Efficacy of lycopene, beta-carotene and Lactobacillus johnsonii in the maintenance treatment of melasma during the summer

Received on: 8 November 2011
Approved on: 10 December 2011

This study was carried out at the Cosmetic
Dermatology Outpatient Clinic of the
Hospital Federal de Bonsucesso.

Financial support: Medication provided by La
Roche Posay (Brazil) and INNÉOV (France).
Conflicts of interest: None

Abstract

Introduction: Melasma, a very frequent acquired hypermelanosis can be treated topically, however some studies have shown that oral antioxidants could reduce the deleterious effects of ultraviolet radiation on the skin.
Objective: To evaluate the effects of oral antioxidants and UVA/UVB sunscreen on the development of melasma during the summer months in Rio de Janeiro (RJ), Brazil – a period when the condition recurs more frequently.
Methods: Patients (n = 68) with melasma were randomized to receive one capsule/day of the nutri-concentrate (containing lycopene, beta-carotene and Lactobacillus johnsonii) and apply sunscreen every 3 hours (Group A) or sunscreen only (Group B). The patients were photographed and evaluated according to the Taylor Hyperpigmentation Scale and the Melasma Area Severity Index.
Results: The study was conducted from December 2010 to March 2011. Group A presented reductions in melasma of 8.5% on the Taylor scale and 19.5% on the Melasma Area Severity Index (p < 0.001). In Group B, the melasma worsened on the Taylor scale and improved 4.6% on the Index.
Conclusions: The use of a nutri-concentrate containing beta-carotene, lycopene and Lactobacillus johsonii combined with an SPF 60 sunscreen was an effective treatment for melasma during the summer. The treatment had a statistically significant reduction according to the Melasma Area Severity Index.

Keywords: MELANOSIS, CAROTENOIDS, LACTOBACILLUS, CLINICAL PROTOCOLS

INTRODUCTION

Melasma is an acquired hypermelanosis that occurs more frequently in women and is characterized by brownish stains located mainly on the face. It has a multifactorial pathogenesis and can be influenced by genetic predisposition, exposure to ultraviolet radiation, pregnancy, hormone therapy and phototo- xic drugs. 1 Melasma can be classified according to the affected area or the depth of deposition of melanin.

Melasma can also be classified according to its topography, and can be extra-facial or facial; the latter category is subdivided into centrofacial, malar and mandibular. Of those subtypes, the most common is centrofacial, which consists of stains on the cheeks, nose, upper lip, chin and forehead regions. 1, 2

In order to assess the location of the pigment, the affected skin can be analyzed through histopathological examination, Wood light and dermoscopy. 3 Through histopathology it is pos- sible to observe the distribution of melanic pigment in the fol- lowing regions: basal and/or suprabasal (epidermal melasma), epidermis and superficial or medium dermis and inside mela- nophages (dermal melasma). With Wood light, melasma can be categorized as more evident (epidermal melasma), less evident (dermal melasma) or irregular (mixed melasma). Using dermos- copy, epidermal melasma is characterized by a brownish color and regular pigmented network, dermal melasma by a bluish- gray color and irregular network, and mixed melasma contains both of these features. 3

Melasma can be treated topically with acid-based medica- tions, bleaching agents,, steroids and sunscreens, in addition to changes in patients'''''''' sun exposure habits. The most studied and successful treatment is a combination of retinoic acid, hydroqui- none and corticosteroids. 4 Nonetheless, not all patients respond satisfactorily to these treatments, and even those who may have improved can experience a recurrence of the condition – espe- cially during the summer, when the intensity of ultraviolet radiation is greater.

Some recent studies have demonstrated that the use of oral antioxidants could reduce the harmful effects of ultraviolet radiation on the skin. 5 Different substances with antioxidant activity have yielded this result and a nutri-concentrate com- pound with lycopene, Lactobacillus johnsonii and beta-carote- ne have also been used for this purpose. 6 Given the clear corre- lation between solar radiation and the worsening of melasma, we hypothesized that taking a nutri-concentrate with that com- position could help stabilize the condition during periods with more intense ultraviolet radiation – especially during the sum- mer in cities such as Rio de Janeiro.

This study evaluates the development of melasma with the use of oral antioxidants and UVA/UVB sunscreen during the summer months in Rio de Janeiro, the time with the highest levels of ultraviolet radiation.

METHOD

This prospective, randomized, controlled study involved 68 melasma patients who were being monitored and treated at the Cosmiatry Outpatient Clinic of the Dermatology Clinic of the Hospital Federal de Bonsucesso, Rio de Janeiro (RJ), Brazil. All patients signed a term of free and informed consent. The study protocol was approved by the Ethics and Research Committee of the hospital. The study began in December 2010 and ended in March 2011.

The inclusion criteria were: women aged 30-60, phototy- pe III, IV or V (according to the Fitzpatrick scale), with facial melasma, who had been treated for at least 3 months. Study par- ticipants agreed to: replace their previous treatment with the study therapy, take the nutri-concentrate capsules as recommen- ded, avoid excessive sun exposure and apply sunscreen as direc- ted, and attend the control visits. The exclusion criteria were: patients with a known allergy or intolerance to the study subs- tances proposed, those who were not willing or unable to use sunscreen during the study, patients who could not attend the control visits, and pregnant or breastfeeding women.

The nutri-concentrate used in this study was Inneov Solar ®, supplied by the company Inneov (INNÉOV, France). The sunscreen used was Anthelios 60 Cream®, supplied by the company La Roche Posay (La Roche Posay, Brazil).

Patients were randomized into two groups of 34 cases each. Patients in Group A were treated with 1 nutri-concentra- te capsule/day and applied sunscreen every 3 hours. Patients in Group B only used the sunscreen, in the same frequency. The patients were photographed and asked to answer a questionnai- re at the first visit (D0) and every 4 weeks until the end of the study (D4, D8 and D12). The melasma''''''''s severity was assessed by the researcher physician using the Taylor Hyperpigmentation Scale 7 (Figure 1) at all consultation visits. The Melasma Area and Severity Index (MASI) 8 was calculated using the pictures taken at each consultation visit by two researcher physicians who were unaware of the classification of patients into groups (blind analysis). All data were subjected to statistical analysis.

Table 1 shows how the degree of each characteristic must be determined when calculating the MASI. The MASI value was calculated using the following formula:

MASI = 0.3 A (D F + H F) + 0.3 A (D RM + H RM) + 0.3 A (D LM + H LM) + 0.1 (D M + H M) where:
"A" = area
"D" = degree of darkening
"H" = homogeneity of the melasma
"F" = forehead
"RM" = right malar
"LM" = left malar
"M" = mentum

The statistical analysis included an exploratory data analy- sis using summarized descriptive statistics (mean, standard devia- tion, minimum, median, maximum, frequency and percentage) and graphs (lines and bars). The between-group comparisons of the MASI scores was conducted using an ANOVA model for repeated measures. For each group, time points were compared using ANOVA models followed by the Tukey''''''''s multiple compa- rison test. The Taylor Hyperpigmentation Scale comparison bet- ween the groups was carried out for each of the follow-up visits using the non-parametric Mann-Whitney U test due to a vio- lation in the normality assumption of the data. The differences between weeks 4, 8 and 12 results compared to week 0 results were used in the analysis. The time points were compared using the non-parametric Friedman test. The Nemenyi test was applied in multiple paired comparisons between weeks. The variables'''''''' normality was assessed using the Shapiro-Wilk test. A 95% confidence level was used in the analysis. The statistical software used in the analysis was XLSTAT 2011.

RESULTS

Three patients in Group A left the study due to vacations taken during the study period. Therefore, the statistical analysis was conducted on 65 patients. Patients were classified according to age as follows: 30-40 years old (19% in Group A and 30% in Group B), 41-50 years old (42% in Group A and 32% in Group B); and 51-60 years old (39% in Group A and 38% in Group B). Most patients were classified as phototype III (55% in Group A and 50% in Group B) or phototype IV (45% in Group A and 41% in Group B). Almost all patients had had melasma for more than 2 years (97% in both groups) and all had undergone some type of treatment. Patients in both groups reported an improve- ment in their melasma (61% of Group A and 53% of Group B). In addition to improvement of the melasma, patients also repor- ted improvements in other characteristics of the skin, such as resistance to sunlight (52% of patients in Group A), skin bright- ness (26% in Group A and 50% in Group B) and firmness (9% in Group A and 11% in Group B) (Graph 1). Group A showed a decrease in their melasma of 8.5% according to the Taylor Hyperpigmentation Scale and of 19.5% according to the MASI; the latter was statistically significant (Graph 2). In Group B, there was a worsening of the melasma according to the Taylor Scale and an improvement of 4.6% according to the MASI (Graph 3).

Among the 31 Group A patients who completed the study, one reported suffering from nausea and another from diarrhoea – sporadic episodes in both cases. In Group B, one patient had comedonal acne due to the use of sunscreen.

(Figures 1, 2, 3 and 4) demonstrate the clinical development of 3 patients in Group A who presented improvement in their melasma during the course of the study.

DISCUSSION

Melasma is a considerably frequent and stigmatizing der- matosis. Although it is widely studied – given the large number of publications on the subject in recent years – its exact patho- genesis is not yet fully determined, and there is no effective treatment for its control and cure. 4 Even in cases that present good clinical results following treatment, recurrences are fre- quent. More recently, treatments with oral antioxidants that decrease the harmful effects of ultraviolet radiation on the skin have been proposed. 5, 9 Several substances have shown such a result, and a nutri-concentrate comprised of lycopene, the pro- biotic Lactobacillus johnsonii and beta-carotene has been used with this purpose. 10

Probiotics are defined as live microorganisms that, when consumed in adequate amounts, benefit the health of their host. The lactic acid bacteria species, including lactobacilli and bifi- dobacteria, are part of the human natural intestinal microbiota. It is known that endogenous intestinal microbiota play a crucial role in the development of the immune system , intestinal inte- grity and defence of the body against pathogens. 6, 9 Some studies have demonstrated that probiotics are able to modulate the immune system at the local and systemic levels, influencing the immunological defence mechanisms and/or assisting in the control of immunological diseases such as bowel inflammations or allergies. 9 In that same study, the authors demonstrated that Lactobacillus johnsonii can decrease UV irradiation-induced depletion of Langerhans cells in the epidermis of mice. 9 Bouilly-Gauthier and others described a reduction in skin damage and skin aging caused by UV exposure with a nutritio- nal supplement containing probiotics and carotenes. 10

In their article on nutritional supplementation, Stahl and colleagues highlight beta-carotene''''''''s photoprotection properties, based on evaluating the skin''''''''s response to sun exposure in a group of patients who took beta-carotene, lycopene and lutein for 12 weeks. The degree of erythema after sun exposure was analyzed at 6 and 12 weeks, and the use of carotenoids was pro- ven to reduce solar radiation-induced erythema. 11

In the present study, due to the high incidence of ultravio- let radiation in the city of Rio de Janeiro, we attempted to veri- fy whether the topical use of a nutri-concentrate composed of lycopene, beta-carotene and Lactobacillus johnsonni would provide additional photoprotection for patients undergoing maintenance treatment for melasma. These patients usually pre- sent a worsening of the condition during the months with the highest intensity of solar radiation. As previously mentioned, we observed that most patients who used the supplement presented clinical improvement in or stability of their melasma during the study period.

Therefore, we conclude that the use of beta-carotene, lyco- pene and Lactobacillus johnsonni was effective as an adjunct treatment in the maintenance of patients with melasma during the summer months.

References

1 . Pandya AG, Guevara IL. Disorders of hyperpigmentation. Dermatol Clin. 2000; 18(1): 91-9.

2 . Gupta A, Gover M, Nouri K, Taylor S. The treatment of melasma: A review of clinicals trials. J Am Acad Dermatol. 2006;55(6): 1048-65.

3 . Tamler C, Fonseca RMR, Pereira FBC, Barcauí CB. Classificação do melasma pela dermatoscopia: estudo comparativo com lâmpada de Wood. Surg Cosmet Dermatol.2009;1(3):115-9.

4 . Rajaratnam R, Halpern J, Salim A, Emmett C. Interventions for melasma. Cochrane Database Syst Rev. 2010; 7(7):CD003583.

5 . Handog EB, Galang DA, de Leon-Godinez MA, Chan GP. A randomized, double-blind, placebo-controlled trial of oral procyanidin with vitamins A, C, E for melasma among Filipino women. Int J Dermatol. 2009;48(8):896-901.

6 . Guéniche A, Philippe D, Bastien P, Blum S, Buyukpamukcu E, Castiel-Higounenc. Probiotics for photoprotection. Dermato-endocrinol. 2009;1(5):275-9.

7 . Taylor S, Westerhof W, Im S, Lim J. Noninvasive techiniques for the evaluation of skin color. J Am Acad Dermatol 2006; 54(5 suppl 2): S282-90.

8 . Pandya AG, Hynan LS, Bhore R, Riley FC, Guevara IL, Grimes P, et al. Reliability assessment and validation of the Melasma Area and Severity Index (MASI) and a new modified MASI scoring method. J Am Acad Dermatol. 2011; 64(1): 78-83.

9 . Pequet-Navarro J, Dezutter-Dambuyant C, Buetler T, Leclaire J, Smola H, Blum S, et al. Supplementation with oral probiotic bacteria protects human cutaneous immune homeostasis after UV exposure-double blind, randomized, placebo controlled clinical trial. Eur J Dermatol. 2008;8(5):504-11.

10 . Bouilly-Gauthier D, Jeannes C, Maubert Y, Duteil L, Queille-Roussel C, Piccardi N, et al. Clinical evidence of benefits of a dietary supplement containing probiotic and carotenoids on ultraviolet-induced skin damage. Br J Dermatol. 2010;163(3):536-43.

11 . Stahl W, Sies H. Photoprotection by dietary carotenoids: concept, mechanisms, evidence and future development. Mol Nutr Food Res. 2011 Sep 23. [Epub ahead of print].