merits (many ignore the other sections entirely). But those easier-to-read sections are what everyone else tends to rely on.

All this makes it difficult to understand papers properly. Critically appraising studies isn’t taught much at undergrad level, often even at postgraduate level, and it takes a lot of practice to get good at it. Many people who haven’t critically assessed many papers tend to take their contents at face value. This included me when I first started – I wouldn’t claim to be an expert now, but I’ve improved immensely.

Working in formulation doesn’t really prepare you for this, compared to just reading papers, guided by people with more experience (e.g. academics) – plus, as Perry and Valerie later mention, there’s less time they can dedicate to it. Properly reading papers is very time-consuming.

Valerie presents three studies claiming to show tranexamic acid working on its own. They don’t directly link the studies, so I’ve made some educated guesses.

None of the three I found used an inactive (placebo or vehicle) control, and tranexamic acid wasn’t actually used on its own in any of them – they all used it along with sunscreen. We know that pigment fades on its own as skin cells turn over, and sunscreen accelerates this by reducing new melanin production. So these studies don’t allow you to separate the impact of tranexamic acid from the effects of time and sunscreen.

“There was one 2007[?] study looking at 5% tranexamic acid against a 3% hydroquinone cream on Indian skin, and researchers found that the tranexamic acid significantly improved existing freckles while preventing new ones from forming over daily use over 12 weeks. I like this study because not all skin lightening agents can be used on darker Fitzpatrick skin types, but tranexamic acid is one of them that certainly can.”

The year was a bit garbled – based on the percentages, I think it’s this 2019 study.

• All subjects used SPF 30 sunscreen, so the decreased Melasma Area Severity Index (MASI) scores could just be showing that sunscreen fades melasma. In fact, the MASI score changes in (12.39 ± 3.34 to 9.48 ± 2.79 for 5% tranexamic acid, 11.63 ± 3.72 to 9.24 ± 3.26 for 3% hydroquinone) were comparable to those from another study on Indian patients, where SPF 19 sunscreen alone was used thrice daily (12.38 ± 14.7 to 9.15 ± 4.7 after 12 weeks).
• The main finding is “the difference between the two groups was not significant (P > 0.05)”. “Not significant” is a far lower bar than the usual “significant” (P < 0.05). You’re more likely to get non-significant results by underpowering your study (e.g. using less participants), so this is weak evidence at best.
• The 5% solution used was simply injectable tranexamic acid diluted in water. Given the expected pharmacokinetics and the lack of a delivery system, I highly doubt this formula would actually be as effective as 3% hydroquinone cream, a well-evidenced melasma treatment.

“There was another study, a 5% solution of tranexamic acid that also looked at its ability to reduce post acne inflammatory marks, and the tranexamic acid performed quite well. Again, just a 5% solution alone, no other skin lighteners.”

This description is vague, but I think it’s this study where 5% tranexamic acid was compared with 20% azelaic acid. Just looking at the tranexamic acid arm:

• Again, there’s no inactive control, so it isn’t actually testing 5% tranexamic acid alone, since all subjects used SPF 30 sunscreen.
• Post acne marks also fade relatively quickly on their own, so you can’t conclude that tranexamic acid (or even sunscreen) were responsible.
• The dropout rate is very high (11/41 = 27%) – this likely inflates the results, as people seeing less improvements are more likely to quit.
• Injectable TXA diluted in water with no delivery system was used – again, this is unlikely to get into skin.

“And then patients with mild melasma also benefited from a 2% solution of tranexamic acid. This 2% tranexamic acid cream was applied to 23 participants with mild melasma for 12 weeks. Out of 23, 22 saw a statistically significant benefit of skin lightening. And this was with tranexamic acid alone.”

The two obvious problems with this study are its small sample size and the lack of any control group for comparison. And again, all participants used sunscreen, so these results really don’t tell us much.

In contrast, there’s one study I know of that compared 5% tranexamic acid in a liposomal gel formula with an inactive vehicle control (the same formula minus tranexamic acid).

• Even though the number of subjects is small (23), the split-face design means the sample size is effectively doubled compared to the designs above.
• SPF 60 sunscreen was used daily, but the vehicle control allows us to see the effect of tranexamic acid alone: although melasma lightened for both the tranexamic acid and control sides, there was no difference in pigment reduction between them.

Industry experience

At the end of the segment, Perry and Valerie talk about why they think I might’ve been misinformed about tranexamic acid, and the value of industry experience:

Perry: I think this does demonstrate one of the issues with information that you learn online. Now Michelle does a great job with her topics. She covers a lot of different topics. It’s hard to be an expert at everything.

Valerie: Yeah she does a lot of great work. There’s some stuff I disagree with-

Perry: I see her quoted a lot in various magazines and such and it makes sense, because you go to Google or TikTok or anything, she’s all over the place. And there, like I said, she puts out great stuff educating consumers, but I do bristle a little sometimes when I see the word cosmetic chemist attached to her because, the thing is she’s well she’s very knowledgeable about the subject.

Valerie: She has a PhD in chemistry.

Perry: Yeah for sure. But not only that, she’s also researched the topics from a journal standpoint more than probably most industrial cosmetic chemists. Because the reality is, as a cosmetic chemist, you get in the lab, you get assigned to, oh, you’re doing hair care, or you’re doing skincare and you work on those formulas and you learn very much details about those formulas. But you might not learn anything about a different type of formula. Like neither Valerie or I are really well-versed in say, color cosmetics, because we just never really worked on them.

Valerie: I know about them because, you know, I used to work in ingredient technology when I was at the big beauty brand I worked at. But I, I wouldn’t say I’m an expert, I don’t formulate with, you know, I kind of have to do a lot of asking and digging about them.

Perry: Sure. But one of the things that we do have is experience in launching products. Industrial chemists have a different perspective on products than someone who’s educated by just reading journals and having a – eh – a consumer interest in it. You can only find out so much as a consumer unless you’re in the lab creating these formulas –

Valerie: And collaborating with other scientists who are working in fundamental research in these areas.

Perry: Absolutely. And you can be easily misled by what you read and what you want to be true. And you just have a different perspective. So, you know, Michelle does a great job of presenting an educated consumer’s standpoint. But she’s not worked for a beauty brand in a cosmetic lab, creating a product, getting it out on the market, interacting with market research and consumers and such. And so –

Valerie: There’s a lot of value at having worked in industry. And I get concerned when I see really any cosmetic chemist putting a year in or two years in, and then starting their own consulting company because – 

Perry: Sure.

Valerie: Much of what we know is because we have worked in the industry. We have worked in places where things have blown up in your face, or you have a problem and you have to work through the problem, or you’re exposed to just a lot of stuff that you wouldn’t get exposed to if you didn’t work in industry. And so online, I often see people in academia or people who haven’t worked in the industry commenting on things and it’s like, your perspective would 100% be different if you actually worked in the industry.

Perry: Right.

Valerie: And had the perspective not just from a lab aspect but from working with marketing, from working with the sales team, from working with quality and regulatory and seeing all the pieces come together, and actually seeing a product launch through in a two or three year product launch cycle, with all the stuff that goes into it. You definitely gain a different perspective.

Perry: Anybody can really call themselves a cosmetic chemist and there is a difference from having worked in the industry on that job, and just learning it from, you know, an online program or something. I also want to add that the people who are really good on social media – it’s a different kind of skill set than the people who are in a laboratory making products. And so it shouldn’t be surprising sometimes that someone who is very successful on social media, they probably don’t have a lot of lab experience because you have to focus on the social media part.

Valerie: I have no time to focus online anymore, that’s why I hardly post anymore. Back when I just worked at a company and I could post about my day to day life, you know, but now I’m really inundated with projects. I’m opening a manufacturing facility, I have my ingredients business, I don’t have time to be online. And I wish I did because it’s, you know, fun to get stuff out there. But it really is, you know, kudos to anyone on social media, because it really is a full time job managing a social media account. That’s why they have to go full time to do it.

Perry: They absolutely do.

While I completely agree that industry experience as a formulating cosmetic chemist is very valuable for some topics, I think this tranexamic acid example better demonstrates the value of industry experience as a science communicator – not so much in terms of creating content and using social media, but in critically assessing information, and understanding the relevance and limits of different expertises.

The areas of contention here – pharmacokinetics and interpreting peer-reviewed studies – are ones in which I have more relevant formal qualifications and (I’m pretty sure) more direct practical experience. As I mentioned earlier, I don’t tend to talk in depth about topics that require industry experience as a cosmetic chemist, and when I do, I check their opinions – the same goes for any other topic outside of my expertise. (I will also note that working in the industry as a science communicator also exposes you to a lot of valuable behind-the-scenes information.)

In my view, creating formulas and launching products wouldn’t add much value to the perspectives presented here, and might actually be a detriment when it comes to being “misled by what you read, and what you want to be true”. While directly working on and testing a tranexamic acid product would give useful insights, nothing Perry and Valerie have mentioned here seem to draw from this sort of direct experience. It’s worth mentioning that I did actually talk to a few people who’ve worked with tranexamic acid, which is how I know about the unpublished negative results.

(I think do they give me too much credit here for how many topics I cover – they release a 50 minute podcast every 10 days on top of doing their day jobs, while I average one 20-ish minute video and 7 minutes of reels a fortnight.)

References

Richard Van Noorden. Medicine is plagued by untrustworthy clinical trials. How many studies are faked or flawed? Nature. 2023;619(7970):454-458. doi:10.1038/d41586-023-02299-w

‌Hubbard KE, Dunbar SD. Perceptions of scientific research literature and strategies for reading papers depend on academic career stage. PLoS One. 2017;12(12):e0189753. Published 2017 Dec 28. doi:10.1371/journal.pone.0189753

Lagut A, Wong M. How to read an academic science paper. Beauty SciComm Group. August 28, 2023. Accessed July 31, 2024.

Janney MS, Subramaniyan R, Dabas R, Lal S, Das NM, Godara SK. A Randomized Controlled Study Comparing the Efficacy of Topical 5% Tranexamic Acid Solution versus 3% Hydroquinone Cream in Melasma. J Cutan Aesthet Surg. 2019;12(1):63-67. doi:10.4103/JCAS.JCAS_40_18

Sarkar R, Ghunawat S, Narang I, Verma S, Garg VK, Dua R. Role of broad-spectrum sunscreen alone in the improvement of melasma area severity index (MASI) and Melasma Quality of Life Index in melasma. J Cosmet Dermatol. 2019;18(4):1066-1073. doi:10.1111/jocd.12911

Sobhan M, Talebi-Ghane E, Poostiyan E. A comparative study of 20% azelaic acid cream versus 5% tranexamic acid solution for the treatment of postinflammatory hyperpigmentation in patients with acne vulgaris: A single-blinded randomized clinical trial. J Res Med Sci. 2023;28:18. Published 2023 Apr 1. doi:10.4103/jrms.jrms_443_22

Kim SJ, Park JY, Shibata T, Fujiwara R, Kang HY. Efficacy and possible mechanisms of topical tranexamic acid in melasma. Clin Exp Dermatol. 2016;41(5):480-485. doi:10.1111/ced.12835

Kanechorn Na Ayuthaya P, Niumphradit N, Manosroi A, Nakakes A. Topical 5% tranexamic acid for the treatment of melasma in Asians: a double-blind randomized controlled clinical trial. J Cosmet Laser Ther. 2012;14(3):150-154. doi:10.3109/14764172.2012.685478

Podcast Transcript

Perry: All right. Our first question comes to us from Lydia. We teased this one last week.

“Hello Perry and Valerie. Thank you for all you do. I do have a couple of questions. I heard Valerie discussing her positive experience with tranexamic acid for hyperpigmentation on Episode 366. I then began to do a little research on it and came across a segment by Dr Michelle Wong aka Lab Muffin Beauty. She is a chemistry PhD, science educator and cosmetic chemist. She said that because tranexamic acid contains an amine that remains positively charged at any pH under 10, then that makes tranexamic acid molecule nearly impossible to penetrate the skin. She said that positively charged AHAs cannot effectively enter the skin. She hypothesized that any dark spot reduction from the tranexamic acid topical treatment is due to other ingredients and not the tranexamic acid. What are your thoughts on her perspective? Did I misunderstand the explanation?” Then she says “For another hyperpigmentation what are your thoughts on the effectiveness of a combination of azelaic acid, niacinamide and vitamin C as the actives in one cream. Would these play nice together and be effective?” All right that’s Lydia. “Thank you both for so much of your excellent advice and a great dash of humor. Lydia.”

Valerie: Well-

Perry: Valerie, you were called out by name in this one.

Valerie: Alright.

Perry: I do remember you talking about your tranexamic acid that you like…

Valerie: Well, I don’t think tranexamic acid is different from any other skin active molecule in that things that are really active and tend to work, you have to get into the skin. Not many things passively and [?] actively penetrate through, the stratum corneum actually is designed to prevent that from happening. So a product has to be formulated with the delivery system in mind and tranexamic is no exception to that.

The pKa that Lab Muffin – Dr Michelle Wong – was talking about relates to the point at which a molecule has a positive, a neutral, or a negative charge. And pKa is only one property that is taken into consideration when we’re talking about skin penetration. There’s other things such as the dimensions, the way the molecule is shaped in 3D, its molecular weight, its hydrophilic/lipophilic propensity to penetrate into the skin, as well as the anatomy and physiology of the skin and what other products it’s formulated with. So to say that just because it has a high pKa and it’s not going to go in… I saw the post, I personally thought it was clickbait to get you to click on it, I think there’s a lot of other factors that go into formulating products.

In addition, there’s a lot of literature out there that shows tranexamic acid does work. Some of the studies are done alone, some of them are done in combination with other skin lightening therapies, and some of the studies are done on showing how to improve the penetration. But that’s literally no different than any other molecule on the market – Vitamin C, retinoids. You know, there’s a lot of work focused on the skin delivery aspect. And so to say “well, it doesn’t work” doesn’t mean anything. Salicylic acid works above a neutral pH to do all the things it could do at a low pH. So I totally wouldn’t put a lot of weight in that. It’s really about the product and the way that it has been used. And in fact if you like Perry, I could go through a little bit of – some of the, you know, things that I think are great about tranexamic acid, if you want me to do some of the studies?

Perry: Yeah, I will mention that I looked through a study on tranexamic acid and they showed evidence of it working topically. And while Michelle has looked at the chemistry of it, looking at the chemistry and then predicting what’s going to happen in real life when it’s used – those are kind of different things, because sometimes surprising things happen. You know, there are people who say hyaluronic acid can’t penetrate because it’s over 500 Dalton, but then there are some studies that show that it penetrates where, when it shouldn’t. So you can’t always predict just from

Valerie: The Daltons is one aspect. There’s a specific log number that tells you its propensity to penetrate into skin.

Perry: Right. And if you have all that data you also don’t know – you have to actually do the study and to see. And you know the power is in the proof, is in the pudding or as they would say If you put uh do a study where tranexamic acid topically applied is applied for a few months and you see hyperpigmentation reduction maybe it’s doing something.

Valerie: Well, tranexamic acid is valuable for a couple things. One – it treats existing pigmentation and can prevent new pigmentation from occurring, because it reacts on two different pigmentation pathways in the body.

There was one 2007[?] study looking at 5% tranexamic acid against a 3% hydroquinone cream on Indian skin and researchers found that the tranexamic acid significantly improved existing freckles while preventing new ones from forming over daily use over 12 weeks. I like this study because not all skin lightening agents can be used on darker Fitzpatrick skin types, but tranexamic acid is one of them that certainly can. There was another study, a 5% solution of tranexamic acid that also looked at its ability to reduce post acne inflammatory marks, and the tranexamic acid performed quite well. Again, just a 5% solution alone, no other skin lighteners. And then patients with mild melasma also benefited from a 2% solution of tranexamic acid. This 2% tranexamic acid cream was applied to 23 participants with mild melasma for 12 weeks. Out of 23, 22 saw a statistically significant benefit of skin lightening. And this was with tranexamic acid alone.

It’s also been widely studied with other skin lighteners. It has a great synergy with them because skin lighteners work on different pathways for reducing skin pigmentation. It’s been studied with hydroquinone, it’s been studied with water soluble forms of vitamin C, arbutin, niacinamide, and in fact it actually has a really great synergy with tranexamic acid. You don’t need a tranexamic acid product to be a low pH, it’s really pH independent. So I always like to say use it with niacinamide, put it at, you know, pH of 6 to 7, which is really important for the niacinamide. But subjects in this study saw with just 2% niacinamide 2% tranexamic acid and an SPF 15 cream twice daily saw a tremendous decrease in skin melanin content and difference in skin pigmentation just in eight weeks. So I thought that was pretty cool as well. All skin lighteners take a pretty significant time to work.

There’s also one Korean publication that looks at tranexamic acid in conjunction with polydatin a resveratrol precursor, and they also showed some skin lightening. It has some synergy with the licorice root extracts, the glycyrrhizates. So there’s lots of information available out there: tranexamic acid alone, tranexamic acid with other lighteners, and these are real cosmetic preparations applied to skin over 4 week to 12 week studies and I say it works.

Perry: Yeah you can look at the molecule and say “oh that shouldn’t work”, but if you have a study that says it works you know there’s a disconnect there. I think this does demonstrate one of the issues with information that you learn online… [continues above]