Topical antioxidant application augments the effects of intensepulsed light therapy
Bruce M Freedman, MD, FACS
Plastic Surgery Associates of Northern Virginia, McLean, VA
Summary Background There has been great interest in improving the efficacy of nonablative
technologies by combining them during facial skin rejuvenation. The purpose of this
study was to determine whether the addition of topical polyphenolic antioxidants to an
intense pulsed light (IPL) treatment regimen augmented the effects of facial IPL
treatments.
Methods Thirty female volunteers, ages 34–52, with skin phototypes 1–3 were ran-
domly assigned into three groups: group A (n = 10) received three full-face IPL treat-
ments spaced 3 weeks apart; group B (n = 10) underwent 6-weekly full-face treatments
of a pneumatically applied topical polyphenolic antioxidant solution; group C (n = 10)
received the combination of the three full-face IPL treatments and the six full-face
topical antioxidant applications. Skin biopsies, skin polyphenolic antioxidant levels, and
skin moisture content levels were obtained and clinical efficacy variables were noted
prior to and following the treatment period.
Results Compared to group A, group C demonstrated significantly greater epidermal and
papillary dermal thickness, decreased lipid peroxide concentration, increased skin
moisture content, and increased polyphenolic antioxidants levels (P < 0.05). There was
qualitative improvement in hydration, texture, and pore size. Compared to group B,
group C demonstrated significantly greater papillary dermal thickness (P < 0.05), and
qualitative improvement in reduction of fine lines, reduction of hyperpigmentation, and
skin dullness. group B and group C had equivalent polyphenolic antioxidant levels, lipid
peroxide concentration, and epidermal thickness.
Conclusion The addition of polyphenolic antioxidants to an IPL regimen improved the
clinical, biochemical, and histological changes seen following IPL treatment alone.
These data support the use of multimodal therapy to create synergy and to optimize
clinical outcomes in nonablative facial skin rejuvenation.
Keywords: intense pulsed light, topical antioxidants, facial rejuvenation
Introduction
In 1994, intense pulsed light (IPL) technology became
commercially available for use in treatment of vascular
anomalies of the skin. Over the following decade, IPL
technology has undergone a series of modifications and
innovations that have broadened its clinical use. IPL has
since become a widely accepted and reliable technique
for the treatment of photodamaged skin. IPL systems
utilize high intensity flashlamps that emit pulses of
polychromatic light in the 515–1200 nm wavelength
spectrum, utilizing the mechanism of selective photo-
thermolysis to target dermal chromophores. The
Correspondence: Bruce M Freedman, MD, 8180 Greensboro Drive #1015,
McLean, VA 22102, USA. E-mail: [email protected]
Presented at the ASLMS Annual Meeting, Washington, DC, April 1–5, 2009.
Accepted for publication July 26, 2009
Original Contribution
254 � 2009 Wiley Periodicals, Inc. • Journal of Cosmetic Dermatology, 8, 254–259
resulting thermal injury affects the dermal vasculature
and initiates a cascade of inflammatory events that
includes fibroblastic proliferation and an increase in
collagen production.1 This type of dermal remodeling is
well suited for nonablative facial rejuvenation. Numer-
ous studies have confirmed that a series of IPL
treatments can decrease facial rhytides, improve skin
texture, correct irregular pigmentation, and reduce
telangiectasis.2,3
The employment of different nonablative technologies
has recently been promoted to improve results and reduce
recovery time. Typically, topical compounds such as
photosensitizing agents or exfoliating acids have been
used in conjunction with microdermabrasion or IPL to
provide multimodal therapy.4,5 Recently, there has been
great interest in exploring the effects of topical antioxi-
dants on the skin. Botanically derived extracts from green
tea, rosemary, and horse chestnut seeds contain polyphe-
nolic compounds that posses significant antioxidant
properties. These polyphenols (i.e., the epicatechins) have
demonstrated an ability to prevent ultraviolet radiation-
induced lipid peroxidation, DNA damage, and carcino-
genesis.6–9 Clinically, topically applied polyphenolic
antioxidants have been shown to decrease inflammation,
prevent erythema, and reverse photoaging.10–12
The purpose of this study was to determine whether
the addition of topically applied polyphenolic antioxi-
dants could augment the effects of IPL therapy in facial
rejuvenation.
Materials and methods
Thirty female volunteers, with Fitzpatrick skin types I-III,
aged 38–52, were randomized into three groups. All
participants consented to partake in a prospective study
to evaluate the effects of IPL and antioxidant application
on facial skin in accordance to the guidelines of the
1975 Declaration of Helsinki.
Group A (n = 10) received three full-face IPL treat-
ments spaced 3 weeks apart delivered by a Sciton Profile
System using the Broad Based Light module (Sciton
Corporation, Palo Alto, CA, USA) set at the following
parameters: 16 J ⁄ cm2, 10 ms, 560 nm filter. This cor-
responded to a calculated fluence rate of 2500 W ⁄ cm2.
Group B (n = 10) underwent six full-face treatments at
7- to 10-day intervals with the HydraFacial Wave
System (Edge Systems Corporation, Signal Hill, CA,
USA). Each treatment consisted of one pass over the
entire face with the spiral tip hand piece of the crystal
free microdermabrasion unit set at 180 mm Hg. A
polyphenolic based antioxidant serum containing poly-
phenolic flavonoids and polyphenolic diterpenes (e.g.,
epigallocatechin, ursolic acid) was pneumatically ap-
plied to the face at 180 mm Hg. The solution contained
no humectants or hydrating agents. Group C (n = 10)
received the combination of the three full-face IPL
treatments at 3-week intervals and the six full-face
topical antioxidant applications at 7- to 10-day inter-
vals. During those weeks when both treatments were
administered, the antioxidant application was performed
immediately prior to the IPL treatment. Skin care
products such as antioxidants, triretinoin, and glycolic
acid agents were avoided 6 weeks prior to and during
the treatment period.
In all groups, digital photographs, 2 mm full-thickness
preauricular skin biopsies, skin moisture content, and
skin polyphenolic antioxidant levels were obtained prior
to treatment (control) and 1 week following the last
treatment session. Side effects such as persistent ery-
thema and blistering following treatment were also
recorded.
Skin antioxidant levels
Skin polyphenolic antioxidant levels were obtained from
the left cheek using a noninvasive optical device
(Biophotonic Scanner, Pharmanex, Provo, UT, USA).
This technology employed laser energy at 473 nm and
10 mW power to stimulate molecules containing car-
bon-carbon double bonds generating an optical finger-
print. The emitted backscattered light was captured by a
sensitive light detector, which was then processed and
calculated using a Raman scattering spectroscopic
technique that has been validated in humans in vivo.13
Using a spectral Raman peak at 1520 cm)1, a linear
relationship has been established between antioxidant
concentration and Raman intensity, indicating that
absolute Raman intensity counts are a biomarker for
skin antioxidant levels.14,15
Lipid peroxidation
The skin biopsies for lipid peroxide analysis were frozen
until assayed. Lipid peroxidation was assessed by deter-
mining the concentration of cutaneous lipid peroxides as
described by Sorg et al.16 Briefly, skin samples were
homogenized in methanol containing butylated hydro-
xytoluene. The homogenates were sonicated and cen-
trifuged and the supernatant separated into two 500 mL
aliquots. One aliquot was incubated with 50 mL of
10 mM triphenylphosphine in methanol while 50 mL
methanol was added to the other aliquot. A 500-mL
mixture containing 25 mM sulfuric acid, 200 mM
ammonium ferrous sulfate, 100 mM xylenol orange,
� 2009 Wiley Periodicals, Inc. • Journal of Cosmetic Dermatology, 8, 254–259 255
Topical antioxidants augment IPL therapy • B M Freedman
and 4 mM butylated hydroxytoluene in 90% methanol
was then added to both aliquots; optical density was
read at 585 nm 1 h later. The specific lipid peroxide
signal was obtained by subtracting the nonspecific signal
(triphenylphosphine) from the global signal. Lipid per-
oxide concentration was determined using cumene
peroxide as a standard.
Histological assessment
The skin biopsies for histology were fixed in a 10%
buffered formaldehyde solution, embedded in paraffin,
and cut in 4-lm sections. Sections were stained with
standard hematoxylin and eosin for light microscopy.
The slides were reviewed in a blinded fashion to evaluate
epidermal and papillary dermal thickness as well as
epidermal and dermal cellular and extracellular ele-
ments. The slides were examined with an Olympus
Microscope and precision measurements were performed
using an Olympus (Olympus Corporation, Tokyo, Japan)
Micrometer at 40· magnification.
Skin moisture content
Water content detection was obtained utilizing interdig-
ital capacitance polyimide film sensor technology.17 Skin
moisture content was measured by calculating skin
capacitivity using a noninvasive skin probe (MoistSense
Skin Sensor, Moritex Corporation, Tokyo, Japan). This
methodology was based on determining the dielectric
constant or relative permittivity of the skin; all mea-
surements were taken under fixed environmental con-
ditions of 23 �C and 50% relative humidity.
Clinical assessment
A panel of three independent medical clinicians examined
each of the patients before and after the study period.
Efficacy variables were scored on a 0–9 scale (0 = none,
9 = severe) for the following skin attributes: (1) fine lines;
(2) pore size; (3) hyperpigmentation; (4) dullness; and (5)
skin texture.18 Differences in clinical outcome for each
skin attribute were tabulated as changes from mean score
baseline (control) in each patient.
Statistical analysis
The Pearson’s chi-square test was used to compare
treatment groups A, B, and C with respect to age,
gender, and skin types. These parameters were found to
be similar indicating that the patients had been effec-
tively randomized such that the subject variables did not
influence outcome. Therefore a two-sided paired t-test
was used to identify statistical differences in epidermal
and papillary dermal thickness, skin moisture content,
lipid peroxide concentration, skin polyphenolic antioxi-
dant levels, and side effects between groups. A P-value of
less than or equal to 0.05 was used to declare statistical
significance. The Wilcoxon signed ranks test was used to
evaluate the change from baseline (control) in the
clinical efficacy variables. Statistical significance was set
a priori at P < 0.05.
Results
After the treatment protocol, the epidermal thickness in
group B increased to 75 ± 9 lm, and in group C
increased to 80 ± 8 lm. These values were statistically
greater than the control epidermal thickness of
50 ± 5 lm (P < 0.05). However, the epidermal thick-
ness in group A did not increase statistically after
treatment. In addition, the epidermal thickness in group
C was equivalent to that found in group B. After the
treatment protocol, the papillary dermal thickness in
group A increased to 370 ± 20 lm, in group B
increased to 360 ± 30 lm, and in group C increased
to 475 ± 40 lm. These values were statistically greater
than the control papillary dermal thickness of
285 ± 20 lm (P < 0.05). Also, the papillary dermal
thickness in group C was statistically greater than that
in both groups A and B (P < 0.05).
The Raman intensity count, a reflection of skin
polyphenolic antioxidant levels, averaged 16 000 ±
2000 in the control tissue. In group A (IPL alone), the
Raman intensity count decreased significantly to
12 000 ± 2000, while in group B (antioxidant alone)
it increased significantly to 24 000 ± 3000 (P < 0.05).
In group C (IPL plus antioxidant), the Raman intensity
count averaged 20 000 ± 2000, a value statistically
greater than in both the control and group A
(P < 0.05). However, this value was statistically less
than that in group C. Lipid peroxide concentration in
group A increased significantly to 260 ± 30 nmol ⁄ gfrom a control value of 60 ± 10 nmol ⁄ g (P < 0.05).
Lipid peroxide concentration in groups B and C did not
increase relative to control and was significantly less
than that found in group A. In group A skin moisture
content was significantly reduced to 35 ± 6 IU from the
control level of 45 ± 5, whereas in group B skin
moisture increased significantly 71 ± 5 (P < 0.05).
However, in group C the skin moisture content was
59 ± 9, a level greater than in control and group A,
but less than in group B. These data are depicted in
Table 1.
256 � 2009 Wiley Periodicals, Inc. • Journal of Cosmetic Dermatology, 8, 254–259
Topical antioxidants augment IPL therapy • B M Freedman
Changes in the clinical efficacy variables are depicted
in Figure 1. At the end of the study periods groups A, B,
and C showed a significant improvement from baseline
in fine lines (P < 05). However, group C demonstrated
statistically greater improvement than groups A and B
(P < 0.05). Pore size in all groups was reduced relative
to control, but equivalent between groups. Following
treatment, groups A, B and C showed a significant
improvement from baseline in hyperpigmentation
(P < 0.05). The improvement in groups A and C was
statistically greater when compared to the improvement
observed in group B (P < 0.05). Clinically, at the end of
the study period, all groups showed a significant
improvement from baseline in skin texture (P < 0.05).
However, group C demonstrated statistically greater
improvement than groups A and B (P < 0.05). Side
effects, particularly persistent erythema and blistering,
differed between the groups. The side effects in group A
were statistically greater than those noted in groups B
and C (Table 2). The minor blistering noted in group A
resolved without scarring.
Discussion
Minimally invasive technologies, such as IPL, have
become increasingly popular in the treatment of
photoaged skin. This trend has resulted from the overall
safety, reduced recovery time, and versatility of these
modalities. These factors have a broad appeal to clini-
cians and patients, indicating that the number of
nonablative procedures will continue to grow. In spite
of the utility of IPL in facial rejuvenation, there are some
questions concerning the predictability of results. Pub-
lished reports indicate a varied response to IPL treat-
ment. Bitter1 observed a 10–90% improvement in
rhytides, while Goldberg and Samady19 reported signif-
icant clinical improvement in only 9 out of 30 patients
after a series of IPL treatments. It has been suggested
that in some patients the repetitive photo-insult may
induce microscopic changes analogous to the dermal
scarring observed with ultraviolet associated photodam-
age.3 In these patients an exuberant inflammatory
response to high intensity visible light exposure could
lessen the overall benefits seen with IPL therapy. In an
effort to deliver optimal clinical improvement with a
reliable safety profile, recent research has focused on
combining multiple modalities to accomplish these goals.
This study sought to determine whether the addition
of topical polyphenolic antioxidants could enhance the
clinical efficacy of IPL therapy. Recently, there has been
an increased focus on antioxidants and their role in skin
health. Several antioxidants, including the botanically
extracted polyphenolic compounds, have demonstrated
anti-aging properties when applied topically. These
compounds have been shown to scavenge superoxide
anions and other radicals, prevent lipid oxidation,
reduce antigenotoxicity, and elevate the antioxidative
capacity in the skin.20,21 Collagen synthesis in the
papillary dermis and decreased elastosis have also been
attributed to topical antioxidant application.22 Fujimura
et al. demonstrated that the polyphenols in horse chest-
nut seed extract induced contraction forces in fibroblasts
resulting in decreased periorbital rhytides.23 Other
studies have suggested that polyphenolic antioxidants
can increase fibroblast density and collagen deposition
during the wound healing process.9–11,24 The effects
have been purported to translate clinically into increased
Table 1 Results comparing data between groups before treatment (control); after IPL (group A); after antioxidant application (group B);
and following IPL plus topical application of polyphenolic antioxidant solution (group C)
Control Group A Group B Group C
Epidermal thickness (microns) 50 ± 5 55 ± 7 75 ± 9*,� 80 ± 8*,�
Papillary dermal thickness (microns) 285 ± 20 370 ± 20* 360 ± 30* 475 ± 40*,�,�
Skin polyphenolic antioxidant level (Raman intensity units) 16 000 ± 2000 12 000 ± 2000* 24 000 ± 3000*,� 20 000 ± 2000*,�
Lipid peroxide concentration (nmol ⁄ g) 60 ± 5 260 ± 30* 65 ± 10� 80 ± 20�
Skin moisture content (International units) 45 ± 5 35 ± 6* 71 ± 5*,� 59 ± 9*,�,�
*P < 0.05 vs. Control; �P < 0.05 vs. Group A; �P < 0.05 vs. Group B.
Figure 1 Mean decreases from baseline score in the efficacy
variables. , Group A; , Group B; , Group C.
� 2009 Wiley Periodicals, Inc. • Journal of Cosmetic Dermatology, 8, 254–259 257
Topical antioxidants augment IPL therapy • B M Freedman
collagen production, ultraviolet radiation protection,
and reduction of fine lines.
The mechanism and timing of antioxidant delivery
was designed to achieve optimal results. Lee et al.
demonstrated that the flux and skin deposition of topical
antioxidants increased by approximately 20 times in
microdermabrasion-treated skin.25 Therefore, the anti-
oxidants in this study were delivered to the skin via a
crystal-free microdermabrasion technique. Other re-
search has shown that applying polyphenolic antioxi-
dants to microdermabraded skin resulted in measurably
increased levels of polyphenolic antioxidants in the
dermis.24 The polyphenolic antioxidants in this study
were applied immediately prior to each IPL treatment
and also between IPL treatments to preserve and
maintain the antioxidative capacity of the skin. A
pretreatment approach was employed based on findings
that polyphenolic antioxidants applied prior to ultravi-
olet and visible light exposure decreased measurable
DNA damage in human fibroblasts and keratinocytes.7
In addition, it has been show that antioxidants applied
topically after irradiation may not decrease oxidative
stress.22
This study demonstrated that the topical application of
polyphenolic antioxidants during IPL therapy enhanced
the known effects of IPL treatment. The benefits
conveyed by the polyphenolic antioxidants in this study
appear to be both reparative and preventative. Polyphe-
nolic antioxidants application enhanced the cellular
mechanisms activated in the skin during IPL therapy.
Papillary dermal thickness and skin moisture content,
ostensibly an indicator of skin barrier function, were
measurably increased when polyphenolic antioxidants
were applied to the skin during the course of IPL
therapy. Clinically, fine lines, texture, pore size, and
overall skin appearance were improved to a greater
extent in skin treated with the polyphenolic antioxi-
dants. These findings most likely accounted for the
histological improvement in the skin architecture as well
as the improvement in skin efficacy variables seen
following polyphenolic antioxidant addition to an IPL
regimen.
Other mechanisms by which the polyphenolic antiox-
idants appeared to exert their impact was through their
anti-inflammatory and anti-oxidative properties. This
was manifest in this study through a reduction in the
adverse effects associated with IPL therapy. Mahmoud
et al.20 reported that visible light could induce DNA
damage through the generation of reactive oxygen
species. Likewise, Sorg et al.16 demonstrated that the
moderate dose of visible light delivered during IPL
therapy increased lipid peroxide concentration in vivo.16
In this study, the pneumatic topical application of
polyphenolic antioxidants during IPL therapy mitigated
the lipid peroxide concentrations observed during a
course of IPL therapy (Figure 2). Furthermore, the
addition of polyphenolic antioxidants to an IPL regimen
decreased the incidence of erythema and blistering
(Table 2). These findings corroborate current views that
topically applied antioxidants exert anti-inflammatory
effects.
In conclusion, the addition of polyphenolic antioxi-
dants to an IPL regimen improved the clinical, biochem-
ical, and histological changes seen following IPL
treatment alone. As such, polyphenolic antioxidants
may confer a protective effect on facial skin exposed to
high-intensity visible light radiation and reduce delete-
rious effects of IPL therapy.
These data support the use of multimodal therapy to
create synergy and to optimize clinical outcomes in
nonablative facial skin rejuvenation.
Acknowledgments
The author would like to acknowledge Dr. James Henry,
Department of Pathology, Reston Hospital Center for his
assistance with the histological analysis and Jacqueline
D Higgins for her assistance with manuscript prepara-
tion and technical support.
Table 2 Side effect profile
Group A Group B Group C
Persistent erythema 3 0 1
Blistering 2 0 0
Total side effects 16% (5 ⁄ 30)* 0% 3% (1 ⁄ 30)
Each subject in groups A and C received three IPL treatments for
a total of 30 IPL exposures.
*P < 0.05.
Figure 2 Lipid peroxide concentration before treatment (control),
after IPL (group A); after antioxidant application (group B); and
following IPL plus topical application of polyphenolic antioxidant
solution (group C).
258 � 2009 Wiley Periodicals, Inc. • Journal of Cosmetic Dermatology, 8, 254–259
Topical antioxidants augment IPL therapy • B M Freedman
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