DERMATOLOGIC ASPECTS OF COSMETICS
OO
A Dermatologist Looks to the Future:
Promises and Problems
The cosmetic industry is a huge worldwide
business, destined to grow rapidly owing to
its universal appeal for improving the quality
of life. In the United States, more money is
spent on skin and hair care products than on
education. There are more Avon ladies in
Brazil than enlisted personnel in the army.
Demographic changes are partly responsible
for this enormous outlay of money to look
and feel better. The postwar generation of
buby boomers is aging, with wrinkles and
blotches clear signs of mortal decay and the
inevitable despoilation of appearance. The
boomer generation has money, is obsessed
with youth, is health conscious, and knows
that it will live a lot longer than their grand-
parents. They are the antiaging generation
and are determined to look young and sexy
until death.
An incredible array of products are avail-
able to combat the ravages of time and to
prevent premature aging. The fashion maga-
zines and the mass media are awash in adver-
tisements that promise eternal youth and hap-
piness. The cosmetic industry is extremely
competitive and is dominated by less than a
half-dozen juggernauts that use every legal
means to capture and hold market share.
From the Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
DERMATOLOGIC CLINICS
VOLUME 18 NUMBER 4 OCTOBER 2000
0733-8635100 $15.00 + .
COSMETICS
Albert M. Kligman, MD, PhD
Consumers do not understand that cosmetics,
in contrast to drugs, are not regulated by
agencies such as the U.S. Food and Drug Ad-
ministration (FDA). No premarketing proof
of efficacy or safety is required. This is afYee-
for-all situation in which claims can be made,
often by unscrupulous start-ups, that lie
clearly in the domain of fantasy and humbug-
gery. These powerful new winds of commerce
are blowing up a set of new problems that
need to be addressed honestly.
COSMECEUTICALS
The author coined the term cosmeceuticals
20 years ago before an annual meeting of the
Society of Cosmetic Chemists.’ To the au-
thor’s astonishment, a storm of protest broke
out immediately. The author was denounced
as a traitor to the industry because he seemed
to be inviting the FDA to regulate cosmetics
in the same way as drugs, a long, expensive
process that would hurt innovation and slow
down the flow of exciting new products into
the marketplace.
The author’s intent was simply to point out
that the definition of a cosmetic in the 1938
Act of Congress was scientifically untenable
699
700 KLIGMAN
and archaic. That statute held that cosmetics
were simply for adornment and beautification
and by law must not affect the structure and
function of skin. This wording established
that cosmetics could be used for camouflage
and improved appearance but had to be com-
pletely inert and pharmacologically inactive.
If it could be shown that a cosmetic had some
biologic effect, strict reading of the statute
would require its reclassification as a drug.
There were only two polar categories: cosmet-
ics and drugs. Drugs were intended to prevent
and treat disease. No cosmetic could mention
the possibility that it did something beneficial
to health, even if nothing more than preserv-
ing healthy skin.
In the 60 years since the act was passed,
clinicians learned that nearly every substance
can affect the structure and function of skin
measurably, under certain circumstances. For
example, the innocuousness of water seems
beyond question. All living cellular processes
occur in a milieu of water. Water can be quite
harmful to skin under certain circumstances,
however. Occupational dermatologists have
long known that chronic exposure to water in
wet-work situations predisposes to chemical
injury and contributes to the production and
persistence of a variety of chronic dermatoses.
Familiar examples include bartenders, can-
nery workers, hairdressers, and multiparous
housewives.
With the advent of sophisticated, modern
technologies, it has been shown that an occlu-
sive exposure of normal skin to water for 48
hours results in a series of striking changes,
including increased blood flow; cytotoxic
changes to keratinocytes, Langerhans' cells,
and melanocytes (shown by transmission
electron microscopy); an inflammatory der-
mal infiltrate; a loosening of the cohesion of
corneocytes; and opening up of empty do-
mains (lacunae) in the intercellular spaces be-
tween corneocytes, which promotes perme-
ability to potentially toxic substances.2 It is
postulated that these dramatic but largely
subclinical changes result from the rapid
swelling of the horny layer with the release
of preformed mediators of inflammation that
are stored in the horny layer.
Powerful new tools in the era of nanotech-
nology have made it possible to detect biolog-
ically significant changes that previously
were hidden. This is the domain of invisible
dermatology, in which most of the important
early changes in the pathogenesis of diverse
disorders are occult and become known only
when powerful new instruments are em-
ployed. An arsonal of noninvasive bioengin-
eering instruments exists that make it possi-
ble to monitor the changes that occur when
seemingly benign exogenous substances, such
as cosmetics and toiletries, are applied to nor-
mal skin.
The author argued that it was scientifically
silly to pretend that cosmetics did not do
anything and that cosmetics might be doing
lots of good things that could improve the
quality of skin. The cosmetic industry could
now make legitimate claims of functional ac-
tivity, and a new era could begin, consonant
with scientific reality. Although controversy
and confusion still persist, the term cosmeceu-
ticals has permanently entered the vocabulary
and is used throughout the world.'j
Cosmeceuticals are topical agents that are
distributed across a broad spectrum of mate-
rials lying somewhere between pure cosmet-
ics (lipstick and rouge) and pure drugs (anti-
biotics, corticosteroids). They partake of both
categories. Some cosmetics are closer to the
drug pole, and some drugs are closer to the
cosmetic pole. The term cosmeceutical has no
legal status. Its prominence is due to its oper-
ational usefulness. Most products made by
manufacturers of cosmetics are cosmeceuti-
cals. They do something beyond improving
appearance through concealment and camou-
flage.
The term cosmeceutical has stimulated mar-
keting professionals to offer a number of se-
man& -variations, denoting functional activ-
ity, for example, as follows:
1. Performance cosmetics
2. Dermatocosmetics
3. Bioactives
4. Functional cosmetics
5. Neoceuticals
These terms apparently have such resonance
that analogous terms have been created for
foods and supplements that are deemed to
promote health and well-being, for example,
neutraceuticals. A flood of new materials can be

incorporated into cosmetics under the rubric of
cosmeceuticals.
The cosmetic industry is not subject to fed-
eral regulations under FDA rules. There is no
requirement to show premarketing safety or
efficacy. An infinitude of materials deriving
from the sea, plants, animals, minerals, and
thousands of synthetic chemicals can be in-
corporated into cosmetics. In this free-for-all
environment, the claims for these ingredients
cover the range from the credible to the fan-
tastic, from sense to nonsense, from fact to
fraud. Provided that no drug claims are made
and no one is seriously injured, the field is
open for full exploitation by marketers not
constrained by ethical standard^.^
Competition for market share has created a
near-maniacal marketplace where in the
name of science preposterous promises are
made to credulous consumers. This open-
door policy has led to situations in which
some regulatory action within the industry or
by federal authorities is indicated; otherwise,
one may envision a backlash of disbelief that
undermines the credibility and integrity of
the cosmetic industry. Some prominent exam-
ples follow.
HERBS
Herbal texts list thousands of plant-derived
materials that date back thousands of years
and can be found in all cultures. For every
known malady, there are herbal remedies, es-
pecially from China, whch are now being
rediscovered, often under the now respect-
able name of alternative or cornplementay rnedi-
cine. The great resurgence of interest in herbal
remedies and the incorporation of herbs in
cosmetics stem from popular beliefs that have
great appeal to modern consumers.
The first belief goes under the salutary
name of natural. Many supposedly educated
consumers, especially the younger constitu-
ency, are suspicious of the myriads of syn-
thetic substances made by the chemical in-
dustry, which they see as polluting the
environment and poisoning humans. This
doctrine of chemophobia is a mobilizing man-
tra for many environmentalists with many
links to the green movement. These consum-
COSMETICS 701
ers scrupulously avoid agents that are not
natural and have been produced in a labora-
tory. They intuitively equate natural with
safety and wholesomeness. The assumption
that natural equates to safety is ridiculous and
irrational.
In regard to skin, nothing is more destruc-
tive to appearance than natural sunlight, the
cause of premature aging with its repertoire
of despoilations, such as wrinkles, blotches,
sallowness, and laxity. Sunlight causes more
cases of skin cancer than all other cancers
combined.
Other natural toxins are the heavy metals,
such as mercury and arsenic, all quite natural,
which for centuries poisoned millions of suf-
ferers of various skin diseases, especially vic-
tims of syphilis. Some of the most lethal tox-
ins are natural, such as botulinus toxin, which
has come to international prominence as a
menace in chemical warfare. Many propo-
nents of natural products believe that the vi-
tamin C in citrus fruits is somehow different
than synthetic vitamin C. This irrational de-
votion to the natural knows no bounds and,
surprisingly, has more adherence among col-
lege graduates than high-school dropouts.
This concern for the benefits of the natural
applies equally to foods; devotees believe that
the foods grown by organic farming are
healthier and safer than those grown with
chemical fertilizers.
There are innumerable serious problems
with the expanding incorporation of herbs in
cosmetics, not the least of which is the com-
plete lack of quality control, identification and
quantification of the active ingredients, mode
of preparation, and presence of potentially
harmful ingredients. Another problem has
come to light that has serious safety overtones
for an unsuspecting public. Not only is the
composition of unregulated herbs unknown,
but also an unscrupulous merchant can add
components secretly that can increase efficacy
but that are actually drugs, in violation of the
statutory laws. There are now proven in-
stances of adulteration in which medium-po-
tency anti-inflammatory corticosteroids have
been included in herbal concoctions. The label
does not list the corticosteroid ingredient, and
the consumer is never told about steroid atro-
phy and addiction after long-term use.
702 KLIGMAN
Large amounts of Oriental herbs, whose
composition is largely unknown, are taken
orally in the belief that safety has been proved
by their having been used for thousands of
years. Not all herbs can be discredited per-
emptorily, but the toxic effects of many are
coming gradually to light. The most serious
adverse effects of some well-known herbs in-
clude end-stage renal disease and death.
There is no limit to the amount of herbal
cocktails that consumers can buy.
TOPICAL VITAMINS
Many Americans take an extraordinary
number of vitamins on a daily basis, often in
amounts hundreds of times greater than the
daily recommended requirements. This irra-
tional vitamania is mostly harmless for water-
soluble vitamins but can produce serious, life-
threatening side effects in the case of the
readily absorbed fat-soluble ones, such as vi-
tamins A, D, and E. A new marketing ploy on
the part of some manufacturers of cosmetics
exploits the high popularity of vitamins by
including these in a large array of cosmeceuti-
cals, under the aegis of bioactives. In this case,
the benefits that are touted are targeted to
skin, especially improving appearance by
combating the aging process. Vitamins are
favorite ingredients of antiaging skin care
products. These formulations may contain
every known vitamin, in association with a
multitude of minerals, micronutrients, antiox-
idants, Chinese herbs, and other unpro-
nounceable, nonexistent chemicals. These
megacocktails of antiaging cosmeceuticals are
largely harmless but are an insult to the con-
sumer and do no credit to the credibility and
integrity of the cosmetic industry.
Vitamin A
Vitamins are named alphabetically in the
order of their discovery. Vitamin A was syn-
thesized more than 50 years ago. The parent
compound is retinol, which the body metabo-
lizes to retinoic acid. The latter is now known
everywhere as a pharmacologic agent that
can partially reverse the cutaneous stigmata
of excessive exposure to the sun (photoaging).
Retinoic acid is a drug that can be obtained
only by prescription. Substances that have
activity similar to vitamin A are generically
known as retinoids. Retinol, the vitamin itself,
has grandfather status and is exempt from
FDA regulations. Retinol has been incorpo-
rated into many skin care products, hoping
to benefit from the positive pharmacologic
image of retinoids. Most can be dismissed as
useless. The doses are usually homeopathic.
Retinol is exceedingly unstable. For most of
these products, data supporting efficacy in
reducing the signs of photodamage are non-
existent. Most are worthless. Retinyl acetate,
another metabolic derivative of retinol, is in-
corporated into innumerable products under
the banner of retinoids. The author’s studies
show that it totally lacks retinoid activity, al-
though it is inexpensive and harmless. Reti-
no1 is a prodrug that can be converted to
retinoic acid by skin. In stable formulations
and in appropriate concentrations, it can pro-
duce retinoid effects. Few formulations meet
this standard.
Many well-formulated skin care products,
regardless of their ingredients, can improve
the appearance of photodamaged skin. In the
skin care business, there are no placebos be-
cause the basic formulations generally are
good moisturizers and enjoy the long-stand-
ing benefits of emollients in moderating com-
mon skin conditions. The rogue marketer
rarely can be discovered. The consumer expe-
riences some benefit willy-nilly, especially if
the formulation has agreeable sensory proper-
ties, such as slip, nontackiness, rub in, and
fragrance.
Vitamin C
At least a half-dozen companies offer prod-
ucts in which the chief active ingredient is
vitamin C. (Note vitamin C also benefits by
being natural). A great deal is known about
vitamin C. Its absence in the diet causes
scurvy. It plays a crucial role in the synthesis
of collagen, the fibrous material that makes
up about 95% of the dermal matrix and
whose loss with photoaging mainly accounts
for laxity and sagging of skin. That being

the case, one can make out a great story for
incorporating vitamin C in products for mu-
ture skin, a euphemism for photodegraded
facial skin. Vitamin C tissue levels decrease
with age, and local application could result
in concentrations in the skin far greater than
can be attained by oral consumption of inor-
dinately high doses.
Theoretically the administration of vitamin
C topically is reasonable and scientifically ex-
plicable for correcting sagging, wrinkled,
photoaged skin. The problem lies in the proof
of performance. The warriors in the vitamin
C battles furnish consumers with seductive
technical information, singling out specific at-
tributes of their particular products. For ex-
ample, product A may be vitamin C in a lipo-
philic form, which logically promotes its
penetration through the stratum corneum
barrier, attaining high tissue levels. The sup-
plier of product B uses an ester derivative of
vitamin C that is said to be converted to the
biologically active form after application to
the skin. There are other formulations in
which pH and special vehicles have been ma-
nipulated to create products that are reputed
to have the highest capacity to synthesize and
replace lost collagen. Also, a barrage of irrele-
vant in vitro studies show that fibroblasts
fed vitamin C produce greater amounts of
procollagen. Vitamin C is grandfathered, and
manufacturers are not required to provide
proof of efficacy.
The consumer has no way of expressing an
informed opinion regarding the superiority
of one product over another or whether any
vitamin C product owes its presumed anti-
aging effect to the presence of vitamin c. The
literature does not, in the author’s opinion,
contain a single study that provides unassail-
able proof of efficacy. Clinical judgments
alone are worthless. A good moisturizing
cream, such as nonmedicated Nivea Cream,
now 100 years old, also improves wrinkles,
blotchiness, and firmness. The requirements
for indisputable proof are formidable, as for
drugs, and include double-blind, vehicle-con-
trolled, randomized studies, preferably with
outside surveillance. No vitamin C product
has met these criteria.
COSMETICS 703
Antioxidants
The theoretic importance of antioxidants in
preventing tissue damage has been appreci-
ated for more than 50 years. Antioxidants
have been the subject matter of thousands of
reports that cover such broad areas as cancer,
wound repair, inflammation, and ameliora-
tion of the aging process. Antioxidants have
the property of scavenging highly reactive
oxygen species, the so-called free radicals,
which are known to be capable of degrading
lipid constituents of cell membranes, proteins,
and DNA. Vitamin E is perhaps the best
known of the free radical scavengers, along-
side vitamin C and, to a lesser extent, vitamin
A. Vitamin E taken orally is highly popular
as a dietary supplement. Numerous articles
have been published in peer-reviewed jour-
nals, including the most prestigious ones, that
purport to provide evidence that vitamin E is
beneficial in such varied disorders as heart
disease, Alzheimer’s disease, macular degen-
eration of the retina, and senescent changes
in body organs. No consensus exists regard-
ing the value of vitamin E, including high
doses of vitamin E in the diet, to combat any
of the conditions in which a scientific case
could be made for its well-known free radical
scavenging activity. The case for vitamin E
supplementation is subjudice. High doses,
which many prefer, can be harmful.
The same situation prevails in the case of
vitamin E-containing antiaging skin care
products, of which there are now hundreds
in the marketplace. As with vitamin C, the
story is a good one theoretically, but proof
lies in performance and not in casuistic pseu-
doscientific rationalizations. Several books
tout antioxidants for a wide variety of skin
conditions. It is known that vitamin C and
vitamin E stored in the horny layer are de-
graded by UV light and can be depleted in
photodamaged skin. It seems reasonable to
replace these deficiencies in a convenient
manner by incorporating them into moistur-
izers that individuals use every day as a mat-
ter of good grooming. Also, endogenous anti-
oxidants such as superoxide dismutase have
a solid sound that educated consumers like to
look for in the labels. Superoxide dismutase
704 KLIGMAN
is a protein that has no chance of achieving
biologically active concentrations in skin.
Nonetheless, it is present in innumerable for-
mulations anyway. The supporting evidence
for the efficacy of another antioxidant, lipoic
acid, derives from in vitro studies, which do
not translate into clinical practice. Reports of
the value of antioxidants in skin care formula-
tions cannot stand up to critical scrutiny as
having met the rigorous standards of proof of
efficacy. Topical antioxidants appear not to be
harmful, however.
THERAPEUTIC COSMETOLOGY
(DERMATOCOSMETOLOGY)
In keeping with the trend to produce bio-
logically active products that improve the
structure and function of skin, it is timely to
envision a new mission and role for the cos-
metic industry. Cosmetic firms intuitively shy
away from promoting products that treat skin
diseases, which is seen as the domain of the
medical profession. The reality is that the in-
dustry already produces therapeutic prod-
ucts, whether or not these are called over-the-
counter drugs or are regarded as cosmeceuti-
cals. The exact category depends not so much
on the active ingredients, which may be iden-
tical, but rather what the label says regarding
the intended use. Acne vulgaris epitimizes
the problems and possibilities.
Most adolescents experience some degree
of acne and usually go to the drugstore rather
than consult a physician for treatment. Acne,
although a genuine pathologic process, is
dominantly a cosmetic problem, which de-
spoils appearance and affects psychosocial
behavior negatively. For the affected individ-
ual, there is no such thing as mild acne. Two
pustules and three comedones may ruin the
life of an emotionally vulnerable individual.
Drugstore therapy is just as effective for
moderating mild-to-moderate acne as a visit
to the dermatologist. Salicylic acid is an excel-
lent comedolytic agent that prevents comedo-
nes, the primary event in the pathogenesis of
acne. It is available in many agreeable forms
to suit every kind of personal preference (i.e.,
creams, gels, solutions, and lotions). Salicylic
acid mild washes can be combined effectively
with topicals. Also, there is an array of ben-
zoyl peroxide products, which have an un-
matched capacity to eliminate the follicular
population of Propionibacterium acnes, the or-
ganism responsible for converting comedones
into inflammatory lesions (papulopustules),
which may leave scars. Benzoyl peroxide is
far more effective than the topical antibiotics
that dermatologists prescribe to suppress P.
acnes. I? acnes does not become resistant to
benzoyl peroxide, which is a major problem
with antibiotics.
The combined use of benzoyl peroxide and
salicylic acid attacks acne at two of its most
vulnerable points, the formation of comedo-
nes and the suppression of I? acnes. Over-the-
counter products provide self-treatment of
the vulgar forms of moderate acne, treat-
ments that are at least as effective as most
physicians can provide with expensive pre-
scriptions.
The introduction of film-forming polymers
to extract microcomedones qualifies as a
breakthrough in cosmetic technology. For-
merly, dermatologists used cyanoacrylate
polymer (Krazy Glue) to seep into the follicles
and harden into a film, which then could be
lifted off to pull out I? acnes-laden horny
plugs. With products such as Biore, the pro-
cess has been simplified greatly because all
one has to do is wet the skin and apply a
polymer-impregnated patch for about 15 mi-
nutes. Other polymers are in development.
This novel technology is an invitation for
the industry to consider the exciting possibil-
ity of moving into a new but related territory
where it already has the resource to expand
its traditional services, a field that might be
called diagnostic cosmetology. For example, pre-
pubertal children, as young as age 8 for girls,
who show subclinical microcomedones are
destined to develop clinical acne and visible
comedones (whiteheads and blackheads) 4 to
5 years later. High-risk children, whose
mother, father or both had scarring acne, can
be tested periodically with polymer-impreg-
nated patches starting at age 7, keeping an
archival record of the results. If crops of mi-
crocomedones start to appear on the nose at
age 8, 9, or 10, comedolytic treatment can be
inaugurated. Prevention of disease is always

more desirable than treatment. The latter can
be viewed as a failure of prevention.
Another diagnostic technique can be used
to predict which children are likely to develop
clinical acne. Sebutapes (CuDerm, Dallas, TX)
are prepackaged adhesive-coated disks that
yield black-and-white pore prints of sebum
droplets. Sebum output is low in children but
increases when the glands begin to respond
to androgens at prepuberty in girls, even be-
fore menstruation. The presence of numerous
droplets, especially with copious outlet, pres-
ages the early development of clinical acne. It
is not too far-fetched to envision the time
when a company will create an educational
program to head off acne, producing diagnos-
tic kits of Sebutapes and polymer patches,
along with treatment cosmetics based on sali-
cylic acid and benzoyl peroxide therapies.
Rosacea is another serious cosmetic disorder
that is not only an embarrassment when the
face turns bright red, but also threatens the
quality of life because of its emotional impact.
The red face syndrome mainly afflicts women
and is growing in prevalence among adults.
An ambitious, enterprising, innovative cos-
metic company could take up an active
position that could be extremely helpful to
rosacea sufferers. Two openings can be envi-
sioned. The first is therapeutic based on the
fact that the current topical treatments pre-
scribed by physicians are far from satisfac-
tory. Ancient formulations containing 5% to
10% elemental sulfur are probably more con-
sistently effective than pharmacologic agents
approved by the FDA. Colloidal sulfur, rather
than the elementary sulfur in current prod-
ucts, is more effective because of its small
particle size. The problem is that sulfur stinks,
is irritating, and is cosmetically unattractive.
Over-the-counter sulfur is an unpatentable
substance.
It is precisely the cosmetic industry that
has the technical know-how to solve each one
of the above-mentioned negative features of
sulfur. An encapsulating system, such as lipo-
somes, microsponges, or nanospheres, could
be used to entrap sulfur and to release it
slowly to avoid a bolus effect, while making
it less malodorous. Sulfur is an ancient ingre-
dient that may prove to have therapeutic
properties if it could be made palatable to the
COSMETICS 705
consumer, a fact well within the capabilities
of the modern cosmetic industry. Is it more
than folklore that accounts for the widespread
use of sulfur over centuries for the treatment
of acne and rosacea?
Rosacea offers another great possibility to
the new field of diagnostic cosmetology. The
diagnostic hallmark of rosacea is long-lasting
blushing, triggered by a variety of factors.
Girls who are flusher-blushers in adolescence
are at high risk of developing rosacea when
they reach their 30s and 40s. A drop of a
vasodilating substance, such as sorbic acid (a
familiar preservative), applied to the cheek
provokes a spreading erythema that may last
15 to 20 minutes in a prerosacea flusher. Sor-
bic acid could be incorporated into a small
adhesive disc similar to Sebutape, making it
easy to apply the patch for a prescribed time
and follow the pattern and intensity of the
erythema. Treatment could be started in ado-
lescence, long before the clinical stigmata of
rosacea become apparent.
With patients playing a greater role as part-
ners in treatment programs, these devices
could have a great future in identifying in-
dividuals who are at high risk for develop-
ing common skin diseases, not excluding
atopic dermatitis, another growing problem
throughout the world. There is no reason why
the cosmetic industry should not play an in-
fluential role in this new field of preventive
dermatology.
MISCELLANEOUS INGREDIENTS
The ingenuities of some cosmetic manufac-
turers are great, and so is the number of ex-
otic ingredients that are appearing in topical
antiaging products. Most of these are mar-
keted without proof of efficacy or safety. The
inventory of such substances is endless. The
sea contains thousands of mostly unexplored
materials that are now appearing in cosmet-
ics. There are hundreds of thousands of
plants, most of them unclassified, providing
an endless source of new ingredients. This is
traditionally an attractive area because plants
have been the source of drugs that have bene-
fited humans immensely (e.g., digitalis and
morphine). Botanicals have come to the fore,
706 KLIGMAN
providing a source of new bioactives that
might match the benefits that have been
achieved by pharmacologists. As always, the
proof is in the performance.
There are an endless number of ingredients
derived from animal sources: hormones, such
as melatonin, dehydroepiandrosterone, and
estrogens, enzymes, such as telomerase,
which has created a sensation by promising
an extension of human longevity; fats (from
exotic animals such as the emu); placenta;
growth factors; cytokines; chicken embryos;
and transforming growth factor, a wonder
drug that supposedly allows wounds to heal
without scarring, as in fetal skin, which is
rich in transforming growth factor-p. Because
all of these ingredients are natural and exempt
from regulation by the FDA, how long will it
be before these will enrich antiaging topicals?
Finally, there are luxury high-end cosmetics
that cater to people who believe that value
is proportional to price. These examples are
ludicrous and include such ingredients as
caviar and gold dust, at prices exceeding $200
per ounce. There is no known relationship
between price and function in any category
of cosmetics. There is no justification for the
American credo that more is better.
One example is cited of a newly successful
product that illustrates the limit in absurdity
has not yet been reached. This boutique-type
formulation contains the following active in-
gredients: (1) 8 antioxidants, (2) 11 vitamins,
(3) 12 minerals, (4) 6 hydroxy acids, (5) 21
Chinese herbs, (6) 6 sunscreens, (7) 3 en-
zymes, (8) 2 phytoestrogens, (9) 6 marine
principals, and (10) 4 plant anti-idammator-
ies. If this cosmetic was classified as a drug,
it would take more than $3 billion and two
lifetimes to prove according to FDA rules that
each ingredient contributed to the overall per-
formance.
PSEUDO-ISSUES
Marketing and merchandising in the ebul-
lient, fast-track competitive cosmetic industry
plays such an enormous role in capturing the
market share that some insidious and egre-
gious practices have practically become an
obsession. These are disguised under the eu-
phemism of creative marketing, in which lead-
ing celebrities receive salaries orders of mag-
nitude greater than the sober scientist who
creates and validates new products. These
practices speak unfavorably on the industry
and lead many to question whether standards
of ethical conduct can be violated indefinitely,
without a damaging backlash of publicity.
The obvious instances of phony, unmeritori-
ous issues include the following.
Negative Advertising
Negative advertising plays into the hands
of misinformed chemophobic consumers who
are certain that some ingredients in skin care
products are harmful and should be elimi-
nated. Industry often caters to this irrational
end, and the ploy of the marketers is to em-
phasize blatantly what is not in the product;
for example, lanolin-free, fragrance-free, preser-
vative-free. Allergen-free is designed for sensi-
tive skin. Such warnings come with no evi-
dence that such products are safer for people
with sensitive skin. Some dermatologists have
made a career of reporting the supposedly
high frequency of contact allergy resulting
from cosmetics, sometimes arguing that 10%
of users may have become sensitized to one
or more components. These political toxicolo-
gists do a great disservice to an industry
whose safety record is exemplary. Many pa-
tients with various problems believe they
have sensitive skin when this cannot be vali-
dated by testing. They buy products for sensi-
tive skin, which generally cost more.
Lanolin allergy, in particular, is a fiction of
the political toxicologists who do not under-
stand the limitations of patch testing and who
fail to recognize the frequency of false-posi-
tive patch tests in patients with chronic der-
matoses, who compose a small segment of
consumers. Tons of lanolin are sold world-
wide every year with an extremely low inci-
dence of contact allergy.
Contact allergy to preservatives and fra-
grances can be a problem in patients with
chronic skin disorders, but these are special
cases and not representative of the general
population. Lacking are corresponding fig-
ures for an unselected, normal population.

No manufacturer selling products on a global
scale could afford to put a product on the
market in which the prevalence reached 1 in
a 1000 (0.1%) much less 15%. At that rate,
the incidence of contact allergy would be 1000
for every 1 million users, a prohibitively high
level that would require pulling the product
off the market to avoid litigation. These criti-
cisms do not argue against the worthiness
of providing fragrance-free and preservative-
free products for individuals who are truly al-
lergic.
Fragrances are a much enjoyed and pleas-
ing feature of the products into which they
are incorporated. Overall the risks are low
and the benefits great. Preservatives are a pre-
requisite for most cosmetic creams, which are
water-containing emulsions in which bacteria
can thrive. Poor preservation is a danger to
health, as has been evident in the case of
contamination by gram-negative organisms
in sick and immunosuppressed patients. Pa-
tients who are sensitive to preservatives
should have access to preservative-free prod-
ucts.
Claim Substantiation: The
Bioengineering Paradox
Responsible manufacturers of cosmetics ap-
preciate the importance of supporting their
claims by credible procedures that meet the
international rules of scientific evidence. The
last 2 decades have witnessed the emergence
of the new specialty of bioengineering, in
which the principles of material science are
applied to skin with the intent of providing
quantitative objective proof of efficacy, rather
than relying on subjective criteria, which may
be irrelevant and misleading. Nearly 100 bio-
engineering devices exist for measuring some
physical feature of skin. The familiar ones
include (1) the Evaporimeter (Servomed,
Sweden), to measure transepidermal water
loss; (2) ultrasound scans, to estimate dermal
thickness; (3) laser-Doppler velocimetry, to
measure blood flow; (4) estimation of the hy-
dration of the stratum corneum by electric
conductance; (5) biomechanical properties,
such as viscoelasticity; (6) thermography; and
(7) chromammetry.
COSMETICS 707
These devices not only furnish quantitative
data on some particular property of human
skin but also have the advantage of being
noninvasive, replacing procedures such as bi-
opsy, which are not only disagreeable to sub-
jects, but also may leave scars and unsightly
hypopigmentations or hyperpigmentations.
These instruments have become convenient
and powerful in delineating a defined physi-
cal feature of skin, with high precision and
reproducibility.
In the proper hands, noninvasive bioengin-
eering methods are extremely valuable for
obtaining a battery of diverse measurements
that characterize the structure and function of
skin obtainable in no other way. As with all
powerful tools, however, bioengineering
methods can be manipulated to obtain results
that are not only misleading, but also spe-
cious. The game of claim substantiation is a
sophisticated one in which unscrupulous
manufacturers exploit bioengineering tech-
niques to prove every claim that the market-
ers need to show superiority over a competi-
tive product. Statis tical significance deriving
from reams of numbers is not the same as
clinical significance.
Anyone can place a probe on the skin and
make a measurement. It takes a knowledge-
able scientist to know exactly what is being
measured, to know how to interpret the re-
sult, and to understand its relevance. Each
device is monodirectional and measures one
defined function, whereas it may require a
battery of instruments to capture multidirec-
tional effects. The misuse of bioengineering
methods to substantiate false claims does not
necessarily involve chicanery or overt dishon-
esty. It is simply a matter of choosing the right
instruments to obtain the desired, predeter-
mined result. After making a battery of mea-
surements using different instruments, it usu-
ally turns out that some are favorable in
support of the claims and others are unfavor-
able, that is, counterproductive. It is not diffi-
cult to imagine which data are presented to
the world and which are kept out of sight.
FUTURE POSSIBILITIES
Petrolatum
Petrolatum is the king of moisturizers and
emollients. Why not develop a synthetic pet-
708 KLIGMAN
rolatum with chemically defined ingredients
instead of the mishmash petrolatum that con-
tains hundreds if not thousands of hydrocar-
bons, most of which escape identification.
New technology is beginning to meet the
challenge of creating nongreasy, nontacky
topical drugs that often have to be used for
long periods. A corticosteroid cream has
come on the market that is delivered as a fast-
breaking foam that is esthetically agreeable
and promotes penetration.
Perfect Sunscreen
Solar radiation encompasses an exceed-
ingly broad range of frequencies: UV-B, UV-
A I and 11, visible light, and the infrared (the
last-mentioned accounting for 40% of the total
flux). Infrared (heat) can cause severe photo-
damage ending in cancers and can act syner-
gistically with UV-B and UV-A to promote
photodamage. Most current sunscreens have
gaps that allow certain wavelengths to pass
through. Broad-spectrum sunscreens as cur-
rently understood include UV-B and UV-A
radiation but ignore the infrared. Infrared can
be blocked by ultrafine zinc and titanium di-
oxide. The currently available agents tend to
be cosmetically unacceptable by imparting a
whitish color to the skin, however.
The technology exists to overcome this es-
thetic defect by using high-energy pulses to
break down the oxides into particles of a nan-
ometer size that leave no unsightly residue
after being rubbed in. Sunscreens are becom-
ing available in Europe that are approaching
true broad-spectrum protection. The cosmetic
industry deserves great praise for its great
achievements in the sunscreen market.
Tars
For hundreds of years, coal tars were the
mainstay for treating chronic dermatoses in
the presteroid era. They are the ultimate ex-
amples of substances that sting, stain, and
smell. The fact is, however, they still have
a place in the over-the-counter treatment of
psoriasis, dandruff, and other common prob-
lems. They also have some unexplained anti-
inflammatory activity as well as being anti-
pruritic. Could the cosmetic industry help the
pharmaceutical industry clean up coal tars?
HEURISTICS VERSUS HEDONICS
The paradox of heuristics versus hedonics
is rarely discussed, but in the new age of
bioactives and functional cosmetics it consti-
tutes a significant problem. This tension arises
because consumers desire products that are
pleasant, are enjoyable, are easy to apply, feel
good, look good, are mild (nonirritating), and
furnish a full range of sensory satisfactions.
Active products may be antithetic to hedonics
because they are specifically designed to
achieve a corrective, beneficial effect. As they
become more functional, they become less
pleasing and rank poorly in premarketing
tests in which panelists give undue emphasis
on esthetic and sensory properties.
The marketing decision in this conflict usu-
ally is determined in favor of hedonics based
on the operative rule that ”consumers won’t
buy products they don’t like.” This is a reality
that cannot be ignored completely but comes
at a high cost when the benefit that is sought
is sacrificed in favor of pleasing the customer.
This situation may mean that the producer
has to educate the consumer and to explain
why the product has some downsides. For
example, it is easy to make antiaging reti-
noids less irritating-decrease the concentra-
tion, but then the product becomes less effec-
tive. This tactic may be successful from the
standpoint of sales based on the fact that
consumers often cannot discern true differ-
ences in efficacy, especially if the vehicle is
enriched in traditional emollients. Cosmetics,
in contrast to drugs, do not qualify as place-
bos. They nearly always have an appreciable
beneficial effect.
Hydroxy acids, such as lactic acid and sali-
cylic acid, furnish another compelling exam-
ple. Among other things, these are exfoliants
that remove coarse superficial scales from
rough-dry skin. They become active if the
pH is lowered, but they also become more
irritating at the low pH values at which they
work best. The cheap solution is to raise the
pH to the point where they still work a little

but are less likely to produce stinging and
burning. Sophisticated formulators usually
arrive at some compromise, depending on the
products that are to be mass marketed or
targeted to salons, dermatologists, or spas.
Now that cosmetics have ascended to the
bioactive, functional category, it is timely to
ask whether aromachology will soon be pro-
moted to a similarly respectable position. The
concept of using fragrances to alter moods
and behaviors is as old as civilization. Evi-
dence is accumulating that certain odors can
jog memory, enhance cognitive performance,
and produce a state of tranquility. Some fra-
grances are associated with localized patterns
of brain activity that now can be recorded by
modern imaging techniques. All that is
needed is for the science to supplement the
smell. The selection of a fragrance for a given
soap and moisturizer may then depend less
on hedonics than on desired psychologic ef-
fects. Osmoceuticals may be the next great
wave in the sea of cosmeceuticals.
CONCLUSION
The major manufacturers produce an array
of products that contribute enormously to the
daily satisfactions and pleasures of modern
life. These products are tested routinely for
safety and often test marketed to ensure that
consumers will perceive claimed benefits. The
central issues raised in this article relate to
the problems that come from an essentially
unregulated marketplace. No one wants to
see cosmetics regulated as drugs; still, there
COSMETICS 709
is a need for some middle ground or compro-
mise.
Europeans are ahead in this regard. The
EEC publishes directives on the standards
that manufacturers are required to meet re-
garding safety and claims? These directives
do not have the backing of strict laws for
enforcement, but the industry makes serious
efforts to cooperate. There are advisory com-
mittees made up of academics and industry
scientists who meet regularly with the Euro-
pean commission to revise and implement
standards.
Self-regulation has not worked well in the
booming capitalistic economy of the United
States. The self-imposed safety record is a
credit to the industry. The next stage is an
agenda to set reasonable policies for claim
substantiation. Academics must participate in
this development and work at educating the
public. Finally, as regards the future, the au-
thor recommends Skin: Interface of a Living
System: Perspective for Skin Care in the Future.4
References
1. Kligman AM: Hydration injury to the skin. In Vander
Walk DG, Maibach HI (eds): The Irritant Contact Der-
matitis Syndrome. Boca Raton, FL, CRC Press, 1996,
pp 187-194
2. Kligman AM: Cosmeceuticals as a third category. Cos-
metics and Toiletries 113:33-40, 1998
3. Rogiers V Efficacy claims of cosmetics in Europe must
be scientifically substantiated from 1997 on. Skin Res
Techno1 1344-48, 1997
4. Tagami H, Parrish JA, Ozawa T Skin: Interface of a
Living System: Perspectives for Skin Care in the Fu-
ture. New York, Elsevier, 1998
Address reprint requests to
Albert M. Kligman, MD, PhD
Department of Dermatology
University of Pennsylvania
226 Clinical Research Building
415 Curie Boulevard
Philadelphia, PA 19104