Improvement of Melasma by Niacinamide Through Reducing Vascularity and Inhibiting

Improvement of melasma by Niacinamide through Reducing Vascularity and Inhibiting

Melanogenesis

Ju Yeon Kim1, Sun Hwa Lee1, Bora Kim1, Nam Soo Kim1, Tae Kee Moon1*

1Skin&Bio Research Ellead, 325, Hwangsaeul-ro, Bundang-Gu, Seongnam-Si, Gyeonggi-Do,

463-824, South Korea

*Correspondence: Tae Kee Moon, M.S.

Skin&Bio Research Ellead, 325, Hwangsaeul-ro, Bundang-Gu, Seongnam-

Si, Gyeonggi-Do, 463-824, South Korea

Tel.: +82-31-709-9070; Fax: +82-31-703-9071

E-mail address: [email protected]

Keywords: Melasma lesions, Lentigo lesions, Non-lesional skin, Redness, Vascularity Abstract

Background: Melasma has several well-recognized etiologic factors, but most researches focus on melanogenesis. Therefore, studies for melanogenesis as well as other etiologic factors are needed. The purpose of this study is to show improvement of melasma by reducing vascularity – another etiologic factor distinguished from melanogenesis.

Method: In this study, we examined 20 Korean women with both melasma and solar lentigo which were visually assessed by a dermatologist. The subjects applied 2% niacinamide lotion, essence and emulsion, in this specific order, to their face twice a day for 8 weeks. We measured the skin color of each subject’s melasma lesions, solar lentigo lesions, and non- lesional skin using chromameter CR-400.

Results: We analyzed the results obtained by the chromameter, evaluating the skin color of three areas on the face in which the subject applied 2% niacinamide. There was a statistically significant improvement in the brightness and redness of melasma lesions compared to those of non-lesional skin after 8 weeks. Also, we observed that the improvements in the brightness of melasma lesions and solar lentigo lesions were similar. But on the other hand, the redness of melasma lesions improved more than that of solar lentigo lesions with statistical significance after 8 weeks.

Conclusion: In this study, we have shown that niacinamide is an efficient cosmetic material which improves not only brightness but also redness in melasma lesions. So, we suggest redness to be an additional suitable parameter for the evaluation of melasma lesions. Introduction

Melasma on the skin is a common problem to Asian and Hispanic women [1]. A lot of researchers have studied to investigate causes of melasma. According to the results, melasma has several well-recognized etiologic factors (UV light exposure, hormone change, defective barrier function, increased vascularity, and inflammation), but its exact pathogenesis has not been yet fully understood [2, 3, 4, 5, 6].

Melanin is the key material that leads directly to melasma. Researchers have developed medications and cosmetics that are focused on the melanin for the treatment of melasma.

Thus, the value L* is a good parameter to investigate brightness improvement in melasma lesions [7]. To investigate improvement in melasma through treatment for other cause such as increased vascularity, we have to depict and analyze a new parameter, which is the value a* for redness [8]

Niacinamide has various functions for skin. First of all, it is widely known as a skin- whitening substance [7, 9]. Previously, the studies have shown niacinamide inhibit melanosome transfer, suggesting that the substance reduces melasma [9].

Niaciamide decreases redness through improving stratum corneum barrier function and hydration in rosacea [10, 11]. And it decreases vascularity thereby acting as an inhibitor of vasoactive amines [12]. Furthermore, niacinamide has a strong anti-inflammatory effect for acne which is a chronic inflammatory disease [12, 13]. Among these symptoms, damaged stratum corneum barrier function caused by UV light exposure, increased vascularity related to vasoactive amine, and inflammation by melasma - all of them are involved with redness

[10, 11, 12, 13].

As mentioned above, niacinamide which has various functions for skin can improve brightness and redness. Therefore, this study was conducted to assess the effects of niacinamide which improved brightness and redness in melasma. Materials and Methods

Subjects:

The protocol was reviewed and approved by the Institutional Review Board (IRB) in Ellead

Co., Ltd.

We included twenty healthy Korean females (aged 44.45 ±5.29) who had melasma and solar lentigo simultaneously on the face. Our inclusion criteria were women at least 18 years old without any clinical skin care investigation and dermatologist treatments on the face within the last three months. Women were excluded if they were pregnant, planning to be pregnant, nursing or had a history of hypersensitivity to any of the components of the study.

Method:

Subjects applied 2% niacinamide lotion, essence and emulsion in this specific order to their face twice a day (in the morning and evening) during the treatment phases, but they were not allowed to use other whitening cosmetics during the study. When subjects went out, they applied their usual sunscreen product which did not include whitening material.

Each subjects visited our facility, four times during two months (at base line, 2 weeks, 4 weeks and 8 weeks) for measurement. No use of facial cosmetics was allowed on scheduled evaluation days. When they arrived at our lab, they washed their faces with the supplied clean sing foam. After washing their faces, the subjects stayed to equilibrate at 22°C±2° and

50%±5% RH condition for 30 minutes before being tested.

The skin brightness and skin redness (erythema) were measured three times by Chromameter

CR-400 (Minolta, Japan), on melasma lesions, solar lentigo lesions and non-lesional skin.

Total color difference (ΔE) is calculated from CIE L*a*b* [14]. ΔE was calculated between solar lentigo lesions and non-lesional skin, between melasma lesions and non-lesional skin, between melasma lesions and solar lentigo lesions.

All measurements were conducted three times and an average was obtained to evaluate correlations. The relationship between each measured areas at baseline was tested with with the paired t-test (p<0.05) and repeated measures of ANOVA (p<0.05). All efficacy evaluation parameters were analyzed using descriptive statistics. The follow-up results were compared to baseline results using repeated measures of ANOVA (p<0.05).

The statistical software used was IBM SPSS statistics version 21.0 (SPSS, Chicago, IL,

USA). Results

1. Measurement of skin brightness and redness at melasma lesions, solar lentigo lesions and non-lesional skin

According to the L* for brightness, melasma lesions and solar lentigo lesions showed lower than non-lesional skin with statistical significance of p<0.05* at baseline in Table 1. Also, melasma lesions in the redness showed higher than non-lesional skin with statistical significance of p<0.05, but there was no statistical significance between solar lentigo lesions and non-lesional skin. The ΔE was calculated between non-lesional skin and other areas such as with melasma lesions and solar lentigo lesions. There was no statistical significance between the two ΔEs at baseline in Table 1.

2. Improvement of skin brightness, redness and ΔE in three lesions of the face

The brightness and redness were improved in melasma lesions, solar lentigo lesions and non-lesional skin with statistical significance of p<0.05* at 8 weeks (Table 2). Also, ΔE of melasma lesions and solar lentigo lesions were decreased. Table 2 shows this decrease with statistically significant of p<0.05* at 8 weeks.

3. The overall statistical analysis between three lesions of the face

The statistical analysis of chromameteric values between three lesions of the face are shown in Table 2. The analysis of a * shared higher improvement rate in melasma lesions than solar lentigo lesions with statistical significance of p<0.05* at 8 weeks, but value of L* and ΔE were not. The value of L* and a* improved higher in melasma lesions than non-lesional skin with statistical significance of p<0.05* at 8 weeks. On the other hand, the analysis of L* shared higher improvement rate in solar lentigo lesions than non-lesional skin with statistical significance of p<0.05* at 8 weeks, but the value of a* was not. Discussion

Most middle aged women are concerned about hyperpigmentation such as melasma and solar lentigo. A few pathogenesis of melasma such as UV light exposure, hormone change, increased vascularity, defective barrier function, and inflammation have been identified [2, 3,

4, 5, 6, 15]. In this study, we considered solar lentigo. The pathogenesis of solar lentigo is commonly known in relation to UV light exposure [16, 17]. According to the previous studies, pathogenesis of melasma is more varied and complex than pathogenesis of solar lentigo.

Although the most of clinical studies showed increased melanin in the both of the lesions, alteration of vascularity was referred an another pathogenesis in case of melasma.

In this paper, we analyzed the results obtained by the chromameter in evaluating the skin color of three areas on the face of which subject applied 2% niacinamide lotion, essence and emulsion in this specific order for 8 weeks. After 8 weeks, the brightness of mealsma lesions, solar lentigo lesions, and non-lesional skin increased 1.14%, 1.13%, and 0.37% respectively.

According to the result, we observed that the brightness of melasma lesions and solar lentigo lesions increased more than that of non-lesional skin with a statistical significance of p<0.001***. However, after 8 weeks, the increased rates of brightness between melasma lesions and lentigo lesions did not have statistical significance. Also, according to the result comparing of colors difference between melasma lesions and solar lentigo lesions through ΔE, which was calculated with non-lesional skin after 8 weeks, both melasma lesions and solar lentigo lesions colors were getting close to non-lesional skin color with statistical significance of p

<0.05*. Through these results, we knew that the brightness of mealsma lesions and solar lentigo lesions was similarly improved.

On the other hand, after 8 weeks, we observed that the redness of melasma lesions decreased more than that of solar lentigo lesions and non-lesional skin with statistical significance of p<0.01**. The redness of mealsma lesions, solar lentigo lesions, and non- lesional skin decreased 8.19%, 2.81%, and 2.96% respectively after 8 weeks. According to the previous studies, the value of a* was higher in the melasma lesions than in non-lesional skin because vascularity was increased in melasma lesions [5]. In our study, the value of a* was higher in the melasma lesions than in non-lesional skin with statistical significance of p

<0.05*. These results showed that increased redness because of increase in vascularity could be improved by niacinamide. So, it is possible to speculate that melasma lesions improved not only in brightness but also redness because niacinamide was involved in decrease in vascularity.

In this clinical study, we showed that the efficacy of niacinamide as a cosmetic material. We also observed that the improvement rate of redness in melasma lesions was particularly higher than solar lentigo lesions and non-lesional skin. Through this study, we propose that redness can be the foundation for a new parameter to evaluate melasma lesions. References

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Table 1. The statistical analysis of chromameteric mean values between each measured areas (melasma lesions, solar lentigo lesions and non-lesional skin) at baseline.

(Melasma lesions vs. Melasma lesions Melasma lesions Solar lentigo Non-lesional skin) vs. Baseline vs. Solar lentigo vs. Non-lesional lesions vs. Non- (Solar lentigo lesions vs. lesions skin lesional skin Non-lesional skin) L* 0.117 <0.001*** <0.001*** a* 0.831 <0.05* 0.083 ΔE 0.266

Probability p (Paired t-test) Probability p (Repeated Measures ANOVA: *p<0.05, **p<0.01, ***p<0.001)

Table 2. The chromameteric mean values and statistical analysis with melasma lesions, solar lentigo lesions and non-lesional skin.

Baseline 8 weeks P Value Melasma lesions 62.66±2.71 63.37±2.63 <0.001*** L* Solar lentigo lesions 61.95±1.89 62.65±1.79 <0.001*** Non-lesional skin 65.37±2.26 65.62±2.29 <0.01** Melasma lesions 13.14±2.00 12.06±1.67 <0.001*** a* Solar lentigo lesions 13.03±1.64 12.66±1.43 <0.05* Non-lesional skin 12.21±2.14 11.85±2.08 <0.05* Melasma lesions vs. Non-lesional skin 3.71±1.70 3.31±1.53 <0.05* ΔE Solar lentigo lesions vs. Non-lesional skin 4.28±1.78 3.96±2.01 <0.05* Probability p (Repeated Measures ANOVA: *p<0.05, **p<0.01, ***p<0.001)

Table 3. The statistical analysis of chromameteric values between three areas on the face (melasma lesions, solar lentigo lesions and non-lesional skin) after 8 weeks.

(Melasma lesions vs. Melasma lesions Melasma lesions Solar lentigo Non-lesional skin) vs. 8 weeks vs. Solar lentigo vs. Non-lesional lesions vs. Non- (Solar lentigo lesions vs. lesions skin lesional skin Non-lesional skin) L* 0.854 <0.001*** <0.001*** a* <0.01** <0.01** 0.982 ΔE 0.665 Probability p (Repeated Measures ANOVA: **p<0.01, ***p<0.001)