Nigella Sativa Oil Lotion 20% vs. Benzoyl Peroxide Lotion 5% in the Treatment of Mild to Moderate Acne Vulgaris

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THE IRAQI POSTGRADUA TE MEDICAL JOURNAL VOL.9, NO.4, 2010
TREATMENT OF ACNE VULGARIS
Nigella Sativa Oil Lotion 20% vs. Benzoyl Peroxide Lotion 5%
in the Treatment of Mild to Moderate Acne Vulgaris
Naseer A. Hadi* ,Ammar Waham Ashor**
INTRODUCTION:
Acne vulgaris is the most common chronic
inflammatory disease of the skin to affect humans (1).
The reported prevalence of acne varies from 35% to
over 90% of adolescents at some stage (2). Acne is a
multi-factorial disease involving hormonal
influences, altered keratinization, inflammation and
immune changes (3). Current treatments of acne
include topical and oral antibiotics, topical
antimicrobial, topical and oral retinoids. All acne
treatment has potential side effects some of which
may be severe (4). Many patients fail to improve with
these agents due to the cost, adverse effects leading
to noncompliance (irritation) or lack of therapeutic
*Department of Clinical Pharmacology, Baghdad
College of Medicine, Baghdad, Iraq
** Depat of Pharmacology College of Medicine AL-
Mustansiriyah University.
benefit (antibiotic resistance). The use of oral
antibiotics and systemic retinoids increase both the
cost and risk of adverse effects (5). To overcome the
problems of conventional therapies many studies
have been done to find new effective and safe
treatment of acne vulgaris. One of these methods to
overcome the problems of conventional therapy is the
use of medicinal plants in the treatment of acne
vulgaris (6). One of the well-known medicinal plants
used is Nigella sativa, this plant have been used
traditionally in Middle Eastern folk medicine as
natural remedy for various diseases for over 2000
years (7). More than 150 studies conducted since 1959
confirmed the pharmacological effectiveness of
Nigella sativa seed constituents (8). It has been shown
that Nigella sativa seed and oil are effective anti-
microbial (9), immunomodulatory ( 10), antioxidant (11),
anti-inflammatory (12) and antitumor activity (13).
ABSTRACT:
BACKGROUND:
Acne vulgaris is the most common chronic inflammatory disease of the skin. Many patients fail to
improve with the current anti-acne therapy due to the cost of therapy, adverse effects leading to
noncompliance or lack of therapeutic benefits of current antibiotics (resistance).
OBJECTIVE:
To evaluate the efficacy and tolerability of Nigella sativa oil lotion 20% in comparison with well-
known drug benzoyl peroxide lotion 5%.
METHODS:
This is a double-blind, active-controlled, randomized study to compare between Nigella sativa oil lotion
20% and benzoyl peroxide lotion 5%. 70 patients enrolled in this study, their age ranged between 12-23
years with less than 100 non-inflammatory lesions and less than 50 inflammatory lesion counts
(according to the Combined Acne Severity Classification).
RESULTS:
62 patients complete the study. Patients on Nigella sativa lotion show a reduction of (-63.3%), (-64.6%)
and (-63%) in the non-inflammatory, inflammatory and total lesion counts respectively while patients
on benzoyl peroxide demonstrate a reduction of (-43.8%), (-50.9%) and (-45.9%) on the above lesion
counts respectively. The difference between groups was statistically significant (P< 0.0001, P<0.016,
P< 0.0001). 97% of patients on Nigella sativa lotion show good to excellent improvement (more than
50% reduction in total lesion counts), while only 50% of patients on benzoyl peroxide lotion show good
to excellent improvement. Patients on Nigella sativa lotion 20% had a milder and fewer side effects,
than those who receive benzoyl peroxide lotion 5%. Both groups demonstrate statistically significant
increase in lesion counts after 8 weeks from the end of therapy.
CONCLUSION:
Nigella sativa oil lotion 20% is more effective and safe than benzoyl peroxide lotion 5% in the
treatment of mild to moderate acne vulgaris.
KEY WORDS: acne vulgaris, nigella sativa, benzoyl peroxide
THE IRAQI POSTGRADUA TE MEDICAL JOURNAL VOL.9, NO.4, 2010
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TREATMENT OF ACNE VULGARIS
MATERIALS AND METHODS:
The present study is randomized, double-blind,
active-controlled, parallel assignment, safety/
efficacy trial, done between October 2006 and
October 2007. The number of patients examined was
70 and their ages varied from 12-23 years, 38 were
females and 32 males. Patients with mild to moderate
facial acne vulgaris; defined as having comedones
number below 100, and inflammatory lesion counts
(papules and pustules) below 50 and no more than 5
nodules or cysts according to the combined acne
severity classification (14) were included in the study.
Patient with severe acne excluded from the trial
(those having more than 100 comedones and/or
inflammatory lesions above 50). Pregnant and
lactating women excluded from the trial, as well as,
patient with known hypersensitivity to the drugs of
the trial. Nigella sativa oil lotion (20%) prepared
through the following methods: Firstly we prepare
the solvent by adding 200 ml of ethylene glycol to
200 ml of ethyl alcohol and 600 ml distilled water in
a ratio of 2:2:6 (15.16). Nigella sativa oil lotion 20 %
prepared by taking 80 ml from the above solution and
adds to them 20 ml of Nigella sativa oil; the oil lotion
putted in dark container. The active control of the
present study is benzoyl peroxide lotion 5% (Ben-
Oxide® lotion 5%, DOMINA pharmaceuticals,
Syria). The study performed with 35 patients
randomly allocated to each study arm. Oral consent
was taken from the patients before the beginning of
the study; group A given 20% Nigella sativa oil
lotion, group B given benzoyl peroxide 5% lotion.
Patients instructed to wash their face with a mild
nonmedicated cleansers and wait 15 minutes until
drying and then add the lotion to the entire face, the
procedure done twice daily in the morning and
evening. No other lotions, creams, medicated
powder, or solutions were allowed on the treatment
area. The patients followed up each two weeks and
assessment done with each visit to the following:
number of comedones, number of inflammatory
lesions (papules, pustules), total lesion count
(comedones + papules + pustules) and ask the
patients about any side effects of the treatment. The
active treatments continue for two months, after that
patients followed up for another two months to
monitor disease flare up. The response of the patients
to treatment classified as: excellent response: 75%
reduction in lesion counts, good response: 50%-75%
reduction in lesion counts, fair response: 25%-50%
reduction in number of acne lesions and poor
response: no response or less than 25% reduction in
the number of acne lesions (17, 18). The satisfaction of
the patients to the treatment classified into: full
satisfaction, partial satisfaction, no satisfaction.
Statistical analysis done with statistical package for
social sciences (SPSS version 12), both descriptive
and analytic data used, and two-sided P ≤ .05
considered statistically significant. Paired t-test used
to compare means in the same group, while
independent t-test used to compare means between
two study groups. Chi-square test used for qualitative
data.
RESULTS:
Out of 70 patients included in this study, 62 patients
completed the treatment and follow up period. Those
who stopped the treatment were for unknown reasons
and considered as default. The number of female
patients was 32 (51.6%); the number of male patients
was 30 patients (48.4%). Their (mean age ± SD) was
(16.24± 2.5), and their range between (12-23) years.
Table 1 : Patients demographic features
Nigella sativa Benzoyl peroxide P. values
Patients 32 30 ….
Men / Women 14/18 16/14 ….
Age, years 16.7±2.9
Ω
15.7±2.0 0.135(n.s)*
Lesion counts
Total 39.5±8.5 39.1±8.5 0.855(n.s)
Inflammatory 16.93±5.4 17.06±5.7 0.928(n.s)
Non-inflammatory 22.62±4.9 22.10±5.3 0.688(n.s)
Ω values shown as mean±SD unless otherwise indicated, * (n.s): not significant
Efficacy on comedones (non-inflammatory) lesion
count
Regarding, Nigella sativa oil lotion 20%, the mean
lesion count reduced to (8.38±2.64) after 8 weeks of
treatment from the baseline mean count
(22.63±4.93), which was statistically significant (P <
0.0001). Benzoyl peroxide lotion 5% recorded a
decrease of lesion counts from (22.10±5.31) to
(12.43±4.00) after 8 weeks of treatment; this
reduction was statistically significant (P < 0.0001).
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Nigella sativa oil lotion was statistically more
effective than benzoyl peroxide lotion at 6 weeks
visit (P < 0.003) and at 8 weeks visit (P < 0.000).
After 8 weeks of treatment, the mean difference
between the two groups (4.05) and the class interval
of the difference (2.3 – 5.7).
Efficacy on inflammatory lesion counts (papules
and pustules)
Nigella sativa: the mean inflammatory lesion count
at the start of therapy (16.94± 5.46) was reduced to
(6.19±3.41) after 8 weeks of treatment this reduction
was statistically significant (P < 0.0001). Benzoyl
peroxide: After 8 weeks, there was a reduction of
(8.90±4.99) from the baseline lesion counts
(17.07±5.72) this is statistically significant (P <
.0001). At the end of 8 weeks, there was statistically
significant difference in favor of Nigella sativa vs.
benzoyl peroxide (P < .016). The point estimate of
the difference (mean difference) between the two
treatment is (2.7), the class interval of the difference
(0.55-4.87 ).
Efficacy on total lesion counts (comedones,
papules & pustules)
Nigella sativa oil lotion 20%: the baseline total
lesion counts was (39.56±8.50) and after 8 weeks the
mean lesion count was (14.56±4.28) which was
statistically significant (P < .0001). Benzoyl peroxide
lotion 5%: the baseline lesion counts were
(39.17±8.52) and after 8 weeks the mean lesion count
dropped to (21.33±7.03) and this statistically
significant (P < 0.0001). Nigella sativa oil lotion
20% showed a significant difference from benzoyl
peroxide lotion 5% at 6 weeks and at 8 weeks (P
<0.002 and P < 0.0001) respectively. After 8 weeks,
the mean difference between the groups was (6.7)
and class interval of the difference (3.83-9.70) in
favor of Nigella sativa oil lotion.
The percent reduction in lesion counts
The following table shows the percent reduction in
lesion counts of both Nigella sativa oil lotion 20%
and benzoly peroxide lotion
Table 2: Percent reduction of lesions counts for Nigella sativa lotion and benzoyl peroxide after 8 weeks of therapy
Non-inflammatory
(comedones)
Inflammatory lesion
(papules and pustules)
Total lesion counts
(comedones, papules, pustules)
Nigella sativa 63.3% 64.6% 63%
Benzoyl peroxide 44% 51% 46%
P value
0.0001
0.016
0.0001
Overall response to treatment
Regarding Nigella sativa oil lotion 20%, the overall
response of the patients to treatment at the end of 8
weeks was as follows: four patients have excellent
improvement (12.5%), 27 patients show good
improvement (84.4%), fair improvement seen in one
patient (3.1%). Benzoyl peroxide lotion 5%: one
patient only showed excellent improvement (3.3%),
14 patients had good improvement (46.7%), 13
patients showed fair improvement (43.3%), only two
patients had poor improvement (6.7%). The
comparison between the two drugs shows that there
was a significant difference (P < 0.0001).
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Figure 1: Overall response of patients treated with Nigella sativa oil lotion 20% and benzoyl peroxide
lotion 5%. Excellent response > 75% improvement, Good > 50%, fair 25%-49%, poor < 24%. * (P ≤
0.05) significant with chi square test.
Patients’ satisfaction to treatments
Patients on Nigella sativa oil lotion 20%, 20 of them
showed full satisfaction to treatment (63%), eight
patients showed partial satisfaction (25%) and four
patients showed no satisfaction to treatment (12%).
Regarding benzoyl peroxide lotion 5%, 14 patients
showed full satisfaction (47%), another 14 patients
showed partial satisfaction (46%) and two patients
showed no satisfaction (7%).
Total lesion counts after 8 weeks from the end of
therapy
Nigella sativa oil lotion 20%: at the end of 8 weeks
therapy, total lesion count was (14.56±4.28), after 8
weeks of stopping therapy the total lesion count was
(17.09±4.76). The mean percent increase in total
lesion count from the end of therapy was (18.71%).
This increase in total lesion count was statistically
significant (P < 0.0001). Regarding benzoyl peroxide
lotion 5%, the total lesion count was (21.33±7.03) at
the end of 8 weeks, after 8 weeks from the end, the
total lesion count became (25.60±7.01). The mean
percent increase in total lesion count from the end of
therapy was (23.10%), this change in lesion count
was statistically significant (P < 0.0001). The
comparison between the two drugs was statistically
not significant (P < 0.19).
Side effects reported in response to treatment
Of the 32 patients treated with Nigella sativa oil
lotion 20%, two patients (6%) complained from mild
irritation, burning sensation and slight erythema. Six
(20%) patients out of 30 treated with benzoyl
peroxide lotion 5% complained from irritation,
burning sensation, erythema.
DISCUSSION:
The study done by Dr. Ali Ismail (15) was the first to
show the efficacy of Nigella sativa oil in the
treatment of mild to moderate acne vulgaris. The
reduction in the papules and pustules count was
47.5% and 51.6% respectively. In this study, there
was no report of any side effects to Nigella sativa oil
lotion.
This study done to confirm the results of previous
study, and to show the effectiveness of Nigella sativa
oil lotion in comparison with a well-known drug used
in the treatment of acne, which is benzoyl peroxide.
The other difference with the previous study is the
dose, we increase the dose to show any change in the
effect in comparison with previous work (dose-
response curve) and also we include the non-
inflammatory lesion count to see the effect of Nigella
sativa on comedone counts. Benzoyl peroxide, the
active-control of our study is widely used by
dermatologist and considered one of the two main
pillars of acne treatment with retinoids (19). Benzoyl
peroxide is a powerful antimicrobial agent that
rapidly destroys P. acnes, also has a secondary
comedolytic effect and is shown to be more effective
than topical antibiotics with no known resistance to
it(20).
After 8 weeks of the study, Nigella sativa oil lotion
effects on the non-inflammatory, inflammatory and
total lesion counts were (-63.2%),(-64.6%) and
(63%) respectively, these results, were statistically
more effective than benzoyl peroxide, which had an
effects of (-43.8%), (-51%) and (-46%) on the non-
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inflammatory, inflammatory and total lesion counts
respectively.
Both drugs showed statistically significant difference
from the baseline lesion counts as early as 4 weeks of
treatment for the all the lesion counts. Ninety seven
percent of patients on Nigella sativa lotion showed
good to excellent improvement, in comparison with
50% in patients with benzoyl peroxide lotion.
Patient on Nigella oil lotion were more satisfied than
those on benzoyl peroxide lotion and have fewer and
milder side effects. After 8 weeks from the end of
therapy, there was statistically significant increase in
total lesion counts for both treatments.
This increase may be because lesions tend to recur
even after discontinuing a successful treatment
regimen (21). In a study done by Thielitz et al.(22)
tretinoin and combination of tretinoin with
clindamycin showed a significant decrease in the
lesion count after 12 weeks of therapy, but lesions
were seen to recur after 4 weeks of discontinuation of
the above therapies. Another study done by
Thiboutot et al. (23), found that discontinuation of
adapalene plus doxycycline or doxycycline alone
showed also acne lesions flare up within 3 months
follow up period. Recently, a study done by Thielitz
et al. (24) showed that microcomedones recur after
adaplene end of therapy within 3 months follow up
period.
Regarding the benzoyl peroxide, our results are
consistent with previous studies, which showed the
effect of benzoyl peroxide on non-inflammatory
lesion counts ranging from 11-70% and on
inflammatory lesion counts ranging from 37-71% (25).
Nigella sativa lotion (20%) showed more effect on
inflammatory lesion than the previous study done by
Ismail (15), who used a concentration of 10%. In
comparison with the other topical therapies, Nigella
sativa oil lotion showed similar efficacy or even
better effect than the conventional anti-acne therapies
(26).
CONCLUSION:
Nigella sativa oil lotion 20% is more effective and
safe than benzoyl peroxide lotion 5% in the treatment
of mild to moderate acne vulgaris.
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