Clinics in Dermatology (2013) 31, 750–758

Anti-aging cosmetics: Facts and controversies

Marcia Ramos-e-Silva, MD, PhD ⁎, Livia Ribeiro Celem, MD, Stella Ramos-e-Silva, MD,
Ana Paula Fucci-da-Costa, MD
Sector of Dermatology and Post-Graduation Course, University Hospital and School of Medicine,
Federal University of Rio de Janeiro, Rio de Janeiro, 22280-020 Rio de Janeiro, Brazil

Abstract The authors review ageing in its extrinsic and intrinsic mechanisms, as well as the therapies
available for improving its effects, and present some of the facts and controversies related to anti-
aging cosmetics.
© 2013 Elsevier Inc. All rights reserved.

Introduction come no matter what, and this population obviously cannot

In modern society, there is a great increase in the search
for eternal youth and an insatiable appetite for methods
which could turn back the clock. This has triggered an
explosion in the cosmeceutical industry. The term
“cosmeceutical” was coined by Albert Kligman at the
national scientific meeting of the Society of Cosmetic
Chemists in 1984, referring to topically applied products
capable of making changes to the skin status that are not
considered drugs nor cosmetics that are applied to the
skin.1,2 The term remains controversial, especially among
European authors.2 In the United States and Europe,
cosmeceuticals are commercialized as cosmetics, although
in Japan “a novel category of quasi-drugs exists that
encompasses these biologically active formulations sold
directly to consumers.”3
In addition, technological advances in medicine for the
prevention and treatment of deadly diseases help to increase
life expectancy. The elderly population has increased
significantly in recent years, both in developing and
developed countries.4 As an example, the baby boomers,
the 40 million Americans born between 1946 and 1963, are
approaching that stage of life where youthful good looks are
becoming more of a memory than a reality. Skin aging will
⁎ Corresponding author. Tel.: + 55 21 22864632.
E-mail address: ramos.e.silva@dermato.med.br (M. Ramos-e-Silva).
remain young forever, but a youthful appearance and good
health are essential.4,5
These days, many cosmetic innovations come about
through scientific investigations. A wide range of skin-care
products and their uses have become so extensive and
complex that physicians and consumers alike are often
confused about their indications and effectiveness. In the
cosmetic field, many materials are commercially used and
claim to provide certain skin effects when used topically. In
general, although the effects may be small, they are
significant and can improve skin feeling and appearance
with their continued use. It is difficult to compare and
quantify the degree of the effects among the various
materials, because there are so many variables: measurement
of different specific end points; variation in equipment;
sensitivity of methods and formulation types, which can
affect material delivery into skin; and studies with different
body sites.
Facial remodeling with the skin aging process
Ageing produces a number of changes to the face, starting
from childhood, which transforms the rounded contours of a
child's angelic face into a more angular face with defined
features, which will characterize the individual from the
teenage years through adult life. These changes occur in the

0738-081X/$ – see front matter © 2013 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.clindermatol.2013.05.013
Anti-aging cosmetics
structures responsible for the formation of the facial
anatomy: skin, soft tissues, and bones.5,6
In childhood, the face, due to the great skin elasticity and
distribution pattern of fat, presents a round format. The nose
and ear cartilage provide subtle and delicate contours, while
the bones are still in development.
In adolescence, bones and cartilage reach the expected
growth and then define facial contours.
From the third decade onwards, eyebrows start dropping,
causing the eyes to appear smaller. With the progression of
aging, in the fourth decade, the eyelids become more flaccid,
leading to a pseudo-herniation of the retro-orbital fat and the
formation of rhytidosis. The nasolabial groove is more
prominent, and the eyebrows continue to drop.
In the fifth decade, deep wrinkles appear in the forehead,
and sagging eyelids result from the excess of skin. The jaws'
arch loses regularity, and vertical wrinkles form around the
perioral region.
In the sixth decade, wrinkles become more pronounced
and evident, even at rest. The dropping of the nasal tip and
mid-face structures is observed, which leads to the growth of
the nasogenian groove and loss of the jaw contour. The
presence of excess of chin fat and platysmas sagging also
contributes to the modification of the jaw.
In the seventh decade, the skin becomes thinner,
the eyelid opening gets further reduced, and facial fat
resorption occurs.
In the eighth decade, all prior changes are much
more evident. Thinning of skin and fat resorption
continue progressing.7
Intrinsic and extrinsic aging
The two types of skin aging have distinct sources: the
intrinsic and extrinsic; however, their results become
synergistic, leading to the aged look of the skin.8,9
Intrinsic aging
Intrinsic aging, also called true or chronological aging,
inevitably occurs as a natural consequence of physiological
changes over time. In this case, individual genetics are
responsible for the interference, among other factors that are
also present but with less effect.10 Currently, telomeres,
small DNA sequences present at the ends of chromosomes,
are considered as essential elements in the intrinsic aging
process. These structures, when intact, tend to extend the life
of cells. With aging, due to a continuous replication, a
shortening of these structures occurs, which can be repaired
by telomerase. The maintenance of telomeres by the action of
telomerase would lock the aging process, but this action can
lead to carcinogenesis.11 There are still no systemic or
topical treatments based on this theory, and more studies
are necessary.12
751
Factors related to intrinsic aging
Ethnicity. The main effect of ethnicity on aging relates to
the difference in pigmentation. High levels of melanin
pigmentation protect from the cumulative effects of
photoaging. Black skin is more compact and has a greater
amount of lipids, also considered a factor that influences the
increased resistance to aging. 13 Asian subjects were
observed to develop wrinkles later and to a lesser degree of
intensity as compared to Caucasians.14
Anatomic variations. Some areas of the skin are thinner
than others and, in those thinner skin regions, aging becomes
more evident. This is especially noted on the eyelids, the
thinnest area of skin in the human body. There is also
variability in both the composition and the distribution of
lipids in the skin.15
Hormonal changes. Estrogens influence the synthesis of
collagen by fibroblasts, lead to the increased synthesis of
hyaluronic acid, promote water retention, and increase the
extracellular matrix. Conditions of hypoestrogenism, such as
occur in the menopause, can have a deep effect on the skin,
because it becomes thinner and less hydrated. The
replacement of estrogens provides benefits in the skin
rejuvenation of women during menopause.16
Extrinsic aging. Extrinsic aging is due to controllable
factors and occurs at different degrees of intensity, due to
solar exposure, smoking, and gravity, as well as other general
lifestyle factors, such as diet, sleep, and overall health.10
Extrinsic aging related factors
Ambient conditions. High temperatures lead to increased
water evaporation, while low temperatures provide a
hardening and reduced water loss through the same
mechanism, even with abundant air moisture. The appropri-
ate formation of structural proteins and lipids in the skin
depends on the environmental temperature.17
Drugs. Hypocholesterolemic agents can induce xeroderma
and desquamation.18
Smoking. Smoking has been identified as an important
contribution to facial wrinkles, even more than solar
exposure. There is a parallel between the smoking load and
the emergence and intensity of wrinkles.19 Smoking induces
several harmful modifications: elastosis, telangiectasias, and
decrease of blood flow in the capillary vessels, leading to the
deprivation of nutrients in cutaneous tissues.20 Additionally,
there is a reduction of collagen fibers and elastin in the
dermis and in the lung, plus an increase of free radicals.
There is also an increase of keratinocytic dysplasia and
skin roughness. 21 Hormone replacement therapy does
not bring cutaneous benefits to patients who have been
long-time smokers.22
Sunlight exposure. Photo-exposure induces an avalanche
of molecular and cellular changes that trigger a fast and
dynamic disorder in the skin, unlike intrinsic changes, which
occur slowly, producing a generalized atrophy and few
structural changes until age 50. The effects of sunlight on the
skin are deep and represent up to 90% of the visible aging of
752 M. Ramos-e-Silva et al.

the face's skin, mainly in patients with light skin.17 The
changes induced by exposure to sunlight will be cited and
compared in the table below.
These two forms of aging are responsible for different
skin changes accountable for generating the senile face in a
synergistic manner (Table 1).23–34
Current treatments for aging skin
Rabe et al.35 proposed the creation of 3 groups of
strategies for planning the treatment and prevention of aging
skin (Table 2). They are listed below:
2. The second strategy uses formulations with active
substances to try to postpone or even reduce the signs
and symptoms of aging. Retinoic acid, alphahydroxy
acids, antioxidants, estrogens, and growth factors have
been deployed in this sense.
3. The third strategy is employed when a more serious
form of aging presentation is already manifested,
requiring more invasive mechanisms, such as chemical
peeling with a higher acid concentration, use of lasers,
injection of fillers and botulinum toxin, and so forth.
4. The next sections will focus on what we have now for
cosmetic treatment, including retinoids, alpha hydroxy
acids, antioxidants

1. The first approach aims at preventing photoaging through

the use of sunscreens with chemical or physical broad- Retinoids
spectrum filters. Gaining a more conscious behavior in
relation to photo-exposure must also be stimulated in In the epidermis, retinoids normalize the life cycle of
patients, in an attempt to prevent solar damage. keratinocytes, reduce keratinocytic atypia, and normalize the

Table 1 Comparing photoaging to intrinsic aging23

Characteristics Photoaging Intrinsic aging References
Overall
Metabolic processes Pronouncedly increased Slowed down Soter24
Clinical appearance Nodular, leathery, blotchy Smooth, unblemished Glogau25
Coarse wrinkles, furrows Loss of elasticity, fine wrinkles
Skin color Irregular pigmentation Pigment diminishes to pallor Rees26
Skin surface marking Markedly altered, often effaced Maintains youthful geometric patterns Gilchrest27
Onset As early as late teens Typically 50s-60s (women earlier than men) Kligman28
Severity Strongly associated to degree of pigmentation Only slightly associated to degree of Rees29
pigmentation
Epidermis
Thickness Acanthropic in early stages, Thins with aging Takema30
atrophy in later stages
Proliferation rate Higher than normal Lower than normal Lavker31
Keratinocytes Atopic and polarity loss, numerous dyskeratoses Modest cellular irregularity Kligman32
Dermo-epidermal Extensive reduplication of lamina dense Modest reduplication of lamina densa Gilchrest27
junction
Vitamin A content Destroyed by the sun exposure Plasma content of retinol increases Seité33
Dermis
Elastin Marked elastogenesis followed by massive Elastogenesis followed by elastolysis – Kligman32
degeneration, dense accumulation on fibers 'moth-eaten fibers'
Elastin matrix Massive increase in elastic fibers, replacing Gradual decline in production of dermal Hanson34
the collagenated dermal matrix matrix, only modest increase in the number
and thickness
of elastic fibers in the reticular dermis
Lysosyme deposition Increased Modest Gilchrest27
on elastic fibers
Collagen production Decrease in amounts of mature collagen Mature collagen more stable in degradation Lavker31
Grenz zone Prominent Absent Lavker31
Microvasculature Abnormal deposition of basement membrane- Normal Gilchrest27
like material
Microcirculation Vessels become dilated, deranged Microvessels decrease; remaining vessels Gilchrest27
do not change
Inflammatory response Pronounced inflammation, perivenular No inflammatory response observed Gilchrest27
histiocytic-lymphocytic infiltrate
Anti-aging cosmetics
Table 2 Photoaging therapies categorized by type of
treatment/prevention strategy and disease severity35
Primary Secondary Tertiary
Photoprotection Photoprotection Chemical peelings
Retinoic acid Microdermabrasion/
microcoblation
Antioxidants Laser
Estrogens Botulinum toxin
Growth factors/ Fillers
cytokines
spread of melanosomes. Dermal changes are represented by
an increase of collagen, elastin, and glycosaminoglycans.
Histopathologically, these changes are expressed by struc-
tural changes in solar elastosis and collagen degeneration,
Langerhans cell restoration, and correction of dysplastic
changes.28,36,37
Retinoic acid (tretinoin) is considered one of the most
powerful compounds to treat the signs of aging, including
fine lines and stains, but it should be used cautiously to
avoid producing undesirable effects, such as stinging
and burning. Newer delivery systems may diminish the
unwanted effects.38
Retinol (vitamin A), the biologically active form of
vitamin A, presents topically only a small retinoid-like action
when compared to the topical retinaldehyde and retinoic acid
in in vivo studies.39 It also has antioxidant action.
Retinaldehyde, an intermediate formed during the con-
version of retinol into retinoic acid, also shows benefits in
reducing wrinkles.40
Much of the published literature on the use of retinoids to
improve skin wrinkle appearance is focused on topical
retinoic acid, but there is also information on the cosmetic
vitamin A compounds, such as retinol and retinyl propio-
nate.14 In general, retinoids are very potent, so topical doses
of less than 1% are typically sufficient to obtain significant
effects. At low doses, in double-blind, split-face, placebo-
controlled facial testing lasting 12 weeks, retinol and retinyl
propionate were both significantly effective in reducing the
appearance of facial wrinkles and hyperpigmentation.
Clinical studies have also been published on other retinoids.
Retinaldehyde, typically at a dose of 0.05%,15–17 is clinically
effective. Retinylpalmitate has low irritation potential but
also weaker efficacy, even with a very high concentration of
2% required to observe an effect.18
The choice of retinoid may reduce skin irritation. Retinol
is better tolerated by skin than trans-retinoic acid, 5
retinaldehyde has an irritation potential similar to retinol,19
and retinol esters are better tolerated than retinol.14 Irritation
may also be mitigated to some extent by formulation to
control skin delivery or inclusion of other ingredients such as
anti-inflammatory agents. The second main concern is
instability, especially in the presence of oxygen and light.
To increase retinoid stability in the finished product,
formulation and packaging should ideally be done in an
753
environment with minimal exposure to oxygen and light. The
primary package of the final product should also be
impermeable to oxygen and opaque. Other strategies can
also be used, such as retinoid encapsulation and inclusion of
stabilizing antioxidants.41
The use of retinoid in relation to its safety for women of
child-bearing age is still controversial. During the past 20
years, no long-term side effects have been observed in young
adults using tretinoin, but there may be a problem for women
who want to become pregnant. Oral retinoid is a known
teratogenic drug, and this creates a dilemma for prescribing
topical tretinoin. There is a need for studies that could
establish beyond doubt whether it is absorbed and at what
percentage. Some studies have demonstrated that less than
2% of topical tretinoin is absorbed, and the quantity that can
be detected in blood after many applications is much less
than blood levels of vitamin A. Researchers reported a case
of ear malformation in a baby born to a woman using
tretinoin cream.42 In a study of 215 women exposed to
topical tretinoin early in pregnancy, topical tretinoin was not
associated with an increased risk for major congenital
defects.43 At present, it is best to advise young women not
to use topical retinoids during pregnancy or when they are
trying to become pregnant.44
Another question to be considered is the use of retinoids
in sun protection. Topical retinoids have been used in
sunscreens as antioxidants, but this use is controversial.
Retinoids do not offer any ultraviolet blocking or protection,
although they may offer some beneficial effect on free
radical scavenging. Retinylpalmitate is an ester of retinol and
is also believed to have antioxidant properties. It is included
in some sunscreens to reduce the risk of skin cancer. It is
also used as a vitamin supplement and sometimes added
to low-fat milk. It is neither an active sunscreen nor a
sunscreen preservative.45
Because topical retinoids may cause a reaction with
erythema, desquamation, pruritus, and a burning sensation
(“retinoid reaction”) in a high percentage of patients, some
people may think that retinoic acid improves photoaging,
because it irritates the skin. Some patients end up not
adhering to the treatment, although many patients show
improvement without any retinoid reaction. For this
reason, each treatment must be individualized, and the
dermatologist needs to explain very carefully what the
patient can obtain, as well as the possibility of side effects.
The dermatologist must be sure that there are no contrain-
dications, such as the existence of photosensitivity and
pregnancy. Tolerance will depend on skin type, race, age,
and the extent of photodamage.
Alpha hydroxy acids (AHA)
AHA were introduced by Eugene Van Scott in 1984.46
There are several types of AHA, with the most used being
glycolic, citric, lactic, malic, pyruvic, and tartaric acids. They
754
present an action mechanism that is not well-clarified, but
one hypothesis suggests that AHA would reduce the
concentration of calcium ions in the epidermis and, through
chelation, would remove the ions from the cells' adherence,
resulting in desquamation. The reduction of calcium ion
levels tends to promote growth and cell differentiation, thus
generating younger-looking skin. Its action, on the other
hand, is known to be beneficial to the photo-aged skin by
reducing the corneal layer, normalizing the cohesion of the
stratum corneum, and inducing epidermal and dermal
thickening by the accrual of dermal glycosaminoglycans,
besides improving lines and wrinkles and increasing
collagen density.36,47,48
AHAs in high concentrations are used as chemical peels
for exfoliating the stratum corneum, allowing its renewal and
thus leaving the skin smooth and with fewer stains.48,49 The
use in these higher concentration is controversial, because
skin erythema and flaking are listed as major side effects,
which become more pronounced as the concentrations of the
products increase. AHAs are also known to increase skin
photosensitivity, and it has been shown that glycolic acid and
ultraviolet-B (UVB) radiation inhibit proliferation and
induce apoptosis in human keratinocytes.50
Antioxidants
Antioxidants are responsible for reducing the damage
caused by free radicals, thus avoiding damage at the
cellular level. They also help to inhibit inflammation and
offer protection against photo-damage and skin cancer.
Antioxidants include alpha-lipoic acid (ALA), L-ascorbic
acid (vitamin C), niacinamide (B3 vitamin), α-tocopherol,
and ubiquinone.
Because the topical application of sunscreens does not
offer complete protection against UV damage, antioxidants
play a major role in the prevention and therapy of UV-
induced skin aging and are being added to the formulations
for sun protection.51
A new concept, such nutricosmetics are also known as
“beauty pills,” “beauty from within,” and even “oral
cosmetics.” This product category is formed by the
intersection of cosmeceuticals and nutraceuticals. The term
nutraceutical was defined by DeFelice as “any substance that
is a food or part of a food that provides medical or health
benefits, including the prevention and treatment of disease.
The major claim is the antiaging effect, reducing wrinkles by
fighting free radicals generated by solar radiation. Among
the ingredients used in nutricosmetics, antioxidants are the
most crucial.1 The concept of nutricosmetics is new and has
recently been a frequent subject of scientific research;
however, they deserve greater attention in relation to clinical
studies and regulation.
Alpha-lipoic acid (ALA)
Alpha-lipoic acid has anti-inflammatory properties and
acts as an exfoliant, possibly helping in reducing roughness,
M. Ramos-e-Silva et al.
wrinkles, and lentigines, but it is unable to protect against
induced erythema or UV damage.52
L-Ascorbic acid (vitamin C)
Vitamin C is routinely used in topical formulations, due
to its stimulating effect on the synthesis of collagen and
antioxidant property. It inhibits tyrosinase, reducing areas
with hyperpigmentation, and provides some protection
against UV radiation by its antioxidant properties.53 Some
authors report that there is no consistent clinical data
supporting the use of topical C vitamin for improving fine
lines and reducing pigmentation and inflammation. 54
Others who share the same view state that these
formulations are not effective on the skin due to a very
low concentration of L-ascorbic acid or because the product
is affected by exposure to air and light, compromising its
stability. Additional studies report that the L-ascorbic acid
molecule (in the form of an ester or a mixture of isomers)
could not be effectively absorbed or metabolized through
the skin.49.54
One concern about the addition of ascorbic acid to
cosmeceuticals is that it is innately unstable in formulation;
it is unclear how much, if any, intact molecule remains on
the skin. This problem has been partially overcome by
chemically modifying ascorbic acid through esterification
of the hydroxyl group, but for the skin to use the supplied
ascorbic acid, it must convert it to L-ascorbic acid. Many
of the stabilized commercially available forms have not
been examined to determine whether this conversion is
possible or if they penetrate cutaneous tissues to the same
extent as L-ascorbic acid. One study revealed that optimal
delivery of stable L-ascorbic acid into the skin occurred at
a pH of less than 3.5 and at a concentration less than 20%.
This same study showed that magnesium ascorbyl
phosphate, ascorbyl-6-palmitate, and dehydro ascorbic
acid (other ascorbic acid derivatives) on a daily application
did not increase levels of L-ascorbic acid in the skin,
calling into question their ability to improve the aged skin.
Not all formulations containing ascorbic acid should be
considered equal; it is essential to determine which specific
modified form is included and to examine whether that
particular form has been tested for clinical efficacy.
Presently, it seems prudent to recommend the use of L-
ascorbic acid for the treatment of photoaging, because
there are promising clinical results and no major side
effects, but there is not sufficient evidence in the form of
clinically controlled trials to support the use of the more
stable derivatives of ascorbic acid, which are most
commonly found in today’s cosmeceuticals.55
Vitamin E
Vitamin E has an antioxidant and moisturizing property.
Some studies have demonstrated that it has topical action in
the protection against UVB radiation damage.56. Other
actions are the acute reduction of erythema in sunburns,
tanning, and photoaging. Its association with vitamin C
Anti-aging cosmetics
demonstrates synergistic effects, in particular, because it is
capable of regenerating oxidized vitamin E.57
Unlike oral vitamin E, the application of topical vitamin E
has been recognized as a safe substance with adverse
reactions generally limited to a slight irritation.58; however,
there are no data to support any effect of vitamin E in topical
therapies purporting improvements in skin wrinkling,
discoloration, or texture, although there is a plethora of
products available on the market that contain various forms
of vitamin E. Scientific data also has not shown which, if
any, commercial form of the vitamin might have the best
penetration and bioavailability. What this means clinically
with respect to photoaging remains a question requiring
further investigation.55
Ubiquinone or idebenone (CoQ10)
Derived from co-enzyme Q10, idebenone is a powerful
antioxidant able to stimulate collagen production, to inhibit
the oxidative stress generated by UVA and UVB,59 and to
protect the dermal matrix, both in intrinsic and extrinsic
aging.60 So far, only one study showed wrinkle improve-
ment, using 1% CoQ10 cream for 5 months.51
Niacinamide (vitamin B3)
Niacinamide is a powerful and well-tolerated antioxidant.
It promotes improvement in the lipid compound of the
epidermal barrier, reducing transepidermal water loss. It also
acts as a melanosome transfer inhibitor, improving hyper-
pigmentation. Studies have shown a significant reduction of
fine lines, wrinkles, and hyperpigmentation, as well as
improvement in skin elasticity.61,62
Several reports have documented the range of cosmetic
effects of topical niacinamide. These data emerged from
several double-blind, placebo-controlled, left-right random-
ized, split-face studies. Topical niacinamide has significantly
improved skin color, for example, including the reduction of
hyperpigmented spots and red blotchiness. The latter effect,
in particular, may be related to the skin barrier improvement,
reducing skin sensitivity and responsiveness to environmen-
tal insult, such as from surfactant exposure. Fairly high doses
(2% to 5%) of vitamin B3 have been used to achieve these
desired effects. Because the skin has a very high tolerance to
niacinamide even with long-term usage, high doses can be
used acceptably. Some clinical data on myristoyl-nicotinate
have also been presented34 to suggest that a similar broad
array of effects occurs with this agent when used topically at
doses of 1% to 5%.
The most important challenge of working with niacin-
amide and nicotinate esters is avoiding hydrolysis to
nicotinic acid. Nicotinic acid, even at low doses, can induce
an intense skin reddening (flushing response).63 Formulating
in the pH range of 4 to 7 is preferred to avoid hydrolysis. For
this reason, formulations containing both niacinamide and
acids, such as salicylic acid, or bases, such as zinc oxide, are
problematic. Many commercial options are available for the
nicotinate esters.
755
Moisturizers
Moisturizing agents are responsible for keeping water
in the epidermis; besides promoting a protective film
against water loss, they help maintain the barrier. They
should be used in support of the use of home formulations for
skin rejuvenation.49
Peptides
Peptides are part of a group of agents that seem to act as
cellular messengers. They are formed from amino acids that
mimic fragments of endogenous peptides with biological
activity.64
There are three categories of peptides: carrier peptides
(matrixyl), neuro-transmitters (argyreline), and enzyme
modulators (rice and soy proteins).3 Opinions are still
conflicting, and some people state that there is no significant
evidence that they work better than moisturizers, although
investigators claim that it could be a group of substances with
future potential.65
Peptides are already found in a large number of cosmetic
products,3 but because there are plausible severe conse-
quences of introducing materials into cells and modulating
transcription factors and because there is very little
information in the literature concerning adverse events
after the use of topical peptides, peptides should be used
with extreme caution.66
Hormone replacement therapy
Hypoestrogenism affects the skin, producing less hydra-
tion and thinning the skin; therefore, its replacement, when
well prescribed, including hormones in topical formulations,
is effective in rehydration, collagen increase, and dermal
thickness.16
Long-term prospective, randomized, double-blind, place-
bo-controlled studies on hormone replacement therapy in
women have shown that skin aging signs were reversed
and skin elasticity, hydration, and thickness were signifi-
cantly increased.67
Enhancing collagen production with topical estradiol
seems to be restricted to intrinsically aged skin51; however,
long-term studies to evaluate the safety of systemic HRT
for skin anti-aging purposes are necessary because
contraindication to HRT includes a history of breast cancer
or endometrial cancer, recent undiagnosed genital bleeding,
active severe liver disease, and a history of thromboem-
bolism. On the other hand, topical therapy with estradiol
preparations was reported to have significant anti-aging
effects and may therefore provide an alternative to
systemic therapy.68
756
Sun blockers
Sun blockers are essential for skin health and rejuvena-
tion, given that they provide protection against the most
important factor for skin aging: exposure to sunlight.
They must be of broad spectrum, that is, they must protect
from both UVA and UVB. The photo-protection is physical
when the sun blockers contain reflective agents such as zinc
oxide or titanium dioxide. These substances are inert and
present a lower possibility of causing allergic reactions.
Chemical blockers absorb and react to sunlight to make it
nondamaging. Some blockers are an association of both.
Their use on the face and other photo-exposed areas must
become a daily habit.69
Controversies as to the daily use of sun blockers
remain. Concerns have been raised about the safety of
micronized titanium dioxide, topical oxybenzone, and the
sunscreen additive retinylpalmitate. The FDA and con-
sumer groups are conducting studies about the localized
effects, such as carcinogenesis, and potential side effects of
systemic absorption.70 Many discussions are arising daily
regarding use of sunscreens versus vitamin D and calcium
metabolism. In theory, correct usage of sunscreens should
significantly reduce vitamin D levels, but this is not the
case in practice.
Several studies have demonstrated that sunscreens are
rarely applied correctly, in the right dosages, and with
appropriate frequency. In real-world conditions, it is likely
that the improper use of sunscreen and/or increased exposure
time results in production of vitamin D among sunscreen
users.71 The FDA standard for application of sunscreen is 2
mg/2 cm. Actually, 25% to 50% of that amount is applied.
This results in a protection factor of 8 to 15 when using a
sunscreen labeled 30 FPS.72
Dimetilaminoetanol
Dimetilaminoetanol (DMAE) is an analog of choline and
a precursor of acetylcholine. It can be used orally or
topically, its natural source being from salmon. Some
studies have shown its capacity in promoting thickening of
dermal and collagen fibers;73,74 however, its use remains
controversial.
Conclusions
With the increasing longevity of the population world-
wide, good health is essential for a better quality of life, even
in advanced age, with more independence and sometimes
with intense professional and social activity. Good health
includes the improvement of the appearance of aged skin,
with the possibility of using safer and more effective
products and procedures to diminish unaesthetic aspects.
The dermatologist needs to know the mechanisms of the
M. Ramos-e-Silva et al.
cosmetics therapies available and the controversies related to
their efficacy.
Before trusting the promises of each cosmetic product,
one should analyze the hormonal and genetic factors, as well
as anatomical variants, considering that they, alone, generate
limits to the success of the cosmetic product to each type of
skin. The dermatologist must remember that many of these
products are still controversial.
Factors related to intrinsic aging have their value, when
we think about choosing the best cosmetic for each type of
skin. The selected site for treatment greatly influences the
result, because there some areas of skin are thinner and others
thicker. Patients with more melanin due to ethnicity will
present with different results from the same product.
Similarly, we should consider sun exposure and smoking,
among other extrinsic factors, because they can modify the
skin and reduce the effectiveness of treatments that give
good results in people who systematically avoid exposure to
the environment.
To avoid all existing controversies related to the
efficacy of specific cosmetic treatments, it is advised that
we know exactly what we, as physicians, and our patients
are looking for with a specific treatment and with what
type of skin we are dealing, so we can choose the ideal
product or products.
References
1. Anunciato TP, da Rocha Filho PA. Carotenoids and polyphenols in
nutricosmetics, nutraceuticals, and cosmeceuticals. J Cosmet Dermatol.
2012;11:51-4.
2. Kligman AM. What are cosmeceuticals? In: Draelos ZD, editor.
Procedures in Cosmetic Dermatology: Cosmeceuticals. Philadelphia,
PA: Elsevier; 2005. p. 1-2.
3. Draelos ZD. The art and science of new advances in cosmeceuticals.
Clin Plastic Surg.. 2011;38:397-407.
4. Ramos-e-Silva M, Carneiro SCS. Cosmetics for the elderly. Clin
Dermatol. 2001;19:413-23.
5. Nascimento LV. Tipos de envelhecimento. In: Kede MPV, Sabatovich
O, editors. Dermatologia Estética. 2nd ed. São Paulo: Atheneu; 2009;.
p. 53-6.
6. Larrabee WF, Makielski KH, Henderson JL, editors. Surgical Anatomy
of the Face. 2nd ed. Philadelphia: Lippincott Willians & Wilkins; 2004;.
p. 195.
7. Friedman O. Changes associated with the aging face. Facial Plast Surg
Clin North Am. 2005;13:371-80.
8. Lapière CM. The ageing dermis: the main cause for appearance of “old”
skin. Br J Dermatol. 1990;122:5-11.
9. Ramos-e-Silva M, Carneiro S. Elderly skin and its rejuvenation:
products and procedures for the aging skin. J Cosmet Dermatol.
2007;6:40-50.
10. Bergfeld WF. The aging skin. Int J Fertil Womens Med. 1997;42:57-66.
11. Kosmadaki MG, Gilchrest BA. The role of telomeres in skinaging/-
photoaging. Micron. 2004;35:155-9.
12. Pendino F, Tarkanyi I, Dudognon C, et al. Telomeres and telomerase:
pharmacological targets for new anticancer strategies? Curr Cancer
Drug Targets. 2006;6:147-80.
13. Robinson MK. Population differences in skin structure and physiology
and the susceptibility to irritant and allergic contact dermatitis:
Anti-aging cosmetics
implications for skin safety testing and risk assessment. Contact
Dermatitis. 1999;41:65-79.
14. Südel KM, Venzke K, Mielke H, et al. Novel aspects of intrinsic
and extrinsic aging of human skin: beneficial effects of soy extract.
Photochem Photobiol. 2005;81:581-7.
15. Elias PM. Stratum corneum architecture, metabolic activity and
interactivity with subjacent cell layers. Exp Dermatol. 1996;5:191-201.
16. Brincat MP. Oestrogens and the skin. J Cosmet Dermatol. 2004;3:41-9.
17. McCallion R, Li Wan Po A. Dry and photo-aged skin: manifestations
and management. J Clin Pharm Ther.. 1993;18:15-32.
18. Jackson SM, Williams ML, Feingold KR, Elias PM. Pathobiology of
the stratum corneum. West J Med. 1993;158:279-85.
19. Kennedy C, Bastiaens MT, Bajdik CD, et al. Effect of smoking and sun
on the aging skin. J Invest Dermatol. 2003;120:548-54.
20. Leow YH, Maibach HI. Cigarette smoking, cutaneous vasculature, and
tissue oxygen. Clin Dermatol. 1998;16:579-84.
21. Bernhard D, Moser C, Backovic A, Wick G. Cigarette smoke – an
aging accelerator? Exp Gerontol. 2007;42:160-5.
22. Castelo-Branco C, Figueras F, Martinez de Osaba MJ, Varnell JA.
Facial wrinkling in postmenopausal women. Effects of smoking status
and hormone replacement therapy. Maturitas. 1998;29:75-86.
23. Farage MA, Miller KW, Elsner P, Maibach HI. Intrinsic and extrinsic
factors in skin ageing: a review. Int J Cosmet Sci. 2008;30:87-95.
24. Soter NA. Acute effects of ultraviolet radiation on the skin. Semin
Dermatol. 1990;9:11-5.
25. Glogau RG. Chemical peeling and aging skin. J Geriatr Dermatol.
1994;2:30-5.
26. Rees JL. Molecular phototypes. In: Ballotti JP, Ortonne R, editors.
Mechanisms of Suntanning. London: Martin Dunitz; 2002;. p. 333-9.
27. Gilchrest BA. A review of skin ageing and its medical therapy. Br J
Dermatol. 1996;135:867-75.
28. Kligman AM. The treatment of photoaged human skin by topical
tretinoin. Drugs. 1989;38:1-8.
29. Rees JL. The genetics of sun sensitivity in humans. Am J Hum Genet.
2004;75:739-51.
30. Takema Y, Yorimoto Y, Kawai M, Imokawa G. Age-related changes in
the elastic properties and thickness of human facial skin. Br J Dermatol.
1994;131:641-8.
31. Lavker RM. Cutaneous aging: chronologic versus photaging. In:
Gilchrest BA, editor. Photodamage. Cambridge: Blackwell Science;
1995. p. 123-35.
32. Kligman AM, Lavker RM. Cutaneous aging: the differences between
intrinsic aging and photoaging. J Cutan Aging Cosmet Dermatol.
1988;1:5-12.
33. Seité S, Bredoux C, Compan D, et al. Histological evaluation of a
topically applied retinol-vitamin C combination. Skin Pharmacol
Physiol. 2005;18:81-7.
34. Hanson KM, Simon D. Epidermal trans-urocanic acid and the UV-A-
induced photoaging of the skin. Proc Natl Acad Sci USA. 1998;95:
10576-8.
35. Rabe JH, Mamelak AJ, McElgunn PJ, Morison WL, Sauder DM.
Photoaging mechanisms and repair. J Am Acad Dermatol. 2006;55:1-19.
36. Ramos-e-Silva M, Hexsel D, Rutowitsch MS, Zechmeister M. Hydroxy
acids and retinoids in cosmetics. Clin Dermatol. 2001;19:460-6.
37. Kligman AM. Topical retinoic acid (tretinoin) for photoaging:
conceptions and misperceptions. Cosmet Dermatol. 2003;16:S3-6.
38. Mukherjee S, Date A, Patravale V, et al. Retinoids in the treatment of
skin aging: an overview of clinical efficacy and safety. Clin Interv
Aging. 2006;1:327-48.
39. Kafi R, Kwak HS, Schumacher WE, et al. Improvement of naturally
aged skin with vitamin A (retinol). Arch Dermatol. 2007;143:606-12.
40. Creidi P, Vienne MP, Onchonisky S, et al. Profilometric evaluation of
photodamage after topical retinaldehyde and retinoic acid treatment.
J Am Acad Dermatol. 1998;39:960-5.
41. Bissett DL. Common cosmeceuticals. Clin Dermatol. 2009;27:435-45.
42. Camera G, Pregliasco P. Ear malformation in baby born to mother using
tretinoin cream [letter]. Lancet. 1992;339:687.
757
43. Jick SS, Terris BZ, Jick H. First trimester topical tretinoin and
congenital disorders. Lancet. 1993;341:1181-2.
44. Torras H. Retinoids in aging. Clin Dermatol. 1996;14:207-21.
45. Chapman MS. Vitamin A: history, current uses, and controversies.
Semin Cutan Med Surg. 2012;31:11-6.
46. Van Scott EJ, Yu RJ. Hyperkeratinization, corneocyte cohesion, and
alpha hydroxyl acids. J Am Acad Dermatol. 1984;11:867-79.
47. Smith WP. Epidermal and dermal effects of topical lactic acid. J Am
Acad Dermatol. 1996;35:388-91.
48. Ramos-e-Silva M, de Castro MCR, Carneiro S. Alpha-hydroxyacids:
unapproved uses or indications. Skin Med.. 2004;3:141-8.
49. Rivers JK. The role of cosmeceuticals in antiaging therapy. Skin
Therapy Lett. 2008;13:5-9.
50. Lai WW, Hsiao YP, Chung JG, Wei YH, Cheng YW, Yang JH.
Synergistic phototoxic effects of glycolic acid in a human keratinocyte
cell line (HaCaT). J Dermatol Sci. 2011;64:191-8.
51. Kohl E, Steinbauer J, Landthaler M, Szeimies RM. Skin ageing. J Eur
Acad Dermatol Venereol. 2011;25:873-84.
52. Beitner H. Randomized, placebo-controlled, double blind study on the
clinical efficacy of a cream containing 5% alpha-lipoic acid related to
photoageing of facial skin. Br J Dermatol. 2003;149:841-9.
53. Farris PK. Topical vitamin C: a useful agent for treating photoaging and
other dermatologic conditions. Dermatol Surg. 2005;31:814-7.
54. Gaspar LR, Maia Campos PMBG. Photostability and efficacy studies of
topical formulations containing UV-filters combination and vitamins A,
C, and E. Int J Pharm. 2007;343:181-9.
55. Zussman J, Ahdout J, Kim J. Vitamins and photoaging: do scientific
data support their use? J Am Acad Dermatol. 2010;63:507-25.
56. Maalouf S, El-Sabban M, Darwiche N, Gali-Muhtasib H. Protective
effect of vitamin E on ultraviolet B light-induced damage in
keratinocytes. Mol Carcinog. 2002;34:121-30.
57. Burke KE. Interaction of vitamins C and E as better cosmeceuticals.
Dermatol Ther. 2007;20:314-21.
58. Thiele JJ, Hsieh SN, Ekanayake-Mudiyanselage S. Vitamin E: critical
review of its current use in cosmetic and clinical dermatology. Der-
matol Surg. 2005;31:805-13.
59. Choi CM, Berson DS. Cosmeceuticals. Semin Cutan Med Surg.
2006;25:163-8.
60. Burke KE. Nutritional antioxidants. In: Draelos ZD, editor. Cosme-
ceuticals. Philadelphia, PA: Elsevier; 2005. p. 125-32.
61. Bissett DL, Miyamoto K, Sun P, Li J, Berge CA. Topical niacinamide
reduces yellowing, wrinkling, red blotchiness, and hyperpigmented
spots in aging facial skin. Int J Cosmet Sci. 2004;26:231-8.
62. Bissett DL, Oblong JE, Berge CA. Niacinamide: a B vitamin that improves
aging facial skin appearance. Dermatol Surg. 2005;31:860-5.
63. Tsuji T, Yorifuji T, Hayasaki Y, Hamada T. Light and scanning electron
microscopic studies on wrinkles in aged person´s skin. Br J Dermatol.
1986;114:329-35.
64. Buraczewska I, Berne B, Lindberg M, Törmä H, Lodén M. Changes in
skin barrier function following long-term treatment with moisturizers, a
randomized controlled trial. Br J Dermatol. 2007;156:492-8.
65. Bowler JP. Impact on facial rejuvenation with dermatological
preparations. Clin Interv Aging. 2009;4:81-9.
66. Thomas JR, Dixon TK, Bhattacharyya TK. Effects of topicals on
the aging skin process. Facial Plast Surg Clin North Am. 2013;21:
55-60.
67. Sator PG, Sator MO, Schmidt JB, et al. A prospective, randomized,
double-blind, placebo-controlled study on the influence of a
hormone replacement therapy on skin aging in postmenopausal
women. Climacteric. 2007;10:320-34.
68. Patriarca MT, Goldman KZ, Dos Santos JM, et al. Effects of topical
estradiol on the facial skin collagen of postmenopausal women under
oral hormone therapy: a pilot study. Eur J Obstet Gynecol Reprod Biol.
2007;130(2):202-5.
69. Rivers JK. Sunscreens: Skin. Ther Lett Pharm Ed. 2007;2:6-7.
70. Bergstrom KG. Sunscreen update: the controversies, what's safe,
what's next. J Drugs Dermatol. 2010;9:1451-4.
758
71. Burnett ME, Wang SQ. Current sunscreen controversies: a critical
review. Photodermatol Photoimmunol Photomed. 2011;27:58-67.
72. Glaser DA, Waldorf HA. Sunscreens. In: Draelos ZD, editor.
Procedures in Cosmetic Dermatology: Cosmeceuticals. Philadelphia:
Elsevier; 2005. p. 139-47.
M. Ramos-e-Silva et al.
73. Nolan KA, Marmur ES. Over-the-counter topical skincare products: a
review of the literature. J Drugs Dermatol. 2012;11:220-4.
74. Draelos ZD. The application of cosmeceuticals to dermatologic
practice. In: Draelos ZD, editor. Procedures in Cosmetic Dermatology:
Cosmeceuticals. Philadelphia: Elsevier; 2005. p. 159-87.