SCIENCE OF MEDICINE
Cosmeceuticals: The New Medicine of Beauty
by Katherine I. Martin, MS4 & Dee Anna Glaser, MD
“Cosmeceuticals”
blur the line between
drug and cosmetic,
doctor and aesthetician,
and patient and consumer.
Katherine Martin, MS4, and Dee Anna
Glaser, MD, MSMA member since 1997, is
the Vice Chair and Professor of Cosmetic
and Laser Surgery in the Department of
Dermatology at the Saint Louis University
School of Medicine.
Contact: kmarti49@slu.edu
This Cosmetic Surgery Mini-Theme Series is
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60 | January/February 2011 | 108:1 Missouri Medicine
Abstract
Cosmeceuticals represent
a new category of products
placed between cosmetics
and pharmaceuticals that are
intended for the enhancement
of both the health and beauty of
skin. Encompassing an ever-
increasing part of the skin care
industry, cosmeceuticals are
formulated from a multitude of
ingredients, the main categories
of which are discussed in this
article. Given the growing
interest in these products
among patients and the strong
claims made by manufacturers,
it is important that physicians
recognize these agents and
understand their benefits,
limitations, and potential
adverse effects.
Introduction
The American population is
becoming older and more affluent
than ever. With many people willing
to trade wealth for youth, there has
been a surge in demand for high-
end anti-aging products, and the
skin care industry has responded in
force. Moving beyond traditional
cosmetics—which only temporarily
adorn and beautify the skin—
cosmetics companies have tapped
into the biomedical revolution,
adding biologically active ingredients
to their products that enhance the
function of healthy skin. Because
these products are not intended to
improve or to cure diseased skin,
they have avoided pharmaceutical
regulation and scrutiny. Thus,
“cosmeceuticals” blur the line
between drug and cosmetic, doctor
and aesthetician, and patient and
consumer.
Patients can flounder in the flood
of new products, finding it difficult
to select the right product and
becoming frustrated when a product
fails to produce its beneficent effect.
Patients remain enthusiastic about
these products, however, and seek
their physician’s help in choosing the
best products available. Physicians
educated in these cosmeceuticals can
serve their patients by (1) managing
expectations to realistic, evidence-
based effects and (2) warning against
and monitoring for potential side
effects.
There remains much controversy
surrounding the “active ingredients”
found within cosmeceutical products,
particularly in regards to their
mechanism of action, formulation,
optimal concentration, penetration
and retention in skin. Some clinical
trials and tests have been done to
address these questions, but on the
whole there is little validation to
support cosmeceutical claims. In
vitro testing for some products has
shown that these ingredients do have
a protective and repairing effect on
aging skin; however, there has been
little translation of this evidence into

in vivo testing to determine the possibility of delivering
adequate doses to skin that will produce clinical or
histologic results.1
Vitamins
Many cosmeceutical agents are developed and
advertised for prevention and treatment of aging skin,
particularly photoaging skin. Photoaging refers to
the damage that is done to the skin from prolonged
exposure, over a person’s lifetime, to solar UV radiation.
While the most important protective measure against
photoaged skin is the daily application of UVA and
UVB sunscreen, potential treatment options for already
damaged skin involve the use of topical antioxidants and
compounds that help repair DNA and stimulate collagen
synthesis. Topical vitamins are substances that are
purported to provide some of these benefits.
The efficacy of topical synthetic Vitamin A or
retinoids—in various forms such as tretinoin, adapalene,
and tazarotene—is evidence-based, and the cosmetic
benefits of these prescription retinoids are well supported
by ample research.2,3 Tretinoin induces production of
type I and II procollagen in skin and reduces collagen
breakdown by inhibiting metalloproteinases. The overall
effect is a thickening of the dermis as the skin is “filled
in” with glycosaminoglycans, helping to reduce fine lines
and wrinkles.
Other retinoids, such as retinaldehyde, retinol, and
the retinyl esters, are marketed as over-the-counter
cosmeceuticals and may have similar actions to their
prescription counterparts despite having less evidence
proving their efficacy.1 Patients should be cautioned that
all of the retinoids are able to produce skin irritation and
dryness, even in over-the-counter formulations, although
the latter much less than prescription-strength products.
Vitamin E is another vitamin that is purported to
have advantageous cosmetic effects on skin. Functioning
as an epidermal antioxidant by absorbing the solar
spectrum of UV light, endogenous Vitamin E becomes
depleted after years of excessive exposure to free radicals,
with resulting oxidative damage. Thus, many studies
have looked at the benefit of applying topical Vitamin E,
especially in its most active form alpha-tocopherol, as a
means of protecting against sunburn and improving the
wrinkling and hyperpigmentation caused by free radicals.
Studies in human subjects have demonstrated its efficacy
in preventing UV-induced skin erythema, with topical 2%
Vitamin E reducing the redness value by approximately
SCIENCE OF MEDICINE
20%.4 A four-month facial study of topical 5% vitamin
E resulted in improved wrinkling and UV-caused
inflammation around the eye area.5 Importantly, Vitamin
E can reduce UV-associated erythema and edema when
applied before UV exposure, with little benefit noted if
Vitamin E is applied after the exposure.6 Also, almost no
side effects have been reported from the use of topically
applied vitamin E.
One of the most recently recognized “cosmeceutical
vitamins” is Vitamin B3, also called nicotinamide or
niacinamide. A precursor to the key metabolic cofactor
NAD(P) and its powerful reduced form NAD(P)
H, niacinamide’s role as a key player in antioxidizing
reactions has been the focus of most of the studies.
Well-tolerated in topical form, niacinamide has been
shown to improve skin barrier by increasing lipids
and epidermal protein.7 This action leaves skin more
resistant to irritation and blotchiness, most likely by
decreasing water loss from skin. Niacinamide also
reduces facial dyspigmentation via a mechanism that
inhibits melanosome transfer from melanocytes to
keratinocytes.8 Other beneficial effects with chronic
topical niacinamide application include improvement
and prevention of skin yellowing and a smoothing of
skin texture. However, even with these benefits, topical
niacinamide remains one-third to one-fifth as effective as
topical 0.025% tretinoin.9
Vitamin C, also known as L-ascorbic acid, is one
of the vitamins that humans must obtain from dietary
sources. However, oral supplementation of Vitamin C
only minimally increases its concentration in skin. Thus,
topical Vitamin C application is a popular research area.
In addition to its well-known and essential contribution
to collagen biosynthesis, research data demonstrates
that topical Vitamin C has anti-inflammatory and
antioxidant properties,10 such that it has been used to
reduce the erythema associated with postoperative laser
resurfacing. A double-blind, placebo-controlled, split-
face 12-week study examining the effects of topical 3%
ascorbic acid showed that Vitamin C is well-tolerated
in topical application and causes a reduction in facial
wrinkles.11 Higher doses of 5-17% ascorbic acid
revealed improved skin texture and the appearance of
photoaging. With ongoing research confirming and
maximizing the benefits of topical Vitamin C and the
other cosmeceutical vitamins, these agents will continue
to grow in their usefulness and value in protection and
restoration of skin.
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SCIENCE OF MEDICINE
Hydroxy Acids
The hydroxyacids—comprised of the α-hydroxyacids,
β-hydroxyacids, polyhydroxyacids, and bionic acids—
represent a class of compounds with unprecedented
cosmetic benefits. The most well-known and commonly
used is the α-hydroxyacid glycolic acid for its proven
antiaging benefit and ability to improve hyperpigmentation
and acne-prone skin. Both the α-hydroxyacids and
β-hydroxyacids work by removing or decreasing
hyperkeratinized skin and restoring the epidermis, making
them useful for treatment of dry skin, verrucous growths,
and ichthyosis.12 Furthermore, application of hydroxyacids
causes dermal thickening by stimulating biosynthesis of
glycosaminoglycans, collagen, and elastic fibers, improving
wrinkles and fine lines.13 The polyhydroxyacids and
bionic acids are newer agents with the same benefits as the
α- and β-hydroxyacids but without their characteristic
irritation or burning and with additional antioxidant
and barrier functions to improve moisturization. Their
gentleness on skin makes them ideal for treating sensitive
skin. Gluconolactone is a polyhydroxyacid widely used
in skin care products that has been shown in vitro to
protect against UV radiation by trapping free radicals.14
The hydroxyacids, especially glycolic and lactic acid, are
commonly used as peeling agents. Applied to the skin in
high concentrations for short periods of time, hydroxyacid
peels are increasingly used to accelerate exfoliation and to
stimulate skin renewal to improve hyperpigmentation and
texture of skin.
Peptides
The role of peptides in cosmeceuticals revolves around
the hypothesis that peptide fragments of collagen and
elastin can act as positive feedback signals for their own
continued synthesis. Peptides are highly successful in the
current cosmeceutical market, and there are increasing
numbers of double-blinded, placebo-controlled studies to
examine their effects on human skin. Peptides of interest
include pal-KTTKS (Matrixyl), Ac-EEMQRR (Argireline),
and Cu-GHK. The peptide pal-KTTKS is a fragment of
dermal collagen that stimulates new collagen synthesis in
vitro and is postulated to facilitate wound healing.15 It has
high potency and was shown to improve wrinkled skin when
applied topically at very low doses and with minimal skin
irritation. Cu-GHK is also a fragment of dermal collagen,
and the copper moiety is a necessary cofactor for collagen
synthesis. Many peptides, such as Ac-EEMQRR, mimic
botulinum toxin and function to cause muscle relaxation
by inhibiting neurotransmitter release;16 however, a
62 | January/February 2011 | 108:1 Missouri Medicine
2006 study comparing topical nonprescription products,
including those containing peptides, to botulinum toxin
type A injections concluded that the injections provided
significantly greater efficacy and patient satisfaction in the
treatment of glabellar frown lines.17 The cost of all of these
peptides remains a challenge to cosmeceutical companies,
especially if the peptide has low potency and requires
greater concentrations to achieve efficacy.
Growth factors
Growth factors function as regulatory proteins that
mediate signaling pathways, particularly those associated
with wound healing. Kinetin, also known as N-6
furfuryladenine, is a plant growth factor studied in human
skin fibroblast cultures. In vitro studies have demonstrated
that the continuous application of kinetin may have the
ability to delay the skin changes associated with aging as well
as decrease the severity of these changes. Kinetin prevents
the alteration in cell size and shape and delays growth
rates and macromolecular synthesis associated with aging.
Kinetin acts as both an inhibitor of free radical formation
and a scavenger of reactive oxygen species by mimicking
superoxide dismutase. Other clinical studies have suggested
that topical kinetin may improve skin texture, decrease
hyperpigmentation, and impede transepidermal water
loss, but the mechanisms for these actions have much less
evidence to support them.18
Botanicals
Cosmeceutical agents derived from plant sources make
up an increasing niche in the cosmetic market. A huge
variety of botanical products exists, and many claims are
made regarding their dermatologic benefits; however, few
studies have been conducted to substantiate these claims
and examine the safety and efficacy of these ingredients.
Among these botanical substances, Ginkgo biloba,
silymarin, ginseng, soy, and green tea have exhibited capacity
to promote skin health and appearance. Ginkgo biloba is
a common botanical added to moisturizers for its anti-
inflammatory and antioxidant properties.
Although no controlled trials exist regarding the
cutaneous benefits of Ginkgo biloba, studies carried out in
vitro have shown that topical G. biloba extracts stimulate
fibroblast proliferation and collagen synthesis.19 Silibinin,
or silymarin, is a phytochemical from the milk thistle
plant Silybum marianum that exhibits strong antioxidant
activity and has been shown in various studies to neutralize
toxic effects of different chemicals and UVB radiation in
skin.20 Ginseng is another botanical that has demonstrated

significant dermatologic potential when applied topically,
with the apparent action of reversing the manifestations of
decreased hyaluronan levels that occurs with aging; other in
vitro studies show that ginseng extracts have the ability to
inhibit melanogenesis in melanoma cells, suggesting a possible
role as a depigmentation or whitening agent for skin.21
Soy and its isoflavones have been purported to have a
variety of dermatologic benefits, many of which are ascribed
to its antioxidant effects and the estrogen-type action of
its metabolites. Its phytoestrogen effect is thought to be
mediated by binding to estrogen receptors in the cell’s
nucleus, potentially slowing the skin thinning and collagen
loss that occurs post-menopause. Soybean protease inhibitors
and soy milk have been found to have depigmenting activity as
well as the ability to reverse UV-induced hyperpigmentation.22
Lastly, green tea polyphenols are being aggressively marketed
for their antioxidant and anti-inflammatory properties, which
include limiting UV-induced lipid peroxidation in vitro.23
There is also evidence that green tea polyphenols inhibit the
activity of collagenase and increase biosynthesis of collagen in
human fibroblasts.
Thus, all of the above botanical cosmeceuticals have been
shown to influence mechanisms on skin that repair or prevent
aging effects. For many of these products, however, there has
yet to be a split-face, double-blind, randomized trial involving
different concentrations of these ingredients and reporting
side effects on which to base recommendations for use of
these products.
Conclusion
Cosmeceuticals offer both challenges and rewards to
patients and their physicians. As society holds a youthful
and healthy appearance to be of utmost importance, many
people feel anxious about their aging skin and seek physician
advice on what to do.
Helping patients understand the degree of
improvement that can realistically be achieved as well as
potential side effects remains the primary responsibility of
the physician with regard to these products. Many of the
new cosmeceuticals in development sound very exciting, but
the physician’s concern is to help patients choose the best
products available today.
Some experts recommend that physicians pick one or
two products with which they have experienced good results
and advise their patients on how to incorporate them into
their daily skin regimen--always reminding patients that
even a safe product can evoke redness, cause irritation, or
clog pores if used inappropriately.
As technology advances and cosmeceuticals continue
SCIENCE OF MEDICINE
to become more sophisticated and more widely used,
the medical profession must continue to take an active
role in familiarizing themselves with these products and
in educating patients about the benefits and risks of
cosmeceuticals.
References
1. Manela-Azulay M, Bagatin E. Cosmeceutical Vitamins. Clinics in Dermatology
(2009) 27, 469-74.
2. Kang S, Voorhess JJ. Photoaging therapy with topical tretinoin: an evidence-based
analysis. J Am Acad Dermatol 1998;39:S55-S61.
3. Stratigos AJ, Katsambas AD. The role of topical retinoids in the treatment of
photoaging. Drugs 2005;65:1061-72.
4. Dreher F, Gabard B, Scwindt DA, et al. Topical melatonin in combination with
vitamins E and C protects skin from ultraviolet-induced erythema: a human study in
vivo. Br J Dermatol 1998;139:332-9.
5. Moeller VH, Ansmann A, Wallat S. Topical application of vitamin E and its effects
on the skin. Fett Wissenschaft Technol. 1989;91:295-305.
6. Thiele JJ, Ekanayake-Mudiyanselage S, Hsieh SN. Cosmeceutical vitamins:
vitamin E. In: Draelos ZD, editor. Cosmeceuticals. 1st ed. Philadelphia: Elsevier
Saunders;2005. p. 47-54.
7. Bisset DL, Oblong JE, Saud A, Berge CA, Trejo AV, Biedermann KA. Topical
niacinamide provides skin aging appearance benefits while enhancing barrier
function. Journal of Clin Derm 2003; 31: S9-S18.
8. Hakozaki T, Minwalla L, Zhuang J, et al. The effect of niacinamide on reducing
cutaneous pigmentation and suppression of melanosome transfer. British Journal of
Dermatology. 2002; 147:22-33.
9. Bisset DL, Oblong JE, Berge CA. Niacinamide: a B vitamin that improves aging
facial skin appearance. Dermatol Surg 2005;31:860-66.
10. Pinnell SR, Yang HS, Omar M, et al. Topical L-ascorbic acid: percutaneous
absorption studies. Dermatol Surg 2001;27:137-42.
11. Raschke T, Koop U, Dusing HJ, et al. Topical activity of ascorbic acid: from in
vitro optimization to in vivo efficacy. Skin Pharmacol Physiol 2004; 17: 200-206.
12. Green BA, Yu RJ, Van Scott EJ. Clinical and cosmeceutical uses of hydroxyacids.
Clinics in Dermatology 2009; 27: 495-501.
13. Yu RJ, Van Scott EJ. -hydroxyacids, polyhydroxyacids, aldobionic acids and
their topical actions. In: Baran R, Maibach HI, editors. Textbook of Cosmetic
Dermatology. 3rd ed. New York: Taylor & Francis;2005. 77-93.
14. Berstein EF, Brown DB, Schwartz MD, et al. The polyhydroxy acid
gluconolactone protects against ultraviolet radiation in an in vitro model of cutaneous
photoaging. Dermatol Surg 2004;30:1-8.
15. Robinson L, Fitzgerald N, Berge C, et al. Pentapeptide offers improvement in
human photoaged facial skin. Ann Dermatol Venereol 2002;129:1S105.
16. Mas-Chamberlin C, Lintner K, Basset L, et al. Relevance of antiwrinkle
treatment of a peptide: 4 months clinical double blind study vs. excipient. Ann
Dermatol Venereol 2002;129:1S456.
17. Beer K. Comparative evaluation of the safety and efficacy of botulinum toxin type
A and topical creams for treating moderate-to-severe glabellar rhytids. Dermatol
Surg 2006;32:184-192.
18. Levin J, Del Rosso JQ, Momin S. How much do we really know about our
favorite cosmeceutical ingredients? Journal of Clinical and Aesthetic Dermatology.
2010;3: 22-41.
19. Kim SJ, Lim MH, Chun IK, Won YH. Effects of flavonoids of Ginkgo biloba on
proliferation of human skin fibroblast. Skin Pharmacol. 1997;10:200-205.
20. Singh RP, Agarwal R. Cosmeceuticals and silibinin. Clinics in Dermatology.
2009;27:479-484.
21. Baumann L. Botanical Ingredients in Cosmeceuticals. Journal of Drugs in
Dermatology. 2007; 11:1084-1088.
22. Paine C, Sharlow E, Liebel F, Eisinger M, Shapiro S, Seiberg M. An alternative
approach to depigmentation by soybean extracts via inhibition of the PAR-2 pathway.
J Invest Dermatol. 2001;116:587-595.
23. Nakagawa T, Yokozawa T, Terasawa K, Shu S, Juneja LR. Protective activity of
green tea against free radical and glucose mediated protein damage. J Argic Food
Chem. 2002;50:2418-2422.
Disclosure
None reported. MM
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