Anti-inflammatory Effects of Topical Formulations Containing Sea Silt and Sea Salt on Human Skin In Vivo During Cutaneous Microdialysis

Abstract

Silt is sediment formed in estuaries and coastal regions along the seashore. It occurs along the entire North Sea coast and it is used in skin therapy. A single mud treatment induces normalization of stratum corneum hydration, transepidermal water loss, skin surface pH and sebum content (1). Mud therapy has been used successfully in several inflammatory skin diseases, such as psoriasis vulgaris (2), atopic dermatitis (3), acne vulgaris (4) and skin ulcers (5). The aim of this study was to elucidate possible anti-inflammatory effects of sea silt and sea salt-containing topical formulations on human skin in vivo. MATERIALS AND METHODS Different topical formulations containing sea silt essences and sea salt were tested: La mer MED Sea-salt cream ® (SSC, 7.5% sea silt, 10% sea salt), La mer MED sea salt lotion ® (SSL, 5% sea silt, 3.5% sea salt) and La mer MED fat cream ® (FC, 7.5% sea silt, 0.5% sea salt) (La mer, Cuxhaven, Germany). The silt extract in these formulations contains approximately 0.6% fatty acids (hexadecanoic acid, hexadecenoic acid, eico-sapentaenoic acid, octadecatrienoic acid and eicosatetraenoic acid) and 0.3% sulphur. All formulations (except for SSL) also contain 1% hydrolysed enteromorpha compressa extract and up to 5% hydrogenated vege table and palm kernel oil, which contains 82% saturated and 18% unsaturated fatty acids (i.e. oleic acid and linoleic acid). Twenty healthy volunteers aged 22–29 years were tested for tolerability and efficacy of sea silt formulations after approval by the local ethics committee. To test tolerability, ten healthy volunteers (age range 22–27 years) applied SSC to one-half of the body's skin surface (either left or right). In addition, five volunteers applied SSL to one side of the body and FC to the other half; the head and back were left as untreated control areas. After 2 h, skin areas on the left and right upper and lower arms, legs and back were measured for skin pH, transepidermal water loss (TEWL) (Derma Unit SSC3 and Tewameter TM300, both from Courage & Khazaka, Cologne, Germany) and skin colour (Chromameter CR-300, Minolta, Osaka, Japan) (6, 7). Measurements were repeated 0.5 h and 24 h after irradiation with a minimal erythematous dose (MED) of ultraviolet A (UVA) and ultraviolet B (UVB) (Waldmann UV 3003K, Herbert Waldmann GmbH & Co. KG, Villingen-Schwenningen, Germany). To test anti-inflammatory efficacy, well-defined areas of 9 cm 2 on the volar forearms of 10 healthy volunteers (age range 23–29 years) were exposed to UVB irradiation with twice the minimal erythematous dose (450–550 mJ/cm 2), followed by treatment with test formula-tions, diclofenac gel (DG, Voltaren Emulgel ® , Novartis AG, Nuremberg, Germany) or base cream (BC, a cream composed primarily of water, paraffin, citric acid, sodium cetearyl sulphate and cetearyl alcohol; Laticort base cream ® , Almirall Hermal, Reinbek, Germany) as a negative control. Two hours after ir-radiation, a thin layer of each formulation (approximately 500 mg) covering the entire test area was applied six times every 2 h and gently rubbed in for approximately 5 min until it was absorbed. Cut-off membranes of 20 kDa (CMA71 60/20 mem-branes, CMA microdialysis, Sweden) were placed in the dermis at 0.7–1.2 mm depth, as determined by 22 MHz ultrasound (taberna pro medicum, Luneburg, Germany) and cutaneous mi-crodialysis was started 24 h after UVB irradiation in irradiated and treated skin as well as in non-irradiated and untreated skin as described earlier (8). After flushing the membranes at a rate of 5 µl/min for 1 h for equilibration, membranes were perfused at a flow rate of 0.5 µl/min with sodium chloride (NaCl) 0.9%, using a CMA107 microdialysis pump (CMA Microdialysis, Solna, Sweden). Microdialysate samples were collected at 30-min intervals for 8 h and analysed for 5-and 8-iso-PGF 2α F 2 -isoprostanes and 9α,11α-PGF 2α and PGE 2 prostaglandins using sensitive gas chromatography-mass spectrometry and negative ion chemical ionization, as described previously (8). Since it has been demonstrated previously that the intensity of skin erythema correlates with levels of prostanoids (9), skin darkness and erythema of all test areas were measured at the end of microdialysis, 36 h after UVB irradiation in six volunteers (Chromameter CR-300, Minolta, Osaka, Japan). Mean values, standard errors (SE), significance (Wilcoxon signed-rank test) and area under the curve (AUC) were calculated with MedCalc 10 (MedCalc, Mariakerke, Belgium).

Full text

Acta Derm Venereol 91
1
Letters to the Editor 2011 Epub ahead of print
© 2011 The Authors. doi: 10.2340/00015555-1128
Journal Compilation © 2011 Acta Dermato-Venereologica. ISSN 0001-5555
Silt is sediment formed in estuaries and coastal regions
along the seashore. It occurs along the entire North Sea
coast and it is used in skin therapy. A single mud treatment
induces normalization of stratum corneum hydration,
transepidermal water loss, skin surface pH and sebum
content (1). Mud therapy has been used successfully in
several inammatory skin diseases, such as psoriasis
vulgaris (2), atopic dermatitis (3), acne vulgaris (4) and
skin ulcers (5). The aim of this study was to elucidate
possible anti-inammatory effects of sea silt and sea salt-
containing topical formulations on human skin in vivo.
MATERIALS AND METHODS
Different topical formulations containing sea silt essences and
sea salt were tested: La mer MED Sea-salt cream® (SSC, 7.5%
sea silt, 10% sea salt), La mer MED sea salt lotion® (SSL,
5% sea silt, 3.5% sea salt) and La mer MED fat cream® (FC,
7.5% sea silt, 0.5% sea salt) (La mer, Cuxhaven, Germany).
The silt extract in these formulations contains approximately
0.6% fatty acids (hexadecanoic acid, hexadecenoic acid, eico-
sapentaenoic acid, octadecatrienoic acid and eicosatetraenoic
acid) and 0.3% sulphur. All formulations (except for SSL) also
contain 1% hydrolysed enteromorpha compressa extract and
up to 5% hydrogenated vege table and palm kernel oil, which
contains 82% saturated and 18% unsaturated fatty acids (i.e.
oleic acid and linoleic acid). Twenty healthy volunteers aged
22–29 years were tested for tolerability and efficacy of sea silt
formulations after approval by the local ethics committee. To
test tolerability, ten healthy volunteers (age range 22–27 years)
applied SSC to one-half of the body’s skin surface (either left
or right). In addition, five volunteers applied SSL to one side
of the body and FC to the other half; the head and back were
left as untreated control areas. After 2 h, skin areas on the left
and right upper and lower arms, legs and back were measured
for skin pH, transepidermal water loss (TEWL) (Derma Unit
SSC3 and Tewameter TM300, both from Courage & Khazaka,
Cologne, Germany) and skin colour (Chromameter CR-300,
Minolta, Osaka, Japan) (6, 7). Measurements were repeated
0.5 h and 24 h after irradiation with a minimal erythematous
dose (MED) of ultraviolet A (UVA) and ultraviolet B (UVB)
(Waldmann UV 3003K, Herbert Waldmann GmbH & Co. KG,
Villingen-Schwenningen, Germany). To test anti-inflammatory
efficacy, well-defined areas of 9 cm2 on the volar forearms of
10 healthy volunteers (age range 23–29 years) were exposed
to UVB irradiation with twice the minimal erythematous dose
(450–550 mJ/cm2), followed by treatment with test formula-
tions, diclofenac gel (DG, Voltaren Emulgel®, Novartis AG,
Nuremberg, Germany) or base cream (BC, a cream composed
primarily of water, paraffin, citric acid, sodium cetearyl sulphate
and cetearyl alcohol; Laticort base cream®, Almirall Hermal,
Reinbek, Germany) as a negative control. Two hours after ir-
radiation, a thin layer of each formulation (approximately 500
mg) covering the entire test area was applied six times every
2 h and gently rubbed in for approximately 5 min until it was
absorbed. Cut-off membranes of 20 kDa (CMA71 60/20 mem-
branes, CMA microdialysis, Sweden) were placed in the dermis
at 0.7–1.2 mm depth, as determined by 22 MHz ultrasound
(taberna pro medicum, Luneburg, Germany) and cutaneous mi-
crodialysis was started 24 h after UVB irradiation in irradiated
and treated skin as well as in non-irradiated and untreated skin
as described earlier (8). After flushing the membranes at a rate
of 5 µl/min for 1 h for equilibration, membranes were perfused
at a flow rate of 0.5 µl/min with sodium chloride (NaCl) 0.9%,
using a CMA107 microdialysis pump (CMA Microdialysis,
Solna, Sweden). Microdialysate samples were collected at
30-min intervals for 8 h and analysed for 5- and 8-iso-PGF2α
F2-isoprostanes and 9α,11α-PGF2α and PGE2 prostaglandins
using sensitive gas chromatography-mass spectrometry and
negative ion chemical ionization, as described previously (8).
Since it has been demonstrated previously that the intensity of
skin erythema correlates with levels of prostanoids (9), skin
darkness and erythema of all test areas were measured at the end
of microdialysis, 36 h after UVB irradiation in six volunteers
(Chromameter CR-300, Minolta, Osaka, Japan). Mean values,
standard errors (SE), significance (Wilcoxon signed-rank test)
and area under the curve (AUC) were calculated with MedCalc
10 (MedCalc, Mariakerke, Belgium).
RESULTS
All test products were well-tolerated without any side-
effects or increase in skin pigmentation throughout
the study (data not shown). All preparations prevented
a decrease in pH and an increase in transepidermal
Anti-inammatory Effects of Topical Formulations Containing Sea Silt and Sea Salt on Human Skin
In Vivo During Cutaneous Microdialysis
Sven R. Quist1, Ingrid Wiswedel2, Jennifer Quist1 and Harald P. Gollnick1
1Clinic of Dermatology and Venereology, and 2Department of Pathological Biochemistry, Otto-von-Guericke University, Magdeburg, Leipziger Str. 44, DE-
39120 Magdeburg, Germany. E-mail: squist@gmx.de
Accepted February 2, 2011.
Table I. Changes in skin pH, transepidermal water loss (TEWL in
g/m2 ∙ h) and skin erythema (values > 0 indicates increasing skin
erythema) at baseline (2-h treatment with topical formulations
containing sea silt and sea salt or untreated), 0.5 h, and 24 h after
ultraviolet A/ultraviolet B (UVA/UVB) irradiation (mean of 10
volunteers with standard error (SE))
Skin pH TEWL Erythema
Untreated skin
2 h treatment 5.15 ± 0.57 7.74 ± 0.19 9.92 ± 2.89
0.5 h post-UV 4.96 ± 0.13 7.74 ± 0.18 10.56 ± 0.35
24 h post-UV 5.14 ± 0.14 7.81 ± 0.26 11.73 ± 0.67
Fat cream
2 h treatment 5.00 ± 0.49 6.94 ± 0.22 10.65 ± 1.28
0.5 h post-UV 5.04 ± 0.45 6.97 ± 0.29 10.83 ± 1.22
24 h post-UV 5.30 ± 0.56 5.90 ± 0.4 11.16 ± 1.24
Sea salt cream
2 h treatment 5.11 ± 0.42 6.72 ± 0.19 10.10 ± 1.15
0.5 h post-UV 5.17 ± 0.40 7.59 ± 0.23 10.26 ± 0.75
24 h post-UV 5.28 ± 0.47 6.05 ± 0.32 11.06 ± 1.56
Sea salt lotion
2 h treatment 5.35 ± 0.26 6.75 ± 0.17 9.66 ± 1.16
0.5 h post-UV 5.42 ± 0.29 7.13 ± 0.15 9.78 ± 1.01
24 h post-UV 5.17 ± 0.42 5.22 ± 0.23 10.47 ± 1.49

2Letters to the Editor
water loss (TEWL) observed at 24 h post-UVA/UVB
in untreated skin (Table I). Furthermore, FC and SSL
strongly decreased TEWL and all sea silt preparations
inhibited increase in skin erythema 24 h post-UV
irradiation compared with untreated skin (Table I).
Microdialysis showed lower mean values of AUC for
8-iso-PGF
2α
and total F2-isoprostanes, obtained from
dialysates of treated skin areas in all 10 volunteers with
any treatment compared with BC (Table II). Treatment
with DG resulted in lower amounts of mean AUC for
all markers, whereas treatment with SSL resulted in
lower amounts of mean AUC for 9α,11α-PGF
2α
in all
10 volunteers tested. In six volunteers, we were able to
analyse changes in skin darkness and erythema of trea-
ted skin areas at the end of microdialysis 36 h after UVB
irradiation (Table III). There was a signicant decrease
in skin redness and darkness at 36 h for untreated non-
irradiated skin and skin treated with SSC, SSL and DG,
but not for FC compared with skin areas treated with BC
as a negative control (Table III). When comparing these
results with the mean values of AUC for 5- and 8-iso-
PGF2α, total F2-isoprostanes and 9α,11α-PGF2α and
PGE2 prostaglandins from the microdialysates of the
same volunteers, decreases were observed in untreated
non-irradiated skin and skin areas treated with the same
topical formulations; that is, SSL, SSC and DG.
DISCUSSION
We used cutaneous microdialysis to detect differences
in prostanoid levels of irradiated and treated skin. Ho-
wever, microdialysis is an invasive method (10), leading
to release of prostanoids. This, together with the small
number of patients, may have prevented the detection of
signicant differences between treatment areas, although
sufcient time was allowed for tissue recovery and
equilibration as determined in previous experiments (8,
11). Sea silt extract contains various active substances
from sea silt, such as unsaturated fatty acids, sulphur and
algae. These ingredients could contribute to sea silt’s anti-
inammatory efcacy, which are known to derive from
omega-3 and omega-6 fatty acids (12). Omega fatty acids
inhibit the formation of pro-inammatory eicosanoids,
but can also form potent anti-inammatory lipid medi-
ators, such as resolvins and protectins, suppress NFκB
activity and reduce the production of pro-inammatory
enzymes and cytokines (COX-2, TNF-α, IL-1β) (13).
We were able to demonstrate that all tested sea silt- and
sea salt-containing topical formulations suppressed the
UVB-provoked release of 8-iso PGF
2α
, which is a well-
known marker of oxidative stress. Furthermore, skin
redness and skin darkening was signicantly decreased
by sea silt- and sea salt-containing formulations (more
for lotion than for cream). However, the effect was lower
than that observed following treatment with oral diclo-
fenac, a known inhibitor of COX-1 and -2. FC, the only
formulation that did not contain sea salt, failed to exert a
suppressive effect on prostanoids 9α,11α-PGF2α, PGE2
and 5-iso-PGF2α.
ACKNOWLEDGEMENTS
We would like to thank Ines Doering for excellent technical
assistance. The study was supported by La mer cosmetic AG,
Cuxhaven, Germany.
Conflict of interest: Sven R Quist received financial support
from La mer cometics AG for materials (microdialysis cathe-
ters and topical formulations) in order to conduct this trial. No
further conflict of interest by any of the author is reported.
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