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Role of zinc in acne: a study of 77 patients

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p class="abstract"> Background: Acne vulgaris is a chronic inflammatory disease of pilosebaceous unit occurring in adolescent age group. Though not life threatening it can cause physical and psychological scars which can produce social problems in house, school and office. It is a multifactorial disease. Many treatment options are available, but not optimal. Zinc was found to be effective in pustular acne in a patient with acrodermatitis enteropathica. Hence a study on the level serum zinc in acne patients and the effect of zinc on acne is worthwhile. The aim was estimation of serum zinc level in acne patients and correlation of serum zinc level and improvement of acne. Methods: Pre-treatment serum zinc level was estimated in acne and non-acne patients. Acne patients were given oral zinc 220 mg two times a day and control group was given placebo. Post treatment serum zinc levels were estimated and the serum zinc level and improvement of acne was correlated. Results: Study subjects attained average serum zinc level of 5.829 µg/ml from 1.33 µg/ml. 59.5% patients on zinc therapy showed more than 50% improvement in acne severity. 10.6% showed >75%, 48.9% showed 50-75%, 36.1% showed 25-50% and 4.25% patients showed less than 25% improvement. Conclusions: Statistically significant low levels of zinc were not observed in acne. Oral zinc sulphate 220 mg two times a day raised serum level to 5.82 µg/ml Exponential response in acne was noticed as serum zinc level was raised. Inflammatory lesions showed better response than comedo. Oral zinc has definite role in treatment of acne.</p
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International Journal of Research in Dermatology | July-September 2018 | Vol 4 | Issue 3 Page 1
International Journal of Research in Dermatology
Thomas J. Int J Res Dermatol. 2018 Aug;4(3):xxx-xxx
http://www.ijord.com
Original Research Article
Role of zinc in acne: a study of 77 patients
Jacob Thomas*
INTRODUCTION
Acne vulgaris is a chronic inflammatory disease of
pilosebaceous unit occurring in the adolescent age
group.1,2 Approximately 85% of the population of 15-18
years of age have some degree of this disorder.3
Acne is rarely life threatening, but its cosmetic effects
leave scars both physical and psychological that can be
life long.4 It can cause social problems in house, at school
and at work.4
Acne is a multifactorial disease depending on genetic
predisposition, endocrine factors, keratinisation pattern of
follicular epithelium, colonisation of sebaceous follicle
and inflammatory response of the host.5
Treatment of acne is far from optimal. Treatment of acne
is still a perplexing problem.6 The various pathogenetic
mechanisms direct to different approaches to therapy-
methods of reducing sebum production, reducing
pilosebaceous duct blockage, reducing bacterial
colonisation and modifying inflammation in the host.7
Topical therapy with benzoyl peroxide, antibiotics, vit A
acid, sulfur, salicylic acid and systemic agents like oral
antibiotics, 13, cis-retinoic acid, oestrogens,
antiandrogens, are tried with varying results. Each one
has its own advantages and disadantages.8
ABSTRACT
Background:
Acne vulgaris is a chronic inflammatory disease of pilosebaceous unit occurring in adolescent age
group. Though not life threatening it can cause physical and psychological scars which can produce social problems
in house, school and office. It is a multifactorial disease. Many treatment options are available, but not optimal. Zinc
was found to be effective in pustular acne in a patient with acrodermatitis enteropathica. Hence a study on the level
serum zinc in acne patients and the effect of zinc on acne is worthwhile. The aim was estimation of serum zinc level
in acne patients and correlation of serum zinc level and improvement of acne.
Methods:
Pre-treatment serum zinc level was estimated in acne and non-acne patients. Acne patients were given oral
zinc 220 mg two times a day and control group was given placebo. Post treatment serum zinc levels were estimated
and the serum zinc level and improvement of acne was correlated.
Results:
Study subjects attained average serum zinc level of 5.829 µg/ml from 1.33 µg/ml. 59.5% patients on zinc
therapy showed more than 50% improvement in acne severity. 10.6% showed >75%, 48.9% showed 50-75%, 36.1%
showed 25-50% and 4.25% patients showed less than 25% improvement.
Conclusions:
Statistically significant low levels of zinc were not observed in acne. Oral zinc sulphate 220 mg two
times a day raised serum level to 5.82 µg/ml Exponential response in acne was noticed as serum zinc level was raised.
Inflammatory lesions showed better response than comedo. Oral zinc has definite role in treatment of acne.
Keywords: Acne, Acne vulgaris, Zinc, Serum zinc
Department of Dermatology, Amrita Institute of Medical Sciences, Kochi, Kerala, India
Received: 10 June 2018
Revised: 04 July 2018
Accepted: 09 July 2018
*Correspondence:
Dr. Jacob Thomas,
E-mail: jacobthomas@aims.amrita.edu
Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under
the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial
use, distribution, and reproduction in any medium, provided the original work is properly cited.
DOI: http://dx.doi.org/10.18203/issn.2455-4529.IntJResDermatol20182980
Thomas J. Int J Res Dermatol. 2018 Aug;4(3):xxx-xxx
International Journal of Research in Dermatology | July-September 2018 | Vol 4 | Issue 3 Page 2
The striking effect of zinc on severe pustular acne in a
patient with acrodermatitis enteropathica aroused interest
in zinc in acne.9
Zinc is anti-inflammatory. Zinc stabilises macro-
molecules and biological membranes. It influences
migration rate and phagocytic activity of macrophages
interfering with dynamics of inflammatory process.10
Elevated levels of zinc in vitro as well as in vivo affects
various functions of cells.11 Functional immobilisation,
inactivation, paralysis of cell wall were proposed for such
an inhibitory effect of zinc. This effect is demonstrated so
far on mast cells, platelets, macrophages, poly-
morphonuclear cells and spermatozoa.11 Action on cell
membranes has shown that mast cells are inhibited from
releasing histamine and could modify inflammatory
state.11
Zinc adversely affect neutrophil chemotaxis and
complement activation.12
Do patients with acne have zinc deficiency or can zinc
modify acne is a question that has not yet been settled.
Aim of the study
Estimation of serum zinc level in acne patients.
Correlation of serum zinc level attained and
improvement in acne.
METHODS
Total of 100 patients with a clinical diagnosis of acne
vulgaris attending dermatology out-patient department of
medical college, Kottayam were enrolled for the study.
Inclusion criteria
Inclusion criteria were those patients having minimum
number of 15 lesions; those who were not on any
treatment four weeks prior to the onset of trial.
Exclusion criteria
Exclusion criteria were those patients with any systemic
illness; those on systemic steroids; pregnant patients.
After obtaining consent, fasting blood samples were
collected from 100 patients and serum was freezed and
stored. Blood samples were collected after 12 weeks of
treatment from 50 patients in the treatment group. Serum
from fifty patients without acne was also collected.
Serum was later analysed using Perkin Elmer atomic
absorption spectrophotometer model 4000AAS.
Counting of lesions
Different types of lesions on well-defined areas of face
were counted.
Each type of lesion was given a severity index. Definition
of individual lesion and the severity index given to each
type of lesion are shown in Table 1.
Table 1: Showing type of lesion and severity index.
Type
Definition
Severity
index
Comedone
Horny follicular plugs with
insipient inflammatory
change(black head)and pin
head sized superficial shiny
follicular papules
0.5
Papule
Independent infiltrated solid
elevation of less than 1 cm
1.0
Pustules
Circumscribed collection of
free pus of more that 2 mm
size
2.0
Infiltrate
Nodules and infiltrate of
more than 10 mm in
diameter and coalescent
papules when cannot be
counted separately
3.0
Cyst
Lesions where infiltrates
have broken down and
formed a cyst
4.0
Severity of disease in each patient was calculated
multiplying the total number of each type of lesion with
the alloted severity index and adding each sum to get a
total score which corresponded to the total severity of the
disease.
Patients in treatment group were given 220 mg zinc two
times a day orally after food. The second group was
given placebo (vit B complex tablets) in similar capsules.
Patients were followed up at 3rd, 6th, 9th and 12th weeks
after starting treatment. Each time lesions were counted
and severity index score was calculated.
All patients were asked for any untoward effects.
Results were analysed using student ‘t’ test. The mean
and standard error of the mean were used.
RESULTS
Thirty male and 17 females completed study in treatment
group. Twenty males and ten females completed in
placebo group. Age of patients ranged from 14-23 years
for males with average 18.8 yrs. Age of females ranged
from 16-21 years with average of 19.6 years. In the
Placebo group age ranged from 14-22 years for males
with average 20.75 and females 16-23 years with average
17.6 years.
Thomas J. Int J Res Dermatol. 2018 Aug;4(3):xxx-xxx
International Journal of Research in Dermatology | July-September 2018 | Vol 4 | Issue 3 Page 3
Severity of disease
At the beginning average total score was 60 in treated
group (61.63 in males and 58.29 in females). In placebo
group initial score was 46.6.
Reduction in severity in treated group and placebo group
after 3, 6, 9 and 12 weeks are shown in Table 2.
Maximum reduction in score was observed in 3-6 wks.
After that reduction was minimal. Mean severity index in
treatment group fell to 24.89 from 60 and in placebo
group it fell from 46.6 to 37.15.
Four out of 27 patients in placebo group showed
worsening while in treated group, none showed
worsening.
Table 2: Showing reduction in severity index at 3, 6, 9, 12 weeks of treatment.
Treatment group
Control group
Weeks
0
3
6
9
12
0
3
6
9
12
Severity
60
40.4
32.4
27.5
24.8
46.6
37.4
33.9
36.2
37.1
Table 3: Percentage of improvement at the end of treatment with zinc.
Improvement
>75%
50-75%
25-50%
<25%
Total
No. of patients
5
23
17
2
47
% of patients
10.6
48.9
36.1
4.25
100
Five (10.6%) patients in treated group had more than
75% improvement, 23 (48.9%) had 50-75% and 17
(36.17%) had 25-50% improvement respectively. Two
(4.25%) had less than 25% improvement (Table 3).
There was significant improvement (60.9% reduction) in
pustular lesions after 12 weeks of treatment. Comedones
showed only 23.18% reduction.
Serum zinc level
S zinc level in acne patients at the beginning was 0.24-
0.29 µg/ml with a mean 1.33 µg/ml while in control
group, mean serum zinc level was 1.29 µg/ml (0.92-2.28
µg/ml).
Only 4/77 patients had S zinc level below 0.7 µg/ml
After 12 weeks treatment, S zinc level ranged from 1.496
to 22.15 µg/ml with a mean of 5.82 µg/ml.
Serum zinc level and degree of response to therapy was
correlated.
Mean reduction in severity index at various levels of
serum zinc is shown in Table 5.
Table 4: Mean serum zinc level in acne patients and controls.
S zinc level in acne patients
SD
S zinc level in normal
SD
1.33 µg/ml
0.492
1.29 µg/ml
0.389
Table 5: Mean reduction in severity index at different levels of serum zinc.
S Zinc level µg/ml
1-2
2-3
3-4
4-5
5-6
6-7
7-8
8-9
9-10
11-12
12-13
13-14
22- 23
Reduction in count
32.5
32
32.7
29.2
33.8
21.8
31.3
42
42
14
82
48.5
67
No. of pts
01
04
13
10
05
04
03
01
02
01
01
01
01
Those who attained higher S zinc levels showed greater
reduction in severity index.
DISCUSSION
Out of 100 selected cases, 77 completed study-47 in
treatment group and 30 in placebo group. Three patients
in treatment group could not attend clinic as per schedule.
Twenty patients in placebo group lost to follow up
probably because of lack of clinical response.
Age ranged from 14-25 years with an average of 19 yrs.
S zinc level
Mean S zinc level in acne patients was 1.33 µg/ml in
treatment group while in control it was 1.29 µg/ml. Zinc
level in acne patients in this study was not below that of
normal controls or normal zinc level reported by other
workers. Valquist et al found in untreated acne patients S
zinc level was 0.923 µg/ml which was similar to healthy
controls-0.9 µg/ml.13
Michaelsson observed initial S Zinc level was 0.863
µg/ml for boys and 0.832 µg/ml for girls.14 Low serum
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International Journal of Research in Dermatology | July-September 2018 | Vol 4 | Issue 3 Page 4
zinc level in acne patients was reported by Ghorpade et al
who observed 0.58 and 0.81 µg/ml in acne patients and
normal controls respectively.15 Michaelsson also noticed
in acne Gr III and IV patients low initial S zinc level of
0.89 µg/ml while in controls 0.962 µg/ml.14
In this study only 4/77 had serum zinc level below 0.70
µg/ml which is reported as lower limit of normal range.
Post treatment serum zinc level
Mean serum zinc level in treated group raised to 5.829
µg/ml from 1.33 µg/ml after treatment for 12 weeks in
the present study.
Weissman found that mean S zinc level increased from
0.923 µg/ml to 1.255 µgm/ml in 4 wks and to 1.17 µg/ml
after 12 weeks of treatment with oral zinc.11
There was no further significant increase after 4 wks.
Ghorpad et al found that S zinc level rose to 0.781 µg/ml
after 12 weeks of treatment from 0.581 µg/ml. Orris et al
observed an increase by 50% in zinc treated group.16
Serum zinc level attained in our patients was
significantly higher than in other studies.
Placebo treated patients showed no rise in serum zinc
level. 1.19 µg/ml was the initial value while 1.33 µg/ml
was the level after 12 wks.
Correlation of initial serum zinc level and severity of
acne
Those with normal S zinc level had lower severity of
score than those with low S zinc level who had a higher
severity score. In treatment group mean severity index at
the beginning was 60 in those with normal zinc level.
Mean initial acne score was 78.87 with S zinc level of
0.472 µg/ml.
Michaelsson observed that mean score was 63.9 who had
normal serum zinc level.14 Ghorpade et al observed high
initial severity index of 138 in those with low S zinc.15
Response to treatment
220 mg zinc twice a day orally for 3 months gave better
results than placebo.
After 12 weeks of treatment 59.5% patients on zinc
therapy showed more than 50% improvement in acne
severity. 10.6% showed >75%, 48.9% showed 50-75%,
36.1% showed 25-50% and 4.25% patients showed less
than 25% improvement. None had worsening while on
zinc.
Verma et al found that in a group of 35 males and 25
females 41.37% showed 75% improvement 10.3%
showed >50% and 6.85% showed 25% improvement with
oral zinc 600 mg/day for 12 weeks. 0.6.8% showed
worsening.17
In another study by Ghorpade in 46 pts with 220 mg oral
Zinc three times a day, 17.35% showed 61-80%, 67.3%
showed 31.6% and 4.35% showed 30% improvement.
04.35% showed no significant change while 6.5% had
worsening.15
Fall in severity score was 30% after3 weeks, 40% after 6
weeks, 46% after 9 weeks and 55.45% after 12 weeks in
the present study.
Post treatment serum zinc level and severity of acne
As mean S zinc level raised to 5.82 µg/ml mean acne
severity score came down to 24.8 from pre-treatment
score of 60. It was also observed that there was an
exponential increase in improvement as the serum level
of s zinc level increased. All 29 patients who attained s
zinc level of 4 µg/ml had 50% or more improvement
which was clinically observable.
Ghorpade et al also found that increase in S zinc level
resulted in considerable clinical improvement.15
Weissman et al also made a similar observation.11
A difference in response of inflamed and non inflamed
lesions (comedones) was observed in this study with oral
zinc. Reduction of 60.17% in inflammatory lesions was
seen where as in comedones it was only 32.73%.
Ghorpade et al observed mean reduction of 55.46% in
inflammatory lesions while non-inflammatory lesions
(comedones) showed only 15.4 reduction.15
Verma et al observed 75-100% reduction in papules,
pustules and infiltrated lesions in 12 weeks of treatment
with zinc.17
CONCLUSION
In 77 acne patients pre-treatment serum zinc level ranged
from 1.291.33 µg/ml.
Subnormal level of serum zinc was found only in 5% of
acne patients. Those with low serum zinc had initial
higher acne score of 78.8.Treatment with oral zinc 200
mg two times a day increased serum zinc level to an
average level of 5.82 µg/ml. Mean severity score came
down to 24.8 from 60 in treated group. Inflammatory
lesions showed 60% reduction in severity while
comedones reduced by only 23%. After 12 weeks of
treatment with oral zinc 10.6% showed >75%
improvement while 48.9% showed 50-75%, 36.1%
showed 25-50% and 4.4% showed <25% improvement.
59.5% of patients showed >50% improvement which was
clinically appreciable. Percentage of improvement in acne
was directly proportional to the level of serum zinc level
attained. 50% of patients were satisfied by the treatment
Thomas J. Int J Res Dermatol. 2018 Aug;4(3):xxx-xxx
International Journal of Research in Dermatology | July-September 2018 | Vol 4 | Issue 3 Page 5
response. It could be concluded that increase in serum
zinc level can improve acne. Response to treatment was
more evident in inflammatory lesions. Oral zinc treatment
with 220 mg two times a day can increase serum zinc
level to appreciable levels.
Low serum zinc did not have a statistically significant
association with acne vulgaris.
Oral zinc treatment can increase serum zinc level and
raised serum zinc level cause response in acne severity.
Oral zinc definitely has a role in treatment of acne
particularly inflammatory lesions. Placebo has no role in
controlling acne.
Funding: No funding sources
Conflict of interest: None declared
Ethical approval: The study was approved by the
institutional ethics committee
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Cite this article as: Thomas J. Role of zinc in acne:
a study of 77 patients. Int J Res Dermatol
2018;4:xxx-xx.
... Daily supplementation of 20 mg of zinc sulphate for 8 weeks, the acne severity score (GAGS score) significantly decreased from the baseline in the intervention arm. One study revealed the maximum acne severity score reduction was observed after 3 to 6 weeks of supplementation with zinc sulphate [11]. Another trial found a significant decrease in papules, infiltrates, and cysts after 12 weeks of zinc supplementation [12]. ...
... The present study revealed a significant increase in serum zinc level in response to 8 weeks of oral zinc sulphate supplementation. Similarly, serum zinc level was increased with zinc supplementation after 12 weeks [11]. ...
... It reduces acne severity by maintaining the structural movement of skin epithelium [3]. Zinc determines macrophages' phagocytic activity and migration rate, interfering with the inflammatory process [11]. Increased levels of zinc influence several functions of cells. ...
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... Which was quite similar to our study where, one study revealed the maximum acne severity score reduction was observed after 3 to 6 weeks of supplementation with zinc sulphate. [13] Another trial found a significant decrease in papules, infiltrates, and cysts after 12 weeks of zinc supplementation. [14] However, other study reported no difference between the zinc supplementation and control groups. ...
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... Zinc is a key cofactor in the regulation of protein and lipid metabolism and, specific to AV, it has been shown to be bacteriostatic against C. acnes, as well as reduce the pro-inflammatory cytokine TNF-α. 43 Deficiency in selenium has also been reported in AV patients. 44 Additionally, selenium supplementation has been shown to play a role in hormone regulation by decreasing the levels of the testosterone precursor dehydroepiandrosterone (DHEA) in female patients with polycystic ovary syndrome (PCOS), an endocrine disorder associated with AV as an established manifestation of androgen excess. ...
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In a double-blind controlled comparison that lasted eight weeks, tablets of zinc sulfate monohydrate, 411 mg total daily dosage, and a lactose placebo were administered orally to 22 male subjects with moderate acne. At the same time, levels of zinc were determined in serum and urine. There were no statistically significant differences in the lesion counts (papules, pustules, open comedones, and closed comedones) in the zinc-treated and lactose-treated cases, despite evidence in serum and urine of absorption of zinc. The data from this study indicate that oral zinc therapy has no early clinical effect on male patients with moderate acne.
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At the patient's initial visit an assessment of general medical health and degree, type, and extent of acne is made. A careful history is obtained to determine possible aggravating factors, such as the ingestion of hormones or drugs, or the use of moisturizing or corticosteroid creams. If the patient has a few comedones and papules, benzoyl peroxide alone may be adequate. If comedones are large and numerous, retinoic acid plus benzoyl peroxide is useful. If there are a significant number of deep pustules and nodules, tetracycline or erythromycin orally can be prescribed. The dosage of antibiotic should be tapered and the drug discontinued as soon as the inflamniatory lesions subside. The patient should be informed that topical medications must be used indefinitely even when the eruption improves because the medications will prevent formation of new lesions. The patient should also be told that acne responds over a period of weeks, not days, and that improvement may not be noticed for four to eight weeks. Provision of a realistic time frame helps the adolescent to maintain confidence in the peeling medications which, at times, will cause irritation and redness of the face. Frequency of cleansing and appropriate cleansing agents and shampoos should be discussed. Dietary facts and fictions should also be mentioned, and, in some instances, parents should be included to preveiit confrontations at home. Girls who feel the need to cover blemishes should be advised to avoid greasy foundations and substitute one of the many cosmetically acceptable water-based formulations now available. Patient compliance will increase if a brief explanation of the pathogenesis of acne lesions and the effects of therapeutic agents is provided. Above all, the teenager should be told that the outlook for improvement is good, that acne can be treated successfully, and that for most patients, excellent control can be achieved if there is cooperation and interest on the part of both physician and patient.
Article
Three patients with acrodermatitis enteropathica (AE), a disorder of zinc metabolism, demonstrated a zinc-responsive defect in chemotaxis of neutrophils and monocytes. Monocyte chemotaxis was depressed during a controlled period of zinc deficiency and increased to normal values after administration of oral zinc sulfate supplements that was sufficient to restore normal plasma zinc levels. In the only patient in whom neutrophils were also studied, a similar defect in chemotaxis of neutrophils was corrected by administration of zinc sulfate supplements. Preincubation of defective cells in vitro with zinc sulfate increased chemotaxis in an almost linear dose-response relationship. These findings suggest an important role for zinc in neutrophil and monocyte chemotaxis and demonstrate a correctable immune defect in AE.
Article
Treatment for acne is far from optimal. This is understandable when we consider that the pathogenesis of the disease is still controversial and there are only limited means of controlling the process at different levels. Of the therapeutic agents that are available, benzoyl peroxide and vitamin A acid used in combination have given the best results in the majority of patients. Benzoyl peroxide inhibits the formation of free fatty acids in sebum, and vitamin A acid prevents follicular hyperkeratosis.
Article
The effect of zinc sulphate and placebo was compared in a double-blind trial in 56 patients suffering from acne vulgaris. Serum vitamin A levels were studied in all, before and at the end of therapy, 29 patients received zinc sulphate 600 mg daily and 27 patients received placebo. Patients on placebo showed no improvement. After 12 weeks of treatment with zinc sulphate, 17 patients (58%) showed significant improvement. There was a statistically significant decrease in the number of papules, infiltrates and cysts. In zinc-treated cases there was statistically significant increase in serum vitamin A levels, while no change was found in the placebo group.