By Catheleen Anne Ysulat, Harumi Suzuki, Shodai Ushijima, Satoshi Yoshimoto – NIKKOL GROUP NIKKO CHEMICALS
The number of people suffering from sensitive skin caused by atopic dermatitis, allergies, air pollutants, temperature changes, stress, etc., is increasing, and sensitive skin cosmetics which claim low irritation and skin barrier repair have become essential products for such people. According to “The prevalence of sensitive skin,” 60-70% of women and 50-60% of men report having some degree of sensitive skin on surveys conducted in 20 different countries in 5 continents.1
Furthermore, in recent years, harsh skin care routines have spread among Gen Z and Millennials, and many consumers’ skin has become thinner with weakened barrier function due to the side effects of peeling and care with retinol. There are 1.77 million posts about #sensitiveskin and 540,000 posts about #skinbarrierrepair on Instagram. #sensitiveskin has been tagged over 122,000 times on TikTok videos (as of February 2024). Not only patients with atopic dermatitis, but also people with originally healthy skin conditions are starting to suffer from sensitive skin.
The growing demand for truth-based and scientific evidence is pushing the rise of clinically proven ingredients. The lysophosphatidic acid introduced here as NIKKOL LECINOL® MFL is rooted in long term scientific studies and addresses a wide range of skin barrier disorders to recover sensitive skin. In this article, we named the skin benefits from NIKKOL LECINOL® MFL (INCI: Lysolecithin) as “POWER of 6”.
NIKKOL LECINOL® MFL is an optimized product of lysophosphatidic acid for cosmetic material

One way to improve the skin barrier is to increase the barrier component derived from keratinocytes that can help in retaining the moisture in the skin. We are especially focused on lysophosphatidic acid, which is a type of lecithin, because our body originally uses lysophosphatidic acid as a support system for the skin barrier. It has long been known that lysophosphatidic acid regulates the fate of keratinocytes (e.g. differentiation, migration, proliferation), and contribute to the construction of skin barrier. Literature on such skin wound healing has been published since the 1990s. Therefore, we have newly developed a Lysolecithin containing lysophosphatidic acid as the active substance, using “whole-cell enzyme technology.”
Bioprocessing technology that uses enzymes and other beneficial biological reactions have mild manufacturing conditions compared to chemical reactions and are a promising technology for realizing a “Recycling Society.” NIKKOL LECINOL® MFL is developed by industrialization
of whole-cell enzyme technology, which allows bacteria to produce highly targeted enzymes without genetic modification. This technology can greatly improve the production process by utilizing the culture solution itself or its solid content as a biocatalyst for reactions without isolating and purifying the enzyme.2 The production uses plant-derived materials, soybeans, that also are not genetically modified. Both the bacteria and soybeans are non-GMO. Furthermore, our whole-cell enzyme technology upcycles lecithin derived from the by-products of soybean oil production and turns it into a high percentage of bioactive lysophosphatidic acid.

Gives keratinocytes the ability to produce healthy skin barrier
The main purpose of the skin barrier is for protection and moisture retention. The skin barrier serves to keep foreign materials out and to keep moisture inside. When the barrier function becomes weak, the skin will allow entry of foreign materials, resulting to irritation. A skin barrier dysfunction often surfaces in the form of problems such as sensitive skin and dry skin. There are several ways to produce healthy skin barrier, and one is to supply components to the skin that will hold onto water. Filaggrin, which degrades into amino acids (NMF) in the stratum corneum, retains moisture and thus passively increases skin moisture.3 The other way to hydrate the skin is by creating a barrier, to prevent the moisture from going out of the skin. It involves the ceramides, which make up almost 55% of intercellular lipids that hold the corneocytes together at the stratum corneum. To investigate the effects of NIKKOL LECINOL® MFL on the stratum corneum components, a full 3D skin model was used. Pro-filaggrin, which was detected using dot blot, was increased 4.8 times after one week of treatment of NIKKOL LECINOL® MFL in comparison to the control (Figure 2a). Another SC component, which correlates well with skin moisture and TEWL, are ceramides. After treatment of a 3D skin model with NIKKOL LECINOL® MFL, total ceramides (detected by LC-MS), significantly increased by 1.4 times compared to the control (Figure 2b). Occludins are parts of your tight junction barrier. They form an impenetrable wall located between the cells2 so that no water or foreign materials can pass (Figure 2c).
In addition, cell proliferation, cell migration, and resistance to stress are also important factors. It is reported that lysophosphatidic acid promotes wound healing. A good method to study wound healing is to analyze the migration of confluent cells in a scratch assay. A silicon chamber was used to create artificial scratches that are uniform in size. In this experiment, each scratch was made by the removal of the silicon sheet, and afterwards the cells were treated with NIKKOL LECINOL® MFL for 24 hours on one of the scratches and left untreated on the control. The cells of both samples were then treated with Calcein in order to visualize the results in a fluorescent microscope. In the resulting figure, the thick black area is the scratch, and the blue area is the keratinocytes. The results have shown that the NIKKOL LECINOL® MFL-treated scratch has better closing capability compared to the control. The cells in the leading edge of the scratch, presented by arrows, have migrated towards the center. In the NIKKOL LECINOL® MFL-treated scratch, there are more cells migrating towards the center. In a wound, this is important because the faster the cells can get to the wound site, the faster it will heal. Therefore, NIKKOL LECINOL® MFL was found to promote migration of the cells in a scratch assay (Figure 2d).


Resolves sensitive skin symptoms A clinical study was conducted to investigate the changes in skin physiological indicators before and after continuous use of NIKKOL LECINOL® MFL in subjects with sensitive skin (LAST positive subjects). The formulation used is in a form of milky emulsion. The composition of the formulation is shown in Table 1. The clinical study was done on 13 female subjects, ages 37 to 50. In the study, half of the face was used for placebo cream and the other half for 0.1% NIKKOL LECINOL® MFL. The subjects applied the test samples twice a day (once each in the morning and evening), which lasted for 4 weeks. The skin parameters that were analyzed are: lactic acid sting test reaction as sensitive skin characteristic (LAST score), redness, water content, TEWL, pore size and skin roughness. Each measured value was summarized in Table 2.
■Resolves sensitive skin’s hyper-reactivity
Sensitive skin has hyper reactivity to various stimuli like cosmetics or temperature.4 Although the pathophysiology of sensitive skin is not entirely understood, it can be related to the damage on the skin barrier function.5 Lactic acid stinging test is a classical method to identify sensitive skin. When a dysfunctional skin barrier is restored, the degree of stinging that can be felt from lactic acid also decreases with the level of repair. In our study, the score of the lactic acid sting in the nasolabial groove was significantly improved from 4.0 (score at median value) to 2.0 at week 4 after using NIKKOL LECINOL® MFL (Table 2a). The difference value (∆) of the lactic acid sting score in the NIKKOL LECINOL® MFL-treated test area was significantly lower compared to the placebo (Figure 3a). This shows that, from the subjective feeling of the subject, NIKKOL LECINOL® MFL alleviates the tingling sensation from lactic acid after four weeks of use.


Figure 3: The factors related to healthy skin supported by NIKKOL LECINOL® MFL are shown in the hexagonal image. (a) Box plot of DLAST score, (b) Subject images of cheek , visible pores and redness. For the lactic acid stinging test, subjects were asked to score their self-perceived symptoms that was recorded by a trained professional researcher. Skin erythema Index EI was measured using a heme tester Mexameter® MX 18. Facial image capture was done using VISIA® and Derma TOP. Measurement of the moisture content in the stratum corneum of the cheek was done using Corneometer® CM 825. TEWL was measured using a moisture loss tester Tewameter® TM 300. Skin texture was analyzed using VisioScan® VC20 Plus and acquiring R2 value. All the mentioned skin parameters were analyzed before the test and after 4 weeks of use. Statistical significance was determined by paired t-test, (n=13).

Table 3: Summary of the in vivo parameters (0.1% NIKKOL LECINOL® MFL)
Leads to healthy skin
Furthermore, reduction in sensitive skin symptoms correlated well with improve major skin parameters such as hydration, water loss, redness, pore size and roughness (Figure 3b).
■Improves hydration
It was found that the moisture content of the stratum corneum increased from 32.4 to 35.4 after 4 weeks of continuous placebo use. Surprisingly, a Corneometer® reading of 32.7 increased to 48.6 after 4 weeks of using NIKKOL LECINOL® MFL (Figure 3c). This is a massive 1.5 times increase, in comparison to the initial measurements done on skin. This also made skin moisture by NIKKOL LECINOL® MFL significantly higher in comparison to the placebo. In literature, Corneometer® reading of less than 30 indicates very dry, less than 40 as dry, and more than 40 as normal or hydrated.6 In the clinical study, the average Corneometer® reading of the volunteers reveals that the skin is on the dry side at the point of initial value. From in vitro tests, NIKKOL LECINOL® MFL increases moisture-related genes: AQP3, FLG, INV, SPT, OCLN (data not shown) and skin barrier components. In human trials, this combined effect meant 0.1% NIKKOL LECINOL® MFL significantly increased total skin moisture.
■Restores barrier
Trans-epidermal water loss has long been a measure of skin barrier integrity. It measures the amount of water that escapes per area of the skin. In the clinical test, the TEWL of the cheek detected by Tewameter® was significantly decreased from 19.5 g/m2/h to 15.5 g/m2/h after 4 weeks of use of 0.1% NIKKOL LECINOL® MFL, compared to the initial measurements done on skin. This shows that NIKKOL LECINOL® MFL can improve the skin barrier and can help the skin retain moisture.
■Reduces redness
Objectively, skin sensitization can also be evaluated by measuring the redness of the skin using Mexameter®. Skin redness is a condition that arises from skin irritation and inflammatory reaction that results to vascular dilation that is making the face appear red.7 This response is attributed to the increase in skin permeability due to a dysfunctional skin barrier.8 Similar to the degree of LAST response, the amount of repair on skin barrier is mirrored by the amount of the alleviated redness. The erythema index of the skin was significantly decreased at week 4 after using NIKKOL LECINOL® MFL, compared to the initial. In comparison to the placebo, the erythema index in NIKKOL LECINOL® MFL-treated skin was also significantly lower.
■Shrinks visible pores
The appearance of visible pores depends on the skin condition. On humans, it was reported that pore sizes increase with age, so older skin has more visible pores compared to younger skin. On younger skin, visible pores are correlated mainly with excessive sebum secretion.9 An oily skin, however, is said to occur in order to compensate for being dehydrated. As for dry skin, it is reported that fluctuations in trans-epidermal water loss, or ∆TEWL, was correlated with pore size.10 The higher the ∆TEWL, the more visible pores were observed. These 3 skin conditions with visible pores also have another thing in common, and that is moisture loss. By improving the skin barrier, skin moisture can be improved, and in effect, the appearance of visible pores can be resolved. Figure 3c shows the representative picture of volunteer # 12 after using NIKKOL LECINOL® MFL for 4 weeks. Using an instrument called Derma TOP, the pores were converted into white spots that can be easily seen and analyzed. In the figure, the effect of 0.1% NIKKOL LECINOL® MFL on skin can be visualized compared to placebo. The treated skin has a smaller pore area after 4 weeks of continual use. In comparison, the placebo has no visible change in pore area before and after 4 weeks of use. Measuring the pore area on the cheek that used NIKKOL LECINOL® MFL showed that the pore area was significantly decreased, from 4.8 mm2 to 2.9 mm2 after 4 weeks of use, in comparison to the initial values. In comparison to the placebo, NIKKOL LECINOL® MFL tended to decrease the pore area more than the placebo after 4 weeks of continual use.
■Smooths out rough skin
Another skin parameter that has correlations with skin moisture and TEWL is skin texture. The R2 value of Visioscan® gives a quantifiable value to the physiological condition of the living skin surface.11 R2 refers to the maximum roughness, and lowering the R2 value lowers the skin texture. In the study, the cheek skin texture R2 was significantly decreased from 82.5 to 75.5 at Week 4 after using NIKKOL LECINOL® MFL.
CONCLUSION
“MFL” is an abbreviation for “Multi-Functionalized Lecithin.” By industrialization of whole-cell enzyme technology, NIKKOL LECINOL® MFL was developed as a product with high naturality and sustainability. NIKKOL LECINOL® MFL can do multiple tasks to improve the skin barrier. It targets multiple skin-barrier related genes and promotes protein and lipid production of skin barrier related components. It can provide multiple skin benefits: improve hydration, restore barrier function, smooth out rough skin, shrink visible pores, reduce redness and ultimately resolve sensitive skin signs (Table 3). NIKKOL LECINOL® MFL, therefore, exhibits total support for skin barrier formation, and is a highly useful functional ingredient.
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- Roh M, Han M, Kim D, Chung K. Sebum output as a factor contributing to the size of facial pores. Br J Dermatol. 2006 Nov;155(5):890-4.
- Miyamoto, K.; Munakata, Y.; Yan, X.; Tsuji, G.; Furue, M. Enhanced Fluctuations in Facial Pore Size, Redness, and TEWL Caused by Mask Usage Are Normalized by the Application of a Moisturizer. J. Clin. Med. 2022, 11, 2121.
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