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Supplementing with Dietary Astaxanthin Combined with Collagen Hydrolysate Improves Facial Elasticity and Decreases Matrix Metalloproteinase-1 and -12 Expression: A Comparative Study with Placebo


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Abstract Photoaging accounts for most age-related changes in skin appearance. It has been suggested that both astaxanthin, a potent antioxidant, and collagen hydrolysate can be used as antiaging modalities in photoaged skin. However, there is no clinical study using astaxanthin combined with collagen hydrolysate. We investigated the effects of using a combination of dietary astaxanthin and collagen hydrolysate supplementation on moderately photoaged skin in humans. A total of 44 healthy subjects were recruited and treated with astaxanthin (2 mg/day) combined with collagen hydrolysate (3 g/day) or placebos, which were identical in appearance and taste to the active supplementation for 12 weeks. The elasticity and hydration properties of facial skin were evaluated using noninvasive objective devices. In addition, we also evaluated the expression of procollagen type I, fibrillin-1, matrix metalloproteinase-1 (MMP-1) and -12, and ultraviolet (UV)-induced DNA damage in artificially UV-irradiated buttock skin before and after treatment. The supplement group showed significant improvements in skin elasticity and transepidermal water loss in photoaged facial skin after 12 weeks compared with the placebo group. In the supplement group, expression of procollagen type I mRNA increased and expression of MMP-1 and -12 mRNA decreased compared with those in the placebo group. In contrast, there was no significant difference in UV-induced DNA damage between groups. These results demonstrate that dietary astaxanthin combined with collagen hydrolysate can improve elasticity and barrier integrity in photoaged human facial skin, and such treatment is well tolerated.
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Supplementating with Dietary Astaxanthin Combined with Collagen Hydrolysate
Improves Facial Elasticity and Decreases Matrix Metalloproteinase-1 and -12
Expression: A Comparative Study with Placebo
Hyun-Sun Yoon,
*Hyun Hee Cho,
*Soyun Cho,
Se-Rah Lee,
Mi-Hee Shin,
and Jin Ho Chung
Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea.
Institute of Human-Environment Interface Biology, Seoul National University, Seoul, Korea.
Department of Dermatology, Seoul National University Boramae Hospital, Seoul, Korea.
Institute on Aging, Seoul National University, Seoul, Korea.
ABSTRACT Photoaging accounts for most age-related changes in skin appearance. It has been suggested that both as-
taxanthin, a potent antioxidant, and collagen hydrolysate can be used as antiaging modalities in photoaged skin. However,
there is no clinical study using astaxanthin combined with collagen hydrolysate. We investigated the effects of using a
combination of dietary astaxanthin and collagen hydrolysate supplementation on moderately photoaged skin in humans. A
total of 44 healthy subjects were recruited and treated with astaxanthin (2 mg/day) combined with collagen hydrolysate (3 g/
day) or placebos, which were identical in appearance and taste to the active supplementation for 12 weeks. The elasticity and
hydration properties of facial skin were evaluated using noninvasive objective devices. In addition, we also evaluated the
expression of procollagen type I, fibrillin-1, matrix metalloproteinase-1 (MMP-1) and -12, and ultraviolet (UV)-induced
DNA damage in artificially UV-irradiated buttock skin before and after treatment. The supplement group showed significant
improvements in skin elasticity and transepidermal water loss in photoaged facial skin after 12 weeks compared with
the placebo group. In the supplement group, expression of procollagen type I mRNA increased and expression of MMP-1 and
-12 mRNA decreased compared with those in the placebo group. In contrast, there was no significant difference in
UV-induced DNA damage between groups. These results demonstrate that dietary astaxanthin combined with collagen
hydrolysate can improve elasticity and barrier integrity in photoaged human facial skin, and such treatment is well tolerated.
KEY WORDS: anti-aging astaxanthin collagen hydrolysate photoaging
Photoaging is caused by the superpositioning of
chronic ultraviolet (UV)-induced damage on the intrin-
sic aging process and accounts for the majority of age-
associated changes in skin appearance. Aged skin, especially
photoaged skin, manifests as a decrease of skin thickness and
elasticity, skin dryness, epidermal barrier dysfunction, and
changes in pigmentation.
Reactive oxygen species (ROS)
likely contribute to this process.
UV radiation has numerous direct and indirect effects on
the skin.
The indirect damage induced by UV irradiation is
suggested to be initiated by ROS,
which are involved in
connective tissue alterations.
Numerous antioxidants have
been tested for their ability to prevent or reverse clinical
signs associated with photoaging secondary to ROS. Stra-
tegies utilizing endogenous skin antioxidants as well as
plant-derived or synthetic compounds have been examined.
Although both topical and systemic application of antiox-
idants can significantly increase antioxidant levels in skin,
systemically applied supplements and topical agents are often
combined to enhance efficacy through their synergistic af-
Furthermore, the systemic application of antioxidants
has produced more pronounced and sustained effects than
topical application.
Thus, antioxidants are one of the most
popular categories of nutraceutical ingredients used to im-
prove skin health. Among the various antioxidants, astax-
anthin has a long history of use as an antioxidant dietary
and its antioxidant properties can be 10-fold
greater compared with other carotenoids, such as lutein and
b-carotene, and 100-fold greater compared with a-tocopherol.
Collagen hydrolysate is also a popular nutraceutical, and
collagen polypeptides have exhibited numerous bioactivities,
including antioxidant activity, mineral binding capacity,
*These authors contributed equally to this work.
Manuscript received 10 September 2013. Revision accepted 1 May 2014.
Address correspondence to: Jin Ho Chung, MD, PhD, Department of Dermatology, Seoul
National University College of Medicine, 101 Daehak-ro Jongno-gu, Seoul 110-744,
Korea, E-mail:
J Med Food 17 (7) 2014, 810–816
#Mary Ann Liebert, Inc., and Korean Society of Food Science and Nutrition
DOI: 10.1089/jmf.2013.3060
antihypertensive activity, lipid-lowering effects, and immu-
nomodulatory activity.
Collagen hydrolysate has also
been shown to be involved in the synthesis of the extracellular
matrix and is used for improving pathological conditions
involving the joints, nails, and hair.
In the skin aging pro-
cess, collagen hydrolysate might be beneficial for slowing
chronological aging
and photoaging
in rats.
When used as nutraceuticals, antioxidants and collagen
hydrolysate have different mechanisms of action, but might
show additive or synergistic effects for preventing or re-
versing the skin aging process. Therefore, we investigated
the effects of a dietary antioxidant, astaxanthin, combined
with collagen hydrolysate on skin aging and UV-induced
damage in human skin in vivo.
We conducted a 12-week, randomized, double-blind placebo-
controlled study to evaluate the effects of dietary astaxanthin
and collagen hydrolysate supplementation on cutaneous aging.
This study was approved by the Institutional Review Board
of Seoul National University Hospital, and written informed
consent was obtained from all subjects participating in the trial.
Study participants
A total of 44 healthy female volunteers, aged 40 years and
who had wrinkles grade 2,
were enrolled in the study. The
subject exclusion criteria for the present trial were as follows:
(1) received medical or cosmetic treatment that interferes with
the general aging process within 3 months of the study; (2)
reported taking functional foods within 1 month of the study;
(3) history of acute or chronic disease such as severe liver or
kidney disease or uncontrolled diabetes; (4) history of allergies
against any component of trial foods; (5) any visible skin dis-
ease that might be confused with a skin reaction to the test
procedure or materials used, or interfere with clinical mea-
surements; and (6) abnormal blood test results (hemoglobin,
hematocrit, aspartate aminotransferase [AST], alanine trans-
ferase [ALT], or fasting glucose).
Dietary supplement
Two types of oral dosage forms (capsules containing as-
taxanthin and tablets containing fish collagen) were pre-
pared. The capsules were manufactured by Cerebos Pacific
Limited (Singapore), and each capsule included 480 mg of
medium chain triglycerides and 20 mg of dark red lipid ex-
tract of Haematococcus pluvialis microalgae, standardized
with safflower oil to yield a minimum 5% content of as-
taxanthin (Cyanotech Corporation, Kailua-Kona, HI, USA;
1 mg of astaxanthin per capsule). The tablets were manu-
factured by Cerebos Pacific Limited (Singapore), and each
tablet contained 0.75 g of enzymatic hydrolyzed fish colla-
gen (Rousselot SAS, Puteaux, France). Identical placebo
capsules with only medium chain triglycerides (500 mg per
capsule) and tablets with hydrolyzed casein (0.75 g per
tablet) instead of hydrolyzed collagen were prepared as
controls. All 44 study participants were randomly assigned
to either the placebo group or the supplement group. Each
participant took two capsules of astaxanthin and four tablets
of hydrolyzed collagen or the control capsules and tablets
per day for 12 weeks.
Noninvasive assessment
Clinical assessments were performed at baseline and at 4 and
3 cm inferior to the lower eyelid) was measured using a Cut-
ometer MPA580 (C +K Electronic, Cologne, Germany). Hy-
dration of facial skin was evaluated on the cheek (at point 5 cm
inferior to the outer corner of eye) measured using a Corne-
ometer and a Tewameter (C +K Electronic). All measurements
20–25C and a constant humidity of 45–55% at the Clinical
Research Institute, Seoul National University Hospital.
Compliance and safety
Adverse events related to the medications and clinical
protocol were evaluated at 4 and 12 weeks of treatment. The
subjects were instructed to return any remaining capsules or
tablets to the investigators, and subjects who failed to take
80% of the study medications were disqualified from fur-
ther participation. Blood samples were drawn at baseline and
12 weeks after the start of treatment, and AST, ALT, glucose,
hemoglobin levels, and hematocrits were measured.
UV irradiation and skin biopsy samples
Two 2-mm skin biopsy samples were obtained taken from
the buttock area at 24 h following UV irradiation at baseline
and after 12 weeks of supplementation in subjects who
agreed to biopsies (n=6/group). For these subjects, skin on
the buttock area was irradiated with two minimal erythema
doses at baseline and the same UV doses again at 12 weeks
of study participation. The UV source was a Waldmann UV-
800 (Waldmann, Villingen-Schwenningen, Germany; 285–
350 nm, peak at 310–315 nm) phototherapy device fitted
with Philips TL-20W/12 fluorescent lamps.
Specimens for immunohistochemical staining were im-
mediately oriented in a low-temperature embedding me-
dium (Tissue-Tek OCT compound; Miles, Naperville, IL,
USA), frozen in liquid nitrogen, and stored at -70C. Skin
samples saved for RT-PCR analysis were frozen in liquid
Immunohistochemical staining
DNA damage induced by UV irradiation was evaluated
by immunohistochemical staining for the presence of thy-
mine dimers and 8-OHdG (8-hydroxy-2-deoxyguanosine),
as previously described.
Quantitative real-time RT-PCR
Expressions of procollagen type I, fibrillin-1, matrix
metalloproteinase (MMP)-1, and MMP-12 were evaluated
using quantitative real-time PCR. Total RNA was prepared
from skin samples and converted to complementary DNA
using the First Strand cDNA Synthesis Kit (MBI Fermentas,
Vilnius, Lithuania). Quantitation of procollagen type I,
MMP-1, and -12 cDNA, and endogenous reference 36B4
was performed using a 7500 Real-time PCR System (Ap-
plied Biosystems, Foster City, CA, USA) and SYBR Green
PCR Master Mix (Takara Bio, Inc., Shiga, Japan) using
the primers for human genes listed in Supplementary
Table S1 (Supplementary Data are available online at www The comparative C
used to quantify relative changes in gene expression.
Statistical analyses
The Mann–Whitney U test was used to identify differences
in values obtained by noninvasive measurements between
two groups (R2, R5, and R7 values; Corneometer values;
transepidermal water loss [TEWL] values). In addition, the
treatment effects at weeks 4 and 12 were further compared
using analysis of covariance (ANCOVA) to adjust for cor-
responding baseline values. The changes from baseline
values for expression of mRNAs for procollagen type I,
fibrillin-1, MMP-1, and MMP-12 were analyzed using the
Mann–Whitney U test. The SPSS version 20.0 (SPSS, Inc.,
Chicago, IL, USA) was used for all analyses. A Pvalue <.05
was considered statistically significant.
Subject demographics
This study enrolled 44 Korean women between the ages
of 41 and 60 years (mean 51.0 years, SD 5.2 years).
Baseline values for most parameters were not significantly
different between groups (Table 1). However, despite ran-
domization, baseline values for gross elasticity (R2 by
Cutometer) were significantly different between groups.
Skin elasticity as measured by Cutometer
An improvement in skin elasticity began to be noticeable
in the supplement group at 4 weeks and was more prominent
at 12 weeks. After 12 weeks of treatment, the mean im-
provement from baseline in elasticity was significantly
greater for the supplement group vs. the placebo group (R2,
0.0252 vs. -0.0294, P=.035; R5, 0.0602 vs. -0.0195,
P=.020; R7 0.0222 vs. -00185, P=.012, Fig. 1). No im-
provements in any parameters representing elasticity (R2,
R5, R7) were noted in the placebo group. Additionally, the
main parameters representing skin elasticity (R2, R5, R7)
significantly improved in the supplement group compared
with those in the placebo group when adjusted for the
baseline corresponding values using ANCOVA (Supple-
mentary Table S2).
Epidermal hydration by Corneometer and TEWL
(barrier integrity) by Tewameter
Figure 2 shows the changes in epidermal hydration pa-
rameters as measured by Corneometer after 4 and 12 weeks
Table 1. Baseline Demographics and Baseline Values
of Key Parameters
Age (years) 50.6 5.3 51.5 5.2 0.580
Weight (kg) 57.5 6.5 55.3 6.4 0.361
Epidermal hydration 44.5 13.2 46.0 14.0 0.573
TEWL (g/h/m
) 9.2 2.8 10.5 3.8 0.162
Gross elasticity, R2 0.6446 0.0675 0.6097 0.0556 0.044
Net elasticity, R5 0.5244 0.0953 0.4799 0.1076 0.146
Biological elasticity, R7 0.3028 0.0502 0.2813 0.0501 0.136
By Mann–Whitney Utest.
TEWL, transepidermal water loss.
FIG. 1. Results of skin elasticity measurements using Cutometer. Subjects receiving supplements showed significant improvements in the three
viscoelastic parameters compared with subjects in the control group. Pvalues by Mann–Whitney U test.
of treatment. Epidermal hydration was not significantly
different between the two groups after 4 and 12 weeks. The
stratum corneum barrier in both groups was significantly
improved with TEWL decreasing from baseline values by
3.4 g/h/m
in the control group and 5.2 g/h/m
in the sup-
plement group at 12 weeks. This difference in changes be-
tween the two groups after 12 weeks of treatment was
statistically significant (P=.045 by Mann–Whitney U test,
Fig. 2) and remained significant after controlling for the
corresponding baseline TEWL values (P=.048 by ANCO-
VA, Supplementary Table S3).
Safety and compliance
Treatment was well tolerated and no subjective adverse
events were reported during the 12-week trial period. La-
boratory evaluations revealed no significant abnormalities
after 12 weeks of treatment. One subject who took only
64.3% of the supplements was dropped from the study, ac-
cording to the study protocol.
Real-time RT-PCR
Supplementing with astaxanthin combined with colla-
gen hydrolysate induced a 3.4-fold increase in procolla-
gen mRNA levels in UV-irradiated skin compared with
those in the placebo group (P=.038 by Mann–Whitney
Utest). Induction of fibrillin-1 mRNA in the supplement
group was greater than in the placebo group, but the
difference was not statistically significant. After UV ir-
radiation, expression of MMP-1 (collagenase) and MMP-
12 (elastase) mRNA was suppressed by 68% (P=.027)
and 77% (P=.050), respectively, in the supplement
group compared with those expressions in the placebo
group (Fig. 3).
UV-induced DNA damage
There were no differences between groups in immuno-
histochemical analyses of thymine dimers and 8-OHdG after
UV irradiation (Fig. 4).
FIG. 2. Results of epidermal hydra-
tion measured using Corneometer, and
skin barrier integrity measured with
Tewameter. TEWL from facial skin in
the supplement group was significantly
lower than those in the placebo group at
12 weeks. Pvalues by Mann–Whiney U
test. TEWL, transepidermal water loss.
FIG. 3. Results of procollagen type I, fibrillin-1, and matrix metalloproteinase-1 (MMP-1) and -12 mRNA induction after UV radiation. While
levels of procollagen type I mRNA in the supplement group increased, levels of MMP-1 and -12 mRNA in the supplement group decreased
significantly compared with those in the placebo group. Expression of mRNA was measured by real-time RT-PCR (n=6 for each group). Pvalues
by Mann–Whiney U test. UV, ultraviolet.
The latest trend in antiaging strategies for skin is to use a
combination of dietary and oral supplements to produce an
appearance benefit. These methods of treatment are thought
to work synergistically with topical agents to enhance effi-
In the antiaging market, there are many nu-
traceuticals, which are products derived from food sources
and provide extra physiologic benefits in addition to their
basic nutritional values.
Recently, astaxanthin and colla-
gen hydrolysate have been described as beauty foods, which
have the potential to prevent skin aging.
We evaluated the effects of dietary supplementation with
the antioxidant astaxanthin combined with collagen hydro-
lysate on facial skin elasticity, hydration, and dermal matrix
homeostasis in photoaged skin. We found that 12 weeks
of oral dosing with astaxanthin plus collagen hydrolysate
improved elasticity and epidermal integrity in photoaged fa-
cial skin. Furthermore, the induction of procollagen type I
mRNA was observed after 12 weeks of treatment, along with
significant decreases in the expression of collagen-degrading
enzyme, MMP-1 mRNA and elastin-degrading enzyme,
MMP-12 mRNA after UV irradiation. The improvements in
facial skin elasticity might be related to these molecular
Astaxanthin (3,30-dihydroxy-b,b0-carotene-4,40-dione) is
one of the pigments that belongs to the xanthophyll subclass
of carotenoids and is widely distributed in marine organisms.
Astaxanthin has been used as a food supplement ever since
experimental studies revealed its antioxidant properties.
Further studies have suggested that astaxanthin has health-
promoting benefits for the treatment and prevention of vari-
ous diseases such as diabetes, cardiovascular diseases, and
inflammatory diseases.
In vitro, astaxanthin effectively
suppresses cell damage by free radicals and induction of
MMP-1 in skin after UV irradiation.
Additionally, topical
administration of astaxanthin prevented UV-induced skin
damage in mice.
These studies suggest that astaxanthin may
prevent tissue damage caused by UV irradiation.
Collagens are the most common family of proteins in the
human body and have been used as dietary supplements for
promoting articular function and for cosmetic purposes.
Ingestion of collagen peptide induces increased fibroblast
density and enhances formation of collagen fibrils in the
dermis in a protein-specific manner.
Collagen hydrolysate
has been demonstrated to have protective effects on chro-
nological skin aging by its influence on collagen matrix
homeostasis in rats.
The proposed mechanisms of action
for collagen polypeptide mainly involve enhancing immu-
nity, reducing the loss of moisture and lipids, promoting
antioxidative activity, and repairing endogenous collagen
and elastin protein fibers.
Consistent with these previous reports, oral dosing with
astaxanthin and collagen hydrolysate improved elasticity in
photoaged facial skin and suppressed UV-induced MMP-1
and -12 expression in human skin in vivo. However, despite
the known antioxidant properties of astaxanthin, DNA
damage caused by endogenous or exogenous ROS, as
measured by 8-OHdG staining, did not significantly differ
between groups in this study. Nevertheless, the suppression
of MMP expression in the supplement group suggests that
oral supplementation with astaxanthin and collagen hydro-
lysate partially protects skin from UV-induced damage.
In addition to the improved viscoelastic property of skin,
which is mainly due to the dermal extracellular matrix, we
also found improved barrier integrity as represented by de-
creased TEWL. Because collagen hydrolysate itself has
good moisture absorption and retention properties,
improvement of skin hydration might be related to the ef-
fects of collagen hydrolysate. In addition, astaxanthin might
contribute to the improvement in TEWL by protecting the
keratinocyte differentiation and cornification from oxidative
damages such as inflammation in epidermis.
This study has some limitations. First, we did not prove
the concentrations of individual ingredients in the skin.
FIG. 4. (A) Thymine dimer immunostaining before and after sup-
plementation. Nuclear staining of thymine dimer in UV-irradiated
buttock skin 24 h after UV irradiation. The figures are representative
images from six subjects (original magnification ·200). (B) 8-OHdG
immunostaining before and after supplementation. Nuclear staining
of 8-OHdG in UV-irradiated buttock skin 24 h after UV irradiation.
Figures are representative images from six subjects (original mag-
nification ·200). 8-OHdG, 8-hydroxy-2-deoxyguanosine.
Previous studies only measured the serum levels of collagen
or astaxanthin. Ninety-five percent of enterally administered
collagen hydrolysate is absorbed within the first 12 h as 2.5–
15 kDa peptides.
Major collagen peptides in serum and
plasma were identified as proline-hydroxyproline; this was
identical to the abundance motif reported for collagen when
healthy human volunteers ingested several food-derived
collagen peptides.
In humans, the absorption of astax-
anthin after 4 h ranges from 6% to 34%.
It should be
elucidated whether the concentration of astaxanthin or col-
lagen-derived peptide in skin is great enough to exhibit
relevant biologic activity. Second, we did not examine
changes in glycosaminoglycans, including hyaluronic acid
in the skin. Ohara et al. reported that collagen-derived di-
peptide, which was detected in circulation after collagen
ingestion, stimulated proliferation and hyaluronic acid syn-
thesis in cultured dermal fibroblasts.
Because hyaluronic
acid is important for tissue elasticity and hydration,
improvement of elasticity might be related to hyaluronic
acid in the dermis.
Despite these limitations, the present study shows that a
combination of astaxanthin and collagen hydrolysate im-
proves elasticity and barrier integrity in human skin in vivo.
Skin elasticity especially began to improve after 4 weeks of
supplementation, and the effect was maintained with con-
tinued supplementation for 12 weeks. Further studies should
focus on the underlying mechanism that produces an im-
provement in skin conditions after dietary supplementation
with a combination of astaxanthin and collagen hydrolysate.
This study was funded by Cerebos Pacific Limited.
The authors declare they have no conflicts of interest.
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... The results of the subgroup analyses are presented in Figure 10. Figure 6. Forest plot for the subgroup analysis of skin hydration expressed as long-term (>8 weeks) and short-term (<8 weeks) in patients supplemented with HC and patients in the placebo group [26][27][28][30][31][32][33][34][35]39,40,43,44,[46][47][48][49][50]. (HC: hydrolyzed collagen, CI: confidence intervals, SD: standard deviation, I 2 : heterogeneity). ...
... (HC: hydrolyzed collagen, CI: confidence intervals, SD: standard deviation, I 2 : heterogeneity). [26,28,29,31,[33][34][35]37,39,41,43,48,49]. ...
... Forest plot for the subgroup analysis of skin hydration expressed as 2, 4, 6, 8, and 12 weeks in patients supplemented with HC and patients in the placebo group[26][27][28][29][30][31][32][33][34][35]39,40,43,44,[46][47][48][49][50]. (HC: hydrolyzed collagen, CI: confidence intervals, SD: standard deviation, I 2 : heterogeneity). ...
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This paper presents a systematic review and meta-analysis of 26 randomized controlled trials (RCTs) involving 1721 patients to assess the effects of hydrolyzed collagen (HC) supplementation on skin hydration and elasticity. The results showed that HC supplementation significantly improved skin hydration (test for overall effect: Z = 4.94, p < 0.00001) and elasticity (test for overall effect: Z = 4.49, p < 0.00001) compared to the placebo group. Subgroup analyses demonstrated that the effects of HC supplementation on skin hydration varied based on the source of collagen and the duration of supplementation. However, there were no significant differences in the effects of different sources (p = 0.21) of collagen or corresponding measurements (p = 0.06) on skin elasticity. The study also identified several biases in the included RCTs. Overall, the findings suggest that HC supplementation can have positive effects on skin health, but further large-scale randomized control trials are necessary to confirm these findings.
... Carotenoids prevent ageing, stimulate fibroblasts to produce collagen and elastin, inhibit the activity of MMPs, and exhibit anti-inflammatory and UV-filtering effects [222,226,231]. They have been shown to improve the elasticity, hydration and texture of skin; reduce TEWL; lighten the skin; reduce discoloration; and delay the signs of photoaging [222,[231][232][233]. Yoon et al. investigated the effect of astaxanthin (2 mg/day) and collagen hydrolysate (3 g/day) supplementation on moderately photoaged skin in humans. ...
... The results indicate that astaxanthin combined with collagen hydrolysate, due to the beneficial effects of the compounds on skin elasticity and hydration, can be used as an anti-ageing agent for photoaged skin [234]. A study by Juturu et al. showed that supplementation with 10 mg of lutein and 2 mg of zeaxanthin isomers daily for 12 weeks improves the appearance of skin and lightens skin tone [233]. Schwartz et al. evaluated the effect of zeaxanthin on skin parameters such as fine and deep lines, total wrinkles, wrinkle severity, radiance/skin color, discoloration and skin pigment homogeneity. ...
... Due to the abundance of collagen throughout the body, and its importance in maintaining the health and integrity of various tissues (Juhl et al. 2018;Holm Nielsen et al. 2021), previous studies have examined the potential benefits of dietary supplements on gene expression as well as biomarkers of collagen synthesis (Proksch et al. 2014;Yoon et al. 2014;Das et al. 2016), and collagen degradation (Keller et al. 2019). For example, Das et al. (2019) reported that 8 weeks of 500 mg·d −1 of Shilajit (PrimaVie®, Natreon Inc.) supplementation resulted in increases in gene expression for the synthesis of type I, III, V, VI, and XIV collagen (Das et al. 2016). ...
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Type 1 collagen is an abundant structural protein with importance to the skin, eyes, bones, ligaments, tendons, and muscles. Shilajit supplementation has been shown to increase gene expression of collagen synthesis, however, it is unclear if increased gene expression translates to increases in circulating levels. Therefore, the purpose of the present study was to examine the effects of 8 weeks of daily supplementation with 500 mg·d⁻¹ and 1000 mg·d⁻¹ of Shilajit versus placebo on serum pro-c1α1, a biomarker of type 1 collagen synthesis. Thirty-five recreationally trained men (mean ± SD: age = 21.1 ± 1.8 yrs; body mass = 80.7 ± 12.4 kg; height = 180.9 ± 6.7 cm) volunteered to participate in this study. Mixed factorial and one-way ANOVAs were used to analyze mean differences between groups, with follow-up t-tests when necessary. Individual subject responses were assessed using the minimal clinically important difference and Chi-squared tests. There were significant (Low dose: p = 0.008, d = 1.2; High dose: p = 0.007, d = 1.3) increases in serum pro-c1α1 from pre- (Low dose: 42.5 ± 12.4 ng·mL⁻¹; High dose: 42.7 ± 12.7 ng·mL⁻¹) to post-supplementation (Low dose: 82.3 ± 46.5 ng·mL⁻¹; High dose: 113.1 ± 78.7 ng·mL⁻¹) for the low and high dose groups, however, no change (p > 0.05) for the placebo group. A greater proportion (p = 0.03) of subjects exhibited increases in pro-c1α1 that exceeded the minimal clinically important difference in the high dose Shilajit group (75%) compared to the placebo group (30%), but no differences (p = 0.06) between the low dose Shilajit group (69%) and placebo. In conclusion, 8 weeks of Shilajit supplementation with 500 and 1000 mg·d⁻¹ increased type 1 collagen synthesis as indicated by serum levels of pro-c1α1.
... For instance, the marine compound astaxanthin has shown potential cardioprotective [148] and immunomodulatory [149] effects. It also shows health benefits in overweight/obese adults [150,151], and cosmetic applications [152]. In a double-blind randomized controlled trial, the marine compound fucoidan improved disease control rate in patients with metastatic colorectal cancer [153]. ...
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The marine environment is important yet generally underexplored. It contains new sources of functional constituents that can affect various pathways in food processing, storage, and fortification. Bioactive secondary metabolites produced by marine microorganisms may have significant potential applications for humans. Various components isolated from disparate marine microorganisms , including fungi, microalgae, bacteria, and myxomycetes, showed considerable biological effects, such as anticancer, antioxidant, antiviral, antibacterial, and neuroprotective activities. Growing studies are revealing that potential anticancer effects of marine agents could be achieved through the modulation of several organelles. Mitochondria are known organelles that influence growth, differentiation, and death of cells via influencing the biosynthetic, bioenergetic, and various signaling pathways related to oxidative stress and cellular metabolism. Consequently, mitochon-dria play an essential role in tumorigenesis and cancer treatments by adapting to alterations in environmental and cellular conditions. The growing interest in marine-derived anticancer agents, combined with the development and progression of novel technology in the extraction and cultures of marine life, led to revelations of new compounds with meaningful pharmacological applications. This is the first critical review on marine-derived anticancer agents that have the potential for targeting mitochondrial function during tumorigenesis. This study aims to provide promising strategies in cancer prevention and treatment.
... In such cases, the role of carotenoid intake especially the supplementation of AST (photo-protective pigment) has proven promising for nurturing the skin physiology [45]. Another study summarizes the positive impact of AST in maintaining skin elasticity, reducing wrinkle formation, preserving epidermal barrier integrity and ultimately controlling the skin ageing-related processes [180][181][182][183][184]. ...
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Astaxanthin (3,3′-dihydroxy-β,β-carotene-4,4′-dione) is an orange-red, lipophilic keto-carotenoid pigment. It is majorly found in marine ecosystems particularly in aquatic animals such as salmon, shrimp, trout, krill, crayfish, and so on. It is also synthesized in microalgae Heamatococcus pluvialis , Chlorococcum , Chlorella zofingiensis , red yeast Phaffia rhodozyma and bacterium Paracoccus carotinifaciens . Some aquatic and terrestrial creatures regarded as a primary and secondary sources of the astaxanthin producing and accumulating it through their metabolic pathways. Astaxanthin is the powerful antioxidant, nutritional supplement as well as promising therapeutic compound, observed to have activities against different ravaging diseases and disorders. Researchers have reported remarkable bioactivities of astaxanthin against major non-communicable chronic diseases such as cardiovascular diseases, cancer, diabetes, neurodegenerative, and immune disorders. The current review discusses some structural aspects of astaxanthin. It further elaborates its multiple potencies such as antioxidant, anti-inflammatory, anti-proliferative, anti-cancer, anti-obese, anti-diabetic, anti-ageing, anti-TB, anti-viral, anti-COVID 19, neuro-protective, nephro-protective, and fertility-enhancing properties. These potencies make it a more precious entity in the preventions as well as treatments of prevalent systematic diseases and/or disorders. Also, the review is acknowledging and documenting its powerful bioactivities in relation with the pharmaceutical as well as nutraceutical applicability. Graphical Abstract
... Photoaging is associated with age-related changes in skin appearance. In a comparative placebo study involving humans with moderately photoaged skin, supplementation of dietary astaxanthin and collagen hydrolysate increased the expression of procollagen type I mRNA and decreased the expression of MMP-1 and -12 mRNAs, thereby significantly improved skin elasticity and transepidermal water loss in photoaged facial skin (Yoon et al. 2014). UV can elevate the levels of MMP-1 that initiate degradation of collagen type I and III, thus MMP-1 plays a crucial role in the initiation of UV-induced wrinkle formation through ECM degradation. ...
Age-related diseases are associated with increased morbidity in the past few decades and the cost associated with the treatment of these age-related diseases exerts a substantial impact on social and health care expenditure. Anti-aging strategies aim to mitigate, delay and reverse aging-associated diseases, thereby improving quality of life and reducing the burden of age-related pathologies. The natural dietary antioxidant supplementation offers substantial pharmacological and therapeutic effects against various disease conditions. Astaxanthin is one such natural carotenoid with superior antioxidant activity than other carotenoids, as well as well as vitamins C and E, and additionally, it is known to exhibit a plethora of pharmacological effects. The present review summarizes the protective molecular mechanisms of actions of astaxanthin on age-related diseases of multiple organs such as Neurodegenerative diseases [Alzheimer’s disease (AD), Parkinson’s disease (PD), Stroke, Multiple Sclerosis (MS), Amyotrophic lateral sclerosis (ALS), and Status Epilepticus (SE)], Bone Related Diseases [Osteoarthritis (OA) and Osteoporosis], Cancers [Colon cancer, Prostate cancer, Breast cancer, and Lung Cancer], Cardiovascular disorders [Hypertension, Atherosclerosis and Myocardial infarction (MI)], Diabetes associated complications [Diabetic nephropathy (DN), Diabetic neuropathy, and Diabetic retinopathy (DR)], Eye disorders [Age related macular degeneration (AMD), Dry eye disease (DED), Cataract and Uveitis], Gastric Disorders [Gastritis, Colitis, and Functional dyspepsia], Kidney Disorders [Nephrolithiasis, Renal fibrosis, Renal Ischemia reperfusion (RIR), Acute kidney injury (AKI), and hyperuricemia], Liver Diseases [Nonalcoholic fatty liver disease (NAFLD), Alcoholic Liver Disease (AFLD), Liver fibrosis, and Hepatic Ischemia-Reperfusion (IR) Injury], Pulmonary Disorders [Pulmonary Fibrosis, Acute Lung injury (ALI), and Chronic obstructive pulmonary disease (COPD)], Muscle disorders (skeletal muscle atrophy), Skin diseases [Atopic dermatitis (ATD), Skin Photoaging, and Wound healing]. We have also briefly discussed astaxanthin’s protective effects on reproductive health.
Dietary astaxanthin exists predominantly as the all-E-isomer; however, certain amounts of the Z-isomers are universally present in the skin, whose roles remain largely unknown. The aim of this study was to investigate the effects of the astaxanthin E/Z-isomer ratio on skin-related physicochemical properties and biological activities using human dermal fibroblasts and B16 mouse melanoma cells. We revealed that astaxanthin enriched in Z-isomers (total Z-isomer ratio = 86.6%) exhibited greater UV-light-shielding ability and skin antiaging and skin-whitening activities, such as anti-elastase and anti-melanin formation activities, than the all-E-isomer-rich astaxanthin (total Z-isomer ratio = 3.3%). On the other hand, the all-E-isomer was superior to the Z-isomers in singlet oxygen scavenging/quenching activity, and the Z-isomers inhibited type I collagen release into the culture medium in a dose-dependent manner. Our findings help clarify the roles of astaxanthin Z-isomers in the skin and would help in the development of novel skin health-promoting food ingredients.
Lycopene as a natural antioxidant that have been studied for ultraviolet radiation (UVR) photo protection and is one of the most effective carotenoids to scavenge reactive oxygen species (ROS). This review aims to summarize the protective effect of tomato and lycopene on skin photo damage and skin photoaging in healthy subjects by reviewing the existing population intervention experiments. A total of five electronic databases including PubMed, Scopus, EBSCO, Web of Science and Cochrane Library were searched from inceptions to January 2021 without any restriction. Out of 19336 publications identified, 21 fulfilled the inclusion criteria and were meta-analysis. Overall, interventions supplementing tomato and lycopene were associated with significant reductions in Δa*, MMP-1, ICAM-1 and skin pigmentation; while tomato and lycopene supplementation were associated with significant increase in MED, skin thickness and skin density. Based on the results of this systematic review and meta-analysis, supplementation with tomato and lycopene could reduce skin erythema formation and improve the appearance and pigmentation of the skin, thereby preventing light-induced skin photodamage and skin photoaging. Lycopene-rich products could be used as endogenous sun protection and may be a potential nutraceutical for sun protection.
Orally administered collagen peptides could contribute to antiaging by replacing the degraded extracellular matrix proteins caused by photoaging. This study aimed to evaluate the efficacy and safety of low-molecular-weight collagen peptides for treating photoaged and dry skin. In this randomized, placebo-controlled, parallel-group, double-blinded trial, we randomly assigned study participants (n = 100) to either the test product group or placebo group at a 1:1 ratio for 12 weeks. The wrinkle scale score, eye wrinkle volume, roughness parameters, such as the average maximum height of the wrinkle (Rz), arithmetic average within the total measuring length of the wrinkle (Ra), maximum profile valley depth of the wrinkle (Rv), and skin hydration, transepidermal water loss (TEWL), overall elasticity (R2), and ratio of elastic recovery to total deformation (R7) were evaluated at baseline, 6 weeks, and 12 weeks. Safety assessments with serial blood tests were also conducted. Efficacy assessments of data from 84 participants were conducted as the per-protocol analysis. After 12 weeks, the 10-grade crow's feet photo scale score, eye wrinkle volume, skin roughness parameters (Rz, Ra, and Rv), skin elasticity (R2 and R7), skin hydration, and TEWL were significantly improved in the test product group compared to the placebo group. There were no adverse events or abnormalities according to laboratory analysis associated with using the test material during the study period. This study showed that the oral supplementation of low-molecular-weight collagen peptides could improve the wrinkles, elasticity, hydration, and barrier integrity of photoaged facial skin. This clinical study was registered with the Korean Clinical Research Information Service and International Clinical Trials Registry Platform (No: KCT0006500).
Astaxanthin, a xanthophyll carotenoid, has attracted considerable attention owing to its unique molecular structure and excellent antioxidant properties. Due to its structural particularity, it has many geometrical and optical isomers in the diet; Interestingly, the human body has considerable quantity of Z- and optical isomers despite the intake of E- and (3S,3’S) isomers. However, there remains no systematic analysis and summary of astaxanthin and its isomers regarding health benefits and bioavailability. To address this need, this review details the latest research progress of biological activities related to oxidative damage, and these effects are more obvious in Z- and (3S,3’S)-isomers from the existing research. In addition, we outline a comprehensive analysis of the bioavailability of dietary astaxanthin and its isomers from the perspective of transporter-mediated process (e.g. SR-BI, CD36). Further nvestigation of astaxanthin and its isomers is expected to improve human health and promote their applications in future healthcare-related products.
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Astaxanthin, one of the dominant carotenoids in marine animals, showed both a strong quenching effect against singlet oxygen, and a strong scavenging effect against free radicals. These effects are considered to be defence mechanisms in the animals for attacking these active oxygen species. The activities of astaxanthin are approximately 10 times stronger than those of other carotenoids that were tested, namely zeaxanthin, lutein, tunaxanthin, canthaxanthin and β-carotene, and 100 times greater than those of a tocopherol. Astaxanthin also showed strong activity as an inhibitor of lipid peroxidation mediated by these active forms of oxygen. From these results, astaxanthin has the properties of a “SUPER VITAMIN E”.
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Astaxanthin, a xanthophyll carotenoid, is a nutrient with unique cell membrane actions and diverse clinical benefits. This molecule neutralizes free radicals or other oxidants by either accepting or donating electrons, and without being destroyed or becoming a pro-oxidant in the process. Its linear, polar-nonpolar-polar molecular layout equips it to precisely insert into the membrane and span its entire width. In this position, astaxanthin can intercept reactive molecular species within the membrane's hydrophobic interior and along its hydrophilic boundaries. Clinically, astaxanthin has shown diverse benefits, with excellent safety and tolerability. In double-blind, randomized controlled trials (RCTs), astaxanthin lowered oxidative stress in overweight and obese subjects and in smokers. It blocked oxidative DNA damage, lowered C-reactive protein (CRP) and other inflammation biomarkers, and boosted immunity in the tuberculin skin test. Astaxanthin lowered triglycerides and raised HDL-cholesterol in another trial and improved blood flow in an experimental microcirculation model. It improved cognition in a small clinical trial and boosted proliferation and differentiation of cultured nerve stem cells. In several Japanese RCTs, astaxanthin improved visual acuity and eye accommodation. It improved reproductive performance in men and reflux symptoms in H. pylori patients. In preliminary trials it showed promise for sports performance (soccer). In cultured cells, astaxanthin protected the mitochondria against endogenous oxygen radicals, conserved their redox (antioxidant) capacity, and enhanced their energy production efficiency. The concentrations used in these cells would be attainable in humans by modest dietary intakes. Astaxanthin's clinical success extends beyond protection against oxidative stress and inflammation, to demonstrable promise for slowing age-related functional decline.
The rising interest in the valorisation of industrial by-products is one of the main reasons why exploring different species and optimizing the extracting conditions of collagen and gelatin has attracted the attention of researchers in the last decade. The most abundant sources of gelatin are pig skin, bovine hide and, pork and cattle bones, however, the industrial use of collagen or gelatin obtained from non-mammalian species is growing in importance. The classical food, photographic, cosmetic and pharmaceutical application of gelatin is based mainly on its gel-forming properties. Recently, and especially in the food industry, an increasing number of new applications have been found for gelatin in products such as emulsifiers, foaming agents, colloid stabilizers, biodegradable film-forming materials and micro-encapsulating agents, in line with the growing trend to replace synthetic agents with more natural ones. In the last decade, a large number of studies have dealt with the enzymatic hydrolysis of collagen or gelatin for the production of bioactive peptides. Besides exploring diverse types of bioactivities, of an antimicrobial, antioxidant or antihypertensive nature, studies have also focused on the effect of oral intake in both animal and human models, revealing the excellent absorption and metabolism of Hyp-containing peptides. The present work is a compilation of recent information on collagen and gelatin extraction from new sources, as well as new processing conditions and potential novel or improved applications, many of which are largely based on induced cross-linking, blending with other biopolymers or enzymatic hydrolysis.
The two most commonly used methods to analyze data from real-time, quantitative PCR experiments are absolute quantification and relative quantification. Absolute quantification determines the input copy number, usually by relating the PCR signal to a standard curve. Relative quantification relates the PCR signal of the target transcript in a treatment group to that of another sample such as an untreated control. The 2(-DeltaDeltaCr) method is a convenient way to analyze the relative changes in gene expression from real-time quantitative PCR experiments. The purpose of this report is to present the derivation, assumptions, and applications of the 2(-DeltaDeltaCr) method. In addition, we present the derivation and applications of two variations of the 2(-DeltaDeltaCr) method that may be useful in the analysis of real-time, quantitative PCR data. (C) 2001 Elsevier science.
Background Up to now rejuvenating treatment of the hands has been challenging and results often disappointing. Aims To determine whether hyaluronic acid (HA) microdroplet placement into the dorsal hands has an impact on skin physiology and clinical appearance and whether there is any difference between stabilized HA (S-HA) and nonstabilized HA (NS-HA). Patients/methods The intra-individual comparison in 15 volunteers involved injection sessions at week 0, 4, and 8 with random assignment of left and right hand to either S-HA or NS-HA. Skin physiology parameters cutaneous elasticity, surface roughness, hydration, and transepidermal water loss (TEWL) were measured in vivo at weeks 0 (before treatment), 4 (before subsequent treatment), 12, and 24. Clinical hand assessment was carried out at weeks 0 and 12 by a blinded dermatologist. Results Intradermal injection of S-HA generated significant improvement in skin elasticity and surface roughness at week 12 compared to baseline. On the hands treated with NS-HA, there was a trend for improvement (not significant). While there was no significant difference in hydration and TEWL between both hands before treatment, at week 12 hands treated with S-HA displayed a significantly higher hydration level and lower TEWL compared to NS-HA treatment. Clinically S-HA proved to be significantly superior to NS-HA. At week 24 the observed effects started to return back toward baseline, with S-HA treatment still offering better results compared to the NS-HA. Conclusions Skin revitalization with injectable HA can improve clinical appearance and skin physiology parameters on the back of the hands. It has been shown that S-HA has better effects when compared with NS-HA.
Astaxanthin (Asx) would be expected to prevent ultraviolet (UV)-induced skin damage, as it is regarded as a potent antioxidative carotenoid in biological membranes. However, it is difficult to administer Asx topically to skin because of its poor water solubility. In this study, we attempted to solve this problem by preparing liposomes containing Asx (Asx-lipo), which were dispersible in the water phase, and therefore, suitable for topical application to the skin. Asx-lipo was shown to have potent scavenging ability against chemiluminescence-dependent singlet oxygen production in the water phase. When Asx-lipo was applied to skin before UV exposure, UV-induced skin thickening was prevented. Interestingly, collagen reduction induced by UV exposure was also prevented by preadministration of Asx-lipo. In addition, topical administration of Asx-lipo containing cationic lipid inhibited melanin production in skin exposed to UV. Consequently, we succeeded in preventing UV-induced skin damage using a topical application of a liposomal formulation containing Asx.
Two human clinical studies were performed. One was an open-label non-controlled study involving 30 healthy female subjects for 8 weeks. Significant improvements were observed by combining 6 mg per day oral supplementation and 2 ml (78.9 μM solution) per day topical application of astaxanthin. Astaxanthin derived from the microalgae, Haematococcus pluvialis showed improvements in skin wrinkle (crow's feet at week-8), age spot size (cheek at week-8), elasticity (crow's feet at week-8), skin texture (cheek at week-4), moisture content of corneocyte layer (cheek in 10 dry skin subjects at week-8) and corneocyte condition (cheek at week-8). It may suggest that astaxanthin derived from H. pluvialis can improve skin condition in all layers such as corneocyte layer, epidermis, basal layer and dermis by combining oral supplementation and topical treatment. Another was a randomized double-blind placebo controlled study involving 36 healthy male subjects for 6 weeks. Crow's feet wrinkle and elasticity; and transepidermal water loss (TEWL) were improved after 6 mg of astaxanthin (the same as former study) daily supplementation. Moisture content and sebum oil level at the cheek zone showed strong tendencies for improvement. These results suggest that astaxanthin derived from Haematococcus pluvialis may improve the skin condition in not only in women but also in men.
High doses of sun-emitted UV-radiation induce reactive oxygen species (ROS) as major pro-oxidants thus inducing premature skin aging. The best prevention of the destructive action of free radicals in human skin is textile coverings, topical sunscreens and the development of a high antioxidative protective network. The effects of topical, systemic and combined application of antioxidants (AO) were investigated on human skin in vivo. Topical application of creams and systemic incorporation of tablets both containing AO was investigated in vivo by resonance Raman spectroscopy. Topical, systemic and combined AO-treatments induced a statistically significant increase of AO levels in human skin while placebo did not show any changes. The highest accumulation was induced by the combination of topical and systemic AO. Carotenoid-tablets combined with placebo-cream induced less carotenoid accumulation than carotenoid-tablets alone. Carotenoid levelling after the end of treatment lasted for around 2 weeks following the topical application of AOs, and up to 5 weeks after systemic administration, depending on the BMI of volunteers. Topically applied AO are stored in the SC for a short time only due to the rapid AO-depletion by desquamation, textile contact, washing and environmental stress. In contrast to topical application, the systemically applied carotenoids are stored in the body fat tissue and slowly released onto the skin surface with sweat and sebum. The combined topical and systemic application of AO represents an optimal form of protection of the AO-network.