How Effective Is Combining Oral Vitamin C with Topical Tranexamic Acid? Reading New Research from Daiichi Sankyo Healthcare

Daiichi Sankyo Healthcare, which published the research, is the manufacturer behind Transino and the sensitive-skin brand Minon. According to the speaker, its parent company, Daiichi Sankyo, was formed through the merger of Daiichi Pharmaceutical and Sankyo, and the former Daiichi Pharmaceutical developed tranexamic acid in 1964.

Tranexamic acid is mainly used as a hemostatic agent and has been used, for example, to control heavy bleeding during surgery. When inflammation occurs in the skin, a substance called plasmin is produced. Tranexamic acid exerts its hemostatic effect by suppressing this plasmin, but it was found that it also suppresses the production of melanin, which causes dark spots. For this reason, it has recently also been used as a drug to suppress melasma, and Transino's Class 1 OTC drug is sold as a treatment for melasma. According to the speaker, the name Transino comes from the "Tra" in tranexamic acid. On the other hand, the speaker said it is also well known that the widely available vitamin C–based "Transino" medicines do not contain tranexamic acid.

Tranexamic acid has been used as an oral medicine, but it is also included in quasi-drug cosmetics. For topical use, it is approved as an active ingredient with efficacy claims for both preventing skin roughness and preventing dark spots. Topically as well, it is approved on the basis of a mechanism in which it suppresses plasmin to calm inflammation while preventing the formation of dark spots. What this research tested was not oral tranexamic acid but this kind of topical tranexamic acid.

According to the presentation, approaches using oral ingredients and approaches using skincare have each been studied for pigmentation such as UV-induced dark spots. However, the effect of combining the two had not been sufficiently confirmed.

The speaker had also previously explained that oral medicines have efficacy against dark spots and that quasi-drug skincare can be expected to have an effect as well. They predicted that using both would have a reasonable effect and had even recommended combining them. However, the speaker reflected that this was merely a prediction that "it will probably work out that way," and there was no sufficient evidence. The research was introduced as aiming to gain new insights into dark-spot care that works from both inside and outside the body.

The research used an "internal-external application model" with excised human skin. It was not tested on living human skin, but rather used excised human skin as a model. The speaker speculated, "I don't know how they did it, but I think they have a model of skin that's been neatly cut out."

The procedure was explained as follows. The excised skin is placed on a culture medium, and ascorbic acid (vitamin C) and L-cysteine are dissolved in the medium so they soak into the skin. This is treated as the "oral intake." Tranexamic acid is applied to the stratum corneum side of the skin. This is the "topical application." UVB is then irradiated, and after several days of culture, the skin's lightness is measured from photographed images. Three conditions were compared: medium addition only, application only, and both performed at the same time.

The speaker acknowledged that this method does constitute an internal-external model but expressed doubts about it. They said there is considerable room for debate about how well soaking vitamin C into the skin through the medium correlates with actually ingesting it by mouth.

The presentation reported that the group in which oral ingredients and tranexamic acid application were used at the same time had significantly higher skin lightness than either single-treatment group. The speaker read the values (L values) from the graph and explained the differences between the conditions.

• Control exposed only to UV: lightness dropped from nearly 58 to around 55, a decrease of about 3 points
• Oral ingredients only: around 56, a decrease of about 2 points. The speaker described this as "reducing the amount of darkening to about two-thirds"
• Tranexamic acid application only: a decrease of less than 1 point, around 0.5 points by the speaker's reading. It barely decreased at all
• Combination: lightness rose above that of untreated skin, to around 59. An increase of about 1 point

For the combination group, this means the skin became lighter than it originally was despite being exposed to UV. The speaker said that skin becoming lighter than its normal state is something that should be almost inconceivable, but because vitamin C and L-cysteine have a reducing action, the possibility that they lightened the color back cannot be ruled out. The presentation concluded that the findings show the potential of dark-spot care research that works from inside and outside the body. The speaker interprets the results as being at the stage where "the possibility of suppression has been suggested," although this is not explicitly stated in the text.

What the speaker considered most important in this data was that the effect of the oral ingredients was surprisingly small, while the effect of topical tranexamic acid was large.

The speaker speculated that when vitamin C is actually ingested, some of it is excreted and so on, and it is quite diluted by the time it reaches the skin. Compared with that, soaking it directly into the culture medium should result in a higher concentration. Despite this, the oral-ingredients-only group differed from the control by only about 1 point (55 became about 56), and it did not prevent darkening very strongly. On the other hand, the group with tranexamic acid applied greatly suppressed the decrease in lightness.

From this, the speaker suggested that applying tranexamic acid may be considerably more effective than the oral ingredients used as medicines. They added that the effects of quasi-drug skincare have rarely been demonstrated quantitatively like this before. The speaker also found it interesting that Daiichi Sankyo, which has long researched tranexamic acid as an oral medicine, released test results for topical use.

The speaker summarized what can be said from the research as a whole as follows. Combining medicines such as vitamin C with tranexamic acid cosmetics can be expected to more strongly prevent decreases in skin lightness. In some cases, it may even lead to increased skin lightness.

The research says "oral ingredients such as vitamin C," but what was actually used was vitamin C and L-cysteine. The speaker has explained in previous videos that both have efficacy in suppressing pigmentation.

What the speaker has consistently recommended and has been taking themselves for a long time is "Vitamin C 2000" (formerly called "Vitamin C Takeda"). Vitamin C medicines list efficacy claims for relieving dark spots, freckles, and pigmentation caused by sunburn or rashes. In other words, the speaker says, their efficacy is recognized as a medicine, so there is a point in taking them.

On the other hand, there are also opinions that vitamin C alone does not have a very strong effect on relieving dark spots. The speaker acknowledged that "that's true, in a sense." As grounds, they cited a study in which guinea pigs were orally given vitamin C, L-cysteine, and vitamin E (the speaker introduced it as a study from around 2002). It compared the rate of increase in melanocytes upon UVB irradiation, and vitamin C alone produced only a slight decrease compared with the control. Combining it with L-cysteine increased the effect, and adding vitamin E improved it slightly further.

Even among beauty experts, there are rare cases of people who say "taking vitamin C has no effect at all." In response, the speaker explained that this data shows it is not that it has no effect, but that it is "gentle." That is, it does have some effect on its own, but the effect is mild.

Taking vitamin C together with L-cysteine and similar ingredients is said to be more effective than vitamin C alone. The speaker said they can recommend that, while sharing their own experience.

The contents of the products the speaker compared are as follows. Vitamin C 2000 contains 2,000 mg of vitamin C in 6 tablets per day, with vitamin C as its only ingredient. Transino's product in the blue package (White C Clear) contains 1,000 mg of vitamin C and 240 mg of L-cysteine in 4 tablets per day, plus natural vitamin E, but somewhat less vitamin C. The higher-tier version (White C Premium) contains 2,000 mg of vitamin C, 240 mg of L-cysteine, and 50 mg of natural vitamin E in 6 tablets per day, and the speaker said it is more powerful.

The speaker went through a period of taking Transino in the past. At that time, they felt that their skin became rough and thicker as they continued taking it. The speaker said they don't know whether it is related, but L-cysteine is originally a building block of skin proteins; since rough skin was a problem, they stopped taking it. They also considered that L-cysteine is an ingredient that tends to solidify, so taking it continuously over a long period carries various risks. They currently take only vitamin C. The speaker's view is that whether L-cysteine suits you depends on your constitution. Even so, they said they have recommended products with added L-cysteine and vitamin E to people who want to lighten their skin further or to better prevent dark spots and darkening.

As for this particular research, the speaker said that honestly the effect of oral intake is unclear, and that "it's questionable whether the method of adding it to the culture medium is really producing an effect."

As topical products to combine with oral intake, the speaker introduced medicated lotions containing tranexamic acid. All of them contain tranexamic acid with an approved whitening efficacy claim, and according to the speaker, they contain the highest concentration of tranexamic acid permitted for use in Japan.

Transino Medicated Brightening Clear Lotion (Daiichi Sankyo Healthcare) contains tranexamic acid and dipotassium glycyrrhizate as active ingredients. It has a whitening efficacy claim from tranexamic acid and a skin-roughness prevention claim from dipotassium glycyrrhizate. It contains a small amount of ethanol and is not alcohol-free.

Shirojun is a product the speaker has introduced many times, with tranexamic acid and allantoin as active ingredients. It is glycerin-free, also contains the vitamin C derivative magnesium ascorbyl phosphate among other ingredients, and has a quite light, watery feel. The speaker said it suits people who prefer a refreshing feel.

Hadabisei Medicated Whitening Lotion has a vitamin C derivative, glycyrrhizic acid, and tranexamic acid as active ingredients. The product itself does not claim whitening for tranexamic acid, but according to what the speaker heard from Kracie, it contains enough tranexamic acid to obtain a whitening efficacy claim. However, because they wanted to prioritize obtaining the skin-roughness prevention claim, they obtained the whitening claim with the vitamin C derivative and listed tranexamic acid as an anti-inflammatory ingredient. It is alcohol-free, fragrance-free, and colorant-free, and the speaker rated it as easy to use.

Chifure Whitening Lotion TA is a formula with tranexamic acid as the sole active ingredient. Its moisturizing ingredients are BG and glycerin, and it is a simple formula that also contains trehalose. It suits people who want to use only tranexamic acid. However, the speaker cautioned that because it contains a fair amount of glycerin, it has a moist, sticky feel.

IHADA Medicated Clear Lotion is the whitening type, and the speaker asked viewers to note that it is different from the regular moisturizing type. It contains tranexamic acid and dipotassium glycyrrhizate as active ingredients and has whitening and skin-roughness prevention claims.

CeraCure White Lotion is a new medicated lotion from Ceralabo, the brand the speaker runs. It contains tranexamic acid as its sole active ingredient, with BG as its only moisturizing ingredient. It is glycerin-free, alcohol-free, fragrance-free, colorant-free, and oil-free, with a refreshing, silky feel. It contains three types of human-identical ceramides and was developed as a lotion that supplies ceramides and tranexamic acid at the same time. Its whitening and skin-roughness prevention claims are obtained through tranexamic acid.

The prices the speaker gave are as follows. Chifure Whitening Lotion TA is 1,100 yen (list price) for 180 ml. Shirojun's list price is unknown, and it is sold at drugstores in a 170 ml size (the subtitles sound like "about 7,800 yen," but this may be a transcription error). Hadabisei is 1,540 yen (tax included) for 170 ml. IHADA Medicated Clear Lotion is 180 ml and, as the speaker recalled, 1,980 yen (excluding tax). Transino's lotion is 3,630 yen for 150 ml. CeraCure White Lotion is 3,500 yen (tax included) for 150 ml.

As for medicines, Vitamin C 2000 is 2,521 yen for 300 tablets. The speaker noted that the price has continued to rise compared with before. For Transino White C Clear, the small size (120 tablets) the speaker bought at a drugstore was a little over 2,000 yen. On Amazon, 120 tablets are 2,183 yen, and 270 tablets of White C Premium are 3,774 yen. The speaker said prices vary considerably by store, so these should be taken only as a reference.

The speaker expressed the view that combining oral medicines such as vitamin C or Transino with tranexamic acid skincare might maintain skin lightness, relieve dark spots, and also improve pigmentation.

Finally, the speaker shared their personal thoughts on this research. A while ago, the speaker had released a video arguing, in essence, that "tranexamic acid is better used topically than taken orally."

At the time, the speaker said, there were too many cases of clinics prescribing tranexamic acid for cosmetic purposes. Tranexamic acid is also highly popular as an oral medicine to reduce throat inflammation, and throat colds were going around at the time. The speaker recalled that, as a result, it was a period when there were rumors that it sometimes could not be prescribed as a remedy for sore throats. They had also heard talk about whether or not some doctors were prescribing it for cosmetic purposes even to people without melasma. There was also a situation in which influencers were casually saying "take tranexamic acid orally," and too many people were getting prescriptions without thinking it through.

However, according to the speaker, oral tranexamic acid is approved only as a treatment for melasma among the various types of dark spots. Unlike vitamin C, it is not approved for improving common dark spots or post-acne pigmentation. According to the explanation in the package insert, melasma is a type of dark spot that frequently appears on women's faces, and it develops with the involvement of female hormones. It is characterized by being slightly worsened by UV, light brown and somewhat large, and appearing roughly symmetrically on both sides along the cheekbones, and it is said to be rarely seen in elderly people. The argument of the earlier video was that taking it under the assumption that it will lighten the skin when you don't have melasma is misguided, and that for people without melasma, applying a quasi-drug with an approved whitening claim would likely be more effective than taking it orally.

The speaker also pointed out the risks of oral intake. Because tranexamic acid is a hemostatic agent, taking it orally inevitably produces a hemostatic effect. Although cases are rare, it is not to be used by people who have thrombosis or who are at risk of developing thrombosis. Blood becomes more likely to clot, and the risk of blood vessels becoming blocked is not zero. Many people are warning that it should not be taken indiscriminately, and the speaker thinks so as well. The speaker's position is that topical use is better if you want to minimize the risk as much as possible.

The speaker sees this research as one kind of answer to that argument. Their assessment is that it is highly significant that the very manufacturer that sells oral tranexamic acid has shown it is highly likely to be effective topically as well.

However, this was strictly an in vitro test using excised skin, not a test on actual human bodies. The speaker expects that clinical trials on humans will be conducted in the future and concluded by saying they would like to wait for that further research.