Cellex-C Skin Care Research

USE OF TOPICAL VITAMIN C AND ITS EFFECTS
ON PHOTODAMAGED SKIN TOPOGRAPHY
1998 Award for Best Scientific Paper by The American Academy of Facial Plastic
and Reconstructive Surgery
Abstract
Dr. Steven S. Traikovich
Chronic insults to the skin such as ultraviolet light, ozone, cigarette smoke,
pollutants and other natural and synthetic environmental stimuli lead to cumulative
damage, and can result in photoaging and "heliodermatitis".1 Chronic
ultraviolet sun exposure leads to clinical changes in the skin such as laxity,
roughness, dryness, sallowness, pigmentation, telangectasia and wrinkles.2 Reactive
oxygen species such as free radicals unquestionably produce oxidative damage
in skin. Ultraviolet light contributes directly to photodamage, not only by
generation of reactive oxygen species but also by depression of antioxidant
levels.3 Antioxidants are obviously necessary for neutralizing oxygen molecular
species such as oxygen free radicals, which damage and destroy skin. Vitamin
C (ascorbic acid) has been shown to have antioxidant effects as well as a role
in collagen stimulation. Ascorbic acid appears to influence production of collagen
by post-translational and transcriptional mechanisms.4 This is thought to occur
by ascorbate stimulating collagen synthesis directly and specifically activating
collagen gene regulation, both by increasing transcription rate and by stabilizing
pro-collagen mRNA, therefore, genetically signaling collagen synthesis.5 6 7
8 9 Another mechanism is initiation of lipid peroxidation, which leads to an
increase in a byproduct, malondialdehyde, which somehow stimulates collagen
gene expression.10
Ultraviolet light exposure depletes up to two-thirds of cutaneous Vitamin C
stores.4 Cutaneous levels not obtainable by ingestion of Vitamin C can be reached
with topical application. Topical Vitamin C provides more than twenty times
the amount of Vitamin C found in normal skin.16 17 Ascorbic acid stereoisomers
D-ascorbic acid and L-ascorbic acid exist, but only the L-ascorbic acid form
can be used by the body.16 18 This stable form of L-ascorbate has allowed pharmacological
levels of Vitamin C penetration targeted directly into the skin by topical application
to effect antioxidant and collagen stimulation. Because topical Vitamin C does
not absorb light in UVB/UVA range, it is not a sunscreen but exerts its effects
by neutralizing oxygen free radicals.20 21
Skin inflammation, which is mediated by reactive oxygen species, has been reported
to be alleviated by topical use of Vitamin C on ultraviolet radiation-induced
erythema on porcine and human skin.14 This same study also showed a protective
effect on the inflammatory response when applied, even after sun exposure from
ultraviolet sunburn.14 Topical Vitamin C has also been used as a priming agent
as well as a postoperative agent in laser resurfacing erythema treatment.30
Furthermore, the introduction of a stable preparation of L-ascorbic acid is
now available that can penetrate the skin, delivering L-ascorbate to the epidermis
and dermis. It is anticipated that this enhanced delivery technology utilizing
a unique formulation of L-ascorbic acid, zinc sulfate and L-tyrosine, will show
an enhanced and longer-lasting effect on photodamage, prevention and aging.
The central hypothesis of this study is that a daily regimen of topical Vitamin
C will lead to subjective as well as objective improvement in human facial photoaging/photodamage.
Optical profilometry is an objective method for quantification of facial wrinkles.31
Skin replica analysis of photodamaged skin was well described and utilized in
previous studies with the use oftretinoin.32 33 No previous studies have utilized
this technology with the use of topical Vitamin C.
Main Outcome Measures: Specific clinical parameters evaluated: fine wrinkling,
tactile roughness, visual dryness, coarse rhytids, telangectasia, laxity/tone,
pigmentation, keratoses and sallowness. Each of these parameters were graded
on a 0 to 9 point scale (0=None, 1-3=Mild, 4-6=Moderate and 7-9=Severe). Reference
photographs were used to standardize grading criteria. Overall investigator
global scores were compared to baseline as: excellent (much improved), good
(improved), fair (slightly improved), no change or worse. Patient self-appraisal
questionnaires rated the degree of improvement (much improved, improved, slightly
improved, no change or worse) and reported side effects (burning, stinging,
redness, peeling, dryness, discoloration, itching, rash). Standard photography,
including AP as well as left and right oblique views, were obtained at baseline
to facilitate subsequent clinical evaluations and at the end of therapy for
comparison. Optical profilometry analysis of skin surface replicas of the crows
feet region were obtained, comparing baseline to end-of-study specimens. Utilizing
the Magiscan System, the resulting image was digitally analyzed, and numeric
values were assigned to reflect surface features. The parameters obtained included:
Rz, Ra, and Shadows. These values provided objective data which documents pre-and
post-treatment texture changes.
Optical profilometry analysis of skin surface replicas of the crows feet
region were obtained, comparing baseline to end-of-study specimens. Silicone
skin surface replicas were taken from the periorbital crows feet region
at identical sites bilaterally by the same technician. Alcohol skin cleansing
of the periorbital region was utilized before application of the adhesive rings
and silicone impression material (CuDerm Corporation, Dallas, TX). Precise application
of the adhesive replica locating rings was aided with caliper measurements to
insure consistent distances from reference points of the lateral orbital canthus
and superior auricular tragus. This, as well as use of reference close-up Polaroid
photographs with adhesive rings properly in place for each subject, facilitated
relocating these sites for subsequent end-of-study samples. Results:
Three patients were eliminated from the study secondary to the inability to
follow-up at designated study protocol periods. Seven additional patients were
excluded from analysis because of breach in study protocol for active and control
designations. Of the nineteen evaluable subjects, three were male (mean age=43)
and sixteen were female (mean age=48). Ages ranged from 36 to 72 years. Pre-study
data revealed: 63% of patients had a previous history of smoking, 52% utilized
sunscreens on a regular basis, 52% admitted to excessive lifetime sun exposure.
Side effects were mild and usually resolved within the first two months of therapy.
Side effects included, in decreasing order of frequency: stinging (55%), erythema
(24%), and dryness (.05%). All side effects were easily treated with moisturization.
In no case was topical required or topical study regimen altered. The majority
of initial improvement seen during this time period involved tactile roughness/texture
and skin hydration changes.
Optical profilometry image analysis demonstrated a statistically significant
73.7% improvement in Rz and Shadows North-South values with active greater than
control, as well as a trend for improvement in Rz North-South parameter showing
a 68.4% active greater than control improvement. Clinical investigator assessment
demonstrated statistically significant improvement with active greater than
control for fine wrinkling (p=.002), tactile roughness (p=.035), coarse rhytids
(p=.010), skin laxity/tone (p=.032), sallowness/yellowing (p=.031), and overall
(p=.002). Patient questionnaire results demonstrated statistically significant
improvement overall with 84.2% active greater than control (p=.002). Photographic
assessment demonstrated statistically significant improvement with 57.9% active
greater than control (p=.011).
In this study, a 3 month daily regimen of topical Vitamin C was shown to provide
significant objective and subjective improvement of some of the changes associated
with photodamaged facial skin. These changes were gradual and became progressively
more evident as treatment continued. Clinical
assessment and patient questionnaire/self-appraisal have been the traditional
areas of evaluation. These methods demonstrated significant differences from
vehicle in fine wrinkling, tactile roughness, coarse rhytids, skin laxity/tone,
allowness/yellowing, and overall skin improvement.
Clinical and patient self-appraisal showed an 84% correlation to predicting
active versus control. Stinging did not have any significant correlation with
active or control agents. The vehicle control agent (Cellex-C
International, Toronto, Canada) was matched for color, consistency, and pH to
the active agent to ensure the blindness of the study. Stinging discrepancies
were probably associated with variations in skin type and surface flora among
subjects, as well as environmental exposure, cosmetic use, local tissue reactivity,
variations in serum application, and moisturizer use.
Photographic assessment did show significant improvement with active greater
than control but was found to have the least reliability (58%) in predicting
active and control sides. Inherent limitations in photography include fluctuations
in lighting, head position, facial expression and asymmetries. Consequently,
the use of skin replica optical profilometry to complement subjective evaluations
with an objective method for the quantification of skin surface texture changes
with minimal variability or potential for bias was utilized.
Pre-and post-treatment comparison revealed significant improvement with active
greater than control for Rz North-South (.032) and Shadows North-South (.032).
In the case of Rz North-South, the values approached significance (p=.084).
Therefore, overall active topical Vitamin C treated skin topography is smoother
and less wrinkled than vehicle-control. The fact that Rz and Shadows represent
fine to intermediate depth lines and that Rz is largely a measure of deep wrinkles,
suggests that topical Vitamin C therapy had a more dramatic effect on superficial
topography and less of an effect with major furrows and creases.
It should also be mentioned that there are an increased number of Vitamin C
based topical cosmetics available on the market. It appears that not all preparations
of topical Vitamin C are effective. Many of these products utilize derivatives,
esters and analogs of Vitamin C that are either unable to penetrate into the
skin, unable to be chemically converted to L-ascorbic acid (the only form that
can be utilized by the body), and/or unable to be delivered in adequate concentration
to have an effect. These ascorbic acid substitutes include ascorbyl palmitate,
magnesium ascorbyl phosphate, ascorbic acid magnesium phosphate, which are easily
stabilized but must be converted to L-ascorbate to be effectively useful. There
is no direct evidence that ascorbic acid derivatives enter the skin in appreciable
amounts, and it appears that their conversion to L-ascorbate is largely inefficient,
therefore, precluding effective concentration delivery. "This three-month
study evaluated and did show topographic improvement in facial photodamaged
skin utilizing Cellex-C
(Cellex-C International,
Toronto, Canada)."

