Journal of Dermatological Treatment. 2006; 17: 82–85
ORIGINAL ARTICLE
Open trial of supplements of omega 3 and 6 fatty acids, vitamins and
minerals in atopic dermatitis
BONDEVIK BJØRN ERIKSEN1 & DOTTERUD LARS KÅRE2
1
Dr Bondeviks Dermatological Clinic, Oslo, Norway, and 2Department of Dermatology, University Hospital of North
Norway, Tromsø, Norway
Abstract
Objective: To investigate whether dietary supplementation with polyunsaturated fatty acids (PUFA) of the omega 3 series
(n-3 PUFA: 18:3, n-3; 20:5, n-3; and 22:6, n-3), the omega 6 series (n-6 PUFA: 18:3, n-6), vitamins and minerals have a
clinical effect on atopic dermatitis. Methods: A total of 19 patients aged 17–43 years with moderate to severe atopic
dermatitis participated in an open trial of high oral doses of n-3 and n-6 PUFA in dry form (powder) or omega 3,6,9 fatty
acid capsules, vitamin E tablets (d-alpha-tocopherol), zinc solution or tablets, and multivitamin capsules daily for 16 weeks.
Results: The mean SCORAD improved in 14 of 17 patients by more than 50% after 8 weeks and 16 weeks of treatment
(pv0.01 and pv0.001, respectively). Conclusion: The open nature of this trial and the small number of subjects are major
limitations of this study. The possible role of dietary omega 3 and 6 fatty acids in the treatment of atopic dermatitis should
be tested more extensively in a double-blind trial using high doses of antioxidants combined with PUFA.
Key words: Atopic dermatitis, minerals, omega fatty acids, vitamins
Introduction
Atopic dermatitis (AD) is a chronic, recurrent,
multifactoral skin disease with an increasing incidence
in the western world over the last 30 years (1). Genetic
predisposition in combination with environmental
factors and other unknown factors seem to influence
the prevalence and the course of the disease (1,2). AD
is associated with an immunological dysfunction,
including defects in the T-cell function (alteration of
the Th1/Th2-ratio) and in some patients IgEmediated reactions (3). Patients with AD have a
reduced skin barrier and show high levels of the
enzyme sphingomyelin deacylase in the epidermis,
which reduces the amount of ceramides (4). Reduced
levels of the converting enzyme desaturase have also
been found in patients with AD (5).
The n-3 polyunsaturated fatty acids (PUFA)
alpha-linolenic acid (ALA, 18:3,n-3), eicosapentaenoic acid (EPA, 20:5,n-3), and decosahexaenoic
acid (DHA, 22:6,n-3) and the n-6 PUFA gammalinolenic acid (GLA, 18:3,n-6) are important components of the stratum corneum and are important
for the normal function and structure of the skin
barrier (5). Moreover, patients with AD have a
defect in prostaglandin synthesis and leukotrienes
(6), which can result in selective hyperactivity of the
immune system (7–9). Furthermore, n-3 PUFA can
reduce allergic reactions because of its ability to
reduce prostaglandin E2 (PGE2). Arachidonic acid
(AA) is the precursor of secondary inflammatory
mediators, especially PGE2. PGE2 has a strong
inhibitory effect on interferon gamma (IFN-c) and
increases interleukin 4 (IL-4), thus promoting the
Th2 allergy response. EPA can be metabolized into
15-hydroxyeicosapentaenoic
acid
(15-HEPE),
which restricts lipoxygenase and thus the creation
of the highly potent leukotriene LTB4 (10).
AD has traditionally been treated with moisturizing creams, local steroids, phototherapy and
immune-suppressive substances (azothioprine and
cyclosporine). Over the past 15 years there has been
a growing interest in dietary supplements, and
essential fatty acids can be effective in treating AD.
Based on recent experience and research within
orthomolecular nutrition, we tested the effects of n-3
Correspondence: Bjørn Eriksen Bondevik, Dr Bondeviks Dermatological Clinic, Von Øtkens vei 14, N-1169 Oslo, Norway. Fax: 47 22 74 48 98. E-mail:
[email protected]
(Received 5 July 2004; accepted 25 January 2006)
ISSN 0954-6634 print/ISSN 1471-1753 online # 2006 Taylor & Francis
DOI: 10.1080/09546630600621946
Effect of dietary supplementation on atopic dermatitis
PUFA and n-6 PUFA and antioxidants in patients
with AD (10–13).
Materials and methods
The study was approved by The Human Subjects
Committee at the University of Oslo, Norway.
A convenience sample of 19 patients aged 13–47
years participated in an open study in a dermatological clinic in Oslo, Norway, during the period
September 2000 to June 2001. The treatment period
was 16 weeks per patient. Seventeen of 19 patients
(89%), nine of whom were female, completed the
study. Two patients suspended the study of their
own accord (lack of motivation). Patients who had
previously or who were at the time of selection taking
dietary supplements were excluded from the study.
A total of 12 participants suffered from an IgEmediated allergy, five suffered from allergic rhinitis
and/or asthma, and eight patients were taking
pharmaceutical medicines, either regularly or intermittently (B2-stimulator/corticosteroid inhalor, and/
or antihistamines).
83
from start to end, were evaluated with the SCORAD
index at each visit. The other six patients, receiving
Nutraceutical KAL 3,6,9 capsules, were evaluated
with an intention-to-treat analysis together with the
11 other patients (pooled group 2). The SCORAD
values for the six patients after 4 weeks were carried
forward into the 8- and 16-week evaluation.
Upon completion of the treatment the patients
gave a subjective evaluation of the treatment effect
(much improvement: w50%; improvement: 25–
50%; unchanged; and worse).
The patients received daily supplements in the
form of n-3 and n-6 PUFA for 16 weeks.
All patients were given the same vitamin E tablet
(BioCare MicroCell), multivitamins (two capsules of
Solaray Spektro Multi-Vita-Min) and the mineral
zinc, either in solution (Metagenics ZincDrink) or in
the form of tablets (Zinc Asportate). The patients
could choose between tablets (five patients) and the
solution (Table I).
The difference in total concentration of vitamin C,
vitamin E and zinc is due to the different concentration of these supplements in the fatty acid powder
and the capsules.
Previous treatments
A total of 16 patients had previously used topical
steroids, while three of them had also been using
systemic steroids at least once a year. Six of the
patients had received phototherapy, two of whom
reported a good effect and one a moderate effect
(11). Patients had used alternative/complementary
therapies, for instance acupuncture and/or homeopathic therapy. Three of these patients reported
good effects, while four reported no effect. Two
patients had tried an ‘anti-Candida diet’ with no
effect.
Allergy tests
Total IgE values varied from 5.8 kU/l to 23 100 kU/l
(mean value 2070 kU/l). Eight patients had elevated
total IgE w120 kU/l. One or more positive specific
IgE tests (type 1 sensitization) were found in 11
patients.
Evaluation and treatment
The primary outcome was the SCORAD index
(severity scoring of atopic dermatitis) before treatment, after 4 and 8 weeks and after 16 weeks of
study (14). The dosage of the products included in
the study, as well as any possible changes in other
treatments, were registered at every control. Because
of side effects from the omega 3,6 powder, six of the
patients had to switch medication after 4 weeks of
treatment. Owing to this, it was necessary to make
two statistical evaluations. Eleven patients (group 1),
receiving the BioCare DriCelle OmegaPlex powder
Table I. The daily dose of supplements for each patient with
atopic dermatitis.
Total daily dose
of PUFA
Powder DriCelle
OmegaPlex
10 g contains the
following:
Vitamin C
Vitamin E
Zinc
375 mga
450 mga
23 mg
120 mga
384 mga
23 mg
GLA: 120 mg
LA: 475 mg
ALA: 200 mg
EPA: 375 mg
DHA: 300 mg
3 capsules KAL
Ultra 3,6,9
3,6 g contains
the following:
GLA: 228 mg
LA: 525 mg
ALA: 636 mg
EPA: 216 mg
DHA: 144 mg
a
The difference in total concentration of vitamin C and vitamin E
is due to the different concentration of these supplements in the
fatty acid powder and the capsules.
Polyunsaturated fatty acids (PUFA):
LA5linoleic acid, omega 6 fatty acid (18:2,n-6)
GLA5gamma-linolenic acid, omega 6 fatty acid (18:3,n-6)
ALA5alpha-linolenic acid, omega 3 fatty acid (18:3,n-3)
EPA5eicosapentaenoic acid, omega 3 fatty acid (20:5,n-3)
DHA5decosahexaenoic acid, omega 3 fatty acid (22:6,n-3)
EPA and DHA were extracted from fish fat; ALA and LA from
flaxoil; and LA and GLA were extracted from borago.
84
B. B. Eriksen & D. L. Kåre
Exclusion
Patients who did not adhere to the treatment (cut-off
point being set at 70% compliance) for a total of 8
weeks were excluded from the study. In cases were
patients’ rashes got worse after 8 weeks of treatment,
this was considered treatment failure, and the
patients were not replaced.
Statistical method
The statistical method used was MANOVA (multivariate analysis of variance), with repeated measurements being taken to describe a decrease in the
SCORAD values.
Results
The SCORAD improved after 4 weeks of treatment
(Figure 1). Moreover, symptoms continued to
improve at 8 (pv0.01) and 16 weeks (pv0.001),
respectively (Figure 1). When excluding the six
patients receiving 3,6,9 omega capsules after the
first examination (4 weeks), we found no significant
difference between the group 1 patients treated only
with omega 3,6 powder and the pooled group 2
(Table II).
There was a good correlation between the
patients’ subjective evaluations and the objective
SCORAD evaluation stated in the study. Fourteen
patients reported more than 50% improvement, and
three patients did not seem to benefit from the
treatment with dietary supplements. No patients had
to terminate the study due to side effects.
Figure 1. The SCORAD values for 17 patients (pooled group 2)
with atopic dermatitis after 16 weeks of taking the dietary
supplements omega fatty acids n-3 and n-6, vitamin E, multivitamins and zinc.
Table II. SCORAD evaluation after 4, 8 and 16 weeks of
treatment with omega 3,6 powder alone (n511, group 1), omega
3,6 powder and/or omega 3,6,9 capsules (n517, group 2).
Mean SCORAD
Treatment
week
0
4
8
16
Group 1
Pooled group 2
p-value
65.1
45.6
33.2
24.4
60.8
42.8
34.8
29.1
ns
ns
ns
ns
Discussion
This study was a small open trial showing that the
treatment of AD with PUFA and antioxidants led to
a clinical improvement. Better results were obtained
than previous studies with dietary supplements,
possibly for several reasons. According to the
literature, most studies have been carried out with
n-6 PUFA GLA alone (11,12,15–17), and only a
few with the n-3 PUFA EPA and DHA (18,19) or in
combination with GLA (20). In a placebo-controlled
trial of n-3 PUFA versus n-6 PUFA, there was a
significant effect on AD with both EPA and GLA
(21).
A lower serum level of omega 6 fatty acids has
been found in patients with AD, possibly due to the
lack of or a reduced effect of the converting enzyme
delta-6 desaturase. As a result, the level of GLA and
the omega 6 metabolite dihomo-gamma-linolenic
acid (DGLA) and their effects on AD is reduced
(22). At the same time, the stratum corneum will get
a lower supply of fatty acids, as the skin receives
these fatty acids from the blood. Previous studies
with the combination of vitamin E and fatty acids
have shown that the level of vitamin E is significantly
reduced by intake of PUVA (13). Thus, we used
high doses of antioxidants in combination with fatty
acids, and this may explain the efficacy we observed.
It is commonly known that a mild climate and
sunshine often leads to a clear improvement in
symptoms for most patients with AD. In our study,
15 out of the 17 patients completed the study in
mid-April, a time of year that should not have
strongly influenced our results.
In conclusion, we found that the 16 weeks of
dietary supplements may have a clinical effect on
AD. However, the results of this open study have its
limitations and are at most only suggestive.
Therefore, it should be followed up by a randomized, double-blind, placebo-controlled, threearmed study which compares the treatment results
for AD of PUFA used as monotherapy and PUFA in
combination with antioxidants.
Acknowledgements
We would like to thank Tore Rolstad for organizing
the study, both with regard to the study design and
Effect of dietary supplementation on atopic dermatitis
as a sponsor of the products used. We would also
like to thank Lars Erik Peterson at the Institute
for National Economics and Statistics of the
Handelshögskolan at the University of Gothenburg.
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