Various studies have shown that niacinamide can suppress melanocyte transfer and thus reduce hyperpigmentation of the skin. The underlying study provides clinical evidence that niacinamide also has this effect on melasma. In addition, various positive effects of topical application of niacinamide on the skin have been demonstrated, such as the prevention of photoimmunosuppression and photocarciogenesis as well as anti-inflammatory effects in acne, rosacea and psoriasis. In addition, niacinamide increases the biosynthesis of ceramides and other lipids of the stratum corneum with improved barrier function of epidermal permeability. Furthermore, anti-aging effects have been demonstrated in randomized test series.

The underlying, randomized, right-left-blind, double-blind study aims to compare the effect and safety of use of 4% niacinamide with that of 4% hydroquinone using subjective and objective methods. The study involved 27 adult women. They were required not to have received any topical, systemic, surgical or laser treatment on the face in the previous year.

Pregnant or breastfeeding women, women with a hypersensitivity to the ingredients of the formulations tested and women who had been affected by similar pigmentation diseases at the same time during the study were excluded from participation.
Precise statistical data were recorded for each participant, such as age, occupation, ethnicity, employment, pregnancy history if applicable, use of hormonal contraceptives (“pill”), duration of sun exposure and onset of the pigmentation disorder.

At the start of the study, two 2 mm biopsies were taken from each of the 27 participants, one from the pigmented skin and one from the facial skin not exposed to sunlight. These were stained with hematoxylin and eosin to determine the general histopathological characteristics of the epidermis and dermis.

The number of infiltrates was counted manually by two independently blinded observers. A 0.5 x 0.5 mm ocular grid with a hundredfold magnification was used for this purpose. The cells of the entire section were counted and the result was defined as the number of cells per square millimeter. The same procedure was used to count the melanocytes (stained according to the Fontana-Masson method) and the metachromatic granules (stained according to the Wright-Giemsa method). Forty-fold magnification was used to count the epidermal melanin. A digital camera mounted on a microscope (Olympus CX 31) was used to take photographs of the entire 2 mm sample of epidermis.

This image material was examined using the Image-Pro Plus version 4.5 analysis program from Media Cybernetics, Silver Spring, MA, USA. In order to detect possible abnormalities in melanin in study participants with melasma, a qualitative Raman spectrophotometry examination was also performed by Horiba, Jobin-Yvon T64000, Edison, NJ, USA, before and after the actual study. Edison, NJ, USA.

The study participants were given one application on the right side of the face and another application on the left side of the face in a double-blind procedure. Each participant was given a container labeled “right” or “left” containing either 4% niacinamide or 4% hydroquinone. All study participants were instructed to apply the correct amount of both creams to the corresponding side of the face and to apply a broad-spectrum sunscreen (SPF 50+) for three hours a day.

During the course of the study, the participants were not permitted to use other skin care products at the same time or to undergo corresponding treatments. The treatment took place over a period of 8 weeks, with a baseline and follow-up examination being carried out after 4 and 8 weeks respectively. At these times, an examination of the skin pigment was carried out using a chromameter (model CR-300, from Minolta, Osaka, Japan) and an assessment of the severity of the area affected by melasma was carried out using the “severity index” (MASI), as well as a general examination (PGA) by an independent observer. Both conventional photography and infrared thermography (Flexcam S from Infrared solutions, USA) were used to detect and document skin irritation. Any side effects that occurred were documented.

Eight weeks after the start of the study, it was unblinded in order to take a 2 mm biopsy of the side of the face treated with niacinamide. The Student t-test and X2 were used for statistical analysis, with a value of P less than 0.05 being treated as significant.

Of the twenty-seven study participants with melasma, 12 (33%) were type IV (according to the “Fitzpatrick skin scale”) and 13 (48%) were type V.
The melasma was localized centrofacially in 13 (50%), malar in 10 (37%) and mandibular in 4 (14%). The age range of the study participants was between 25 and 53 years (mean 37 years), with the duration of melasma ranging from 4 to 8 years (mean 6.5 years). 19 (70%) of the participants had melasma within the family. Exposure to sunlight was found to be the most common trigger factor for melasma formation, followed by pregnancy. Eight study participants (29%) were taking oral contraception. At the beginning of the study, the average MASI score for the hydroquinone-treated side of the face was 4 (5% CI, 90.9-1.8) and after eight weeks (P<0.001) it was 1.2 (95% IC, 0.8-1.6)

The side of the face treated with hydroquinone was rated as excellent by seven study participants, good by eight, moderate by six and mild by a further six. The data obtained showed statistical significance for both treatments, with that of niacinamide (P = 0.005) being higher than that of hydroquinone (P = 0.003). Colorimetric examinations were performed at the beginning and at the end of the study; both the luminosity axis (L∗) and the redness axis (a∗) were evaluated. The lightening effect of both hydroquinone and niacinamide was visible after a treatment period of four weeks and became even more evident after eight weeks. Colorimetric measurements showed no statistically significant differences between the two treatments.

However, the reddening of the skin was more intense on the half of the face treated with hydroquinone. Thermographic examinations carried out with infrared light at an ambient temperature of 21 degrees Celsius showed a reduction in temperature of 0.8 degrees Celsius on both halves of the face after treatment, but with no statistical differences between the two treatments.

Side effects occurred with niacinamide in only 5 study participants (18%), but with hydroquinone in 8 study participants (29%). The most common side effects were skin redness (erythema), itching (pruritus) and burning. With niacinamide, most of these symptoms were mild, while with hydroquinone these side effects were described as moderate. Skin redness (erythema), itching (pruritus) and burning occurred in 5 study participants (18%) with hydroquinone, but only in 2 (7%) with niacinamide, but decreased with continued treatment throughout the course of the study.

Conclusion

Melasma is a chronic and permanent hyperpigmentation of the skin and poses a therapeutic challenge due to its high rate of recurrence. In the underlying study, 4% niacinamide was shown to be effective against melasma by clinical investigations and objective methods.

It was shown that the amount of epidermal melanin and inflammatory infiltrate was significantly reduced in the tissue samples obtained after treatment. Actinic elastosis was also reduced.

The possible mechanisms of action of niacinamide in the successful treatment of hyperpigmentation are the reduction of melanocyte transfer, its protective effects against the effects of light irradiation and its anti-inflammatory properties. A direct or indirect anti-ageing effect through the reduction of acinic elastosis is also addressed in the underlying study.

The scientific conclusion of the underlying study is that niacinamide is an effective, integral and safe agent for the treatment of melasma, as it not only significantly reduces pigmentation and inflammation levels, but also damage caused by sunlight exposure with minimal side effects.

Underlying study:

Navarrete-Solis, J. et al: A Double-Blind, Randomized Clinical Trial of Niacinamide 4% versus Hydroquinone 4% in the Treatment of Melasma; in: Dermatology Research and Practice, Volume 2011, Article ID 37917