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LE Magazine January 2003
Combating Skin Aging
The concept of controlling human aging
remains controversial. No one disagrees, however, that
individuals can significantly influence the rate at which
their skin ages.
For instance, if a person wants to
accelerate skin degradation, all they have to do is expose
themselves to lots of ultraviolet radiation, cigarette smoke,
and ethanol. Even second-hand cigarette smoke prematurely ages
the skin.
Factors that induce skin damage
involve the excessive production of free radicals. Protecting
against these free radical insults is a proven way to slow the
effects of aging.
Recently published papers confirm that
a decline in natural antioxidant systems is a key factor
responsible for the unsightly appearance of aged skin.
The ultimate question becomes: Can the
application of topical antioxidants to the skin's surface
induce a noticeable anti-aging effect? This article reveals
novel findings made by research scientists working on the
front lines in the battle to prevent and reverse skin
aging.
The skin, as the outermost barrier of the
body, is exposed to various sources of oxidative stress, in
particular UV-irradiation and environmental toxins such as
cigarette smoke, air pollution, etc. Internally, the skin is
attacked like any other organ, through processes involving
glycation (protein cross-linking), collagen-elastin
degradation and free radical-induced injury.
One way of mitigating this process is to
increase levels of protective antioxidants through a diet rich
in fruits and vegetables or by direct topical application.
Indeed, various animal and human studies have proved that
topically applied antioxidants, especially vitamins C and E,
as well as alpha lipoic acid exert protective effects against
free radical damage (oxidative stress).1
Free radicals form in skin upon
ultraviolet exposure. Acute and chronic photo radiation damage
depletes the body's natural antioxidant enzyme systems and
increases oxidative protein modifications (cross-links). These
pathological effects are found in the upper and lower layers
of the skin. Cross-linked (glycated) proteins are classic
characteristics of skin aging. Cross-linked proteins in the
skin result in stiffening, wrinkling and the unsightly
leathery appearance.2
New studies confirm efficacy of topical
antioxidants
In a double-blind study, a topical vitamin C complex was
applied to one-half of the face and a placebo gel to the
opposite side. Clinical evaluation of wrinkling, pigmentation,
inflammation and hydration was performed prior to the study
and at weeks 4, 8 and 12. The results showed a statistically
significant improvement of the vitamin C-treated side, with
decreased photoaging scores of the cheeks and the peri-oral
area. The overall facial improvement of the vitamin C side was
statistically significant. Biopsies showed increased collagen
formation in the vitamin C group. This study showed that
topically applied vitamin C results in clinically visible and
statistically significant improvement in wrinkling when used
for 12 weeks. This clinical improvement correlated with biopsy
evidence of new collagen formation.3
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ORALLY INGESTED
NUTRIENTS IMPROVE SKIN APPEARANCE
It is well known that
destructive alterations in collagen, elastin and
glycosaminoglycans contribute to degenerative changes
seen in aging skin. A randomized, controlled study was
conducted with 53 female volunteers who were supplied
with an oral supplement containing glucosamine, amino
acids, minerals and various antioxidant compounds.
Hydration properties of the skin as well as textural
analysis of the women's fine lines and wrinkles were
assessed following five weeks intake of the oral
supplement and results were compared with those of a
control group of 12 individuals who did not take the
supplement.
The results showed a
statistically significant reduction in the number of
visible wrinkles and a reduction in the number of fine
lines in the group of women who took the
supplement.
This study showed that an
oral supplement containing glucosamine, minerals and
various antioxidant compounds can potentially improve
the appearance of visible wrinkles and fine lines. It
did not, however, affect epidermal hydration. Topically
applied agents are usually required to keep aging skin
moist.*
* Murad H, et al. The
effect of an oral supplement containing glucosamine,
amino acids, minerals, and antioxidants on cutaneous
aging: a preliminary study. J Dermatolog Treat 2001
Mar;12(1):47-51.
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Human studies have demonstrated pronounced protective
effects of antioxidants when applied topically before
ultraviolet radiation exposure. With respect to UVB-induced
skin damage, the photoprotective effects of antioxidants are
significant. Topical application of such combinations may
result in a sustained antioxidant capacity of the skin,
possibly due to antioxidant synergisms. Free radicals are a
culprit behind UVA-induced skin alterations, thus indicating a
basis for topical antioxidant administration. In a human
study, topical application of antioxidants resulted in
diminished severity of UVA-induced sun damage. Thus, regular
application of skin care products containing antioxidants may
be of the utmost benefit in efficiently preparing skin against
exogenous oxidative stressors occurring during daily life. Sun
screening agents may also benefit from combination with
antioxidants resulting in increased safety and efficacy of
such photoprotective products.4
Collagen is the chief constituent of connective tissue that
supports the structure of the skin. The skin requires constant
synthesis of new collagen to remain firm and youthful.
Epidemiological studies strongly indicate an association
between tobacco smoking and skin aging. One study showed that
collagen biosynthesis was reduced by 40.1% following treatment
with tobacco smoke extract. When an antioxidant mixture that
included vitamins C and E were applied, the destructive
alteration of collagen induced by both tobacco and UVA
radiation was prevented.5
A randomized, double-blind controlled study was conducted
on human volunteers to determine the efficacy of topical
vitamin C application in treating mild to moderate photodamage
of facial skin. Methods of evaluating efficacy included an
objective computer-assisted image analysis of the skin
surface, subjective clinical photographic analysis, along with
patient self-appraisal questionnaires. Topical vitamin C was
applied to one side of each patient's face and a control
vehicle on the other side for three months.
The results using the optical image analysis demonstrated
that compared to the placebo-vehicle, the vitamin C-treated
side of the face showed a statistically significant 71%
combined score improvement. Clinical assessment parameters
demonstrated significant improvement with vitamin C treatment
compared to the placebo vehicle for fine wrinkling, tactile
roughness, skin laxity/tone, sallowness/yellowing and overall
features. Patient questionnaire results demonstrated
statistically significant improvement overall with the vitamin
C treatment 84.2% greater than control. Photographic
assessment demonstrated significant improvement with vitamin C
treatment 57.9% greater than control. This three-month study
using topical vitamin C provided objective and subjective
improvement in photodamaged facial skin.6
Considerable interest has been generated about combining
antioxidants with sunscreens to provide enhanced protection
against UV rays. Two of the best-known antioxidants are
vitamins C and E, both of which have been shown to be
effective in different models of photodamage. In a study done
on swine skin, vitamin C provided additive protection against
acute UVB damage (sunburn cell formation) when combined with a
sunscreen. When a combination of vitamins E and C were used,
very good protection from a UVB insult occurred. Vitamin C,
however, was significantly better than vitamin E at protecting
against a UVA-mediated phototoxic insult in this animal
model.7
A study of vitamin C and E in young, aged and photodamaged
human skin was conducted to evaluate the various levels of
these antioxidants. Compared to young skin, the concentration
of vitamin E in the epidermis of photodamaged skin was 44%
lower, while aged skin had 39% less vitamin E. There was no
difference in the dermis. Vitamin C levels were 31% lower in
the epidermis of photodamaged skin and 39% lower in aged skin,
while in the dermis region, vitamin C levels were 37% lower in
photodamaged skin and 30% lower in aged skin. Glutathione
concentrations were also lower. These results showed that the
antioxidant defense system in normal aged and photoaged human
skin is significantly reduced compared to young skin.8
Chronic inflammation is an underlying cause of common
degenerative diseases. One study found that pro-oxidative
factors that accelerate skin aging might activate a
self-maintained micro-inflammatory process that interferes
with skin elasticity and thickness. This study stated that
topical antioxidants decrease this inflammatory cascade and
thus afford protection to the skin structures.9
The effect of exposure to even ambient UV-irradiation
increases the risk for long term detrimental effects
characterized by wrinkles, loss of skin tone and resilience.
Photoaged skin displays prominent alterations in the cellular
component and the extra cellular matrix of the connective
tissue. UV-exposure results in an accumulation of disorganized
elastin and a severe loss of collagens, the major structural
proteins of the dermal connective tissue. The unifying
pathogenic agents for these changes are UV-generated free
radicals. As well as causing permanent gene mutations, free
radicals activate signal transduction pathways that are
related to growth, differentiation, senescence and connective
tissue degradation.10
Critics used to claim there was no evidence that topically
based products affected skin aging. Over the past three years,
a remarkable number of published studies have proven these
skeptics wrong! The science clearly substantiates the role
that free radicals play in causing skin aging and the fact
that topically applied antioxidants confer significant
protection and can even partially reverse some aspects of skin
aging.
Promoting cell renewal
Vitamin A and its retinoid analogs stimulate skin cell
renewal by increasing the rate of mitotic cell division.11-13 One mechanism where vitamin A
induces this phenomenon is to act as a signaling agent to
stimulate the binding of epidermal growth factor to skin
cells.12
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MEDICAL
SCHOOL
SAYS "EVERYONE"
SHOULD APPLY
TOPICAL PHOTOPROTECTANTS
A report released from Tulane
University School of Medicine stated "every patient
should topically apply photoprotectants in order to
prevent photodamage to the skin."* This report indicates
the critical importance of applying a sunscreen with
antioxidants every time you go out into the
sun.
* Flynn TC, et al.
Topical revitalization of body skin. J Eur Acad Dermatol
Venereol 2000 Jul;14(4):280-4.
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A characteristic of sun-damaged skin is the degradation of
the supporting structure of skin caused by reduced collagen
synthesis. A study involving 72 individuals of varying age
groups was done to see if the topical application of natural
vitamin A could improve function in both natural aged,
sun-protected and photoaged skin. In one of the study groups
consisting of individuals (80+ years of age), topical
application of vitamin A for seven days increased fibroblast
growth and collagen synthesis, while reducing levels of a
collagen degrading skin enzyme (metalloproteinase). The
overall findings indicated that naturally aged, sun-protected
and photoaged skin share important molecular features
including connective tissue damage, elevated metalloproteinase
levels and reduced collagen production. Topical vitamin A
treatment reduced matrix metalloproteinase expression and
stimulated collagen synthesis in naturally aged and
sun-protected skin, as it does in photoaged skin.14 Synthetic vitamin A drugs (Retin-A)
have shown more profound acute effects in reversing both photo
damaged and naturally aged skin, but some people find these
drugs irritating to the skin.15
One of the most disfiguring skin diseases is the appearance
of cancer. A study was done to compare the effects of dietary
administration of a vitamin A drug (13-cis-retinoic acid) to
the natural form of vitamin A (retinyl palmitate). Female mice
were administered a chemical carcinogen to evaluate the
incidence and severity on mouse skin tumor promotion. The
results showed that retinyl palmitate inhibited the number and
weight of tumors, whereas 13-cis-retinoic acid resulted in a
decrease in weight, but not in the number of tumors
promoted.16
In another study, tumors were chemically induced in a group
of Swiss mice over a 23-week period. The topical application
of 13-cis-retinoic acid was compared to natural vitamin A
(retinyl palmitate). This study showed that both retinyl
palmitate and 13-cis-retinoic acid inhibited the development
of skin papillomas and also had a marked effect on skin
cancers.17 Vitamin A may be one of
the better-documented vitamins to protect against several
types of human cancers. One of its mechanisms is to induce
healthy differentiation and apoptosis of aged cells. The value
of vitamin A in protecting the skin is to help facilitate cell
renewal and possibly prevent skin cancers.
Studies show that the upper layer of the skin (epidermis)
can be easily loaded with natural vitamin A by topical
application. Besides being a precursor for retinoic acid,
vitamin A also has a free radical scavenging potential.
Vitamin A absorbs ultraviolet light to help protect the most
delicate areas of the skin against damaging free radical
attack.18 Natural vitamin A thus functions via several
pathways to guard against normal and sun-induced skin
aging.
Continued on Page
2 of 2
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