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THERAPEUTIC HOTLINE

Evaluation of an oral supplementcontaining Phyllanthus emblica fruit

extracts, vitamin E, and carotenoids in vitiligo treatment

Roberta Colucci, Federica Dragoni, Rossana Conti,Lisa Pisaneschi

, Linda Lazzeri

& Silvia Moretti

Section of Dermatology, Department of Surgery and Translational Medicine,University of Florence, Florence, Italy

ABSTRACT: Phyllanthus emblica, vitamin E, and caroteinods are compounds showing antioxidative,anti-inflammatory, and repigmenting effects, whose role in vitiligo treatment has not been evaluated sofar. Sixty-five subjects (group A) were treated with one tablet of an oral supplement containing P. emblica (100 mg), vitamin E (10 mg), and carotenoids (4.7 mg) three times/day for 6 months andcompared with a control group (group B, 65 patients), which instead was not treated with antioxidants.Both groups were simultaneously treated with a comparable topical therapy and/or phototherapy. Aftera 6 months follow-up, a significantly higher number of patients in group A had a mild repigmentation

on the head/neck regions (p = 0.019) and on the trunk (trend, p = 0.051). The number of patients whopresented no repigmentation in head/neck, trunk, upper, and lower limbs was significantly higher ingroup B (respectively, p = 0.009, p = 0.001, p = 0.001, p = 0.025). Moreover, group B patients showedhigher signs of inflammation (p = 0.002), a more rapid growth of the lesions ( p = 0.039), a higherpercentage of worsening disease (p = 0.003), and more erythema (p = 0.059), whereas group A patientsshowed a higher percentage of steady disease (p = 0.065). Our results suggest that the supplement withantioxidants in patients with vitiligo might represent a valuable instrument to increase the effectivenessof other vitiligo treatments. [Correction added after online publication 06-Oct-2014: the dosages of vitamin E and carotenoids have been updated.]

KEYWORDS: antioxidants, vitiligo

Introduction Vitiligo is a disease characterized by the appear-ance of depigmented macules, whose pathogen-esis is not completely understood yet (1). Varioustheories have been proposed (1) and among them

there is the autocytotoxic-metabolic theory, sug-gesting the role of an oxidative stress as the basis of melanocyte disappearance (2). Several studieshave shown an impairment in redox system of skinand blood of vitiligo patients, thus resulting inreactive oxygen species (ROS) accumulation (2), whose levels could be also increased by the con-stant inflammatory milieu due to autoimmuneprocesses (3,4).

The abovementioned theory suggests the possi-bility that antioxidants could be useful to reducethe oxidative stress and the consequent damage of

Address correspondence and reprint requests to: Roberta

Colucci, MD, Section of Dermatology, Department of Surgery

and Translational Medicine, University of Florence, Ospedale

Piero Palagi, viale Michelangelo 41, 50125 Firenze, Italy, or

email: [email protected].

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Dermatologic Therapy, Vol. 28, 2015, 17–21

Printed in the United States · All rights reserved © 2014 Wiley Periodicals, Inc.

DERMATOLOGIC THERAPY ISSN 1396-0296

mailto:[email protected]

mailto:[email protected]

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melanocyte, thus contributing to a possiblerepigmentation of the depigmented macules, assome studies demonstrated (5,6).

Phyllanthus emblica (Emblica officinalis ,Indian-gooseberry) is a tree whose fruit extractsshow antioxidative, anti-inflammatory, and repig-

menting effects (7). Also, vitamin E and carote-noids have been reported to share with P. emblicasome similar beneficial properties (8,9). However,their possible role in vitiligo treatment has notbeen evaluated so far.

The aim of our study was to assess the efficacy and tolerability of an oral supplement containing the abovementioned natural compounds in agroup of patients affected by nonsegmental vitiligoand subdued to conventional concomitant topicaltherapy or phototherapy.

Materials and methods

One hundred thirty patients affected by nonsegmental vitiligo who referred consecutively to our Florence University specialized vitiligo out-patient service, were examined from October 2012to July 2013.

The study design has been approved by theEthical Board of the “Centro Studi del GruppoItaliano Studi Epidemiologici in Dermatologia(GISED)” and an informed consent was obtainedfrom each patient.

Exclusion criteria were age <18 years, segmentalvitiligo, vitiligo duration <1 year, use of systemicimmunosuppressant drugs, smoke addiction,

pregnancy, breastfeeding, new depigmentedpatches in the past 12 months, and vitiligo exten-sion higher than 20% of total body area.

Concomitant vitiligo treatments, namely corticosteroids, vitamin D analogs, calcineurininhibitors, and narrow band UVB-light (NB-UVB)

phototherapy/excimerlamp werealso investigated.Medical assessment was performed using amodified Vitiligo European Task Force form (10,11)independently by two dermatologists, whichevaluated some clinical aspects of vitiligo (Table 1).Digital pictures under natural and Wood’s light foreach patient were taken.

Patients were subsequently divided into twogroups: group A, including subjects treated withoral antioxidants (n = 65) and group B, which werenot treated with antioxidants (n = 65). Group A patients took one tablet of an oral supplement con-taining P. emblica (100 mg), vitamin E (4.7 mg),

and carotenoids (10 mg) three times a day for 6months and were asked to stop the treatment incase of side effects. Both groups were treated at thesame time with a comparable topical therapy and/or phototherapy.

After a 6-month follow-up, we evaluated thepercentage of repigmentation, vitiligo course(steady or worsening, if an appearance or anenlargement of macules was reported during the 6months of follow-up or not), emotional triggering/precipitating factors, presence and severity of ery-thema, tolerability, and possible side effects of the

oral supplement.The percentage of repigmentation after treat-

ment was classified for each body side as none

Table 1. General characteristics of patients at the baselinea

Group A (65 patients) Group B (65 patients)

Sex M: 25 F: 40 M: 29 F: 36 Years (mean and SD) Age 38.01 ± 19.69 (range 18–64) 36.2 ± 19.37 (range 18–61)

Age at onset 29.16 ± 17.43 27.10 ± 19.27 Vitiligo duration 8.80 ± 9.36 6.61 ± 8.19

Concomitant therapy Corticosteroids 61 (93.8%) 60 (92.30%)

Calcineurin inhibitors 34 (52.3%) 32 (49.23%) Vitamin D analogs 26 (40%) 25 (38.46%)Phototherapy 28 (43.1%) 26 (40%)

Percentage of body area involved

Signs of inflammation 13 (26.4%) 15 (23.1%)Total medium extension 6.1% (range 0.04–20.0%) 8.6% (range 0.03–18%)Medium extension: head and neck 0.73% 0.55%Medium extension: trunk 2.16% 1.80%Medium extension: upper limb 1.48% 1.87%Medium extension: lower limb 2.17% 2.01%Medium extension: hands 0.74% 0.60%Medium extension: feet 0.82% 0.48%

aOnly the features evaluated after repigmentation are reported.

Colucci et al.

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(0%), mild (1–25%), moderate (26–50%), good (51–75%), and excellent (76–100%) and was assessedindependently by two dermatologists blinded totreatment, through a clinical examination bothunder natural and Wood’s light.

The SPSS 15 program (SPSS, Inc., Chicago, IL,

USA) was used for data recording and statisticalanalysis. Characteristics of the study population were described using mean, standard deviations,frequencies and percentages. Chi-square tests andFisher tests for categorical data and the Student’st -test for quantitative data were performed. Results were considered significant for p values ≤0.05;trend for 0.05 < p values ≤0.07.

Results

One hundred thirty patients affected by vitiligo

were enrolled and among them 10 patients did notcomplete the study because of personal matters.Patients’ characteristics are summarized in Table 1.

Group A patients had a significant mildrepigmentation in the head and neck region (p =0.019) and on the trunk (trend, p = 0.051; Figs 1 and2), a higher not significant repigmentation for eachbody site (with different degrees; Figs 1–2), andhigher steady disease (p = 0.065; Fig. 1).

On the contrary, the number of patients withoutrepigmentation in head and neck, trunk, upper andlower limbs was higher in group B (respectively, p =0.009, p = 0.001, p = 0.001, p = 0.025) (Figs 1–2). Inthis group, we also found significant more signs of inflammation (p = 0.002), rapid growth of the

lesions (p = 0.039), higher percentage of worsening disease (p = 0.003; Fig. 1) and erythema (p = 0.059;Fig. 1).

The oral supplement was well tolerated by every patient and no side effect was recorded.

Discussion

In the present study, we demonstrate for the firsttime that a pool of oral supplements containing extracts of P. emblica fruit, vitamin E, andcarotenoids can be useful in vitiligo treatment.

Indeed, only the positive role of oral supple-ments containing alpha-lipoic acid, vitamin C,vitamin E, polyunsaturated fatty acids, andPolypodium leucotomos plant in vitiligo treatment was so far reported (5,6).

The significant higher activity of the disease,signs of inflammation of the lesions, rapid growthof lesions in group B patients, together with anhigher frequency of steady disease in group A

FIG. 1. Repigmentation obtained on each body side and summary of statistically significant parameters: a significantly higher

number of patientsin group A had a mild repigmentation in the head and neck regions and onthe trunk.Thenumber ofpatients

who presented no repigmentation in head and neck, trunk, upper and lower limbs was significantly higher in group B. A higher

(not significant) prevalence of repigmentation for each body site was found in group A, with different degrees, and a higher

percentage of steady disease were also reported in group A patients.Group B patients showed more signs of inflammation,rapid

growth of the lesions, lower percentage of worsening disease and more erythema compared with Group A.

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patients, might be explained by the marked

anti-inflammatory, immunomodulatory, and anti-oxidative properties of P. emblica (7,12,13), whichcould have reduced the oxidative stress responsiblefor the recruitment of inflammatory cells and forthe destruction of melanocytes (14). Indeed, in vivoand in vitro studies demonstrated that this extractcan limit ROS production (12,13,15,16), stimulatethe endogenous enzymatic antioxidant defenses(12,13,15,16), and protect normal human dermalfibroblasts against UVB damages (13).

Our finding also reported a significant less fre-quent phototherapy-induced erythema in patients

of group A. This event might be explained by theuse of carotenoids (8), which could have enhancedthe skin resistance to the erythematous action of UVB (8,17,18). Indeed, some studies demonstratedthat beta-carotenoids can prevent UVB-inducederythema (8), mostly when associated with vitaminE (17) since the latter is able to reverse theUV-induced lipid peroxidation and thus inflamma-tion (9). In addition, since ROS accumulation acti-vates immune system (4), we suppose that themarked antioxidative properties of P. emblicamight have contributed as well to limit the inflam-matory processes leading to the development of erythema.

Finally, we suppose that the higher percentageof repigmentation in sun-exposed body regions ingroup A patients could be due to the action of carotenoids (18,19) that could have stimulated theprocess of repigmentation (18,19) acting in synergy with the exposure to sunlight and with vitamin E(19). It has been demonstrated indeed that vitaminE can stimulate the growth of cultured humanmelanocytes when associated with vitamin C andbeta-carotenoids (19).

In conclusion, we suggest that the components

of this supplement can counteract the oxidativestress and the inflammatory processes occurring inpatients with vitiligo, and possibly can interfere with the pathogenetic mechanisms of the disease.

Our results are encouraging and promising,even if a multi-center, randomized, double-blindclinical trial is needed to confirm the beneficialeffects of the evaluated compounds in vitiligotreatment. Nevertheless, our findings suggest thatthe supplement with antioxidants in patients withvitiligo might represent a safe and valuable toolto increase the effectiveness of other vitiligo

treatments.

Acknowledgements

We acknowledge Dr. Luigi Naldi (Centro Studi delGruppo Italiano Studi Epidemiologici inDermatologia) (GISED) for the critical revision of the manuscript.

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FIG. 2. Pretreatment and posttreatment photographs of three group A patients. An improvement of vitiligo macules with signs

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3) of patients treated with the oral supplement.

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