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ORIGINAL PAPER
A. Barel ÆM. Calomme ÆA. Timchenko
K. De. Paepe ÆN. Demeester ÆV. Rogiers
P. Clarys ÆD. Vanden Berghe
Effect of oral intake of choline-stabilized orthosilicic acid on skin, nails
and hair in women with photodamaged skin
Received: 10 January 2005 / Revised: 20 April 2005 / Accepted: 23 June 2005 / Published online: 5 October 2005
Springer-Verlag 2005
Abstract Chronic exposure of the skin to sunlight causes
damage to the underlying connective tissue with a loss of
elasticity and firmness. Silicon (Si) was suggested to have
an important function in the formation and maintenance
of connective tissue. Choline-stabilized orthosilicic acid
(‘‘ch-OSA’’) is a bioavailable form of silicon which was
found to increase the hydroxyproline concentration in
the dermis of animals. The effect of ch-OSA on skin,
nails and hair was investigated in a randomized, double
blind, placebo-controlled study. Fifty women with
photodamaged facial skin were administered orally
during 20 weeks, 10 mg Si/day in the form of ch-OSA
pellets (n=25) or a placebo (n=25). Noninvasive
methods were used to evaluate skin microrelief (fore-
arm), hydration (forearm) and mechanical anisotropy
(forehead). Volunteers evaluated on a virtual analog
scale (VAS, ‘‘none=0, severe=3’’) brittleness of hair
and nails. The serum Si concentration was significantly
higher after a 20-week supplementation in subjects with
ch-OSA compared to the placebo group. Skin roughness
parameters increased in the placebo group (Rt:+8%;
Rm: +11%; Rz: +6%) but decreased in the ch-OSA
group (Rt: 16%; Rm: 19%; Rz: 8%). The change
in roughness from baseline was significantly different
between ch-OSA and placebo groups for Rt and Rm.
The difference in longitudinal and lateral shear propa-
gation time increased after 20 weeks in the placebo
group but decreased in the ch-OSA group suggesting
improvement in isotropy of the skin. VAS scores for nail
and hair brittleness were significantly lower after
20 weeks in the ch-OSA group compared to baseline
scores. Oral intake of ch-OSA during the 20 weeks re-
sults in a significant positive effect on skin surface and
skin mechanical properties, and on brittleness of hair
and nails.
Keywords Photodamaged skin ÆSilicon ÆOrthosilicic
acid ÆNails ÆHair
Introduction
Healthy skin impedes the penetration of microorgan-
isms which can cause infections and protects against
irritants. Ageing leads to several changes in the skin
and its appendages (hair, nails). These changes can be
broadly categorized as either intrinsic ageing (chrono-
biological) or photoageing (actinic ageing). Intrinsic
ageing results in subtle but important alterations of
cutaneous function that are presumed to be due to
time alone, whereas photoageing is the result of
preventable chronic exposure to ultraviolet (UV)
radiation superimposed on intrinsic ageing. Major
changes of photoageing occur in the dermis. A marked
decrease in collagen, glycosaminoglycans and proteo-
glycans is observed combined with a degeneration of
elastic fibers (elastosis) resulting in a rough leathery
skin surface with fine and coarse wrinkles. Further-
more, a loss of elasticity and an increase in mechanical
anisotropy of the skin is observed. Premature age-
ing of the skin due to excessive exposure to UV light
either from the sun or/and from sun benches is an
increasing problem [32].
Silicon (Si) is a ubiquitous element present in various
tissues in the human body [1] and is present in 1–10 parts
per million in hair [29] and nails [1]. Studies of silicon
deprivation in growing animals indicated growth retar-
dation and marked defects of bone and connective tissue
A. Barel ÆA. Timchenko ÆP. Clarys
Faculty of Physical Education and Physiotherapy,
Vrije Universiteit Brussel, Brussels, Belgium
M. Calomme (&)ÆN. Demeester ÆD. Vanden Berghe
Department of Pharmaceutical Sciences
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences,
University of Antwerp, Universiteitsplein 1,
B-2610 Wilrijk-Antwerp, Belgium
E-mail: microfar@ua.ac.be
Tel.: +32-3-820-2550
Fax: +32-3-820-2544
K. De. Paepe ÆV. Rogiers
Faculty of Medicine and Pharmacy,
Vrije Universiteit Brussel, Brussels, Belgium
Arch Dermatol Res (2005) 297: 147–153
DOI 10.1007/s00403-005-0584-6
[9]. Nutritional Si deficiency was found to decrease both
the collagen synthesis and the formation of glycosami-
noglycans in bone and cartilage [7]. In vitro, the activity
of prolyl hydroxylase was reported to be dependent on
the Si concentration in the medium of bone cultures,
suggesting a Si-dependent pathway for collagen type I
synthesis [8]. Others have suggested a structural role of
Si in the cross-linking of glycosaminoglycans in con-
nective tissue [25].
Recent animal studies confirm the involvement of Si
in bone metabolism both in young animals [26,27] and
in models for postmenopausal osteoporosis [15,24].
Subcutaneously implanted sponges of Si-deprived rats
were found to contain less hydroxyproline compared to
rats on a normal diet indicating that Si deprivation de-
creases collagen formation which is associated with
wound healing [28]. In addition, the activity of liver
ornithine aminotransferase, an important enzyme in the
pathway of collagen formation, was lower in Si-deprived
rats compared to Si-adequate rats [28].
Soluble Si is present as orthosilicic acid (OSA) in
beverages and water. It is stable in dilute concentrations
(<10
4
M) but polymerizes at higher concentrations
around neutral pH into a range of silica species.
Absorption studies indicated that only OSA is bio-
available, whereas its polymers are not absorbed [16].
Dietary silicates undergo hydrolysis, forming OSA
which is readily absorbed in the gastrointestinal tract.
Physiological concentrations of OSA stimulate skin fi-
broblasts to secrete collagen type I [23].
A stabilized form of OSA, choline-stabilized OSA
(‘‘ch-OSA’’), was found to have a high bioavailability in
humans compared to other Si supplements that contain
polymerized forms of OSA [3,33]. Supplementation of
animals with low doses of ch-OSA resulted in a higher
collagen concentration in the skin [5] and in an increased
femoral bone density [4,6].
Choline, the stabilizing agent in ch-OSA, is classified
by the Food and Nutrition Board as an essential nutri-
ent [12]. Although humans can synthesize it in small
amounts, dietary sources are needed to maintain normal
health [2]. Choline is important for the structural
integrity of cellular membranes since it is the precursor
of phospholipids (phosphatidylcholine and sphingomy-
elin) which are essential components of biological
membranes. One of its metabolites, betaine, participates
in the methylation of homocysteine to form methionine.
Betaine is also known as an essential intracellular osm-
olyte [35]. Choline directly affects nerve signaling (as a
precursor of the neurotransmitter acetylcholine), cell
signaling (as a precursor for intracellular messengers
such as diacylglycerol or ceramide, platelet-activating
factor and sphingosylphosphorylcholine) and lipid
transport/metabolism (required in the biosynthesis of
very low-density lipoproteins).
In the present study we investigated the effect of oral
intake of ch-OSA on skin, hair and nails in a random-
ized, placebo-controlled double-blind study in subjects
with photo-aged facial skin.
Subjects and methods
Subjects
Fifty healthy Caucasian females, aged between 40 and
65 years, with clear clinical signs of photo-ageing of
facial skin were included in this study after written in-
formed consent. The subjects were assigned to two
groups which were matched on the basis of photo type,
age and actinic ageing. Subjects were randomly supple-
mented with ch-OSA or a placebo in each group. Wo-
men, using silicon supplements less than 3 months
before the start of the trial or any food supplement other
than the study medication during the trial, were ex-
cluded. In addition, subjects following any dermato-
logical or cosmetical antiageing or antiwrinkle therapy
including collagen, hyaluronic or botox injections,
chemical and laser peelings, retinoic and alpha hydroxy
acid treatment during the trial, were excluded. Fur-
thermore, exposure to sun benches or sunlight was
prohibited during the trial. The subjects provided a de-
tailed list of all cosmetic products that they use daily.
Subjects agreed not to change this daily regimen during
the trial. On the day that noninvasive tests took place,
subjects were instructed to refrain from using lotions,
creams or other products on face and forearms. The trial
was started in the autumn of 2003 and was completed in
the spring of 2004.
Ethical approval was obtained from the regional
Ethics Committee (Academic Hospital, Vrije Universi-
teit Brussel, Brussels, Belgium, protocol number 03/4
entitled antiageing effect of ch-OSA on photodamaged
skin in healthy volunteers). The study was carried out in
accordance to the Declaration of Helsinki (1964) chan-
ged by the 29th World Medical Assembly at Tokyo
(1975).
Treatment
All patients were supplemented during 20 weeks with
two capsules daily containing either the excipiens (mi-
crocrystalline cellulose pellets, Pharmatrans Sanaq AG,
Switzerland) or 10 mg of silicon in the form of ch-OSA
pellets (Bio Minerals n.v., Belgium). Subjects were in-
structed to take one capsule in the morning and another
in the evening with a glass of water or juice. Placebo and
ch-OSA capsules were identical in color, taste, odor and
packaging and their content was blinded to the subjects
and investigator.
Serology
Blood samples were collected from fasting subjects at
baseline and after a 20-week supplementation, using Si-
free polypropylene syringes (Sarstedt, Germany) and
needles (Microlance, Becton Dickinson, Spain). Imme-
diately after the sample was taken, the blood was
148
transferred into Si-free polypropylene tubes without
anticoagulant (Sarstedt, Germany).
Si concentration in serum was analyzed in one batch
by electrothermal atomic absorption spectrometry with
inverse longitudinal Zeeman background correction
(AAnalyst 800, Perkin Elmer, Bodenseewerk, Germany).
Pyrolytic-coated graphite tubes were used. The hollow
cathode lamp settings were respectively 30 mA lamp
current, 251.6 nm spectral line and 0.2 nm band width.
The injected sample volume was 20 ll and signals were
measured in the peak-area mode. Serum samples were
measured in duplicate by standard addition. Standards
and serum dilutions were prepared in matrix modifier
solution containing 72 mg/l CaCl
2
(Aldrich, Belgium),
1.508 g/l NH
4
H
2
PO
4
(Merck, Belgium) and 0.5 g/l
Na
4
EDTA (Aldrich, Belgium) in ultrapure water (con-
ductance £0.08 lS). The sensitivity determined as the
amount of silicon yielding a 0.0044 Abs.s signal was
90 pg. A pool of serum obtained from fasting healthy
subjects was analyzed on several days to determine the
inter-assay c.v. and was found to be 8.7% for a mean Si
concentration of 109.09 lg/l (n=16).
To evaluate the safety of oral treatment with ch-OSA,
serum concentrations of urea, creatinine, uric acid, total
protein, cholesterol, HDL-cholesterol, LDL-cholesterol
and direct bilirubin, glutamic-oxalacetic transaminase
(GOT), glutamic-pyruvic transaminase (GPT), gamma-
glutamyltransferase (gamma-GT), cholinesterase, crea-
tine kinase (CK), amylase and lipase were determined.
Other parameters analyzed were sodium, calcium,
phosphorus and zinc. All parameters were measured in
serum at baseline and after 20 weeks of supplementation.
Noninvasive methods
All measurements were performed under standardized
conditions, i.e., room temperature of 19±2Canda
relative humidity level of 45–55%. An acclimatization
time of at least 30 min was respected before measure-
ments started. Hydration and microrelief of the skin
were evaluated on the forearm, whereas visco-elastic
properties were measured on the forehead, at baseline
and after 20 weeks of supplementation, respectively,
with the following noninvasive methods.
Hydration level of the skin surface was measured
with the Corneometer CM 825 (Courage-Khazaka,
Colgne, Germany) [10] and visco-elastic properties of
the skin were measured with the Reviscometer MPA 5
(Courage-Khazaka, Colgne, Germany). The measuring
principle of the Reviscometer is based on resonance
running time. The time to propagate from transmitter to
receiver is measured (shear wave propagation time) and
is expressed in arbitrary units. This parameter is
depending on the direction of the collagen fibers.
Therefore, two measurements are made in a different
angle, i.e., longitudinal vs lateral measurement.
Mechanical anisotropy is an indicator of skin photo-
ageing and was evaluated by the difference between
longitudinal and lateral shear wave propagation time
[14]. Microrelief (roughness) of the skin was measured
with the skin visiometer SV 600 (Courage-Khazaka,
Colgne, Germany). Investigated roughness parameters
were Rt (depth of roughness), Rm (maximum rough-
ness) and Rz (mean depth of roughness) [11].
Evaluation of hair and nail brittleness
Subjects were evaluated at baseline and after 20 weeks
of supplementation; the degree of brittleness of hair and
nails on a 4 point scale with ‘‘0’’ no brittle hair/nails, ‘‘1’’
slight, ‘‘2’’ moderate and ‘‘3’’ severe.
Statistical analysis
Differences between groups were evaluated with a
Mann–Whitney Utest and differences within groups
were analyzed with a Wilcoxon-matched pairs signed
rank test. P<0.05 was considered to be significant.
Results
The mean age (±SD) in the placebo and the ch-OSA
group was 49.2±4.7 years and 51.8±6.0 years, respec-
tively. The mean body mass index was not significantly
different between both groups (placebo: 24.1±4.4, ch-
OSA: 26.3±5.7).
Mean baseline values of total cholesterol, LDL cho-
lesterol and bilirubin were higher than the upper limit of
the normal range in both the placebo and the ch-OSA
group. All remaining parameters were within the normal
range at baseline and after the 20-week supplementation
in both groups. Twenty-four subjects in both the placebo
and the ch-OSA group completed the study. In neither of
the two treatment groups there were adverse effects re-
ported that were related to the study medication.
The mean serum Si concentration was comparable
for both groups at baseline but was significantly in-
creased after 20 weeks of ch-OSA supplementation
(P<0.0001 vs T0 and P=0.0005 vs 20 weeks placebo,
Table 1), whereas no differences were observed in the
placebo group.
Skin hydration decreased significantly after supple-
mentation in both groups but no differences were found
between the placebo and the ch-OSA group (Fig. 1).
Skin roughness parameters increased in the placebo
group (Rt: +8%; Rm: +11%; Rz: +6%) but decreased
in the ch-OSA group (Rt: 16%; Rm: 19%; Rz:
8%). The change in roughness from baseline was sig-
nificantly different between ch-OSA and placebo groups
for Rt (0.12 vs +0.02 mm, P<0.05) and Rm (0.13 vs
+0.05 mm, P<0.05, Fig. 2).
The difference in longitudinal and lateral shear
propagation time increased after 20 weeks in the placebo
group but decreased in the ch-OSA group (P<0.05,
Fig. 3).
149
VAS scores for nail and hair brittleness were signifi-
cantly lower after the 20-week supplementation with ch-
OSA (P<0.05) compared to baseline scores (Fig. 4),
whereas no significant differences were observed in the
placebo group.
Discussion
Several studies have illustrated the beneficial effects of
topical treatment with tretinoin [20] or alpha hydroxy
acid [31] containing creams in cutaneous ageing.
Few studies investigating the effects of oral supple-
mentation of minerals on aged skin have been published.
Combined oral and topical treatment with colloidal si-
licic acid was found to have a positive effect on hair and
nail brittleness in an open study [18]. However, no evi-
dence was presented that the colloidal silica was ab-
sorbed in the gastrointestinal tract. In fact, polymerized
forms of OSA such as colloidal silica are known to have
a very low bioavailability compared to OSA [22]. Oral
intake of extracts, derived from marine fish cartilage,
was reported to have a repairing effect on photodam-
aged skin [19,17]. However, it must be emphasized that
Fig. 1 Skin hydration
(Corneometer CM 825)
measured at the forearm at
baseline and after 20 weeks of
supplementation (T20) with
placebo (n=24) and choline-
stabilized orthosilicic acid (ch-
OSA, n=24). * P<0.05 vs
baseline, Wilcoxon-matched
pairs signed rank test. Mean
values ± SE are given
Table 1 Serum concentrations of silicon and safety parameters at baseline and after 20 weeks of supplementation (T20) with placebo and
choline-stabilized orthosilicic acid (ch-OSA)
Normal range Placebo (n=24) ch-OSA (n=24)
LL UL Baseline T20 Baseline T20
Urea(mol/l) 8.00 5.70±1.10 5.30±1.00 6.07±1.15 6.17±1.44
Creatinine(lmol/l) 53.00 123.00 77.83±6.72 77.53±8.05 81.36±9.75 80.44±7.52
Uric acid(lmol/l) 154.00 428.00 263.29±62.61 236.02±69.76 276.43±72.26 253.12±65.63
Total proteins(g/dl) 7.2±0.3 7.3±0.4 7.5±0.3 7.4±0.3
Cholesterol(mmol/l) 5.00 5.76±0.83 5.55±0.77 6.09±1.27 5.85±1.40
Triglycerides(mmol/l) 2.00 1.10±0.55 0.87±0.35 1.16±0.67 1.07±0.50
HDL cholesterol(mmol/l) 1.00 1.54±0.30 1.55±0.36 1.54±0.26 1.51±0.29
LDL cholesterol(mmol/l) 3.00 3.71±0.75 3.60±0.65 4.01±1.17 3.85±1.31
Bilirubin direct(lmol/l) 7.00 9.00±2.18 8.96±2.64 8.93±2.84 8.08±2.48
GOT(AST)(u/l) 37 22±5 23±5 22±4 24±6
GPT(ALT)(u/l) 38 8±5 12±5 9±6 13±8
Gamma-GT(u/l) 50 18±10 17±6 27±19 24±16
Cholinesterase(u/l) 3,930 11,500 6,847±1427 6,812±1261 7,311±1376 7,286±1510
CK(u/l) 87±101 78±43 77±23 84±46
Amylase(u/l) 96 49±14 48±11 48±15 45±14
Lipase(u/l) 7 60 23±11 23±12 22±7 22±10
Sodium(mmol/l) 136±3 135±3 137±2 137±2
Calcium(mg/l) 86 100 95±4 96±4 98±3 97±4
Phosphorous(mg/dl) 2,7 4.5 3.8±0.4 3.8±0.5 3.6±0.4 3.7±0.5
Zinc(lg/dl) 70 130 91±14 85±20 88±10 89±11
Silicon(lg/dl) 93.4±74.7 97.6±72.8 86.0±53.9 168.8±60.4
a,b
LL, lower limit of normal range; UL, upper limit of normal range. HDL, high-density lipoproteins; LDL, low- density lipoproteins; GOT,
glutamic-oxalacetic transaminase; GPT, glutamic-pyruvic transaminase; gamma-GT, gamma-glutamyl transferase; CK, creatine kinase.
a
P<0.05, vs baseline (Wilcoxon-matched pairs signed rank test);
b
P<0.05, vs T20 placebo (Mann–Whitney Utest). Mean values ± SD
are given. Serum silicon values were normally distributed.
150
none of these studies were double blind nor placebo-
controlled. Consequently, the obtained results could
have been biased by seasonal influence and subjective
evaluation.
The present study is the first randomized, double
blind and placebo-controlled study that illustrates a
positive effect of an oral supplement on skin microrelief
and skin anisotropy in women with photoaged skin. The
dose of ch-OSA supplementation (10 mg Si/day) was
low compared to the average daily Si intake of 20–50 mg
reported previously by Pennington [21]. The major die-
tary sources of Si are cereal/grain-based products and
vegetables but modern food processing, including
refining, is likely to reduce the dietary Si intake as it was
shown that fibers contribute the most to the silicon
content in plant-based foods [30]. After ch-OSA sup-
plementation the serum silicon concentration increased
with more than 90% compared to the baseline level
which confirms the high bioavailability demonstrated in
clinical [3,33] and animal studies [5,4]. In a compara-
tive, bioavailability study [3], the silicon absorption from
a single dose of ch-OSA (20 mg Si) was compared with
colloidal silicic acid and phytolytic silica in healthy
volunteers. Total silicon absorption was evaluated as the
area under the time curve (AUC, serum Si concentra-
tion) and was found to be significantly higher for ch-
OSA compared to the other silicon supplements and a
placebo. In another study [33], the bioavailability of ch-
OSA was compared with a silicon-rich diet and phyto-
lytic silica. After a 4-day intake of ch-OSA (10 mg Si/
day), both the serum Si concentration and the urinary Si
excretion increased, whereas no increase was found after
the intake of a Si-rich diet (45 mg Si/day, 31 days) and a
normal diet (14 mg Si/day, 4 days).
Fig. 2 Change in skin
microrelief parameters
(Visiometer SV 600) from
baseline, measured at the
forearm, after supplementation
with placebo (n=24) or ch-OSA
(n=24). Rt, depth of roughness;
Rm, maximum roughness; Rz,
mean depth of roughness. *
P<0.05 vs placebo, Mann–
Whitney Utest. Mean values ±
SE are given
Fig. 3 Change in mechanical
skin anisotropy (Reviscometer
MPA 5) from baseline,
measured at the forehead, after
supplementation with placebo
(n=24) or ch-OSA (n=24).
Mechanical anisotropy was
calculated as the difference
between longitudinal and
lateral shear propagation time.
*P<0.05 vs placebo, Mann–
Whitney Utest. Mean values ±
SE are given
151
The intake of 10 mg Si in the form of ch-OSA is safe
as no adverse effects related to the study medication
were reported. Serum safety parameters remained within
the normal range. Total cholesterol, LDL cholesterol
and bilirubin levels were already increased at baseline
which is most likely due to the consumption of a diet
high in cholesterol and saturated fats [13].
Both the ch-OSA group and the placebo group
showed a small increase in hydration after 20 weeks of
supplementation compared to baseline. Since all subjects
started the study in October and finished the study in
March, these changes are likely to be the result of a sea-
sonal shift in temperature and relative humidity and are
not related to the study medication. After 20 weeks of ch-
OSA supplementation, both skin microrelief and
mechanical properties improved. We previously demon-
strated that oral intake of low doses of ch-OSA (5% in-
crease of total dietary Si intake) during 24 weeks in calves
resulted in a significant higher hydroxyproline content in
the dermis compared to placebo and found a significant
correlation between the serum Si concentration and the
hydroxyproline content in cartilage [5]. Reffitt et al.
found that low levels of OSA (typical serum concentra-
tions) stimulate the synthesis of collagen type I in cultures
of human osteoblasts and skin fibroblasts [23]. The OSA-
dependent stimulation of collagen synthesis was abol-
ished in the presence of prolyl hydroxylase inhibitors. As
type I collagen and its monomer hydroxyproline are
major constituents of skin, the improvement in skin
parameters after ch-OSA supplementation points to po-
tential regeneration or de novo synthesis of collagen fi-
bers. Silicon was also reported to be involved in the
synthesis of glycosaminoglycans [25] and was suggested
to have a structural role as a cross-linking agent in con-
nective tissue. Accordingly, treatment with ch-OSA
might improve the glycosaminoglycan structure in the
dermis and the keratin structure in hair and nails. Fur-
thermore, the choline compound present in ch-OSA
might have a synergistic effect with OSA since it is well
known that choline is involved in several basic biological
processes [2] including the fact that choline is a precursor
of phospholipids such as phosphatidyl choline which is an
essential component of cellular membranes. The physio-
logical significance of choline is substantiated by the fact
that intentional deprivation of choline disrupts cell
growth and division [34].
To our knowledge, the present study is the first ran-
domized, double blind placebo-controlled trial that
illustrates the positive effect of an oral mineral supple-
ment on skin surface and mechanical properties and on
hair and nails brittleness, respectively.
Acknowledgements The authors thank Dr. Andre
´Moreels and the
technical staff of The Medical Centre, Vrije Universiteit Brussel, for
blood sampling of the study subjects. ch-OSA was developed by
Dirk Vanden Berghe for Bio Minerals n.v. This study was sup-
ported by a grant of Bio Minerals n.v.
Fig. 4 Brittleness of hair and
nails at baseline and after
20 weeks of supplementation
(T20) with placebo (n=24) and
ch-OSA (n=24). Brittleness was
evaluated on a 4-point scale
with ‘‘0’’ no brittle hair/nails,
‘‘1’’ slight, ‘‘2’’ moderate and
‘‘3’’ severe. Plot (a) nails; Plot
(b) hair. * P<0.05 vs baseline,
Wilcoxon- matched pairs signed
rank test. Mean values ± SE
are given
152
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