TO: Russell Aims, Nancy Achin Audesse

FROM:

DATE: October 4,2006

RE: Cosmeceuticals

-
A. Article by Paula Begoun, supposedly a consumer expert for cosmetics industry. She
lists some leading "celebrity dermatologists" & alliances including Skin Effects line for
sale by Dr. Jeffery Dover at CVS.

-
B. Various articles itom Businessweek in 2004 - p 6 quotes Boston's Dr.Dover's
comments on ingredients of Vitamin A prescriptions. States that Dover is a consultant
for Johnson & Johnson Neutrogena.

-
C. Lengthy paper by Harvard Law Student in 2005 (Laurel Brown): ~osemeceutica~s
or
CosmePSEUDOcaLcEramining the FDA's Undersight of Celebrity Dermatologists in
the CosmeceuticalsIndustry. sohe major points:

Ultimate argument of this paper is that because marketing practices may confuse
consumers about the nature of the cosmeceuticals they- -purchase, the FDA should
regulate the industry @2).
The FDA imposes strict regulations on relationship between drug companies,
doctors & info exchanged between the two -there is not such proscrip6on on
relationship between cosmetics compines & doctors @8).
The trust that beauty consumers & the general public generally place in medical
professionals sould not be underestimated. Indeed doctors are legally regarded as
"learned intermediaries" who are liable for ramifications of their advice &
opinions re risks & benefits of products @9).

D.Copy of CVS ad itom 2005 re Dr. Dover with bottom line: "anti-agii,~without the
appointment "

-
E. Table of contents itom issue on Cosmeceuticals itom Dermatologic Surgery, July
2005. Entire issue seems favorable toward use of these products with some caveats.
Introduction explains different vantage points on usefulness of cosmeceuticals.

F. Article h m Am Society of Dermatologic Surgery 2005 on combined use of

Gnablative treatment & cosmeceuticals.
See Also:

Online eMedicine report by RA Schwartz, MD/current as of 9/05/2006

Cosmeceuticals not subject to review by FDA.

Term "cosmeceutical" not recognized by Federal Food, Drug & Cosmetic Act.
Cosmetic ingredients tested for safety, but testing to see if ingredients live up to
nonclaims - not mandatory.
Most studies are poorly designed, and many authorities regard the utility of these
preparations for their stated uses as marginal at best.
Cosmeceuticals: Science, Marketing, or a Little of Both? Page 1 of 2 ->
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I\]
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61
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Cosmeceuticals are looselv defined as woducts mmbinina the benefits of a cosmetic and a pharmaceutical. The term is
used by many skincare cdmpanies. especially those sold& endorsed by dermatologists, togive the impression the
products have more effective or more bioloaicallv active inaredients than iust ordinaw cosmetics. As more and more doctors
get into selling or endorsing skin-care prodk.ts, you will hear more and more about &smeceuticals. Dr. Tina Alster is the
spokesperson for Lancome; Dr. Karyn Grossman is the spokesperson for Prescriptives; Dr. Pabicia Wexleh namesake
products, Pabicia Wexler M.D. Dermatology, launched this fall; Skin Effects by Dr. Jeffrey Dover is at CVS; Dr. Sheldon
Pinnell's SkinCeuticals line has been purchased by L'Oreal; and. of course, there's N.V. Perricone. M.D. Upping the ante in
this group is Dr. Howard Sobel, who added the outrageously priced RMX Maximum-$1.000 for a 28day supply-to his
DDF skin-care line.

Despite all this medical pedigree, the term msmeoeutical is not in any way regulated or controlled, and anyone can slap that
label on their products to promote them as being more "medical."Cosmeceuticalsare nothing more than a marketing term
with illusions of grandeur. Even the FDA says cosmeceuticals don't exist, and considers these products to be merely
cosmetics with clever marketing language &ached.

Do
- cosmeceutlcals
~ . ~ reallv differ from
~ ..~.
~
anv
- .
other cosmetics? The answer is both ves and no. because no matter how a
~ ~

d u c t is labeled and maketed, many skin-care treatments contain ingredients that affect thebiolcgical function of skin:
The biolwicalhr active inaredients to look for include antioxidants lmost of which have an&inflammatorv ~rooerties).cell-
comrnuni&ting ingredients, exfoliants, skin-lightening ingredients,'and intercellular substances (ingred&nts ihat mihic skin
structure).

Antioxidants. applied todcalhr, reduce free-radical damaae. thus helping prevent cellular damaae. collaaen desbuction due
to intlammation,'and imniune iuppression. These actionsare incredibly Gaiuable for skin. But a$de h u m k e insistent claims
bv those who sav their product lines have the best antioxidants. the research is clear: There is no single best antioxidant
j& lots and l o t s b potent options and lots and lots of research showing benefit for skin from everything hum pomegranate.
wrcumin, superoxide dlsmutase, grape-seed extract, green tea. lycopene, vitamin E. vitamin C. DMAE, glutathione, uric
acid, carnosine (beta-alanyl-L-histidine), and glucopyrinosides (risveratrol) to niacinamide, polyphenol~(epigallocatechin-
wallate (EGCG), genistein. pycnogenol, and more.

One other point: Many researchers believe that a single antioxidant, no matter how stable or potent, is not as effective for
-
skin as a group of antioxidants, because antioxidants in combination can exert a synergistic cumulative action on the skin.

~~ ~

-
Cell-communlcatlna lnaredients
~" interact with skin cells via receptor sites or cellular Dathwavs that essentiallv allow these
substances to tell a cell to behave or function better. That is. they i n s h c t the ceU to ripair itself and act nomdlly (or for the
sake of babv boomers. act more Vouthfullv') . . bv. reducina inflammation. enwuraaina - - .production of healthv skin substances.
inhibiting substances that cause collagen to break downrand on and on. Without question, this is the moit promising area in
current skin-care research. The most welkesearched ingredient in this categow is by far the retinoids (vitamin A),
specifically the prescription version hetinoin, which is found in Retin-A and eno ova (ketinoln is also available generically). In
cosmetics. retinol and retinaldehyde are known to have efficacy simllar to that of betinoin. Other cellcommunicating
ingredients that are still the subjed of research are a wide variety of peptides and niacinamide. At the moment, however.
mere is no independent research showing that peptides can perform as claimed on the labels of products containing them.

Exfollants help surface skin cells shed in a mom normal. 'youngef way, which allows skin to function and look more
radiant and healthv. There are manv reasons whv skin cells build up on the surface, but the ~ r i m a w one is sun damaae.
Normalizing cell Grnover does imprbve the feel and appearance ofthe skin's surface, but rekrch-also indicates thacit can
improve collagen production. Topical scrubs are one way to exfoliate, but such mechanical exfoliation can be harsh on skin
and there is little research showing any benefit. On the other hand. certain substances definitely can exfoliate skin. including
glycolic acid. lactic acid, polyhydroxy acids (gluconolactone and lactobionic acid), and salicylic acid.

Skin-lightening lngredlents inhibit melanin formation, thus reducing the appearance of brown discolorations. Skin-
lightening ingredients include hydroquinone, arbutin, azelaic acid, some forms of vitamin C, and glycymhetinic acid.

lntercellular substances. which Ioffen refer to as 'inaredients that mimic skin structure.' should be the backbone of eve^
moisturizer. lntercellularsubstances are those ingredignts that exist naturally in skin, and that work to hold skin cells
twether. A dw environment sun damaae. irritation. inflammation. and aae can all areaUv reduce the presence of these
sukstances iiskin. Adding intercellular~ubstanc&to a moisturizer helps keep the'iayeri of skin whoie, resilient, and in
mod ~hvsicalshape bv ~mvidinothe materials the skin needs to defend against the environment. lnaredients such as
&raniid&, chole&erol; btty acid; (linoleic acid, triglycerides, glycerin, ph&pholipids, and lecithin), &d glycosaminoglycans
(hyaluronic acid and sodium PCA) are essential for helping skin function normally.

Regardless of the name, cosmeceutical or otherwise+ skincare product is only as good as what it contains and how those
hgredients can help your skin function better, or in the vernacular, to act younger. In fact moisturizers (or any skin-care
product claiming to have an effect on wrinkles or sagging
.. .skin) should absolutely contain an elegant mix of antioxidants, cell-
&mmunicatingingredients. and intercellular substances as thiy help skin keepa normal level of hydration. build collagen,
 Cosmeceuticals: Science, Marketing, or a Little of Both?

, 'reduce skin discolorations, and prevent cdlular damage.

SI
Sources for this article: Archives dDermafologicalResearch, April 2005, pages 475481; American Journal of Clinical . UI
->
Dermatology, March-April 2000. pages 81-88 and September-October 2000, pages 261-266; Biofacfws, January-February
2002. pages 29-43; Biological 8 PharmaceuticalBullefin, April 2004, pages 510-514; Biowganic and Medicinal Chemistry.
December 2003. pages 53455352; Brifish Journal of Dennafdogy. November 1995. pages 674685 and September 2000.
pages 524-531; Business Week Online, An Ugly Truth About Cosmefics, November 30,2004; Confad Dermafiiis, June
2002, pages 331-338; Cufis, February 2004, pages 3-13 Supplemental; Clinicaland Geriafric Medicine, February 2002, .F>
1f1
pages 103-120; Dermafology, February 2002, pages 155158. April 2002. pages 281-286: and 2005.210 Supplemental 1.
pages 613; www.emediiine.wmlderndtopic509.hbn; ExperimentalDermafology. 2003. 12 Supplemental2, pages 57-63
and 2004. 13 Su~~lemental4. Daaes 1521: www.fda.aov: FacialPlasfic Suroerv Clinics of NorthAmeffca. Auaust 2004.
pages 363-372; kict Sheet on b l i e r ~ m e r i k n swww~civkventures.org;
. Fre; dadical Research. April 2002. pages 471:
477: Journal of Cosmelrc Science. Se~tember-October 2002. Daaes 269-282: Jounal dfhe Eumean Academv of
~einafolcgy8 Venereolcgy. ~ovemder2002. pages 587-594; ~5urnalof LipidResearch. May 2002. pages 79k804;
Jounal of MedicinalFood, Winter 2003. pages 291-299; Jounal of fhe EuropeanAcademy of Dermafology 8 Veneredcgy,
January 2004. pages 52-55; Jwrnal of Investigative Dennafdogy. May 1996. pages 1 ~ 1 1 0 1Mutation
; Research. April
2005. Daaes 155173: Nutrifion and Cancer. Februaw 2003.. paaes . - 181-187: PackaaedFacfs, U.S. Cosmeceuticals fo 2008.
www:h&foshop.com; ~hofochemishyand ~hotobfdog~. ~anuary-~ebruary 2005,-~a~es3&15; Plastic and ~econsbuctive
Surgery, February 2005, pages 515528 and April 2005, pages 11561162; Progressin lipid Research, January 2003,
pages 1-36; Tha Rose Sheet, www.themsesheet.wm; Skin Phannacdcgy and Applied Skin Physiology, September-
October 2001. maes 305315; Skin Pharmacolwv and Phvsiolw. September-October 2004, paaes 207-213: Skin
Therapy ~etter;~ t i n e ~ u2004,
t y pages 1 3 ; and 6xicdcgicd ~ i e n c e s September
. 2004, pag& i3-49.

Paula Begoun

Enjoy this ariicle? Read more like it in Paula's EREEBeauty_BuUetin.

0Copyighl2005.2006 by Paula Begoun and Bryan Barren. This publYaUon is lhe property d Paula's Chace. Inc. ('Paula's ChoKe'), andtci h
m e n or ahiliales. Reprodudon, republimbon, alleraton, posting. bansmis4on or distnbuUon 01 this rnateMl requires minen permission lrom
Paula's Choice. For mom information see wr T.euns.oWse.
 Page 1 o f 6
-.,

NOVEMBER 30,2004

COMMENTARY
By Pallavi Gogoi

An Ugly Truth About Cosmetics

http:llnetscape.busin~~~~~ek.commwdai1yldnflasnov200nf20041130~2214~db042.htm
Beauty-seekers beware: Largely unregulated ads for skin creams and wrinkle removers often have dubious -(

daims backed by spurious science

[an error occurred while processing this directiveYBetter than Botox?" This StriVectin-SD ad splashed across
magazines and newspapers all over the nation has attracted women in droves. Aching to erase the telltale signs
of age, they're flocking to high-end department stores like Bloomingdale's to grab 6-02. tubes of StriVectin at $135
a pop, making it one of hottest launches ever of a winkle cream. According to market-research firm NPD Beauty,
StriVectin rang in $30 million in the first five months of this year, a feat that even the most successful new skin-
care products have needed 12 months to match. StriVectin sales are expected to top $100 million by yearend.

Little do these buyers know that the government is investigatingStriVectin's maker. Klein-Becker, and exclusive
distributor, Basic Research, for making "false claims" on other products it sells. The U.S. Federal Trade
Commission (FTC) has charged them with making unsubstantiated claims in infomercials and ads in magazines
such as Cosmopolitan, Redbook, and Muscle and Fitness, and on several products, including Pedialean, a
weight-loss supplement for children.

The investigation raises questions about StriVectin's boasts of an anti-wn'nkle breakthrough. In an e-mail to
Businessweek Online, Basic Research says its claims are backed by clinical trials that document a significant
reduction in wrinkles.

CONJURING NAMES. StriVectin certainly isn't alone in using high-tech claims to attract customers. In fact, more
and more ads for skin care are highlighting the "science" and "technologies" behind products. Take Bo-Hylurox in
Avon's (AVP )Anew Clinical Deep Crease Concentrate, or the Mela-NO complex and dermo-smoothing complex
-
DMntraxol in Lancome's anti-age serums, or the Triplesphere Refinishing system in Estee Lauder's (EL )micro-
dermabrasion scrub."

Most of these names don't really exist in cosmetic science. "It's an incredible statement to the consumer that you
don't need to get injected when there's all this science to rid you of wrinkles," says Paula Begoun, author of Don't
Go To the Cosmetics Counter Without Me. Most of these terms were conjured up in company labs by zealous
chemists or marketers, points out Begoun. When asked about the claims and the technologies, none of these
companies commented by deadline.

Problem is, it's also hard to challenge the claims for these products, since they've been tested only internally, and
cosmetic creams don't need to go through any regulatory clearance before being launched. Wrinkle-reducing
creams are expensive, but to litigate against companies is even more expensive, and at the end of the day the
harm to people is mostly economic." says Scott Bass, a partner in charge of international food and drug practice
at law firm Sidley Austin Brown & Wood.

BORDER LINES. Since the cosmetic industry is largely lefl to monitor itself and the Food & Drug Administration
gets involved only when products have adverse reactions or change the structure of the body. consumers are lefl
to their own devices to monitor such daims. "A lot of this might be worded to sound scientific, but people need to
realize that wrinkles don't just disappear as claimed," says Allen Halper, senior compliance officer in the Office of
Cosmetics &Colors at the FDA.

The FTC, which monitors advertising for unfair or deceptive claims, isn't that aggressive on the cosmetics industry
either. "Our priority is to ensure that if a product is claiming a health benefit that there are enough trials to back
that. If there are general appearanceenhancementclaims, those are not high in our prosecution list," says
Heather Hippsley, assistant director for the n%'s advertising-practices division.

However, the indusion of certain drug-like ingredients and chemicals in the creams places them in an area
termed "cosmeceuticals." a category that straddles the cosmetic and medical sectors. Cosmeceuticals are one of
the personalare industry's fastest growing segments, but they aren't regulated by the FDA either. According to
consumer research publisher Packaged Facts, U.S. retail sales of cosmeceutical skin care are estimated to climb
7.3%, to $6.4 billion, from 2003 to 2004.That would be up 22% from 2000."Aging baby boomers looking for ways
 * N O ~ M B E R30 Page 2 of 6
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to stay young and cosmeceutical manufacturers capitalizing on their concerns [are] fueling the growth," says F'I
-,I
\
Timothy Dowd, senior writer and analyst at Packaged Facts.
S;
DOCTOR WHO? Adding to the allure is the fact that most of these cosmeceuticals are endorsed by physicians, 01
>..
though sometimes their qualifications are dubious. For instance StriVectinSD is endorsed in ads by a Dr. Daniel
B. Mowrey, director of scientific affairs at manufacturer Klein-Becker, and Dr. Nathalie Chevreau, director of
women's health at Basic Research. But neither Mowrey or Chevreau is a medical doctor, and the government is
challenging Mowey's credentials.
l',1
In the e-mail to BusinessWeek Online, Basic Research said: "Dr. Nathalie Chevreau holds a PhD in inorganic
chemistry as well as an RD [registered dietician] license. Dr. Mowrey holds a PhD in experimental psychology."
The company says its ads don't claim or imply that Dr. Mowrey is anything more or less than a research scientist
and that in other advertisements he's referred to as Dr. Mowery. Phd. But the Web site that markets StrNectin
didn't say he's a Phd as of the story deadline.

Meanwhile, FTC counsel Laureen Kapin says the commission is now waiting for answers from the companies in
connection with the investigation. If they're found guilty at trial, that wouldn't preclude the government from looking
at the companies' other products. "If we prevail, Basic Research could receive a broad order (legally referred to as
"fencingin"lbaning the firm from making false and deceptive claims and selling any of its products." says Kapin.

BRING IN THE FEDS. The future of StrNectin, a cream originally marketed as a stretch-mark-reducing emulsion
containing an ingredient called oligo-peptide, might be tied to the FTCs investigation. But millions of consumers
continue to be hoodwinked by the cosmetics industry's ingenious marketing. The FDA and the FTC might not
consider this a priority, since cosmetics makers figure low in the agencies' ranking of companies to go after.
However, if people are being deceived, regulators ought to take a closer look.

The creams may not be taking people's lives or inflicting blindness, but the FDA needs to assure that people
aren't d u ~ e dbv false claims. The Office of Cosmetics (L Colors needs to reaulate cosmeceuticals and check out
the various suiplements and ingredients that go into changing people's appearances.

" I a product's claims have reached a point where they're no longer puffery and are deep-penetrating treatments.
where the wsmetics are almost thinly disguised drugs, they have to comply with drug provisions," says Halper
from the FDA's Office of Cosmetics (L Color. But he adds that the agency prioritizes issues on health and safety,
and it doesn't have the resources to examine all the claims out there. So it mostly relies on the cosmetics industry
to monitor claims appropriate for the marketplace.

BIG CLAIMS. The FTC says it tries to discern behveen readily ascertainable claims vs. others. For instance, in
2000 it filed suit against Rexall Sundown for marketing a product that claimed to eliminate cellulite. For topical
creams, the FTCs Hippsley says most reputable companies honor their. satisfaction guarantees no matter how
intlated their marketingdaims. "Consumers can see for themselves if the creams work or not, and if they aren't
satisfied, they can either return the product or not buy the brand again," she says.

Given this cavalier attitude, wsmetics companies certainly seem to have almost free rein when it comes to
daims. Avon says "Look stunning. Not stunned." in one of its ads for a product that contains its "exclusive
multipatentpending Bo-Hylurox technology." Avon didn't comment on the genesis of the name, but Begoun says
it might be a concoction of Botox and hyaluronic acid, the main ingredient in Restylane - a gel that's injected into
the skin to fill in aeases and is approved by the FDA.

Avon daims that its product smooths creases with an ingredient called portulaca, which relaxes the skin, whereas
hyaluronic acid has a filling effect.

Obviously, when examined closely. what looks like a harmless cream might actually be a drug or medical product
that's readily available to the masks. With aggressive marketing, such products can also become very popular,
as in the case of StriVectin. Cosmetics companies shouldn't be lefl to their own devices just because they're
playing with people's vanity.

Gogoi is a reporter for BusinessWeek Online in New York

Edited by Patricia O'Connell
 Page 3 of 6
.
!

NEWS ANALYSIS
ByAmyTsao

The Changlng Face of Skin Care

The rise of "cosmeceuticals" is blurring the lines between dermatology and cosmetology in ways that many
consumers don't understand
1) 1
[an error occurred while processing this directivelln a classic episode of the sitcom Seinfeld, Jeny dates a
dermatologist. who says she's "saving lives" all day by treating skin diseases. Jeny is skeptical, and his sidekick .
George squawks: "Saving lives? She's one step away from working at the Clinique counter."

Think about that before you rush off to get your forehead smoothed or your skin freshened for the holidays.
George's assessment may be a little harsh, but there's no denying that the line between.dermatology the -
- -
medical specialty devoted to skin disorders and diseases and cosmetology the practice of improving a
-
person's appearance is becoming increasingly blurred.

-
Indeed, the term "cosmeceutical" a product marketed as a cosmetic that purportedly has biologically active
ingredients that affect the user - has sprung up to define a broad gray area where the practice of medicine and
the pursuit of vanity meet.

HEAVILY INVESTED. Avanety of factors are behind the rise of cosmeceuticals: the aging of the baby boom
generation; increasingly effective alternatives to plastic surgery, such as Allergan's (AGN ) Botox; and the
financial disincentives of managed care. Add them all up, and cosmeceuticals comes to a booming business that
has implications far beyond the promise of diminished cmw's feet and less-visible laugh lines.

From 2003 to 2004, sales of skin-care cosmeceuticals in the U.S. are expected to grow by 7.3%. to $6.4 billion,
-
according to consumer industry tracker Packaged Facts. Major cosmetic companies including Estee Lauder
(EL ), Avon (AVP ), L'Oreal, and Revlon (REV ) - are already heavily invested in such products and will continue

- So far, relativelyfe6 drugmakers, besides Allergan and Johnson a Johnson (JNJ ), with its Vitamin A-based
drugs, are in the business. That may change, though. The success of Botox, which was a $564 million product in
2003, and the aging of youth-obsessed baby boomers haven't been lost on the drug industry. Pfizer (PFE ), for
one, bought a company called Anaderm in 1996 to focus specifically on cosmeceuticals.

ELEVATED AESTHETICIANS. Certainly, the business of improving appearance by medical means is vast and is
growing in many directions. Along with cosmeceuticals, a wide range of treatments are available in doctors'
offices. Chemical peels, laser treatments, microdermabrasion, which were once primarily the purview of spas and
beauty clinics, are now common offerings at many dermatologists' offices.

Doctors are opening their own spas, lending their names to various product lines, and writing books detailing
methods that allegedly keep skin youthful. About half of all dermatologists sell cosmetic products in their offices,
estimates Howard Maibach, professor of dermatology at the University of California, San Francisco.

As a result, patients increasingly see dermatologists as having the skills and tools to reverse or halt the aging
process -and many doctors are more than happy to serve as elevated aestheticians. The reality is that doctors
in the profession are "tour guides" to patients traversing a confusing world of products and services (Botox,
collagen, lasers, and peels) promising youth, says Richard Glogau, clinical professor of dermatology at University
of California, San Francisco. (Glogau consults for several cosmeceutical makers.)

Plenty of dermatologists view selling cosmeceuticals as good medical practice. "What we love about dispensing
-
[these ~roductslis we reallv know what Datients are using." savs Patricia Farris, a dermatologist based in New
orleans and clinical assistant professor at Tulane ~nivers/ty.

A BLEMISHED REPUTATION?There's no denying that they're good business, too. She says such products are
the beginning of a "stepup process" to prescription drugs or procedures like Botox injections and laser
treatments. which is where the biggest dollars arc. "You don't start with the big guns," says Farrir (Farris consults
for a number of cosmetic companies.)
 Page 4 o f 6
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This emphasis on the aesthetic rather than the medical has some in the field concerned. "Cosmetic dermatology pi I
is really injuring the reputationof dermatology." says Eileen Ringel, a dermatologist in Maine who is also on the -4
\.
Food & Drug Administration's advisory w.mmittee for dermatology. "People come to me and think I'm a
cosmetologist. and they don7 know the difference. That's our fault as dermatologists." (Ringel doesnl perform
5;
%I
cosmetic dermatology services of any kind.) -3

Dermatologists' reputation may not be all that's suffering. As these practitioners Spend more time addressing -
cosmetic &mplaints, they have less time to treat with skin diseases, including potentially fatal skin
cancers. The average wait time to see a dermatologist in major cities around the country is 24.3 days the - J.
longest among highdemand medical specialties including obstetrics and gynecology and cardiology according-
to a 2004 survey by physician staffing firm Merritt. Hawkins &Associates.

"ONE-DIMENSIONAL." According to data from the American Academy of Dwmatologfs 2002 practice profile
survey, 90% of dermatologists interviewed reported a need for more medical or general dermatologists in their
local area, while only 13% cited a need for more cosmetic dermatologists. "A severe shortage of dermatologists
threatens patients' access to care and is likely to further increase the amount of medical and surgicalskin care
provided by nondermatologists," the study's authors wrote.

Though dermatology has become one of the most sought-afler specialties amongmedical students, some fear
that the field's dynamism is faltering. Fundingfrom universities and industry alike for "basic science and research
[on] important diseases is shunted to cosmetics," says Ringel. New York-based dermatologist A. Bernard
A c k q a n agrees: "Instead of being multifaceted and fascinating, it is onedimensional." (Ackerman doesn't
perform cosmetic dermatology.)

Sheldon Pinnell, professor emeritus at Duke University, disagrees. "I'm bullish about the profession fmm a
number of points of view," says Pinnell. "we're researching] everything from conditions that are life-threatening to
ways of protecting skin that improve the cosmetic nature of skin." Advances in technology could soon spur the
FDA and professional societies like the American Academy of Dermatology to make more ligorous demands of
skin science and its practitioners. critics say. Both are now largely
- . absent from the debate. (Pinnell is a consultant
to a line of products called SkinCeuticals.) -

Among consumers, the popularity of cosmeceuticals will continue to rise as long as improving physical
appearance remains a top social priority. The question is: What will be the medical and scientific community's role
in shaping this fast-rising field?

NEWS ANALYSIS
By Amy Tsao

Despite the Hype, No Elixirs of Youth

Lots of products promise to reverse the signs of aging, while providing little or no proof that they work. Here's
what you need to know
[an error occurred while processing this directive] Want to look your best for the holidays? Think you're in need of
a more youthful appearance, but you're not willing or ready to go under the knife? You might be tempted to treat
-
yourself to a liitle something at the dermatologist's office or at the corner drugstore. People hoping to reverse
the signs of aging are increasingly looking to "cosmeceuticals." nonprescription creams, gels, and lotions that
promise dramatic results.

The ugly truth is that most of the age-fighting products available for retail sale lack scientific data to support their
daims. While manufacturers promise dramatic improvements, especially on wrinkles, relatively few products have
been studied scientifically.

That's because the active ingredients in many popular wsmeceuticals are vitamins and plant extracts, which
aren't subject to the rigors of the Food 8 Drug Administration's drug-approval process, consisting of controlled

-
safety and effectiveness trials in human subjects. Indeed, most manufacturers are content to be in this blurry
cosmeceutical zone, with little need - or incentive -to conduct expensive studies.

FEEL-GOOD PRODUCTS? "With a few exceptions, there's precious little good data that any of the anti-aging
pmducts sold over-thecounter are effective," says Eileen Ringel, a dermatologist based in Watewille. Me. Ringel,
 Page 5 o f 6
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v -6
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($1
who's also a consultant to the FDA's dermatology board, says the only data often available are "testimonials" by ;.I'
users who claim they've seen or felt a change in their appearance: When studies have been done, they often lack
8
- "oversight and are poorly designed," she says.

"A lot of skin-care products have rudimentary data to show that they're effective on some level." says Richard
(I,
-5

Glogau, clinical professor of dermatology at the University of California, San Francisco. "Most are just very fancy
overpriced moisturizers that make the skin feel good.' (Glogau consults with several cosmeceutical makers.)

Take Avon's (AVP) latest foray into the battle against aging. In October, it launched a new product in its popular 11

Anew line, Anew Deep Crease, which it bills as an alternative to Botox injections. The marketing pitch: "Look
stunning, not stunned."

UNDISCLOSED DETAILS. Avon says the gel contains hyaluronic acid (the main component of synthetic
collagens) for a filling effect and a "custom" extract of a plant called portulaca for a relaxing effect. "We uncovered
it on our own," says Glen Anderson, senior manager in skin-care product development, of portulaca, which Avon
imports from Asia.

Avon claims that the product showed strong results. After eight weeks of use. 71% of patients tested saw
improvement in their lines. That sounds impressive, but the company declines to disclose the total number of
patients tested or any other study details. Anderson says Avon's legal department has the detailed results ready
should the Federal Trade Commission, which monitors advertising for unfair or decepti~eclaims, ever ask for it.

Indeed, the products that are best supported by published, scientific data are prescriptiondrugs like vitamin-A
derivatives (Renova, RetinA, Differin, and Avage) and FDA-approved injectable treatments, such as Botox,
Hylafon, and Restylane. In the nonprescription arena, some researchers point to data suggesting that some
forms of topical vitamin C may protect the skin from sun damage.

AGGRESSIVE MARKETING. Those, of course, are the minority. A whole universe of cosmeceutical products
exist that contain a variety of plants, herbs, vitamins, and antioxidants. Alpha hydroxy acids are also popular.
Others use relatively new active ingredients, like palmitoyl-pentapeptide, the basis of StriVectinSD - a cream
-
thatwith aggressive marketing as a youth-restoring alternative to Botox has become a big seller in the past
year. Creams containing growth factors, which are traditionally used to treat wounds and burns, are also showing
up in the marketplace as youth-restoling treatments.

Consumers also may not realize that the products dermatologists hawk aren't likely to be any better than items
sold on pharmacy shelves or in department stores, says Ringel. "I don't understand why dermatologists would
recommend these products to patients without being able to examine a welldesigned, peer-reviewed study," she
says. "They might as well base their recommendationson what they heard last week on Oprah."

One silver lining in cosmeceuticals' runaway growth is that for the most part, the giant beauty-products makers
won't risk the type of lawsuits that would result from products that might be proved harmful. Avon's Anderson says
the company runs "a significant amount of safety testing-for toxicity and allergies. Often Avon will do
"exaggerated use" tests in which the ingredient is set on a patch and driven into the skin to see if it causes
adverse reactions. These companies aren't willing to take risks on stuff that's flimsy," says Glogau.

Following is a guide to the good, the bad, and the ugly among popular cosmeceutical products:

Alpha hydroxy acid

-
Loads of products contain alpha hydroxy acid chemicals derived from fruit and milk sugars. Some data suggest
that they may help the appearance of aging skin by exfoliating dead cells. But they're also known to have
damaging effects, including rashes, swelling, and increased sensitivity to sunlight.

Afler conducting its own studies, the FDA in 1994 said products containing alpha hydroxy acid are safe in
concentrations of 10% or less of the product and provided the acidity is also low. Glycolic acid and lactic acid,
which are forms of alpha hydroxy acid, are safe at concentrations of 30% in chemical peels, the FDA said.

Botox
Botulinium toxin type A, popularly known as Botox, works by temporarily paralyzing muscles behind wrinkled skin.
For its FDA tiling for cosmetic use. Botox was studied in placeb-ntrolled randomized clinical trials involving
405 patients with moderate-to-severe eyebrow furrows. In the group receiving Botox, after 30 days, both
researchers and patients rated frown lines as improved or nonexistent. Veryfew patients in the placebo group
 ' NOVEMBER 30 Page 6 o f 6

I
saw similar improvement.
CI
Side effects indude headache, respiratory infection, flu syndrome, droopy eyelids, and nausea. Lesscommon 01
effects are pain in the face. redness at the injection site. and muscle weakness. It's unknown what the impact of (i
I
long-term use might be. Skeptics worry that the shots will render patients' muscles atrophied over time. It's -,
recommended that Botox not be injected more than once every three months.

Hyaluronic acid
This is the main component of the synthetic, injected products Restylane and Hylaform. They make lips plump up UI
and remove deep skin creases by filling the space between collagen and elastin fibers within the skin. The body
absorbs the gel over time, and repeated injections are needed to maintain results.

In studies across the U.S., 138 patients with frown lines were injected with Restylane on one side of the face and
with a bovine collagen product on the other side. Pain and bruising occurred in both groups, but at lower rates on
the Restylane-treated side.

Hyaluronic acid is showing up as an ingredient in all kinds of lotions, but no credible data show that a topical
treatment would penetrate the skin and have a beneficial effect.

Vitamin A
Prescription vitamin A creams and gels such as acne treatment Retin-A, made by Ortho Pharmaceutical, a
Johnson 8 Johnson fJNJ) division, mav also helo with the aooearance of fine lines. coarse skin, and oiamentation
2 problems. "But it's n i t masic," caution; Jeffrey dover, associate clinical pmfessor of dermatology at ~ 2 e
University School of Medicine and director of SkinCare Physicians in Chestnut Hill, Mass. 'Results are modest
and take a long time."

Dover also cautions that products containing watereddown ingredients that sound like RetinA (retinol, retinyl,
etc.) are popular, but probably useless. 's Neutrogena division.) . , '

Vitamin C
Some evidence shows that vitamin C is useful in sunscreens. "It quite surprisingly provides an enormous amount
of photoprotective power," says Sheldon Pinnell. pmfessor emeritus at Duke University. A 1992 study showed
that vitamin C protected pigskin fmm damage caused by ultraviolet rays.

Another study -authored by Pinnellwas published in the Journal of the American Academy of Dermatology last
year. It showed that topical vitamin E and C together protected pigskin better from the sun than vitamin C or E
alone. (Pinnell is a consultant to Skinceuticals, a line of cosmeceuticals.)

Such data are "very exciting," says Dan Rivlin, dermatologist at Skin 8 Cancer Associates in Miami Beach. Fla.
But he doesn't typically recommend vitamin C creams to patients since the only available studies didn't involve
humans. Also, Pinnell's studies were done with a particular strength and type of vitamin C that may not be the
same as those in other vitamin C products.

All the r&t

Hundreds of products are presented as age-fighting remedies. And some are becoming blockbusters despite
uncertainties about whether they work. StrivectinSD, for example, is on track to becoming a $100 million product
-
by yearend even though relatively little evidence of safety or effectiveness has been shown.

Klein-Becker, the maker of StriVectinSD, insists the product works and Is safe, but it dedines to disclose where
research of the product was published. And sincethis summer. the FederalTrade Commission hasbeen
investigating Klein-Becker for making unsubstantiated claims on various weight-loss products it sells.

While alleged anti-aging treatments are plentiful, what's in short supply is the evidence that they can really make
you look younger. Remember, promises and proof aren't the same.
 Cosmeceuticals or CosmePSEUDOcals: Examinina the FDA's Under-
siaht of Celebritv Dermatoloaists in the Cosmeceuticals Industry
By Laurel Brown

Harvard Law School, Class of 2005

May 2005

This paper is submitted in satisfaction of the course requirement for Food and Drug Law

a
 i,
Cosmeceuticals or CosmePSEUDOcals: Examining the FDA's Under-sight dl
Iil
of Celebrity Dermatologists in the Cosmeceuticals Industry .,

%I
Assma
This paper will examine the Food and Drug Administration's regulation of the

cosmeceuticals industry by exploring the legal (and ethical) implications of the industry's

employment of physicians and dermatologists who sell products which the doctors themselves

have a financial stake in. By focusing on famed dermatologist, cosmeceutical entrepreneur, and

bestselling author Dr. Nicholas ~ e n i k n e thk

, paper will elucidate the legal repercussions of

using doctors to market and legitimize the drug-like claims of products that are in essence, just

glorified cosmetics.

INTRODUCI'ION: V. SHAREHOLDERS
BEHOLDERS INTHE COSMECEUTICAL
-
While beauty may be in the eye of the beholder, the money is objectively flying into the

hands of the corporate cosmeceutical shareholders, corporations, and their paid entourage of star

dermatologists. The cosmetics industry used to focus on hawking hot pink lipsticks and lash-

extending mascara. But now the industry has grown up. Rather than just hiding imperfections,

the new age of cosmetics products, known as cosmeceuticals, claim tofighr imperfections. Men

and women are rushing to cosmeceuticals counters to anti-wrinkle creams, Alpha Hydroxy

Acids, Botox, and the like.' Cosmeceuticals are generally regarded as cosmetics with medicinal

- Special
'see Report: Skin Care's Changing Face, Business Week Online,
http://images.businesswe&com/db/04/1 I/cosmeceutica~cosmeeeuticalOl.htm?thisSpee&9000 (last visited May 5,
2M5).
 CI
or drug-like benefits2 The industry promises that its products are the new fountain of youth and 41
VI
-,
consumers are handing over billions of dollars in accord. But with the wide array of (high

priced) cosmeceutical products to choose fiom, consumers must rely on outside experts to help
UI
guide their decisions.

Unfortunately, the Food and Drug Administration (FDA), the agency that administrates

the requirements of the Food, Drug and Cosmetics Act of 1906, does not actively review the

inflated claims of wsmeceutical manufacturers. Recognizing this loophole in FDA regulation,

cosmetics wmpanies have employed dermatologists to legitimize their overstated claims before

consumers. Consumers, in turn, rely on the recommendations of these medical professional in

paying upwards of $25 to $400 per bottle to cosmeceutical wmpanies.

This paper explores the legality marketing practices of cosmeceutical industry i.e. making

drug-like claims about products that are merely glorified cosmetics, and using doctors to market

and legitimize the drug-like claims. The first part of this paper discusses the "under-sight" of the

wsmeceutical industry and the industry's questionable use of dermatologists to promote

cosmetics for profit. The second section explores the growing empire of a well-known

dermatologist, wsmeceutical entrepreneur, and bestselling author Dr. Peniwne, to highlight the

consequences of the business relationship between the cosmeceuticals and dermatologists.

2 Ultimately,-the paper argues that because the marketing practices may confuse consumers about
the nature of the cosmeceuticals they purchase, the FDA should regulate the industry.
-

& Cosmeceuticals, Office of Cosmetics and Colors Fact Sheet U.S. Food and Drug Administration - Center for
Food Safety and Applied Nuhition Febmw 3, 1995; revised February 24, 2000) available at
httD://www.cfsan.fda.gov/-ddcos-217.ht (last visited April 30,2005).
a PART I.
k DO YOU'DRUGS" " BE YOUR LAWFULLY
TAKE ' ~ O S ~ E T I C STO
~ D D E PARTNER?:
D BACKGROUND ON LAWRE GARDING COSMECE UTICALS

Although the so-called cosmeceutical industry is booming, the FDA does not actually

recognize the term cosmeceutica13 nor is there an official definition for the word. Instead, the

cosmeceutical industry exists in a state of regulatory limbo: at times they are regulated as drugs,

but most often they are regulated as co~metics.~

And in the absence of an official definition, the

industry is essentially free to massage and manipulate the definition as it pleases. Thus

synonyms like "quasi-drugs," "therapeutic cosmetics," "cosmetic drugs," "active skin

treatment,"' and "cosmetics with pharmaceutical benefitsw6 abound in the marketing of

cosmeceuticals.

The FDA has created new regulatory space for some of the latest "combination products"
-
such as drug-devices and biologiodrugs -7 but it has not done so for cosmeceuticals. The agency

4
Many cosmeceuticals are created by cosmetics companies. Carol Rados, Science Meets Beauty: Using
Medicine to Improve Appearances, FDA Consumer Magazine (March-April 2004) available at
http:lhvww.f&.govlf&~Ifeahrred20041204~beauty.html (last visited May 5,2005).
Theie are, however, cosmeceuticals that are created by pharmaceutical companies. The Dermagenetics line of
"genetically customized" skin care products is an example. The fact that the parent company, GeneLink, Inc., is a
genetic-biosciencescompany with a focus on biomedical projects and that Pharmaceutical companies and Hospitals
are amongst its primary customers would suggest to most that this is more of a drug like product. However, as this
specific line of "genetically customized" skin care products are solely being marketed as just that, skin care
products, this product will likely be classified as cosmetic. For more information see Cosmeceuticals:
Dermagenetics Launched at ISPA Convention, Biotech Business Week (December 20, 2004) (hereinafter
Dermagenetics Article), ah, Corporate Profile, Gene Link, Inc., available at
ht~~://inuw.~ene~ink.com/nmsileleorate.as~ (last visited April 30,2005).
Santiago A. Centurion, MD, Cosmeceuticals (last updated February 4, 2004) available at
(last visited April 30,2005).
htt~://www.emedicine.com~derm/to~ic509.
Nora Caley, More Than Skin Deep; Company's 'Cosmeceuticals' Aimed at High-End Market, Rocky Mountain
News (April 19,1998) (quoting Francine Porter, owner of Osmotics).
'Recognizing that technological advances are continuously merging the lines between therapeutic products FDA's
Office of Combination Products was created to regulate these "combination products." But its jurisdiction only
covers combinations of drug-device, biologic-device, drug-biologic, and drugdevice-biologic. See 21 C.F.R 5
instead regulates cosmeceuticals through its traditional regulatory categories: either cosmetics,
6
-XI.,
drugs, or a combination of both. If the.status of a product is challenged, the agency will either

determine if a product held out by a company as a cosmetic is "misbmded" or if it.is in fact a -,=,

Drugs and cosmetics undergo very different regulatory treatments. Drugs are "(A)

articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of

disease...and @) articles (other than food) intended to affect the structure or any function of the

body of man or other animal^."^ Before they are released to the market, they must undergo a

burdensome, cost intensive regulatory process.'0 In contrast, cosmetics, including " c r e w ,

lotions, powders and sprays; perfbe; lipstick; [and] fingernail polish,"" are statutorily defined

as "articles intended to be mbbed, poured, sprinkled, or sprayed on, introduced into, or otherwise

applied to the human body ... for cleansing, beautifying, promoting attractiveness, or altering the

appearance."'2 Unlike drugs, the FDA does not review or approve cosmetics before they reach

consumers. In fact, cosmetics do not even have to be proven safe before they reach paying

consumers." It is therefore less costly for cosmetics companies to market their cosmeceuticals

products as cosmetics, rather than drugs, because they can avoid FDA oversight.

3.2(e). - -
See also Overview of the Office of Combination Roducts available at
(last visited April 30,2005).
htt~:llw~u.fda.eovloc/combinati~n/~ve~vie~.html
8
See eenerallv. See Byran A. Liang, It's Only Skin Deep: FDA Regulation of Skin Care Cosmetics Claims, 8
Cornell J.L. &Pub. Pol'y 249,252 (1999).
21 U.S.C. 6 321 @)(I)
'O See Robert Higgs, Hazardous to Our Health, 15 (The Independent Institute 1995) (a drug company must receive
preymarket approval for claims made about the dru& it must demonstrate that the product is efficacious for all
claimed indications, and it will be subject to clinical trial regulations).
Carol Rados, supra note 4.
IZ 21 U.S.C. 8 321 (i)
'' Carol Rados, supra note 4.
 A cosmeceutical's "intended use" - gleaned fkom the labeling, advertising, promotional
8;
-,
materials - determines the regulatory fate of a cosmeceutical as a cosmetic or drug. l4 The actual

effect of the product has no bearing on its intended use.I5 Therefore, cosmeceuticals .,
F,I

might indeed have skin altering properties, but so long as the manufacturers are careful in their

advertising claims, they will not have to worry about FDA oversight.I6

B. A COSMETICBY ANYOTHERNAME
WOULD SMELL. FISHY: A LOOK ..
AT THE MISLEADING NATURE OF THE TERM "COSMECEUTICAL"

It is the job of the FDA to "protect the unwary cu~tomer"'~

against a company's false and

misieading claims. A company must consider how the "ignorant, the unthinking, and the

credulo~s"'~
consumers will understand the products' claims. In fact, even if a product's name

impliedly (but falsely) claims that it is effective at achieving a specified outcome, may render it

misbranded." In that light, when the industry appends "ceutical" (which deceptively implies

that the FDA regulates the products in the same manner as pharmaceutical drugs) to refer to

products that the FDA in actuality regards as mere cosmetics is a legally questionable practice.20

" ...
See Liang, supra note 8, at 252 (citing United States v. An Article Consisting of 216 Individually Cartoned
~ o r e sMore
, or Less, of an Article Labeled in Part: Sudden Change, 288 F.Supp. 29 (E.D.N.Y. 1968) (hereinafter
referred to as "Sudden Change").
-
See id.
j6 -
See (last visited April 30,2005).
h~://www.cfsan.fda.cov/-dmslcos-217.h
D d d P. Hensel, FDA Regulation and the New Anti-Aging Products, FOOD AND DRUGLAW: AN ELECIRONIC
BOOK OF SlUDENT PAPERS, available at h~://leda.law.haryard.emJIeda/&ta/93/e.f(1995) (last visited
March 23,2005) (discussing how the caustic nature of Alpha Hydroxy Acids is overlooked by theFDA because the
manufacturers to not make drug claims on the labeling).
"-
See Liang, supra note 8, at 252 - 253. (citing Sudden Change).
%id.
l9 Peter Barton Hutt and Richard A. Menill, Food and D ~ u gLaw: Case and Materials - Second Edition,
(Foundation Press 1991), at 395 - 96 (citing United States v. 43% Gross...' Xcello's Prophylactics," 65 F.Supp 534
@. h
1946)).
' ~~osmeceuticd," which Dr. pemcone has regis& with the ~ederal
~ovemmentas his trademark, seems to be a
deceptive name under this theory.
 In order to understand consumer perceptions of "cosmeceuticals", I informally surveyed g;
(11
-,
eleven college educated consumers about what they thought the term "cosmeceutical" meant.

Their responses reveal that many consumers are unaware that the products are often times .,3
LLI

officially classified as simple "cosmetics." The participants mistakenly d e k e d cosmeceuticals

a "medicated cosmetics," "cosmetic prescription drugs," and "cosmetics with drugs."' If the

terminology misled these college educated consumers, it is highly likely that the average

consumer, the "unthinking" consumer, and the "credulous" consumers are being similarly

confused.22 In fact, in the past years cosmeceutical sales vastly outstripped sales of regular

cosmetics p r o d ~ c a ,indicating
~ th'at indeed consumers believe that they are purchasing

significantly different than regular cosmetics. Because they often promote their products as

"cosmetics," many cosmeceutical companies avoid the strict regulatoq requirements of "drugs,"

while at the same time profiting &om consumer perception that the products are indeed drugs or

that they have some type of "pharmaceutical benefit." Unfortunately for unsuspecting

consumers, the regulators seem to overlook the fact that the term wsmeceutical in and of itself is

a misleading term that should be cause for regulatoq concern. In the absence of federal

guidelines, consumers are forced to rely on outside sources to guide their product purchases.. .

2' Though some respondents did not extract the medical reference h m the t m , they did nonetheless ascnie some
elevated status to the word as they thought it might mean "able to teach cosmetics," or the "study of cosmetics."
'Ike remining q n s e s were: "'getting people to focus in on the medical side of cosmetics" and simply "cosmetics
in the pharmacy." Not one person said simply "cosmetics."
Jacqueline A. Greff, Regulation of Cosmetics that are also Drugs, 51 Food &Drug L.J. 243 (1996).
& SaUy Beatty, New Wrinkle - Hot at the Mall: Skin-Care Products 6om Physicians; Cosmeceutical Creams
Tap Antiaging Market; Questions About Claims; Dr. Pemcone TV Specials, The Wall Street J o d , A.1 (Nov. 14,
2003) (stating that "[slales of dermatologist and so-called clinical brands have exploded in the last year, becoming
the fastest-gowing segment of the deparbnent sore skin-cm business. W e total skin-care sales in deparbnent
stores g e w just 2.6% in 2002, sales of dermatologistand clinical brands jumped 62% in the same period...").
 C. 1s THERE A DERMATOLOGISTIN THE HOUSE?
A:LOOKAT THE
MISLEADING N A OF DERMATOLOGISTPROMO~ONS
~

Dermatologist recommendations are the Consumer's Digest of the beauty industry. The -5
4,
same reasons that we hold doctor recommendations in such high esteem are the very reasons that

regulators should be wary of an industry that uses doctors to promote cosmetics for profit. In

fact, in other areas, doctors can be held legally liable for referring patients to facilities in which

they have a financial stake." Cosmeceutical customers are denied the same protections.

Nevertheless, it is difficult for consumers to assess the claims of products and therefore they

must rely on experts to guide their decisions?' Because the FDA insufficiently regulates these

glorified cosmetics, from the consumers' perspective, these expert recommendations serve as a

proxy for federal regulatory filters.

Recently, recognizing the large profits to be extracted from the rapidly growing market, a

number of large cosmeceutical companies have rushed to incorporate the medically-trained into

their entourage of ~ales~ersons?~

A growing sect of dermatologists is bringing the industry, their

own books, their products, and their own image to celebrity status.27 Doctors such as Dr.

~ u r a d and
~ ' Dr. Penicone are paraded before consumers to emphasize the "ceutical" nature of

products that are in actuality considered by the FDA as nothing more than cosmetics. Thus, in

addition to the misleading moniker, the FDA should be more concerned with cosmeceuticals

24Sw e e n d v , Sam A. Mackie, J.D., Liability of a Physician for Improper Referral of Patients to a Medical Care-
Facility in Which the Physician Has a Financial Interest, 61 Am. Jur. Proof of Facrp 3d 245 (2004).
25
Rados, Science supra note 4.
26Beatty, supra note 23 (noting that L'Oreal jumped on growing trend of hiring dermatologists and "hired Dr. Tina
S. Alster, who frequently give skin-care advice on daytime talk shows, as a dermatological consultant to help with
product development and deparhent-store appearances [emphasis added]).
27Doctors such as Dr. Howard Murad, Dr. Fredric Brandt, and Dr. Nicholas Perricone. See Beatty, supra note 23.
Dr. Perricone will be discussed in more detail, inza page 9.
orm more information on Dr. M M ~see http://~ww.murad.~m/.
because they are being promoted by doctors whose presence could further act to confuse 8
UI
-,
consumers.

In order to protect consumers, the FDA imposes strict regulations on the relationship -,
(1 I

between pharmaceutical companies, doctors, and the information exchanged between the two.29

There is no such proscription on.. -the relationship between cosmetics companies and doctors.
,.. Y .
These companies have significantly more leeway in recruiting doctors to promote their products.

Of course medical professionals are prohiiited from engaging in false, hudulent, deceptive, or

misleading advertising, and advertising that would lower or demoralize professional standards,"

but beyond that there are no specific ethical standards to which they are bound that directly

address the promotion of products and services." Thus, these doctors have tremendous latitude

with respect to their marketing practices. A large part of the problem is that FDA does not have

jurisdiction o v a the medical profession," instead it is a task left to the whims of state

legislatures33 -- and even state standards may be too vague to effectively regulate doctors'

advertising practices.34 When consumers are running to the cosmeceuticals counters in droves

based solely on the assurances of these trained professionals, the FDA should be concerned. To

l9See Hutt, supra note 19, at 458 (discussing FDA's restrictions against pharmaceutical companies that in essence
bncdoctors with gifts and other promotionals in order to get the doctors to recommend their products to patients).
lo Laura Hunter Dietz, J.D., et al, Adverfising and Soliciting, 61 Am. Jur. 2d Physicians, Surgeons, and Other
Healers $13 (updated 2004).
" B MORE http://www.ama-assuorp/ama~pub/category/512.html.
In contrast, the legal profession has sketched
out ethics standards that directly speak to the propriety of attorney advertising.
"See Peggy Chen, Education or Promotion? Industry-Sponsored Continuing Education (CME) as a Center For the
~oR/commen:ial Speech Debate, 58 Food &Drug L.J. 473,473 (2003) (citing 21 U.S.C. $396 (2000) which states
that the Food, Drug, and Cosmetic Act (FDCA) "[shall not] be construed to limit or interfere with the authority of a
healthcare practitioner to prescribe or administer any legally marketed device to a patient for any wndition of
disease within a legitimate healthcare practitioner - patient relationship.") Instead, the medical profession is
regulated by the states,
"B g e n e k l y ~ i e t zsupra
, note 30.
& Amsel v. Brooks, 141 Conn. 288 (1954) (holding that state's definition of "advertise" in the context of
denture sales through a licensed dentist was unconstitutional as it had no ~easonablerelation to public welfare).
be sure, many medical professions may hesitate to use their status to promote products for a $1
Ul
-\

profit.

-,
One should not underestimate the trust that beauty consumers, and the general public 01

more generally place in medical professionals. Indeed, doctors are legally regarded as "learned

intermediaries" 35 who are liable for ramifications of their advice and opinions given regarding

risks and benefits of products. In some sense, we trust their professional expertise and good

judgment to be the final word on the products that they re~ommend?~Unfortunately for

unsuspecting consumers, (and quite fortune-ately for the cosmeceutical companies and doctors),

learned-intermediary doctrine is likely inapplicable to physicians who promote cosmeceuticals

because these products are not prescription products.'7 This is so despite the evidence that

consumers regard the products as something akin to "cosmetic prescription drugs," supra page 6.

He can make you beautiful in twenty-eight days! The cosmeceutical industry is being

rocketed to a new level of fame by the promotion of Yale Medical School professor and New

York Times best seller, Dr. Nicholas ~enicone." Dr.

Coined the "celebrity dermat~lo~ist,"~~

Penicone has made his indelible mark on the cosmeceuticals field. One need only conduct a

3s
Kimberly Castelas J.D. el al. Learned-Intermediary Dochine; Products Provided by Physicians, 63A Am. Jur. 2d
Products Liabiity 61200.
36 Id.

''&e id. (noting that "the learned-intermediary dochine does not apply to nonprescription products give to a patient
by a physician, since it would be illogical to e a t a plaintiff differently based on the mere fortuity of attaining the
product from his or her physician").
38 - (last visited April 30,2005).
See h~://www.~erricone.com~dmwenicone.hhn
39 ~ o ehg,
l : Become a Cosmetics King, You can't Let Anybidy Ciet "her YOW SXY,
The ~enicone~ o m u l aTo
Hartford Courant ( h k c h 6,2005).
 -,
\ i;,
71

i;
a cursory study of Dr. Penicone's career and empire to understand the distorting effect that a

dermatologists recommendation can have on the sale of cosmetics products. Advising

UI
-,

consumers about the links between beauty, neurology, and health, he has a series of New York -,
-,I

Times Bestselling b0oks.4~ And his celebrity status is not limited to the reading public; Dr.

Perricone lectures about his theory television stations around the country?' Indeed, in the five

years since his media debut, sales of his products reached the millions. Because he is

considered the "father of cosme~euticals"~

this paper will focus on Dr. Perricone as a case study

of the problems incumbent when doctors and profit motives are mixed.

-
1. Dr. Penicone The Doctor

Most consumers would be impressed with the credentials of this "learned intermediary"

and likely will make purchases based on his recommendations - a reality that the FDA should be

concerned about. The doctor started his medical career in the halls of Michigan State Umversity

College of Human Medicine (where he graduated in three years) and Yale University School of

~ e d i c i n e . 4Impressive,
~ extensive, and available to consumers worldwide, his online biography

acts to legitimize and bolster any claims that he makes about skin care products:

Dr. Penicone is an Adjunct Professor of Medicine at the Michigan State

University's College of Human Medicine. He is certified by the American Board
of Dermatology, is a Fellow of the New York Academy of Sciences, and a Fellow
of the American College of Nutrition. He is also a Fellow of the American
Academy of Dermatology and the Society of Investigative Dermatology. Dr.
Penicone has served as Assistant Clinical Professor of Dermatology at Yale

"See Liang, supra note 8.

"-
See id.
42 http:ll~~~.n~~~niconemd.com/ fiereinafter referred to as "Penimne Online") ('The Science" link. "Drug and
Cosmetic Industry" link) (last visited May 5, 2005). Interestingly enough, cosmeceuticals were in existence long
before Penicone's rise to fame. Products first anived on the scene more than 22 years ago, when vitamin A was
added to creams lo help fight wrinkles. Daniela Lamas, Cosmeceutical Controversy; Dermatologists walk a fine

a linewith skin-care product endorsements, The Houston Chronical, p. 14 (October 8,2003).

"See Liang, supra note 8.
 School of Medicine and as Chief of Dermatology at the state of Connecticut's
Veterans Hospital.
Dr. Perricone is the recipient of the Eli Whitney Award, presented by The
Connecticut Intellectual Property Law Association to an outstanding individual
who has made significant contributions to science, invention, and technology.
Prior recipients include National Medal of Science beneficiary, Igor Sikorsky,
(founder of Sikorsky aircraft) inventor of the &st practical helicopter, which
established. the bedrock upon which today's helicopter industry rests, and
Buckminster Fuller, inventor of the geodesic dom+the lightest, strongest, and
most cost-effective structure ever devised. Dr. Perricone is also the recipient of
the American College for Advancement in Medicine (ACAM) 2000 Norman E
Clark, Sr. Lecture Award for his, "dedication and contributions towards
advancing Complementary and Alternative Medicine."
It was during this time of receiving medical training that he developed his theory that .

"chronic inflammation underlays symptoms of aging." Dr. Perricone's theory, despite medical

skepticism, infra next paragraph, now stands as heart of his success because it is the driving

force of his .cosmeceuticals skin care line and books. According to the doctor, inflammation is

caused by stress, dehydration, sun,sugar,and high-glycaemic carbohydrates.

But it would take a bit more research for his trusting clientele to learn about the various

criticisms that have been lodged against the celebrity dermatologist by his professional peers.

Because he has not published studies in peer-raiewed journals proving that the main ingredients

in his products indeed erase wrinkles, it is doubthl that '%e has been able to convincingly prove

efficacy of his products.'d4 Instead, his peers charge that his claims are conhay to scientific

research in the area and that the claims are only based on his own anecdote^.^' Moreover,

although he touts his affiliation with Yale Medical School, his website does not disclose that in

" Beatty, supra note 23 (quoting Dr. Leslie Baumann, director of cosmetic dermatology at the University of Miami,
who conducts clinical trials for the cosmetics and pharmaceutical industry).
'I Knun, supra NOTE x. Buj see George W. Evans and Arnold I. Friede, The Food and Drug Administration's
Regulation of PrescriptionDrug Manufacturer Speech: first Amendment Analysis, 58 Food & Drug L.J. 365,383
- 86 (arguing that courts do not necessarily regard claims made in light of competing scientific claims to be
2002 Yale allowed Dr. Perriwne's appointment to expire because of the aforementioned fi;
(1l
.,
criticism in regards to his anti-inflammatory theories.46

-,
B. Dr. Pemkone - The Ernpin L! I
Dr. Perriwne's theories are founded on shaky science. Yet and still Dr. Perriwne has

managed to amass a large industry and consumer following.47 His name is ubiquitous as his

products are retailed through national chains such as Nordstrom and Sephom Moreover, the

"Perriwne" name reaches worldwide purchasers through his online ~ e b s i t e . ~ He

' even has

connections with big pharmaceutical companies. Though it seems as if he meant to keep his link

to pharmaceutical giant Johnson & Johnson a secref4' the celebrity physician is paid millions by

the company to license his products.

C Dr. Pemkone - The Pmducts

The fact that Perriwne products are intentionally encased in the medicinal-looking brown

jars and bottles with scientific naming, and 6 c t that they are priced at pharmaceutical like prices

contribute to a sense that these products are more than beauty products. And yet the FDA

regulates these products in the same manner that they would regulate a tube of lipstick.

C. The Pemkone Skin G

zz Line
Make no mistake; consumers' economic interests are a stake when they purchase

Perricone products. A 2-ounce vial of Alpha Lipoic Acid Face Firming Activator with NTP

Complex and DM4E costs consumers ~95;~'$120 is the price tag on the Perriwne Face Lipid

Beatty, supra note 8.

"~ d .
" htt~://www.nwemconemd.com/
(hereinafter referred to as ''Perticone Online")
49 See Liang, supra note 8 (stating that "a confidentiality agreement prevented [Dr. Pemcone] h m naming [the
l ~ c o m p a n paying
y him $150 million per year to license= his DMAE formulations").
' ~ v a i l a b l rat perticone O n h e , supra note 42 (last visited May 6,2005).
 CI
UI
~ e ~ l e n i s h m e n and
f ~ ' for his Neuropeptide Facial Conformer, consumers are charged a UI
-,
whooping $570 for 2 ounces. But even his lower priced products are exorbitant: Moisf Lips and

Lip Plumper - products akin to Chapstick-run between $18 and $33.52 2;

D. The NubitionalSuppkments

In addition to the topical products, the Perricone arsenal also includes nutritional

supplements. According to his website "N.V. Perricone Nutriceuticals@ [are] Nutritional

supplements that work on the cellular level, &om the inside out, to help you achieve and

maintain a more youthfbl, healthy look." For instance, Polysaccharide Peptide Blend" described

as "a daily part of the Perricone Program [that provides the body with] alpha-glucans, which help

increase the energy in our cells and help the skin repair, renew, and revitalize itself' are set at

$60 per month. His Benfotiamine Capsules will cost a consumer $40 per month. And the

month long "Weight Management Program" - a cornucopia of nutritional supplements - is sold

-
for $195:'

There is no denying Dr. Perricone's connection to his product line. He "personally

formulates every product" that he promotes:4 This artificially exaggerates the drug-like

mystique of his skin care line. Moreover, he also carries a higher potency professional line only

distributed to "qualified, licensed physicians, and to medical spas with a qualified physician on

staff."" Since they are only distributed fo these qualified professionals, then much like filters on

Id.
For a jocular insight on Penicone product pricing see Jeannie Kever, Paying a price by the Gallon, Tbe Houston
Chronicle (April 29, 2004) (stating "the next time you're filling up your S W , be glad it doesn't run on Dr.
Penicone's Neuropeptide Facial Conformer. Twenty gallons of his \HTinkle-fighting cream would set you back
$729,600").
S3,~vailable
at Perricone Online, supra note 42.
prescription drugs, they are presumably only available to the general public through the same 6;
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professionals. Based on all of this it is almost certain that the "ignorant, the unthinking, and the

credulous"56 consumers would be confused as to the nature of the Perricone products. I\I
$. .

Dr. Pemcone - The Books

E. The Labeling
Although the claims on the products' packaging are relafively "mild,'J7 the Wall Street

Journal noted that in contrast, Perricone's books make claims that seem quite "fanta~tic."~~

Indeed, in one of his book Perricone himself admits that his claims may seem "pretty lofty" he

assures skeptical consume* that his claims "will make perfect sense" once they understand how

his program works.59 One can reasonably assume that the manufacturers differentiated the

product claims and the book claims so that they and the M.D. could avoid the FDA's drug

regulations. Effectively, Dr. Perricone, much like many other cosmeceutical entrepreneurs is

having if cake and eating it too - (or in this case having his cosmetics and selling it too): The

claims on the labels that are directly affixed to his products are diluted.60 All of the real drug

claims are made in his books (and television promotionals) - a strategy which diverts FDA

attention but still entices consumers to purchase his products which they likely think have drug

l i e effects. But Perricone's bifurcated marketing strategy seems to overlook that the FDA might

s6 See Liang, supm note 8, at 252 - 253 (citing Sudden Change).

" For instance his Eye Area Therapy System only states, in relevant part: 'Tbunique eye care combination
pmvides you with the patented, powerful benefits of Vitamin C Ester, Alpha Lipoic Acid, and DMAE.
Vitamin C Ester Eye Area Therapy cares for,the delicate. eye area, minimizing the appearance of fine lines and
revitalizing stressed skin.
Alpha Lipoic Acid Eye Area Therapy provides energy to the skiq relieving the appearance of puffiness and dark
circles."
Beatty, supra note 23.
59 THE PUWCONE PRESCRIF'TION: A PHYSICIAN'S 28-DAY PROGRAM FOR TOTAL BODYAND RFAIVENATION,
HarperResource at xi (2002) (hereinafter referred to as "Perricone Prescription").
" Of course, as argued in this paper, packaging, the pricing, the term "cosmeceutical," and the doctor himself,
should be enough to mislead consumers. But FDA, however, has not ruled as such.
 ~i
very well consider the books themselves product "labeling" whose "fantastic" claims might in 61
,.01
fact elevate the skin care line fiom mere "cosmetics" to more heavily regulated drugs.

As stated in the beginning of the paper, a product's status as a drug or a cosmetic is kr

determined by its "intended use," which can be assessed through its labeling!' Under the law of

the Food, Drug, and Cosmetics Act, labeling includes, inter alia, "all labels and other written,

printed, or graphic matter ... accompanying [an] article."" Furthermore, the Supreme Court

ruled that labeling is broader than the labels that are on or in the article or package that is

transported 63 -- labeling includes freestanding books.64 Rather than a physical connectedness,

the textual relationship between the product and the literature seems most important in

determining whether a book is labeling a product.

There are several cases that provide guidance about what constitutes product labeling.

U.S. v 250 Jars ""Gal's Tupelo Blossom U.S. Fancy Pure ~oney'"'~'involved allegations of

misbranded honey. A retail store owner placed for sale on a shelf, jars of honey and copies of

an independently authored literature about honey.66 The court found that despite being sold

separately, the literature and honey were interdependent and part of an integrated distniution

Then, invoking the imagery of the "wary customer" the court rejected the notion

In general, however, "intended use" can be apprised from statements made by the company in any form or forum,
see Hun and Menile, supra note 19, at 386 (noting that the agency has relied on statements that a company has
made in submissions to the SEC).
21 U.S.C. 8 321.
"-See Kordel v. United States, 335 U.S. 345,350 (1948).
" See see U.S. Undetermined Quantities of Articles of D N ~ 145
, F.Supp2d 692 @.Md.S.Div. 2001) (holding
that"any printed material, including books and pamphlets, which refers to or explains the usefulness of a drug
product and which is used, in any way, in its sale, accompanies the article in the statutoly sense and constitutes
'labeling," for the plirposes of determining whether drug is misbranded.. .").

U.S. v. 250 Jars Calk Tupelo Blossom U.S. Fancy Pure Honey, 344F.2d 288,289 (6' Cu. 1965).
" U.S. v. 25OJars, etc, 218 F.Supp. 208.211-212 @.C.Mich. 1963)
that the literature was not labeling simply because it referred to honey in the generic sense, rather 8
(11
-,
than to the specific honey that was being sold.68 From this case one can infer that literature sold

by the author that specifically refers to products sold by the author will be particularly suspicious I:
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as product labeling.

Of course there are limits. The court in U.S. v. 24 Bottles '"'Sterling Vinegar and Honey

Aged in Wood Cider Blended With Finest Honey Contents 1 Pint Product of Sterling Cider Co.,

Inc., Sterling ass'""^ was faced with the question of whether books displayed in the same shop
as an article "accompanied" the article. The court made clear that "labeling does not include

every writing which bears some relation to the product;"70 but rather "[tlhe distinguishing

characteristic of a label is that, in some manner or another, it is presented to the customer in

immediate connection with his view and his purchase of the pr~duct."~'The court did, however,

intimate that books promoted in an "integrated transaction" with products may constitute

labeling for the products?2 In effect, it is the "textual relationship" between product and book is

a significant consideration?'

Based on these cases, and even though his books are not necessarily in "immediate

connection" with a purchasers view and purchase of his products~4

Dr. Perricone's products and

books should still be of particular concern to the FDA based on these earlier cases. Indeed there

US.v. 250 Jars, etc. of US.Faney Pwe Honcy, 221 F.Supp. 208 at 212. (the appeals court integrated, by
reference, tbis lower court opinion into its h a 1 opinion).
"338 F.2d 157 (C.A.N.Y. 1964).
Id. at 158.
Id. at 159.
U.S. v. 24 Bottles ""Sterling Vinegar and Honey Aged in Wood Cider Blended WithFinest Honey Contents 1 Pint
Product of Sterling Cider Co., Inc., Sterling, Mass."" 338 F.2d 157, 159 (C.A.N.Y. 1964).
7, U.S. v. Diapulse Mfg. Corp. of America 389 F.2d 612, '616 (C.A.Conn. 1968).
" Though it might be argued that the online products which are sold on the same site as his books are indeed sold in
the "immediate connection" of one another.
 -.,
$. .
\
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a
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is a textual relationship between the product and books that make them seem as if they are piut of 01
01
-,
an integrated transaction. Moreover, because Dr. Penicone is both the author of his books and

the creator of his products there is a stronger relationship between these items than there were in
21
t h e other cases where the books were created independent of the products. And even more

incriminatingly, the Penicone books actually direct consumers to his products?5 The points

argued above couple with the wwts' inclination to protect unsuspecting consumers against

sellers' exploitation of 10o~holes,7~

strongly suggests that the doctor's bestselling series are part

of the labeling for his skin care line.

F. The Drug Claims

Based on the legal definition of "drugs claims" there is almost no question that Dr.

Penicone's books assert very strong drug claims. Generally claims that a product has

a physiological effects will be suspect as drug claims?' Among the claims that have rendered

products drugs are that use "scientific buzzwords" [such as] 'biologically aseptic' while being

made in a 'pharmaceutical laboratory"' and claims that the product provides a "face lift without

surgery."78 Even claims that would seem to most as obvious exaggerations, for instance that a

commonplace household cooking sweetener honey is a "panacea for various diseases and

ailments" have been held by the courts to be problematic.79"Less exaggerated" claims, however,

will not promote a product fiom a cosmetic to a drug.''

75 PAGES in PRESCRIPnON.
76 &g a U.S. V. 250 Jars ""Cal'sTupelo Blossom U.S. Fancy Pure Honey"" 344 F.2d 288, *289 (C.A.Mich. 1965)
"Liang, supra note 8, at 253.
" Id. (quoting United States. K An Article ...Consisting of 216 Individually Cartoned Bottles, More or Less, of an
Article Labeled in Part:: Sudden Change, 288 F.Supp. 29 (E.D.N.Y. 1968).
79 U S . v. 250 Jars C a l f Tupelo Blossom U S . Fancy Pure Honey. 344 F.2d 288,289 (
' Cu. 1965).
6
" United States v. An Article of Drug ...47 Shipping Cartons, More or Less, ... "Helen Curtis Magic Secret," 331
FSupp. 912 (D.Md. 1971).
 The genealogy of the title of Perricone's first book reveals that despite his cosmetics
UI
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claims, the Perricone philosophy and product line are truly intended to fit into the medical realm.

Dr. Perricone intended his first book for other medical professionals and accordingly, he h~
01
originally entitled his first book "Antioxidants as Natural Anti-Inflammatories for Improvement

of Cellular Function." Though the substance of the book remained untouched, his publishers

later renamed it to its current more pop-kiendly, consumer-enticing title, The Wrinkle Cure?' In

The Wrinkle Cure Dr. Perricone enlightens readers as the causes of certain dermatological

problems, and then recommends a program of topical solutions 'and foods that can help alleviate

those problems?2

Beyond the "Cure" promised in the title of his first book, the title of his next Bestseller,

n , ~ ~ establishes the pharmaceutical nature of his empire. In this

The Perricone ~ e r s c r i ~ t i ofurther

bestseller, Dr. Perricone emphasized how changes in eating habits can effect dramatic changes in

physical appearance and well-being. Accordingly, he prescriies a specific program to reduce the

cellular inflammation that he claims is related to skin aging and other degenerative dbeasas."

From these two books alone, it is clear that Dr. Perricone intends his products as "prescriptions"

to "cure" what his theory describes as the "degenerative disease" of inflammation and aging.

In his most recent bestselling book, The Perricone ~romise,*~

Dr. Perricone continues

breaking down his theory to his audience of beauty-hungry consumers.86 In this book, the doctor

-
See Liang, supra note 8.
82 -
See Nicholas Perricone, M.D., The Wrinkle Cure,Warner Books (2000).
THEPUWCONEPRESCRIPTION, supra note 58.
"Id.
Nicholas Perticone, M.D., THE PRUUCONE PROMLSE : Look Younger, Live Longer in Three Easy Steps, Warner
Books (2004) (hereinafterreferred to as "F'erriwne Promise")
86 Consumers such as myself.
reveals a "groundbreaking program that helps reverse the aging - inside and out.. Dr.. Si
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Pemcone's revolutionary program' utilizes the biggest breakthrough in anti-aging medicine in

years, protein-like substances called peptides and neuropeptides. These pow& compounds

revitalize skin and hair, promote heart health, help decrease the risk of certain forms of cancer,

strengthen the immune system..."" Thusly, even though the claims on the labels physically

affixed to the skin care products are mild, the claims on made in the Perricone books - books

that consumers are likely to readily associate with his skin care product line, should concern the

FDA.

The Perricone website provides even more fuel for the argument that Perricone products

are intended as drugs?' On one page consumers can "Consult [the] Doctor" through a chart that

prescribes various items in his skin care line to remedy various ailments (such as "dry,

dehydrate'' skin and '105s of tone,

In contrast to the "less exaggerated" claims that past muster in the courts, Dr. Penicone's

assertions have been described by him and others as "fantastic" and "lofty." Moreover, if the

court were concerned that claims that a well-known, household grocery item would confuse

consumers to actually believing that it could cure various diseases and ailments then they would

be even more concerned about the less-familiar Penicone cosmeceuticals promoted in literature

by a famous, well established physician who indeed offers his products as an alternative to

surgery that will cure degenerative diseases. Pemcone cosmeceuticals are drugs and should be

regulated as such.

" Perricone Promise, supra note 84, at fiont cover flap.

Please note that the status of websiies as labeling or advertising is unresolved. Evans and Friede, supranote
45 at 373. id. at 378 -80, for an argument that websites are akin to labeling and therefore should be regulated by
the FDA
w-
~ m & : / / w 'cone.codconsultthed~~tor.htm
. ~ (last visited April 30,2005).
 G. A Drug in Cosmetic's Clothing

In light of the totality of circumstances - the clinical packaging, the clinical monikers, the
RI
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appendage "ceutical," the "Cure," the "Prescription," the drug-lie pricing, the association with

and endorsement by a renowned Yale Medical School dermatologist, - it would be a wonder if

consumers realized that they were purchasing products that have in actuality been regarded by

the FDA as nothing more than cosmetics -- akin to a tube of lipstick or a bottle of nail polish.

Moreover, if his products are indeed drugs, Dr. Perriwne might be forced to prove the

efficacy of his claims under the FDA's new drug approval process.g0 Seeing as he has not

published in any peer-reviewed journals and the veracity of his claims as been strongly

questioned within the medical field a drug designation might shatter his empire.

-
H . Dr. Perricone The Defenses

Admittedly, the case that ~erriconeproducts are d r u s might not be as clear-cut as

implied in the sections above. First, the disclaimers in his books and online might negate the

drug-like nature of the claims in these publications. Second, the First Amendment might protect

his books and claims fiom regulatory scrutiny. Finally, the public may actually benefit fiom the

information that he disseminates in his books and online publications.

The point may seem obvious, but the presence of a disclaimer, might makeit more

difficult to place these Perriwne products in the "drug" box. One such disclaimer reads: "This

book is written as a source of information only. The information contained in this book should

Evans and Friede, supra note 45, at 375.

 -,
~ E ~ b v L a u r $ B m
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by no means be considered a substitute for the advice of a qualified medical professional, who 4
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should always be consulted before beginning any new diet, exercise or other health

program.. .The author and the publisher expressly disclaim responsibility for any adverse effects
hi
arising &om the use or application of the information contained herein. .." Online, his disclaimer

states that "[tlhese statements have not been evaluated by the Food and Drug Administration.

This product is not intended to diagnose, treat, cure, or prevent any disease.'"' However, this

defense might prove weak under the shadow of Pasadena Research Laboratories v. US.,where

the court condemned disclaimers as "scientific doub~stalk."~~

J. Fint Amendment Rights

Though for the sake of regulation and consumer protection the books should be

wnsidered labeling as argued above, Dr. Perriwne and his books might still arguably be

protected by the F t Amendment right to 6eedom of speech. The world of F t amendment

protected speech can be divided into three general categories: 1) low level protection of

commercial speech;932) high level protection of non-commercial speech and 3) non-protection

of fighting words, obscenity, threats, etc. Perricone's books are clearly not "fighting words;"

therefore they will likely be subject to some sort of protection. The question is how much?

In assessing cornmerciality, courts will determine whether "1) the speech at issue is

conceded to be an advertisement; 2) the speech refers to a particular product; and 3) the speaker

Perricone Online, supra note 42.

sz 169 F.2d. 375,383 (9'Cir. 1948).
" See Commercial Adverticing and VirginiaState Bd. of Phann. v. Virginia Citizens Consumer Council, 425 U.S.
748(1976) (ovenuling an earlier decision that exempted commercial speech ftom the protection of the First
Amendment, the Supreme Court here held that commercial speech is low value speech that receives First
hendment protection).
 -,I
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has an economic motive."94 If Perricone's books were actually labels that were physically 8
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&ed to the products in his skin care line, one could be comfortable arguing that they were

commercial speech as they were attached to products that were being sold commercially. But the
4;
idea that these books are "labeling" as we commonly understand the term is merely the magic of

the FDA's broad regulatory definitions. Perricone's books are, in actuality, freestanding

publications; and it is a longstanding practice that the First Amendment protects published

materials?' In that sense, it might seem obvious that the bestsellers are protected speech that

should be exempt fiom regulatory oversight.

The status of the books, however, seems more unclear than not, especially in light of

recent Supreme Court cases grappling with the difficult question of the intersection between

commercial speech, non-commercial speech, and issues of public importance?6 Similarly here

there are two strong competing interests: First the FDA broad mandate to protect consumers
-
against rogue cosmetics (and thkr infirmed labels) and second, the constitutional guarantee of

the right to fiee speech. Ultimately, Dr. Pemcone's best line of defense against the FDA's duty

to protect consumers might be to argue that his books are protected speech because they are

traditional publications rather than mere commercial speech since he does not refer to them as

advertisements and makes no reference to anyparticular products in his product line?'

Evans and Friede, supranote 5, at 383.

, " & Chneck v. US., 249 U.S. 47 (1919) (holding that published materials are protected under the First
Amendment as long as they present no clear and present danger to the public).
% b Nike v. K&, 539 U.S. 654 (2003) (presents what was at the time a novel First Amendment questions
because the speech at issue represented a blending of commercial speech, noncommercial speech, and debate on an
issue of public importance. Commercial enterprise Nike was accused of abusive labor practices which it responded
to in various newspapers and publications.).
5-7
Although Perricone does make passing reference to his own products, his books do not specifically relate to his
products. Instead the books detail a holistic nutrition and cosmetic regime that works "synergistically" with bis
products. In the text of the books there are no direct mentions of specific products of in his product line. He does
however provide the addresses of online websites where consumers can purchase cosmeceuticals that would
 I.;
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One final policy argument aid Dr. Perricone's defense. Even if his products are in fact

drug,they should not receive the burdensome drug regulation because theie are arguable (I!
Cl
benefits to his "diiect to consumer" advertising approach. It is an argument that is broadly

applicable to more than just Dr. Penicone's products. As the argument goes, disseminating

information empowers consumers to make decisions about their healthcare and their health care

regimes, especially when they might have more information about their conditions than do

doctors. He could in fact argue that direct to consumer information is vital for the vitality of our

American c o n ~ u m e r s h i ~ . ~ ~

CONCLUSION

As they have done with the pharmaceutical industry:9 the FDA may have to expand its

jurisdiction to check the practices of these physicians that consumers - the consumers that the

FDA is charged with protecting -- are relying on to guide their cosmetic purchasing choices. Or

perhaps it is just a matter of creating a new regulatory category that would provide clear

guidance to cosmeceuticals companies about exactly how to and to cosmeceuticals purchasers

about what they can expect from the products. No matter the strategy that the FDA ultimately

generally fit into the regimen that he advocates. The sticky issue is that even though he seems to be directing
readers to an array of other online cosmeceutical products, m fact for all of the sites that consumers are directed to
only sell his line of products. So, defacto, his books refer to his particular products.
In another twist, at the back of the Pemwne Promise is a special promotional where the doctor directs w&ers to
his website to pmhase a certain amount of his productsin order to receive two of his eye therapy products for h e .
It is not clear where this type of product placement would fall in the realm of commercial speech jurispmdeice.
98 For the counter to this argument see JeEey P. Kahn, Ph.D., M.P.H, The Double-Edged Sword of Drug Marketing,
Ethics Matters (August 9, 1999) available at httD:llwww.cnn.co~EALTWbioethics/99O8ldrueemarketin~ (last
visited May 8, 2005) (arguing that even though there is value m drug advertising the downsides include a
proliferation of false or misleading information, and an upheaval of the haditionat doctor-patient relationship).

23
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employs, it is clear that the cosmetics industry's parading of dermatologists to sell their products 8
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to credulous consumers should be a matter of concern for us all.

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 ---"
!e 3 1 , Number 7 , P rt 2, July 2005
'.'ALUMNI MEDI~~
LC!
111
Introduction: Why Cosmeceuticals?
Zoe Diam Draelos, MD
Relevance of Cosmeceuticals to the Dermatologic Surgeon
Harold J. Brody, MD
Novel Approach to the Treatment of Hyperpigmented Photodamaged
Skin: 4 % Hydroquinonel0.3% Retinol versus Tretinoin 0.05%
Emollient Cream
Zoe Diana Dmelos, MLI
Vitamin E: Critical Review of Its Current Use in Cosmetic and
Clinical Dermatology
Jens J. Thiele, MD, Sherry N. Hsieh, PhD, and Swarm Ekamyake-
Mudiyanselage, MD
Topical Vitamin C: A Useful Agent for Treating Photoaging and Other
Dermatologic Conditions
Patricia K. Farris, MD
Dietary Supplements: Altered Coagulation and Effects on Bruising
Scott M. Dinehart, MD, and Lance Henry, MD
Endogenous Growth Factors as Cosmeceuticals
Richard E. Fitzpatrick, MD
Cosmeceutical Peptides
Mary P. Lupo, MD
Zinc and Skin Health: Overview of Physiology and Pharmacology
James R. Schwartz, PhD, Randnll G. Marsh, PhD, and Zoe Diana
Draelos, MD
Inhibition of Enzyme Acdvitia and the Antiwrinkle Effect of Polyphenol
Isolated from the Persimmon Leaf (Diospyos bnki folium) on Human
Skin
Bong-Jeun An, PhD, Jae-Hoon Kwak, MS. Jung-Mi Park, MS,
Jin-Young Lee, MS. Tae-Soon Park, MS, Jin-Tae Lee, MD, Jun-Ho
Son, PhD, CheorunJo, PhD, and Myung-Woo Byun, PhD
Double-Blinded, Placebo-Controlled Trial of Green Tea Extracts in the
Clmical and Histologic Appearance of Photoaging Skin
Annie E. Chiu, MD,Joanna L. Chan, AB, Dale G. Kern, MS, Sabine
Kohler, MD, Wingfield E. Rehmus, MD, MPH, and Alera B. Kimball,
MD, MPH
Niacinamide: A B Vitamin that Improves Aging Facial Skin Appearance
Donald L. Bicsett, PhD,John E. Oblong, PhD, and Cynthia A. Bnge, BS
Botanical Extracts Used in the Treatment of Cellulite
Doris Hersel, MD, Cecilia Orkfndi, MD, and Debora.Zechmeictn do
Prado, PHARM
Cosmeceuticals Containing Herbs: Fact, Fiction, and Future
Curl Thomfeldt, MD, FAAD
Efficacy of 1 % 4-Ethoxybenzaldehyde in Reducing Facial Erythema
Zoe Diana Draelos, MD, and Bryan B. Fuller, PhD
Review of Skin-Lightening Agents
Marta I. Rendon, MD, andJorge I. Gaviria, MD.
The Future of Cosmeceuticals: An Interview with Albert Kligman,
MD, PhD
Zoe Diana Draelos, MD
Introduction: Why Cosmeceuticals?
This unique supplement to Dmatologic Surgery was pro-
posed to help the dermatologic surgeon understand how
topical agents might influence surgical outcome. The sup-
plement is a compilation of review articles and original
conuibutions from practicing dermatologists, basic sci-
ence academicians, research dermatologists, and industry
researchers, each focusing on a different group of actives
with defied skin effects. This wide range of expertise cre-
ates a knowledge compendium blending many different
viewpoints in the realm of cosmeceuticals. The conuasting
viewpoints are important because cosmeceuticals are an
undefined, unregulated category of products that impact
the skin. To the cosmetics industry, cosmeceuticals repre-
sent products with well-studied actives that offer more
than adornment to the user. To the dermatologist, cosme-
ceuticals represent products that may or may not deliver
on the advertised claims. To the dermatologic surgeon,
cosmeceuticals represent topical agents that may enhance
or retard healing. To the researcher, cosmeceuticals repre-
@3
.
2005 by the A m i c o n Society for Demurlolozi~Surgery, Inc.
ISSN: 10764512 Dermorol S~urg2005;31:795.
, -
Published by BC Decker Inc
sent the next frontier in biologically active skin care. It is
true that these are dissimilar viewpoints, but all are aimed
at advancing skin technology.
The supplement covers the current knowledge base
regarding the cutaneous antioxidants vitamin C, vitamin
E, and idebenone and the barrier-enhancing vitamins
niacin and panthenol. It reviews the utility of topical met-
als, including selenium and zinc. It examines ski-lighten-
ing preparations and cellulite treatments. An overview is
taken of the broad range of available botanical extracts.
Lastly, state-of-the-art knowledge regarding the role of
peptide messengers, anticoagulants, and anti-inflamma-
tory agents is presented. It is hoped that this overview will
help the dermatologic surgeon deliver better care to
patients inquiring about the use of skin care cosmeceuti-
cals.
-
ZOEDIANAD ~ o s MD
,
High Point, NC

Relevance of Cosmeeeutieals to the Dermatologie Surgeon
HAROLD J. BRODY,MD
Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia
BACKGROUND. The dermatologic surgeon is the dermatologist
with special expertise in the surgical care of the health and beauty
o ~ p kMETHODS,, WVLTS.There is no better arena for the
use of topical regimens to preserve skirt quality than in the time
HAROLD J. BROD& MD, HAS INDICATED N O SIGNIFICANTINTEREST WITH COMMERCIAL SUPPORTERS.
THE DREAM that the application of a miraculous cream
will reverse the aging process has inspired countless nov-
els, movies and television dramas, and documentaries.
This fantasy has persisted into the twenty-first century,
with no signs of abating. But is this a fantasy favored in
marketing and advertising campaigns for new products? It
is not necessarily so. The claims made for many of these
products are backed by scientific study-Others, however,
offer nothing more than novelty.
Skin care products are divided into cosmetics and
drugs, the latter having a biologic effect on living tissue.
The concept of an "in-between, drug-like miracle cream"
that combines the two elements into a single product is not
recognized as an entity by the US Food and Drug Admin-
istration (FDA). As a result, it can be difficult, not only for
consumers but also for physicians, to judge the validity of
the claims made for these "miracle" creams.'
"Cosmeceuticals" is a term that has no standing in US
regulatory law. The term has been credited to several der-
matologists, but Dr. Albert Kligman was one of the first
dermatologists to use the term. His intention was to use it
to connote a cosmetic product that exerts a pharmaceuti-
cal therapeutic benefit but not necessarily a biologic ther-
apeutic benefit, which would then classify it as a
Such products still fall outside the regulations of existing
classifications. The classification of a product depends on
the claims that a manufacturer or.distributor makes for a
product to reflect its intended uses. A suntan preparation
is classed as a cosmetic, but a sunscreen to prevent sun-
burn with a specific sun protection factor that blocks
Address correspondence and reprint requests to: h r o l d J. BIO~Y,
MD, 1218 Wesi Paces Ferry Road, Atlanta, GA 30327. '..
.
O ZOOS by rhe American Society for Dermorologic Surgery, Inc.
ISSN: 10764512 Demoto1 Surg 2005;31:796798.
.
Published by BC Decker Inc
t..
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Fit.
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interval devoted to before and after care with respect to surgical
procedures.
coNcLusIoN. Many of these regimens can be tailor devised with
topical drugs and cosmeceuticals together in proper balance in
the patient's best interest for affordablehealth care.
ultraviolet radiation is subject to regulation as an over-the-
counter drug. The a-hydroxy acids (AHAs) exemplify the
dilemma based on concentration' in a product. Lower
strengths have been present in cosmetics for years. Higher
concentrations are classified as drugs. A similar situation
exists with hydroquinone in over-the-counter products.
Why should the dermatologic surgeon get involved in
this process? Arbitrarily, many practitioners misrepresent
prescription retinoids as cosmeceuticals, when, in reality,
they can be drugs with a biologic effect in the form of all-
trans retinoic acid, known as tretinoin. In the twenty-first
century, a "mix-and-match" philosophy sustains the inter-
est of the public. Patients use prescription drugs along with
suggestions from their doctor, esthetidan, or neighbor.
They devise thei.r own miracle combination that will
change the frog into the prince or the witch into the queen.
By their training, dermatologic surgeons can use the tal-
, ents of their study in dermatology to educate patients.
Classically, dermatologic surgery is divided into surgery of
the skin to elevate the state of, first, health and, second,
beauty. Most classically trained Mohs surgeons show
interest in the latter to the extent that their wound closures
from skin cancer might be as beautiful at the conclusion as
they are when they are conceived. Today the procedural
dermatologic surgery fellowships that concentrate on both
skin cancer and cosmetic dermatologic surgery implore
that the dermatologic surgeon be as familiar with the areas
of cosmetics, cosmeceuticals, and topical drugs as any
newly trained dermatologist. The surgeon can use this
training in the treatment of skin cancer and in cosmetic
dermatologic surgery as well. We owe it to our patients,
and we can influence the wound healing process in the
bargain. Most important, the surgeon can inf:u:o-e the
patient's motivation t o improve his or her appearance.
 Anxiety and depression occurring before or after surgery
can be greatly diminished by gentle but intelligent and
imperative suggestions for skin health and beauty. The
great patient and physician satisfaction that can result
from proper suggestions toward skin health should not be
restricted to any subspecialty within dermatology and
' should be embraced by all dermatologic surgeons.
Of the most common compounds recommended,
retinoids have an extremely valuable property in addition
to restoring a youthful appearance to the skin. They inhibit
tumor growth, decrease inflammation, and enhance the
immune system. Application of these agents reduces the
number and size of actinic keratoses as well as freshens the
skin, a perfect concept for use by the oncologic dermato-
logic surgeon. Retinoids normalize epidermal atypia,
increase dermal collagen deposition, and increase new
blood vessel formation. Cosmeceutical retinol products,
which are considerably less potent than tretinoin, penetrate
the skin well and are converted to a small amount of
tretinoin in the skin. Although less irritating, they are less
efficacious than topical tretinoin. Retinol, which is the pri-
mary alcohol form of vitamin A,, may prove valuable to
the dermatologic surgeon in titrating doses of vitamin A
creams before and during cancer surgery in very sensitive,
fair-skinned patients intolerant of tretinoin.
Ascorbic acid, or vitamin C, is found in citrus fruits and
leafy green vegetables, tomatoes, and potatoes. It is a pow-
erful antioxidant in extracellular fluids and in many cellu-
lar activities. It scavenges ultraviolet light-induced free
radicals that damage cell membranes and deoxyribonu-
cleic acid (DNA). In the presence of vitamin E, the antiox-
idant effect of vitamin C is enhanced. The free radicals are
effectively suppressed, thus allowing ascorbic acid to act as
a photoprotective agent. Topical vitamin C may reduce
ultraviolet light-medicated phototoxicity because of its
antioxidant and anti-inflammatory propemes. Difficulty
in performing its functions topically arises with its insta-
bility and erratic penetration into the skin. The dermato-
logic surgeon can suggest preparations that will cut
through the confusion that the consumer may encounter
and recommend preparations that have a longer-lasting
stability. This group of cosmeceuticals may be an adjuvant
to the treatment of skin cancer.
Sunscreens are considered cosmeceuticals because they
offer epidermal and dermal protection from the sun. It is
axiomatic that dermatologic surgeons who are adept at
chemical, laser, and dermabrasive resurfacing impress the
value of sunscreen use on their patients. It is also impera-
tive that every skin cancer surgeon suggest and emphasize
the value of sunscreens that offer broad-spectrum coverage
against the harmful effects of ultraviolet A ( W A ) and B
rays of the sun. Using these products should greatly
decrease the chances of skin cancer and skin aging, as well
as reduce the incidence of postinflammation hyperpig-
mentation after resurfacing. Those who use sunscreen3
that protect against the deeper-penetrating W A in t h 8
range of 320 to 400 nm are quintessentially using cosmeyl
ceuticals combined with dermatologic surgical proceduresl'
The cancer-producing effects of W A may be aggravated
by the production of reactive oxygen species (ROS), which
have been shown to have effects on cellular functiodjl
apoptosis, aging, and eukaryotic gene e x p r e s s i ~ nW ~C-~I
. ~A
blocking sunscreens are therefore necessary for all skin
cancer patients. The newer Mexoryl SX, L'Orial, Paris,
France, which blocks midrange UVA, is available in
Europe. These screens may assist in shielding the skin from
a wider range of sunlight and eliminate the increase of
ROS from exposure to the sun.
The use of a regimen along with cosmetic dermatologic
surgical skin resurfacing is imperative. Most surgeons
choose the mix-and-match regimen of a cosmeceutical and
pharmacologic combination of sunscreens, hydro-
quinones, retinoids, and AHAs. In all skin types, the
higher-percentage prescription hydroquinones are impera-
tive for maintaining results. The use of exfoliation of the
stratum corneum in the form of shaving the skin, along
with exfoliative scrub pads or granules, will increase pen-
etration of applied products. The cosmeceutical hydroxy
acids may be used to increase penetration of all agents as
well.
Glycolic and lactic acids are the prototypical AHAs.
The application of an 8% glycolic acid cream can reverse
the photodamage incurred by the epidermis and dermis
and produce some increasein dermal collagen.6 It can
induce the shedding of the sun-damaged cells in the upper
skin layers of the stratum corneum and epidermis. The
improvement varies with the pH of the product and the
formulation of the vehicle. AHAs can increase
mucopolysaccharide and collagen synthesis, which may or
may not induce improvement of fine wrinkles.'Combining
two AHAs into triple hydroxy acids has no proven bene-
fit at this time.s
p-Hydroxy acids (BHAs) are compounds that promote
shedding of the skin's cells by increasing epidermal cell
turnover and have possible anti-inflammatory capabilities
as well. They are based on salicylic acid, which has had
FDA approval as an ingredient in antiacne and other med-
ications for many years. The BHAs may sting less than the
AHAs because they do not penetrate to the dermal layer
and are found in many cosmetic moisturizers in concen-
trations of 2% or less. Other BHAs include P-hydroxy
butanoic acid, trethocanic acid, and tropic acid. Combi-
nation hydroxy acids can use use both alpha and beta
acids. However, because the pH requirement of each is dif-
ferent, one ingredient would have to dominate; thus, there
would be no benefit in integrating the two.
Polyhydroxy acids, the larger-molecular-weight AHAs,
are organic carboxylic acids that possess two cr more
hydroxyl groups. They provide skin benefits sir;.i!>r to
those of the AHAs. They may penetrate the skin s o r e
I 798 BRODY: RELEVANCE OF COSMECEW'ICALS TO THE DERMATOLOGIC SURGEON
I
slowly and be less irritating to patients with sensitive skin.
They may act as humectants because of multiple hydroxyl
groups in chemical structure and will increase the skin's
moisture retention. Lactobionic acid and its component
gluconic acid are the chief agents in this group.' Glocono-
lactone, the lactone form of gluconic acid, may diminish
the appearance of fine lines and improve uneven, mottled
pigmentary skin tone. Lactobionic acid possesses antioxi-
dant effects to theoretically retard skin aging through iron
chelation and by inhibiting the oxidation of other sub-
stances, including hydroquinone, a rapid oxidizer. This
group of compounds may have applicability in postresur-
facing regimens, especially after microdermabrasion,
because of the gentleness of the products.
In the realm of other cosmeceuticals that may be com-
bined with topical drugs, alpha-lipoic acid is a potent
antioxidant that is both fat and water s ~ l u b l e . It
' ~ differs
from vitamins that are either fat or water soluble. When
applied topically, it is rapidly absorbed down to the level
of the subcutaneous fat and is protective of both vitamin
E and C within cells. Application of 3% alpha-lipoic acid
has been shown to diminish fine wrinkles and scars, pre-
sumably because it leads to synthesis of new collagen. The
nonsteroidal antiandrogen ethoxyhexyl bi~~clooctanone
(Chantal Pharmaceuticals, Los Angeles, CA, USA) is mar-
keted and promoted as an agent that increases elasticity in
the skin with twice-daily application. The topical applica-
tion of cosmeceutical human growth factors, including
transforming growth factor P,, to photddamaged skin can
induce epidermal thickening, new collagen formation, and
a decrease in the appearance of wrinkles (topical growth
factors are formulated as TNS Recovery Complex, mar-
keted bv SkinMedica Cor~oration.Carlsbad., CA.,USA).
Agents may be combined in the future into one cream for
ease of application. Outside the studies perfomed by the
patent owners, there have been no confirmatory dinical
studies to confirm the efficacy of these products. The der-
matologic surgeon should be aware of ail of these products
and their theoretical and investigative benefits for patients
as possible regimen supplements.
Ideally, a regimen after resurfacing should consist of a
sunscreen followed by an AHA or a BHA appliedwith a
hydroquinone bleach in the morning. In the evening, a
nonirritating retinoid titrated to the patients's skin type
can be used with a vitamin C or combination product,
possibly on alternate days, along with a second hydro-
quinone application. Patients who are very dry may toler-
ate the additional creams above with theoretical benefits.
The use of a combined topical drug and cosmeceutical
regimen in concert with other procedures performed by
. the dermatologic surgeon enhances the effect of the proce-
dures in the vision of both patient and physician. The cos-
Dermatol SUrg 31.7 Part .?:July
ci
metic use of botulinum A exotoxii and a plethora of s%
tissue fillers on dry, nonrejuvenated skin may do 3 2
patient a disservice. Patients notice the improved quality of
their skin even more with topical rejuvenation adjuvants
after furrows and wrinkles are alleviated by soft tissue
augmentation. They appreciate the extra care provide&y
the regimen suggested by the surgeon. The use of retinoids
in the scalp combined with minoxidil for increased pene-
tration as cosmeceuticals in hair transplantation is an
excellent way to combine medical and surgical treatments
for the treatment of alopecia. There is every good reason
for the surgeon who is performing liposuction surgery
with fat transfer, electrosurgery, benign excisions,
cryosurgery, reconstructive surgery, skin cancer surgery,
scar revision, tattoo removal, laser surgery, and scle-
rotherapy to consider the benefits of adjuvant skin rejuve-
nation regimens with combination cosmeceutical and
pharmaceutical recommendations for their patients.
In the future, cosmeceuticals will work exceptionally
well with the nonablative technology of the twenty-first
century. The nonablative lasers for skin rejuvenation, the
intense pulsed light devices for pigmentary and erythema-
tous disorders, and the radiofrequency devices to tighten
the skin all require at least some maintenance treatments.
Many of these devices can be complemented with cosme-
ceuticals or mixed drug-cosmeceuticaI regimens. The
expertise of the dermatologic surgeon and his or her staff
can be used to select the correct topical agents to tailor
simple, easy-to-use regimens for patient comfort and for
every variety of patient budget.
References
1. Brody HJ. Larest ways ro rejuvenare sun-damaged skin. Skin Cancer
.""..",.,,.. -"-,.
F~...-rl 11000.17.7Q-0
2. McNamara SH. Cosmeceutiulr. Cormer Dermatol 1994;7:28-9.
3. Terakis N. Cosmeceuticals:a new bred of cosmetic products. Cos-
met Dermarol 1993;6:4&1.
4. Scharffetter-Kochanek K, Wlaschek M, Brenneisen P. W-induced
reactive oxygen species in phorocarcinogenerisand phoroaging. Biol
Chem 1997:378:1247-57.
5. Burkhan CG, Burkhan CN.Arsessmenr of sunscreens wirh patient
care considerarions. Cosmet Dermatol2001;14:21-2.
6. Stiler MJ, Bartolone J, Stem R, et al. Topical 8% glycolic and 8% lac-
matol1996;132:631-6.
-
tic acid creams for the rreatment of ohotodamaeed skin. Arch Der-
7. Dive CM. Griffin'ID..Murohv . . ,
. , GF. Effects of a l ~ h ahvdroxv acids on
photoaged skin: a pilot clinical, hisrologic and ultrastrucmral study.
J Am Acad Dermatol 1996;3:187-95.
8. Draelos ZD. Hydroxy acid update. Cosmet Dermatol1998;I1:27-9.
9. Green B, Edison B, Wildnauer RH,. Sider - ML. Lanobionic acid and
gluconolacronc: PHAS for photoaged skin. Cosmer Dermacol
2001;14:24-8.
10. PerriconeN. Topical alpha lipoic acid for anti-aging. Skim Aging
1998;6:17-9.
 " Cosmeceuticals Containing Herbs: Fact, Fiction, and Future
?
L CARLTHORNFELDT,
MD, FAAD
cms
I. Private practice, CT Derm, PC, Fruitland, Idaho; Oregon Health Sciences University, Portland, Oregon; EpiSciences,
mJ Inc., Boise, Idaho
'r J
BACKGROUND. Modern medicine is rooted in ethnobotanical tra-
ditions using indigenous flora to treat symptoms of human dis-
ici- eases or to improve specific aspens of the body condition. Habal
13, medicine is now used by over half of the American population.
Yet the American medical community generally lacks knowledge
of the function, metabolism, interanion, adverse reactions, and
preparation of herbal products.
O B J E ~ J V X Because over 60 hotanicals are marketed in cosme-
ceutical formulations, dermatologists need to obtain working
knowledge of the major hotanicals. The preparation, traditional
his uses, mechanisms of action, human clinical data, adverse reac-
11%- tions, and interactions all impact herbal eficacy and are dis-
for cussed below.
'he
ne CARL THORNFELDT, MD, FAAD, HAS INDICATED N O SIGNIFICANT INTEREST WITH COMMERCIAL
'Or SUPPORTERS.
on
THE FOUNDATION of modern pharmacologic medicine
is rooted in ethnobotanical traditions using indigenous
flora. Over 200 indigenous medicinals were listed in the
first U.S. Pharmacopeia in 1820, including podophyllin
resin, white willow bark, wintergreen, and juniper tar,
which are still used today.'
Botanicals used for medicinal, flavoring, or fragrances
are known as herbs.'s2 The guiding principle of herbal
medicine is that the naturally occurring mixture of active
compounds in plants is more effective and safer than indi-
vidual molecules and manufactured combinations of syn-
thetic molecules. The natural composition is the commin-
uted, powdered, or galenic extracts of the whole or specific
'Scientific Issues
anatomic parts of the plant. Botanical medicinals are
focused more on the treatment of signs and symptoms of
disease, while improving the total "body condition," than
the etiology.
Botanical sales in 2002 in the United States exceeded
$4.3 billion and grew by one-third over only 6 years.
Echinacea was the largest selling botanical in 2002, with
sales of nearly $190 million. Botanical product growth has
flourished to now consume 25% of all health- and
lifestyle-related dollars.' Now over 60 different botanicals
are formulated into cosmeceuticals. Thus, dermatologists
Address correspondence and reprint requests to: Carl Thornfeldt,
MD, FAAD, CT Derm, PC. 8 1 1 . N W 12th Street, Fruitland, ID
83619, or e-mail drcarl@epionce.com.
. .
O 2005 by the American Society for Dermntologic Surgery, Inc. Published by BC Decker Inc
ISSN: 10760512 D e n m o l Surg 2005;31:873+80.
6
OI
VI
-$
bl
-.I
METHOD. English-language medical journal and symposium
searches.
RESULTS. The most important botanicals pertaining to demato-
logic uses, such as cosmeceuticals, include teas, soy, pomegran-
ate, date, grape seed, Pycnogenol, horse chestnut, German
chamomile, curcumin, comfrey, allantoin, and aloe. All are doc-
umented to treat dermatologic conditions. Only green and black
tea, soy, pomegranate, and date have published clinical trials for
the rreatment of parameters of exuinsic aging.
CONCLUSIONS. Preparation of botanical-based cosmeceuticals is
complex. Very few of these products are supported by evidence-
based science.
must have a working knowledge of botanicals to provide
optimal medical care.
Several botanical treatments for cutaneous diseases
have stood the test of time for their effectiveness, as docu-
mented by modern scientific evidence. Podophyllotoxin is
a prescription purified podophyllin resin, a galenic extract
of mayapple
. - - (Podophyllum
. . peltatum). Capsaicin is a non-
prescription therapy for pruritis and pain extracted from
cayenne peppers (Capsicum species). Henna (Lawsonia
inermis) is a hair dye used by people sensitized to other
commercial coloring agents.'
Herbal medicine plays a vital role in current American
health care by (1)providing alternatives to prescription
medications, (2) enhancing the therapeutic effects of other
prescriptives, (3) protecting against adverse reactions to
allopathic therapy, and (4) providing treatment for dis-
eases for which there is no current prescription therapy or
only poorly effective or high-risk therapy. Herbal and
other alternative medical strategies are used by over half of
the population, especially by those suffering from chronic
diseases, such as psoriasis; those with less hope for a cure,
such as human immunodeficiency virus (HIV); and those
with terminal Extensive public use of cmple-
mentary and alternative medicine resultedin thr f.!a:ional
Institutes of Health establishing the Office of Alter.;ative
Medicine in 1995.l

874 THORNFELDT: COSMECEUTICALS CONTAINING HERBS
Unfortunately, two major myths taint herbal medicine.
Most patients believe the myth that there are no side
effectsbecause herbal medicine uses "natural substances."
In fact, experienced Chinese practitioners are concerned
about the well-known side effects of hepatotoxicity and
contact dermatitis with oral and topical Chinese herbal
medicinals and preparations, respectively.'
Many a l l o ~ a t h i cphysicians believe the myth that
double-blinded, placebo-controlled studies d o not exist
for traditional medicines. Yet there are many such studies
conducted throughout Asia and India, including studies
investigating the mechanisms of action of the medicinal
Chinese medicine herbs must be used cautiously
because in Taiwan, 40% were adulterated with cortico-
steroids, nonsteroidal anti-inflammatory drugs, and/or
central nervous system medicines. Over 50% of the Chi-
nese herbal medicines have two or more of these synthet-
The understanding of the function, metabolism, and
interaction of these medicinal botanicals is often lacking.
The specific scientific issues include documenting (1)com-
plete characterization of the multiple active compounds in
each plant solirce; (2)the activity and synergistic or addi-
rive interaction of each of these compounds and their
metabolites; (3) interaction of these active components
with food, nutrients, nutritional supplements, and 'other
medicines; and (4) how the potential toxicity of specific
c6mpounds is reduced.' For example, ~ i c i na, bioterrorist
weapon, and azelaic acid, a nontoxic prescription derma-
tologic medicine, are both extracted from the castor bean.
Preparation of Herbs
Botanicals must undergo a significant amount of chemical
processing prior to incorporation into a c o ~ m e ~ e ~ t i c a l , ~ ~ ~ ~ whole
and this processing greatly affects the biologic activity of
the botanical. The most important factor for the biologic
activity of an herb to he incorporated into a cosmeceutical ,
-product is the source of the plant material because each
plant part may contain hundreds of different individual
chemicals and molecules. Growing conditions, including
soil composition, amount of available water, climate vari-
ations, plant stress, and harvesting conditions, such as
time from harvest to transport, care of plant materials dur-
ing shipping, storage conditions prior to manufacture, and
preparation of the herb and final product, as well as mix-
ing with other herbs, are other factors that may substan-
tially alter solubility, stability, biologic availability, phar-
macokinetics, pharmacologic activity, and toxicity.
Galenic extracts are made from leaves, roots, fruits,
berries, stems, twigs, barks, and flowers by crushing,
grinding, comminuting, boiling, distilling, pressing, dry-
ing, or exposing them to solvents. ~ ~ [he ~ plant
~ l mate-l ~ , ficture: alcoholic solution of whole or ort ti on of pl-lnr or
rial is heated or processed to obtain essential oils or other
.,
Dermaml Surg 31:7 Part 2:l"ly~~005
Al
;"I
+i
distillates that can be easily added to a cosmetic forniula-
tion. However, this processing may destroy or adveasely
modify some of the physiologically active molecules.%e
results are oil, wax, juice, tincture, decoction, tea, infu-
sion, andlor powders, which are then formulated into top-
ical applications, including solutions, gels, lotions, cr ms
ointments, and pastes. Some of these preparations are 91i, r:
ther applied as fomentation, a compress, or a poultice.'See
the glossary inTable l.9
The concentration of the herb, its extract, and the active
molecules affects therapeutic activity. Usually in cosme-
ceuticals, the medicinal botanicals are added in very small,
subtherapeutic amounts for the marketing story. Few
herbs, unlike most synthetic pharmaceuticals, are required
only in a very low concentration to provide the desired
effect because their high potency is so high. Herbal efficacy
is first challenged by the stratum corneum permeability
barriet Delivery across the mucocutaneous surface is dif-
ficult owing to the botanical's multiple active compounds
with different solubility, polarity, and therapeutic concen-
tration, as well as the reactivity of different mucocuta-
neous targets.
These complex biologic science and formulation issue;
indicate that the only validation of. herbal activity in a
cosmeceutical formulation is a human clinical trial con-
ducted by a reputable third-party researcher. Without such
studies, health care providers and the public are being
asked to trust in products based on "voodoo" science.
Table 1. Glossary
Antiphlogistic: preventing and/or relieving inflammation
Astringent: arrests secretions, contracts tissue, and controls
bleeding
i n ~blantt ~or portion
d : broken into multiple
pieces
Decoction: liquid extract produced by simmering the plant
part in water for over 20 min
Elixir sweetened alcohol extract
Essential oil: concentrated oil from the whole plant, usually
volatile and fragrant
Fomentation: liquidextract-soaked 'loth
Galenic: crude plant remedies
Herb: botanical used for medicine, flavoring, or fragrance
liquid extracts in hot water
Mucilage: botanicals that swellwith exposure to water for
soothing application
poultice: liquid extract combined with powdered herb applied
directly to lesions while massis moist
Rubefacient: substance that causes cutaneous erythema by
counterirritant effects
Tea: dried whole or parts of plant simmered in hot wter,
usually 5 1 0 min
extract -
 -5
-5

ermatol Surg 31:7 Part 2:July 2005 THORNFELDT: COSMECEUTICALS C O ~ A I N M GHERBS 87$,
71
'.
>-,
.%
$ Regulation Even simple plants contain multiple reactive and inter- at
8: active compounds, but natural medicine advocates and thy!
;:. Medicinal botanicals used in cosmeceuticals are consid-
media frequently do not warn the public of the impor-
.,ered
.. food additives or dietary supplements by theUSFood
tance of interactions between different herbs and between
and Drug Administration (FDA), which declared them as
'P- herbal and prescription medicines. Moreover, 70% of
safe. The herbs are allowed to be marketed to consumers
1%
patients fail to disclose their use of herbal products pr&
directly without obtaining drug status or being restricted operatively.'l Interactions with medical consequences
1r- by FDA's over-the-counter monograph requirements.
.ee p;obably are underreported. There are many herb-food,
Thus, no standards of herbal potency, concentration in the
herb-drug, and herb-herb interactions, as shown in
marketed product, safety, or efficacy studies exist.
ve Table 3.4
The regulatory authority for herbs in Germany is the
e- "Commission E." It is the best consensus of experts for Table 2. Adverse Cutaneous Reactions
11, weighing the quality of clinical evidence and systemic and
W
topical safety to identify reasonably effective uses of over Anaphylaxis
:d 300 botanicals. German chamomile (Matricaria recutita) and horse
!d chestnut (Aesculus hippocastanurn)
For those herbs or indications not considered by Com-
3' Blistering (immunoglobulin A linear dermatosis)
mission E, one of the most complete herbal compendiums Tea tree (Melaleuca alternifolia)
Y is the PDR for Herbal medicine^.^ This publication com- Carcinogenic
f- pleted an exhaustive literature review conducted by the Aloe Vera (Aloe barbadensis) and comfrey (Symphytum
IS respected PhytoPharm US Institute of Phytopharmaceuti- officinale)
I-
cals for approximately 400 more herbs with regard to their Cutaneous, nonspecific
use and adverse reactions. Tea tree
Death

3
1 Safety Comfrey
Dermatitis
Anews magazine in 2001 revealed that over 2,900 adverse German chamomile, horse chestnut, and tea tree
events requiring medical care were attributed to herbs dur- Dermatitis, allergic contact
ing the previous year. In addition, 104 deaths were attrib- German chamomile and tea tree
uted primarily to ephedra, St. John's wort, ginkgo, and Edematous
ginseng.I0 In 2003, the FDA removed ephedra and ma Aloe Vera
huang (Ephedra sinica) from the market owing to 155 Erythematous
Horse chestnut
deaths directly attributed to it."
Erythema multiforme
The most common adverse cutaneous reactions to Tea tree
herbal products include allergic andlor irritant contact Fasciculation
dermatitis. Cross-sensitivity to the most sensitizing botan- Horse chestnut
icals is not uncommon. For example, 12 of 106 dermatitis Hypesthesia
patients had a positive patch test to tea tree oil (TTO), and Tea tree
all of these patients had positive reactions to 1or more of Mucositis~stomatitis
12 other natural compounds, including lavender (Lavan- Hone chestnut
dula ang~stifolia).'~ Severe cutaneous reactions include Pruritis
angioedemalurticaria, exfoliative erythroderma, linear Horse chestnut
immunoglobulin A bullous dermatosis, lupus erythemato-
sus, malignancies, pemphigus, Stevens-Johnson syndrome, Table 3. HerbDrug Interactions
. Sweet's syndrome, ulcerative stomatitis, and va~culitis.~
Ten herbs used t o treat dermatologic conditions have Aloe
Antiarrhythmics (aloe-induced hypokalemia may affect
induced fatal reactions, including aristolochia (Aris-
cardiac rhythm), digitalis glycosides (increases effect),
tolochia species), arnica (Arnica montnna), cayenne (Cap- corticosteroids. thiazide diuretics, and licorice (increased
sicum annuum), comfrey (Symphytum officinale), henna potassium loss)
(Lawsonia inermis), kava kava (Piper methysticum), German chamomile
mistletoe (Phoradendron species), rue (Ruta species), Alcohol or benzodiazepines (may increase sedative effect),
senna (Cassio species), and yohimbine (Pausinystalia warfarin (may be additive)
... yohimbe). Other severe reactions include anaphylaxis, Green tea
coma, rhabdomyolysis, and shock. Herbs known to pose Alkaline drugs (decreased absorption)
dermatologic surgery dangers include St. John's. wort, Horse chestnut
ginkgo, ginseng, garlic, echinacea, kava, and valerian.'] Anticoagulant drugs (may be additive with anticoagr;;ant
See the adverse reactions listed in Table 2.
 . .,
.,
Dermatol Surg 31:7 Part 2:luly&05
:.I

The medicinal botanicals of proven and potential der- John's wort, tea tree, and oolong tea. Borage, ev ing
&.
matologic significance are listed in Table 4.' Multiple primrose, gotu kola, grape seed, black tea, PYC, and3hi-
herbs are effective for several different indications. Herbal nese herbal mixtures have been documented to treat der-
medicines may be divided into several groups. Clinically matologic conditions when administered orally. The
validated ones have published human-controlled clinical botanicals discussed include teas, soy, pomegranate, date,
trials. These herbs are among the most commonly used by grape seed, PYC, horse chestnut, tea tree, ~ e & a n
the public and alternative medicine practitioners and chamomile, curcurmin, comfrey, allantoin, and aloe vera.
would be expected to be the most commonly used in cos-
meceuticals. Photoaging clinical trials have been published
only on green and black tea, soy, pomegranate, and date. Specific Herbs
Those botanicals with published human studies for der- Allantoin and Comfrey (Symphytum officinale)
matologic conditions using topical formulations include
allantoin and comfrey, aloe, anise, bitter orange, black Comfrey is approved by the German Commission E to
nightshade, black seed, camptotheca, curcumin, German treat blunt injuries owing to the activity of triterpene
chamomile, grape seed, horse chesmut, lemon balm, neem, saponins, tannins, and silicic acid, as well as allantoin.'
olive oil, onion, Oregon grape, Pycnogenol (PYC), St. Allantoin has been extracted from thecomfrey root and
leaves but is now commercially manufacmed. Allantoin is
Table4. Herbal Indications an antiphlogistic, antioxidant, and soothing keratolytic
that has an antitrichomonal effect and induces cell prolif-
Acne eration. It is listed in the FDA over-the-counter mono-
German chamomile (Matricaria recutita) and tea tree graph as a safe and effective skin protectant at 0.1 to
(Melaleuca alternifolia) LO%.'' Allantoin andlor comfrey-based products are
Bites used to treat wounds, ulcers, burns, dermatitis, psoriasis,
Tea tree impetigo, and acne. When formulated with surfactant and
Bruises benzalkonium chloride, it is an effective hand sanitizer and
Comfrey (Syrnphyturn officinale),horse chestnut'(Aescu1us
hippocastanurn), and turmeric (Curcurna longa) onychomycosis therapy."
Burns Comfrey contains hepatotoxic pyrriolizidine alkaloids,
Tea tree which have resulted in deaths with oral consumption. It is
Carcinoma, squamous cell prevention of - carcinogenic and contraindicated in pregnancy and lacta-
Green tea tion.'
Furunculosis/abscess Allantoin formu1ated:with onion (Allium cepa) extract
German chamomile in a proprietary topical formulation improved the signs
Hemorrhoids and symptoms of scars and keloids.16 No photoaging clin-
Horse chestnut ical tiials using topical allantoin andlor coifrey hav; been
Infections, fungal published.
Aloe (Aloe barbadensis, A. capensis, A. vera)
Infections, bacterial and mixed organisms/cellulitiJerysipelas
Tea tree Aloe (Aloe barbadensis, A. capensis, A. vera)
Inflammation
German chamomile, horse chesnut. and Aloe is used in Asian medicine for therapy of fungal and
turmeric other infections, infestations, tumors, and other skin dis-
Leprosy eases. The aloe substance released from comminuted leaves
Turmeric contains mucopolysaccharides; glucomannan, including
Mucocutaneous pain beta mannan; allantoin; anthracenes, such as aloin and
Comfrey.
Mucocutaneous pruritus emodin; alkylchromone, including aletinic acid and choline
Turmeric salicylate; flavonoids; amino acids; hydroxyquinine glyco-
Stomatitis sides; carboxypeptidases; and minerals.'J7 The hydroxyan-
German chamomile, tea tree, and turmeric thraquinone emodin inhibits neuroectodermal tumors,
Ulters, skinldecubitus, leg, vascular such as Merkel cell carcinoma.18Acetylated mannans and
Tea tree lectins appear to have immunomodulatory effects. Aloe is
Venous insufficiency/varicositiedvenousstasis antibacterial to Staphylococcus aureus, Helicobacter
Horse chestnut pylori, and dermatophyte fungus.19 It is viricidal to herpes
Wound care simplex and varicella zoster and is clinically cfiective in
Date palm (Phoenix dactylifera), German chamomile, and treating genital herpes. This herb inhibits thro:n:*oxane
turmeric vasoconstriction. Aloe inhibits photoimmunosupp:ession
 at01 Surg 31:7Part 2:July 2005
traviolet B (UVB)and inhibits cyclooxygenase for anti-
mmatory effects. It also increases collagen biosynthe-
and degradation in granulation tissue. The antin'eopla-
effect is improved with melatonin and ascorbic acid,"
vera applied topically is accepted therapy for radia-
on and stasis dermatitis and ulcers, frostbite, burns, fun-
and bacterial infections, cold sores, pruritis, pain, pso-
is, and contact irritant dermatitis. The latter two were
ocumented in blinded studie~.""~
havebeen pubiished, despite its use as one i f the two most
$ o m o n extracts in s k i care formulations. The 'health
risks of aloe are cutaneous eruptions and mutagenicity.'.''
.It is contraindicted in pregnancy and lactation.'J3
Curcumin Derived from Turmeric (Curcuma
:domestics)
if-
o-
4:.This herb is used in Asian medicine for cutaneous inflam-
mation, pruritis, wounds, and ulcers. Its active compounds
to :'
include volatile oils, such as tumerone; curcuminoids; and
:>.
re :-'f
. .. heptanoids. Tumerone, the volatile oil, provides the
is, unique aroma. This extract provides the yellow color and
~d much of the flavor for curry in foods.' These molecules
~d i provide antioxidant, antitumoc antimicrobial, antifertility,
. . and anti-inflammatory effects. They also repel insects.
3 Curcumin may color cosmeceuticals claiming to be free of
I . smhcial ingredients. Tetrahydrocurcumin,a hydrogenated
1- . form of curcumin, is only off-white in.color. It is also
added to cosmeceuticals to protect the formulation and
:t impact the skin. This aniioxidant appears to be superior to
IS
1.. tocopherol.
1- .. .
Five human studies have found curcumin to be safe and
n " have found definite anti-inflammatory effects. It inhibits
lipoxygenase, cyclooxygenase, leukotrienes, thrombox-
ane, prostaglandins, nitric oxide, tumor necrosis factor,
and interleukin-12. Curcumin has been documented to
inhibitcollagenase, elastase, and hyaluronidase."
I Clinical studies demonstrating the effects on parameters
of photoaging are lacking, but when combined with
another herb, curcumin effectively treated scabies.=
( ' Date Palm (Phoenix dactylifera)
This food stuff is an Asian medicine therapy for inflamed
wounds. The active compounds include 50% sugars, such
as saccharose; 10% fatty oils; oligomeric proanthocyani-
dins (OPC);piperidine derivatives, including pipecolic acid;
and phytohormones. It has no reported health hazards.'
A placebo-controlled trial with 5 % date versus placebo
in 10 patients was applied to the eyelid area twice daily for
5 weeks. A statistically significant reduction in wrinkle
surface (27.6%) and wrinkle depth was achieved. S ix of
I the participants said that visual improvement oc~urred.'~
,
THORNFEU)T: C O S M E C E ~ C A LCONTAINING
S HERBS 87F:
Rl
-,I
German Chamomile CI
UI
Matricaria recutita functions as an antiallergic, antimicrm~
bial, anti-inflammatory, antioxidant analgesic and wa;'
approved by the German Commission E for inflammatory
mucocutaneous diseases and wound and burn therapy.
The major components of German chamomile ~ncludet@
primary anti-inflammatory agents: alpha-bisabolol,
chamazulene, levomenol, and matricine. Other active
compounds include bisaboloxides; farnesenes; choline;
glycosides; flavonoids, such as apigenin and rutin; tannins;
hydroxycoumarins, such as umbelliferone; mucilages; sac-
charides; fatty acids; and ~alicylates.~~J'
Chamazulene inhibits leukotriene B, synthesis via inhi-
bition of lipoxygenase and cyclooxygenase, lipid peroxi-
dation, leukocyte infiltration, and histamine release. Lev-
omenol is an anti-inflammatory hydrating agent that
diminishes the signs of photodamage and reduces pruritis.
Apigenin inhibits adhesion molecules. Bisabolol promotes
granulation tis~ue.~~2'
Clinical studies showed that topical chamomile cream
was superior to 0.5% hydrocortisone in treating dermati-
tis and sunburn and statistically significantly decreased the
wound area and healing time.'This herb is administered as
an oil for infusion, tea, ointment, gel, wash, gargle, or cap-
sule?
Chamomile is a member of the Compositae family and
has a significant risk of contact sensitization, conjunctivi-
tis, angioedema, and anaphylaxis. It also has an additive
anticoagulant effect to warfarin.'
Grape Seed (Vitis vinifera)/PYC/OPCs
The pharmacologic activity of grape seed extract, along
with French maritime pinebark (Pinus pinaster) extract,
primarily resides in the potent antioxidant proantho-
cyanidins. These are the two richest natural sources and
the most commercially viable. Other rich natural sources
~ncludegreen and black tea, red wine, red apple, red cab-
bage, black currant, sangre de drago, bilberry, blackberry,
blueberry, strawberry, black cherry, cranberry, peanut
skins, almonds, cocoa, parsley, onions, legumes,
hawthorn, and witch hazel bark.'J3 The standardized
pinebark extract is patent-protected PYC, which has been
thegeneric term for proanthocyanidins. These polypheno-
lic bioflavonoids are also known as procyanidins, pro-
cyandiol oligomers, leukoanthocyanidins, condensed tan-
nins, and OPCs."J9 OPCs consist of dimers of catechins
and oligomers of epicatechin and catechin and their gallic
acid esters. These compounds are scavengers of both reac-
tive oxygen and nitrogen specie^.^'.^^ Grape seed also
includes other therapeutic compounds, including
flavonoids, such as kaempferol and quercetin g!u;csides;
stilbenes, such as resveratrol and viniferins; frui: zcids;
 . - 878 THORNFELDT: COSMECEUTICALS CONTAINING HERBS
'
tocopherols; essential fatty acids; and phenylacrylic acids,
such as caffeoyl and fer~lo~lsuccinic acid. Resveratrol is a
potent antioxidant that inhibits angiogenesis and carcino-
genesis, is antiviral against herpes, and has phytoestrogen
activity.- PYC also contains monomeric epicatechin and
catechin?""
Grape seed applied topically improved cutaneous pho-
toprotection to UVB, inhibits histamine synthesis, pro-
motes wound healing, reduces apoptosis induced by
chemotherapy, reduces vascular engorgement, is cytotoxic
to adenocarcinoma, and inhibits Streptococcus. Grape
seed protects deoxyribonucleic acid (DNA) against oxida-
tion more effectively than vitamins C and E and stabilizes
collagen and elastin by inhibiting matrix metallopro-
teinases. It treats chronic venous insufficiency (CVI) and
, postoperative edema in clinical studies. All of these func-
tions of grape seed strongly suggest that it should improve
photoaged skin and protect against further damage. Grape
seed has been used for centuries in Asia to treat a variety
I ' of cutaneous conditions?*J"'
-PYCincreases nitric oxide levels,stimulates T- and Bcell
function, and inhibits nuclear receptor transcription factors
: nuclear factor KB (NF-KB)and activating protein (AP)-1
and the adhesion molecule intercellular adhesion molecule
1, as well as interferon-y. It recycles vitamins C and Es,30
Topically applied PYC reduces sunburn, immunosup-
pression, and tumor formation by ultraviolet light while
raising the minimal erythema dose in mice."~" PYC
administered orally reduced the area of severity. of
melasma within 30 days and the signs and symptoms of
i CVI by 60 days.3334
A topical formulation consisting of grape seed, jojoba,
: lavender, rosemary, and thyme was used to treat alopecia
areata. After 7 months of daily use, statistically significant
j improvement in hair regrowth occurred (44% vs 15% for
p l a ~ e b o ) ? ~has
I t been used in antiaging creams for several
1 years." No controlled clinical studies evaluating these
I herbs for treatment of photoaging have been published.
Horse Chestnut (Aesculus hippocastanum)
This herb is approved by the German Commission E for
CVI therapy, In homeopathy, horse chestnut treats hemor-
rhoids. The mechanisms of action include inhibition of elas-
tase and hyaluronase, decreasing capillary permeability,
inhibiting leukocyte activation, and inducing vasoncontric-
tion. The active compounds in the seeds of this herb contain
50% polysaccharides and oligosaccharides, other triterpene
saponins including aescin, the most active component, fatty
oils, and flavonoids, including quercetin and 0~~s.'"'~
Leg circumference, heaviness, and pain were statisti-
cally significantly reduced in multiple CVI trialswith oral
therapy. Topically applied horse chestnut reduced the
symptoms of CVI in one trial and hemorrhoids in
another.J6Photoaging clinical studies are lacking.
Dermatol Surg 31:7 Part 2:July 2D05
,
il
>I
The health risks of horse chestnut include hepatot&ic-
ity, renal toxicity, urticaria, anaphylaxis, and muc&ta-
neous irritant dermatitis. It may also interact with sd!cy-
lates and warfarin. This herb is administered as a tea, a
tincture for infusion, a gel, or an ointment.'
1,
Pomegranate (Punica granatum) P; I
This herb was used in ancient Egypt for inflammation of
the skin, mucosa, and joints. Punica granatum may con-
tain a more potent antioxidant mixture than grape seed
extract, PYC, red wine, or green tea. The major con-
stituents are tannins (25-28%), including punicalagin;
polyphenols, such as ellagic acid; ascorbic acid; niacin;
potassium; and piperidine alkaloids.'J3 Pomegranate func-
tions as an astringent that also inhibits NF-KB.~'It has
documented antimicrobial activity for gram-negative bac-
teria, Saccbaromyces fungus, parasites, and
There are no health hazards reported with pomegran-
ate. It is administered as a decoction? Topical and oral
administration of this herb induced photoprotection to
W B in a human clinical trial.39
Soy (Glycine soja)
This antioxidant, antiproliferative, antiangiogenic extract
is used to treat hyperhidrosis in Asian medicine.') Epi-
demiologic studies indicatingmuch lower malignancy and
cardiac disease rates in people eating a diet high in 'soy
resulted in thorough investigations revealing multiple
medicinal uses. The major components of soy are phos-
pholipids ( 4 5 4 0 % ) , such as phosphatidyl choline, and
essential fatty oils (30-35%). The minor components
include the most active compounds, such as isoflavones,
saponins, essential amino acids, phytosterols, calcium,
potassium, iron, and the proteases soybean trypsin
inhibitor and Bowman-Birk inhibitor. The most potent
isoflavones are the phytoestrogens genistein and
daid~ein.~*".~" Topical estrogens have been shown to
increase skin thickness and promote collagen synthesis;
thus, soy phytoestrogen stimulation of human fibroblast
collagen synthesis is expected. Genistein is the most potent
antioxidant; it inhibits lipid peroxidation and chemical-
and UVB-induced carcinogenesis. The two protease
inhibitors lighten pigmented lesions and reduce unwanted
facial and body hair in human clinical trials."
Soy products have rarely caused dermatitis and pruritis,
as well as asthma and gastrointestinal symptoms.'*
Tea Tree (Melaleuca alternifolia)
This essential oil has become one of the most commonly
used nonpresctiption remedies for mucocutaneol;s disor-
ders. TTO's active compounds include terpinenea, zilch as
cineole. The monoterpene terpinen is the major sensitizing
ia
a-
:I
&'
'
;:
rmmpound in TTO and has become one of the most cdm-
on contact allergens. The terpene alcohols, such as ter-
Y-
a C. ..
::.eO.
'inin-4-01, are the major constiments, comprising 40% of
They reduce. histamine-induced edema and wheal
iolume in type I hypersensitivity reactions. TTO does not
have antioxidant activity, nor does it suppress neutrophil
. .-
&~peroxide..'Its wide antimicrobial spectrum includes Pro-
pionobacterium acnes, Escherichia coli, S. aureus, herpes
of &nplex, Candido albicans, Trichophyton dennatophytes,
n- and Sarcoptes scabiei.4'."
:d Multiple double-blinded clinical trials have docu-
n- mented that TTO effectively treats acne and fungal or
n;
a; 1 yeast infections. TTO failed to effectively treat atopic der-
matitis and CVI.4J3,'2
IT0 is cytolytic to epithelial cells and fibroblasts, so it
should not be used for bums. Photodamaged TTO is a
C-
- sensitizer and has.induced errthema multiforme
suon~er
al
n- I with topical application. Thus, the us; of TTO in cosme-
ceuticals for sun-exposed tissue is not scientifically sound."
Teas: Black, Green, Oolong, and White (Camellia
sinensis)
All true teas are derived from Camellia sinensis. Black tea
is the most processed (fermented), with white tea recently
supplanting green tea as the least processed; oolong is par-
tially fermented. Green tea contains 8 to 12% polyphenols
and 2 to 4% caffeine. White tea is a more potent antioxi-
dant and is more effective than green tea in inhibiting bac-
terial dysplastic m ~ t a t i o n s . 4 ~Green
~ ~ ~ ' tea
~ decreases
melanoma ceUs in tissue culture and squamous cell carci-
noma cell formation with topical and oral administration
in mice. It also increases keratinocyte cell differentiation,
improving wound healing. This tea inhibits Streptococcus
species and E. coli. It also inhibits bradykinin and
prostaglandins in animals." Black tea has a much lower
content of catechins than green tea but a higher content of
other flavonoids, such as kaempferol and theaflavin. The
largest catechin and most active antioxidant in any tea is
epigallocatechin gallate (EGCG). Green tea has the high-
est concentration of EGCG.43'
Topical gieen tea applied to human skin providedpho-
toprotection beginning at 24 hours and lasting 48 to 72
hours. It reduced the number of sunburn cells by 66%
when applied 30 minutes prior to WB. When applied at 1
to 10%concentrations, a dose-response inhibition of ulua-
violet-induced erythema occurred." This emactprevented
psoralen ulnaviolet A photodamage with pre- and post-
treatment by reducing erythema, hyperplasia, and hyper-
kerato~is:~Green tea is used to soothe sunburn, reduce
baggy eyelids, and produce hemostads. Black tea extracts
applied before and after ultraviolet light challenge
decreased signs of cutaneous photodamage, carcinogenesis,
and inflammation in human and mouse skin.= Oral admin-
istration of black and oolong teas, such as green tea, s u p
pressed both type I and IV allergic reactions in the ski11.4','~
Oral oolong tea effectively treated atopic dermatiti~.'~ g,
C.'
5;
A recent double-blinded trial of 51 patients treated for-'
12 weeks with topical green tea extract containing 5.5 to
8.5% EGCG did not reduce the number of actinic ker-
atoses on forearms compared with pla~ebo.'~ 4.
The major adverse reactions are gastrointestinal upset:"
constipation, irritability, and, very rarely, hepatotoxicity,
delirium, and seizures. Caution should be used during
pregnancy and lactation with excessive consumption
(more than four cups per day).=
Summary
Although there is a sharp increase in the use of botanicals
in cosmeceuticals, there is a paucity of human clinical
studies and often a lack of sound scientificrationale. Proof
that thec~smeceuticalformulation has any objective effec-
tiveness is also usually lacking. The most, significant
-
human cosmeceutical data have been generated with for-
mulations containing green and black tea, soy, pomegran-
ate, date, and a grape seed-based mixture. Cosmeceutical
formulations with the highest risk of reactions contain tea
tree oil, comfrey, and German chamomile.
Acknowledgments
I greatly appreciate the assistance of Sheena Beavers,
David Talford, PA-C, Charity Burkheimer, and Elisha
Andrews with the manuscript.
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29. Baumann LS. Cosmeceuticsl cririque: grapeseed. Skin & Allergy
News 2004;35:26.
30. Baumann LS. Cosmeccurical critique: pycnogenol. Skin & Allergy
News 2004;35:36.
31. Saliou C,Rimbach C, Moini H, et al. Solar ultraviolet-induced ery-
thema in human skin and nuclear factor-kappa-B-demndent
..
expression in keratinocyreraremodulared by a French maritime pine
-
Eerie
bark enran. Frec Radic Biol Med 2001;30:154-50.
Commentary
Botanicals are of great interest t o the dermatologist and the con-
sumer. From a dematologic standpoint, topical botanicals are a
source of contact dermatitis, whereas oral botanicals can inter-
fere with blood clotting and create postsurgical complications.
From a consumer standpoint, the idea of topical and oral natu-
ral products inducing improvement in the growth and function-
ing of the skin, hair, and nails is enormousIy appealing. Dr.
Tbomfeldt has taken a systematic evaluative approach t o the
cataloging of those botanicals of dermatologic significance. His
knowledge should help the dematologist in obtaining a better
understanding of the source and effect of plant derivatives.
It is notewonhy, however, t o remember that most botanical
extracts are just extracts. What does this imply? Tbis means that
they are just one fraction of a planr-derived material that bas
been processed t o meet the needs of the cosmetic f o d a t b r .
-,
.-,
Dermatol S u q 3 1:7 Part 2:luly~005
;'I
ii
32. Sime S, Reeve YE. Protection from inflammation, immunosdbres-
sion and carcinogenesis induced by LJV radiation in mice by rppical
Pycnogenol. Phorochem Phorobiol2004;79:193-8. -,
33. Ni Z, Mu Y, Gulati 0 . Treatment of melasma with Pycnogenol. Phy-
torher Res 2002;16:567-71.
34. Arcangeli P. Pycnogenol in chronic venous inrufficency. Fitothcrapie
2000;71:23644. 2,
4,
35. Hey IC. Jamieron M, Ormerod AD. Randomized rrial of aroma-
rotherapy. Arch Dermatol 1998;134:1349-52.
36. Pinlrr MH. Emrr E. ~ o r r e c h k n u sccd
r enracr foc chronic venous
insufficiency.Arch Dcrmarol 1998:143:1356-60.
37. Baumann IS. Cosmeceutical ctimque: pomegranare. Skin & Allergy
News 2004;35:42.
38. De h4, Krishna De A, Banejee AB. Antimicrobial screening of some
Indian spices. Phytother Res 1999;13:616-8.
39. Mutad H, Shellow VRW. Pomegranate extract both orally ingested
and topically applied to augment the SPF of sunscreens. Cosmer
Dermatol2001;14(10):43-5.
40. Weil H, Spencer JM, Gelfand J, et al. The roy isoflavone genisrein: a
new agent in dermatology. Cosma Dermatol2001;14(2):13-9.
41. Walton SF, McKinnson M, Pnzuno S. Acaricidal activity Melolevco
oltmifolio (tea tree oil). Arch Dermarol2004;140:563-6.
42. Baumam LS. Cosmeceutiel crtrlque: tea tree oil. Skin & Allergy
News 2002;33:14.
43. BlakeJ. %for you. TheIdahoSrateman 2004 Feb 22; LifeSect:1,4.
44. Spencer JM. Chemoprevention of skin cancer and photoaging. Cos-
met DermatoI2001;14(6):25-8.
45. Elmets C, Singh D, Tubesing K, et al. Cutaneous photoprotenior~
from ultraviolet injury by green tea polyphenols. J Am Acad Derma-
to1 2001;44:425-32.
46. Zhao F, Zhang YJ, Jinx H, et al. Green tea protects against psoralen
plus ultraviolet A induced photochemical damage to skin. J Invest
Derrnarol 1999;113:1070-5.
47. Zhao J, Jinx, Yaping E, et al. Photoprotection effect of black tea
extracts against W B induced phototoxicity in skin. Photochem Pho-
tobiol 1999;70:637-44.
48. Linden KC, Carpenter PM, Mclaren CE, et al. Chemoprevention of
non melanoma skin cancer: experience with a polyphenol from green
tea. Recent Results Cancer Res 2003;163:165-71.
49. Uehata M, Sugiuru H, Sakurai K. A trial of oolong tea in management
of recalcitrant aropic dermatitis. A d Dermatol2001;137:42-4.
50. Baachi - -
- D.. Baahi M. Srobr 51... er al. Free radicals and era= seed
r~
proanthocyanidin cxrran: importance in human health and disease
prevcncion. Toxicology 2000;148:187-97.
Ground-up leaves and nvigs are not appealing in a skin cream.
The botanical must be processed such that it is a white powder
that can be easily stirred into a moisturizer formulation. It must
be white because few consumers want t o put a gray-pink cream
on their face. It must be a powder because these are the easiest t o
disperse. T h e powder must be very fine because a gritty mois-
turizer is not acceptable t o most consumers. So what does this
mean? Tbis means that everything from rosemary t o lavender t o
aloe t o chamomile t o jojoba t o soy must be distilled down t o a
fine white powder. What happens when all botanical ingredients
are transformed into a fine whitepowder? Perhaps one might say
that they now are not rmly botanicals but chemical extracts of
one sort o r &other derived f r o p a plant source. It is possible that
our natural botanicals have now become unnatural chemicals!
ZOEDIANADRAELCS,
MD
High Point, NC
 Review of Photorejuvenation: Devices, Cosmeceuticals,
@Or
C A ~ ~ F BK. N MD,* SANDRALEE,MD,t AND RICHARD E. FITZPATRICK,
O ROKHSAR, MD*
*Albert in stein College of Medicine, Bronx, NW York; 'Skinphysicians and Surgeons, Uphnd, California; *LaJ o l b
Cosmetic Surgery Center and Department of Medicine, Division of Dermatology, Universiiy of California a t San Diego,
San Diego, California
B A C K G R O ~ L ~Both
. the public and the medical profession have
placed a lot of an- on reversal of signs of aging and photo-
damage, resnlting in numerous cosmeccvtical products and non-
ablative laser tecbniqua designed to achieve thse results.
o ~ ~ ~ The c mpurpose
a of this report is to briefly review both the
cosmeceutical products and nonablative laser techniques that
appear tobe most promising based on published studia. A h this
review, recommendations for potential enhancement of benefits by
combining cosmeceuticals and laser treatmene will be explored.
-TI. Puked dye lasers targeting miaovessels, intense pulsed
CAMERON K. ROKHSAR, MD, AND SANDRA LEE, MD, HAVE INDICATED N O SIGNIFICANT INTEREST
WITH COMMERCIAL SUPPORTERS. RICHARD E. FIZZPATRICK, MD, IS FOUNDER AND BOARD MEMBER
OF SKIN MEDICA.
a Skin Rejuvenation: Lasers versus Creams
he goal of skin rejuvenation has become the focus of a
multibilliondollar cosmeceutical and laser industry treat-
ing an aging population overexposed to the sun. Various
noninvasive treatment modalities and topical cosmeceuti-
cals have been used to treat the visible signs of photodam-
age and photoaging, which include rhytids, telangiectasias,
lentigines, and dyspigmentation. Despite numerous claims
of reversal of some of these signs of photoaging, solid sci-
entific data on this subject are limited. However, in the
past decade, the advent of newer laser technologies and
more extensive research on topical agents has led to a
clearer understanding of effective strategies in the antiag-
ing campaign. In this article, we review the current status
on various modalities, both laser and cosmeceutical.
Aging
- - and Photoaging
Aging can be divided into intrinsic and extrinsic aging.
Inuinsic aging refers to the natural process of chtonologic
aging. Intrinsic aging affects both sun-exposed and
non-sun-exposed skin. This type of aging is characterized
by dryness, laxity, skin atrophy, and fine wrinkles. Histo-
0 2005 by the American Socisry for Demr~tolo~ic
Surgery, lnc. Published by BC Decker Inc
ISSN: 10760512 D m t o l Surg 2005;31:11661178.
L
light targeting both melanin and microvasels, and midinfrared
lasers targeting dermal water and collagen all appear to have
some ability to improve skin texture, color, and wrinkling.
Retinoids, vitamin C, alpha-hydroxy acids, and topical growth
factors may also stimulate repair mechanisms that result in sim-
ilar improvements in photodamaged skin.
CONauSION. Although supported only by theoretic considera-
tions and anecdotal reports, it seems logical that the concurrent
use of appropriate cosmeceuticals with nonablative lasa pho-
torquvenation should result in Enhanced benefits.
IogicaUy, one may see a thin epidermis with an intact sua-
mm corneum, resulting in prominence of vasculature lead-
ing to transparency of the skin. Other characteristicsinclude
flattening of the dermoepidermal junction, a decrease in
dermal thickness, diminished dermal vascularity,' and a
decreased ability of dermal fibroblasts to produce collagen,
manifested as increased time for wound healing. Intrinsic
aging is predominantly genetically mediated. Other con-
tributing factors may be the natural effects of gravity,
expression lines, sleep lines, and hormonal changes.
Extrinsic aging refers to that component mediated by
environmental factors. These factors include smoking,
wind, chemical exposure, and, most important of all, ultra-
violet ( W ) radiation. Ultraviolet B (UVB)is considered to
be the most damaging, causing erythema, sunburn,
deo~~ribonucleic acid (DNA) damage, and, ultimately, skin
cancer. Ultraviolet A ( W A ) can also cause burns when
administered at higher'leveis. Because of its deeper pene- a
tration, its nonseasonal variation in sunlight, and the fact
that, unlike W B , it generally causes no acute injury,
cause as much chronic photodamage to the skin.'Ex
aging is characterized clinically by fine and coarse
kling, roughness, dryness, laxity, pigmentary chang
telaneiectasias. Histologically, photodamage can cause
 3 1 :9 Part 2:September 2005
tered elastic tissue prominent as wrinkles and yellow dis-
$::.
&ranon of skin. The effect on microcirculation is mani-
fested in telangiectasias. In epidemiologic studies, cigarette
;doking has also been shown to be an important factor in
$&mature aging. Cigarette smokers with a history of more
&an 50 pa& per year were five times more likely to be
wrinkled compared with nonsmokers.'
Mechanisms
The free radical theory of aging proposed in 1954 postu-
lates that aging is a result of reactions caused by free rad-
icals? Both chronologic aging and photoaging are associ-
ated with production of excessive amounts of free radicals,
which contain one or more unpaired electrons. When left
unchecked, these can damage cell membranes, proteins,
and DNA. The senescence of cells may also be linked to
mutation in the mitocbondrial DNA.I A causal relation-
ship between telomere shortening and in vitro cellular
senescence has been dem~nstrated.~
The damaging effect of W exposure may be mediated
through the induction of metalloproteinases, which, in
turn, cause collagen breakdown. Pretreatment with
retinoids inhibits this p a t h ~ a yPrecursors
.~ of both type I
and type IU collagen are significantly reduced in photo-
damaged skin? Severely photodamaged skin is h r t h e r
characterized by deposition of blue staining material
known as solar elastosis, which histologically mimics
elastin.
Lasers
The demand for less invasive procedures and decreased
recovery time has caused a move away from traditional
laser resurfacing and toward nonablative procedures.
Nonablative rejuvenation is based on the concept that
through various' light devices, one can selectively cause
thermal damage to the dermis, inducing collagen remodel-
ing while sparing the epidermis. Various substances,
ii;cludi'ng water, hemoglobin, and melanin, can serve as
targets for various lasers. These suuctures can further dis-
sipate heat into the surrounding collagen, thereby causing
shctural remodeling. More specifically, various authors
have documented immediate edema of endothelial cells
. . and connective tissue and recruitment of inflammatory
cells followed several weeks by new collagen and elastin
f o h a t i ~ n It. ~is postulated that the inflammatory cells
may release cytokines and other growth factors, which
couldiniluence collagen rem~deling.~ Furthermore, a low-
energy laser can directly influence fibroblasts to produce
m~recollagen?~ Direct formation of collagen in the dermis
has been histologically confirmed following nonablative
laser <reaunent.ll Such collagen remodeling can continue
for a period of 6 to 12 m~nths,'~ as consistent with tradi-
tional concepts in the field of wound healing.
ROKHSAR ET AL: REVIEW OF PHOTOREIWENATlON 1167 -5
>. .
\
[\
It is now clear that by using appropriate
various lasers can achieve similar clinical results. Mea I
surement of clinical improvement has proven to be the dl
more challenging part of these studies because changes 2
clinical pictures are subtle. Positive subjective impressions
of patients may fall prey to the placebo effect. A lack of
uniform documentation and result analysis makes it diffi-
.PI
cult to effectively compare the various technologies. F w l
themore, histologic improvement does not always corre-
late with clinical efficacy and vice versa. There are two
basic approaches to nonablative photorejuvenation. The
first is to target discrete chromophores (oxyhemoglobinor
melanin) in the dermis or at the dermal-epidermal junc-
tion. The second approach is to use midinfrared wave-
lengths to target tissue water. The relatively long wave-
lengths, combined with poor melanin and oxyhemoglobii
absorption and mild water absorption, allow for deep
penetration and scattering of the light (Figure 1).
With both approaches, multiple treatment sessions are
necessary and the results are gradual and progressive. It is
important to have realistic expectations because the results
are relatively subtle, with textural irregularity and pigment
irregularity improving more than rhytids.
The first approach to photorejuvenation using a dis-
crete chromophore as a target was to target fine vessels in
the papillary dermis using pulsed dye lasers (either 585 or
595 nm). The original efforts were based on reports show-
ing remodeling of collagen in scars and striae13after treat-
ment with the pulsed dye The proposed mecha-
nisms were that heat from blood vessel absorption alters
local collagen through wound healing mechanisms,
Figure 1. Absorption r p m m of hemoglobin and melanin H$ Alex
= alexandrite; Er = erbium; H o = homium; Nd = neodymium:.vrt~ium-
aluminum-garnet; Alex = alexandrite; YAG = ynrium-alu!!,inum-
garnet.
; frared 'group of lasers, which include the 1,320 nm Figure 2. (A) Severe photodamage and wrinkling of the porteriol
I I Figure3. (A) Prior to treatment of facial photodamage with the Vbeam laser. (8) Improvement in fine lines of the medial and upper cheek and
decreased telawiectasia are seen after four treatment sessions (595 nm. 10 rnm, 6 Jlcm', 6 ms). Reproduced with permision from Rostan EF
water as a chromophore and are intended to target dermal
collagen. These devices have Little "downtime," with only
' mild erythema apparent clinically post-treatment. How-
ever, moderate pain associated with these lasers requires
pretreatment of the skin with topical anesthetic creams:
The 1,320 nm Nd:YAG laser was the first commercially
available laser developed for the purposes of nonablative
rejuvenation (Figure 4).11 In two separate studies of 10
patients, Goldberg and colleagues reported substantial
improvement in 2 of 10 patients, with the remainder
showing mild or no improvement.- Various other inves-
tigators have reported similar findings.14 Interestingly, a
study seeking to confirm histologic improvement in
patients treated with this laser failed to show any
changes." The mild improvement achieved with the 1,450
nm diode laser in the treatment of facial rhytids has been
documented in several studies. This laser has been demon-
strated to target collagen and stimulate fibrosis in the
upper dermis:6 with mild clinical improvement in perior-
bital and perioral wrinkles.27* In a study of 60 patients
with the 1,540 nm Er:glass laser in the treatment of peri-
orbital and perioral rhytids, Fournier and colleagues
showed an increase of 17% in the thickness of dermis,
whereas 62% of patients expressed satisfaction with the
trea~ment.~~
Fractional photothe'rmolysis is the term coined by
Reliant Lasers (PaloAlto, CA, USA) to refer to a new tech-
nology and new treatment protocol that treats photodam-
aged skin by targeting only a small fraction of the skin sur-
face in each treatment session, much like the pixels in a
digital photograph. Using a midinfrasd laser, the Fraxel
(Reliant Technologies, Inc., Palo Alto, CA, USA), micro-
scopic vertical 70 to 150 p columns of thermal injury are
created that extend 200 to 700 p deep into the dermis and
represent 15 to 25% of the surface area per treatment ses-
sion. Each column is referred to as a Ymicrothermalzone."
Following the promotion of microthermal zones, the epi-
dermis rapidly heals from the surrounding normal epider-
mis and collagen remodeling results in progressive
improvement m the de~mis.3~ Treatment sessions arc gen-
erally scheduled at 1-to 4-week intervals and usuaily total
three to six sessions. Photodamage of the face? neck,

: chest, and hands has been treated successfully, as have
acne scars,other scars:' and various types of dyschromia,
including m e l a ~ m a This
. ~ ~ treatnient regimen has pro-
duced more significant improvement in texture, color, and
deep lines than commonly seen with nonablative technol-
OFT.
Figure 4. Significant impmvement in skin texture and horizontal
wrillkle lines of the neck are seen following three monthly treat-
ment se6sions with the CoolTouch (CoolTouch, Inc., Roseville, CA,
Dematol Surg 31:9 Part 2:SeptemberiQOS
-,
jl
hl
Cosmeceuticals
Oi .
KLigman coined the term cosmeceuticalto indicate a,typ~-
cal preparation that is sold as a cosmetic but has
ance characteristics that suggest pharmaceutical action."
This is a difficult category of topical agents to evaluate
because marketing hype is well accepted in the cosn@cs
industry and the publication of true pharmace&ical
actions of agents sold in this category could result in the
reclassification of that agent as a drug. This results in a
complex situation in which it is difficult to separate truth
and fiction. This whole arena, however, has been well
accepted by consumers, as evidenced by the 83% increase
in cosmeceutical sales reported in the first half of 2002,
whereas overall skin care sales increased
There are many different cosmeceuticals on the market,
and even with the same basic ingredients, concentration of
active ingredients, the specifics of formulation, and ade-
quate penetration to the sites of activity, there are essen-
tials that may vary tremendously. It is not our goal to
review all of these agents but rather to concentrate on
those that appear to show the most promise (Table 1).
Clearly, the gold standard in this field is the retinoids.
Retinol and Retinoids
Retinol (vitamin A) is now a commonly found ingredient
in many creams marketed for antiaging. Retinol represents
the main dietary source, transport, and stQrage form of
vitamin A. Vitamin A belongs to a family of structurally
and functionally related compounds known as the
retinoids. Vltamin A cannot be synthesized; rather, it is
obtained through dietary means. In the body, retinol is
converted to its biologically active form, all-trans retinoic
acid (tretinoin), through an intermediate product, reti-
naldehyde. Retinol is 20-fold less effective than tretinoin,
and the cutaneous concentration of tretinoin is 1,000-fold
less with topically applied retinol than with a e t i n ~ i n . ~
Table 1. Cosmeceuticals and Potential Benefit
Vitamin C improvement in skin texture and pigmentation
through action as antioxidant-quelling free radical damage
as well as a direct stimulant of new collagen production
Alpha-hydroxy acids: improvement iti?lyspigmentationand
fine textural changes through exfoliation, resulting
in increased epidermal turnover and mild inflammatoly
response stimulating collagen remodeling
Retinoids: normalization of pigment and epidermis with
improvement in texture a; well as rhytid; through
inhibition of metalloproteinases that degrade collagen and
increased epidermal turnover
Growth facton: improvement in pigment. texture, 5r.d rhytids
through regulation of fibroblastsand wound heaiizg
mechanisms
 Surg 31:9 Part 2:September2005
All-tram retinoic acid exerts control at the cellular level
through interaction with specific nuclear receptors.
This class of compound has been die most extensively
studied and arguably the most proven group in the treat-
ment of aging and photoaging. The bulk of the studies in
this area have been conducted on tretinoin.
As mentioned earlier in this article, the mechanism
behind collagen loss in photodamaged skin may be the up-
regulation of matrix-degrading metalloproteinasessuch as
collagenase and gellatinases following UV radiation of the
skin.7 In addition, UV radiation causes significant loss of
procollagen synthesis in the skin.37In effect, pretreatment
with U ~ M Oblocks ~ or significantly reduces UV-induced
up-regulation of metalloproteinases, in addition to nuclear
transcription factors such as AP-1 and nuclear factor-KB,
which are directly responsible for up-regulation of these
degradative enzymes. Pretreatment with tretinoin also pro-
tects skin against UV-induced loss of procollagen synthe-
sis and may, in fact, result in an 80% increase in dermal
collagen I formation after treatment with tretinoin 0.1%
gel for 1 0 to 12 months.3a Interestingly, the protective
qualities of tretinoin seem to be effective in repairing dam-
age related to the intrinsic aging process as ell.'^.^^
Since Kligman and colleagues first reported on the clin-
ical and histologic improvement of photodamaged skin
with the use of tretinoin;' there has been a plethora of
studies confirming these effects. Large double-blind multi-
center studies have repeatedly shown a dose-dependent
improvement in fine wrinkling, mottled pigmentation,
roughness, and laxity with the use of tretin~in.~'The
safety and efficacy of tretinoin have been established for
up to 4 years in clinical trials." Histologically, increases in
e$idermal thickness, in particular thegranular layer, com-
pliction.of stratum corneum, an increase in epidermal and
dermal mucin, a decrease in melanin content, improve-
ment in the structure of the dermoepidermal junction, and
i@iprovement in keratinocyte ultrastructure have all been
n.0ted2~Recently, large multicenter studies have shown
w r o t e n e , a newer topical retinoid, to be at least as effec-
t&e as tretinoin in reducing mottled pigmentation and fine
*inkles of photoaging skin."s4'
:.:There bas been considerable confusion among derma-
tologists
.. .
as to whether topical retinol can provide the
%me benefit in reversal of photodamage as retinoic acid.
This has been true because of the presence of numerous
+tin01 cosmeceutical products marketed as "antiagingn
fdrmulations yet with varying concentrations and the
absence of clinical trials demonstrating efficacy. Further-
more, there bas been disagreement as to whether retinol
@st be convertedto retinoic acid to be active topically.
Qnly a small quantity appears to be converted in human
skin, which would require much higher concentrations to
be used.
Recent studies have provided some data to evaluate.
One study of 24 patients using 0.15%, 0.3%, and 0.6%
ROKHSAR ET ALLREVIEW OF PHOTOREJUVENATION 1171
-,\\
h'
concentrations over a period of 6 months showed hist;!
logic and clinical epidermal improvement in all patie&
using the two higher concentrations and in 40% of t h o 8
using 0.15% retin01.4~ -.,
In addition, a split-face study comparing hydroquinone
4%/retinol0.3% aeam (Alustra Medicis, The Dermatology
Company, Scottsdale, AZ, USA) applied twice daily t g
tretinoin 0.05% emollientcream (Renova)every hour at be&
time showed equivalence in efficacy at 1 2 weeks. Periocular
fine lines, roughness, and melasma severity were evaluated.'
Vitamin C
Vitamin C is among one of the newer products that bas
gained popularity in the antiaging cosmeceutical industry.
Chemically, it is composed of isomers L-ascorbic acid and
D-ascorbicacid, with the former being absorbed percuta-
ne0usly.4~The important role of vitamin C in the produc-
tion of collagen in the skin bas long been recognized. It
serves as a cofactor for hydroxylating enzymes in the syn-
thesis of the collagen triple helix. Vitamin C has been
shown to stimulate type I procollagen synthesis in cultured
human skin fibroblast^.^"^ It is no surprise that the clini-
cal manifestations of severe vitamin C deficiency, known
as scurvy, present most notably as perifollicular purpwa,
attributed to weakened collagen support in the structure of
dermal microvasculature.
Another intriguing property of topical vitamin C is that
it may serve as a biologicsun protectant against UVB-
induced erythema through its antioxidant activity and capa-
bdity of quenching free radicals. In animals, a 5% solution
of ascorbate applied 2 hours before W light exposure
reduced resultant wrinklmg." The addition of vitamin C
can augment the pbotoprotective effects of s~nscreens.~
Besides its important role in collagen synthesis and
maintenance, vitamin C exerts its protective effects
through multiple other mechanisms. It has biochemically
effective reducing properties and tbuscan act as a free rad-
ical scavenger in human tissue." Because it is water solu-
ble, it probably serves as the f i s t line of defense against
ondative damage. However, vitamin C is also known to be
the primary replenisher of vitamin E, a molecule with
lipopbilic antioxidant properties in membranes." Because
reactive oxygen species can play a d i r s role in the UVA-
mediated photoaging of the skin," the part that vitamin C
may play as a free radical scavenger may be crucial in pro-
tecting the skin against oxidative .damage.
Until recently, the majority of the data attesting to vita-
min C's rejuvenating effect on the skin are derived from in
vitro experiments or animal models. The most difficult
hurdle was to formulate a preparation that is stable and
can penetrate past the epidermis to influence dermal col-
lagen protection and remodeling.
In a recent study, Fiupatrick and Rostan showeci sratis-
tically significant improvement in clinical scoring of peri-

1i oral and cheek wrinkles in 10 human subjects after 90
;' d a y s of a formulated vitamin C complex with 10% water-
soluble ascorbic acid and 7% lipid-soluble tetrahexyldecyl
ascorbate in a polysilicone gel (Figure 5).Biopsies of the
improved areas confirmed the presence of increased
amounts of dermal collagen. This was further confirmed
by antisense probe for type I collagen messenger ribonu-
cleic acid. Howeveq they failed to identify any differences
in pigmentation in the treated versus untreated sites?6
Similarly, Humben and colleagues studied the effects of
a 5% vitamin C preparation on 19 patients over a 6-
month period in a double-blind, placeboiontrolled exper-
iment?' They concluded that vitamin C caused a statisti-
cally significant improvement in hydration, wrinkling,
glare, and brown spots on treated sites. In addition, they
demonstrated a change in the elastic fiber makeup of the
dermis in the biopsied skin.
1 Alpha-Hydroxy Acids
Alpha-hydroxy acids are a group of hydrophilic organic
acids that have been used for years as exfoliants, moisturiz-
Derrnatol Surg 31:9 Part 2:Septernbeg005
r;!
-I.
ers, and emollients. They have keratolytic activity, res ting
in reduced adhesion of keratinocytes and increased
of the stratum corneum, thereby causing smoother-aeear-
ing skin. They include glycolic, lactic, citric, pymvic, malic,
and tartaric acids. Their therapeutic effect in treating vari-
ous disorders of keratinization has long been recognized.
Recently, there has been a boom in the use of these &ems
for antiaging purposes in commercially sold creams. The
most commonly used alpha-hydroxy acids in cosmeceuti-
cals include lactic and glycolic acids.
In 1992,Lavker and colleagues reported that 4 weeks
of treatment with 12% lactic acid-ammonium lactate
lotion resulted in a 19% increase in epidermal thickness
and increased amounts of glyc~saminoglycans.~ Smith
studied the effects of 5% and 12% lactic acid in 24 sub-
jects after 3 months.s9 Treatment with 5% lactic acid
resulted in epidermal skin firmness and thickness as meas-
ured by ultrasonography without any accompanying der-
mal change. However, 12% lactic acid resulted in signifi-
cant epidermal and dermal firmness and thickness and in
clinical improvement in smoothness and wrinkles.

Figure 5. (A) Periorbital photodamage and wrinkling are evident prior to treatment. (B) Statinicailv significant im~rovementof ceriorbital
~ noted after 90 days of use of vitamin C complex with 5% vvate-loluble ascorblcacid and 7% lipld-soluble tetrahexyldcrjlarcor-
w r i n k i was
bate (SkinMedica, Carlsbad, C4 USA). Reproduced with permission frorn F'ipatrick RE and Rostan EF.Y
 -,-.. .
905 ~ ~ ~ ? < ~ p r m a t o31:9
Surg / Pa17 2:September 2005
Glycolic acid is a colorless, odorless, water-soluble, and
dontoxic agent if ingested. Its strength is in part dictated
by the pH of the preparation. In cosmetic products, it is
generally found in concentrations less than 10%. It is
edployed in concentrations above 20% in chemical peels,
which require neuualizing.
Ditre and colleagues compared the effects of 25% gly-
colic, lactic, or citric acid to one forearm versus placebo
lotion to another i n 1 7 subjects for an average of 6
months.60 They demonstrated an increase of 25% in skin
thickness on treated versus placebo skin. HistologicaUy,
increased acid mucopolysaccharides, improved quality of
elastic fibers, and increased density of collagen were also
noted.s6 The exact mechanisms behind the rejuvenating
effqts of alpha-hydroxy acids are unknown, but prefer-
ential activation of transforming growth factor p (TGF-p)
at an acidic pH has been proposed."
Kligman reported that the concomitaht use of tretinoin
and alpha-hydroxy acids provides greater benefits than
uetinoin alone in ameliorating fine l i e s and dyspigmen-
tati~n.~' This provides interesting venues for combination
topical therapy of aging skin.
Growth Factors
The use of growth factors or cytokiies for the purpose of
skin rejuvenation is the latest development in the treat-
ment of aging s k i . It has long been known that growth
factors control wound healing. Studies have shoyn that
specific growth factors, such as TGF-B, can increase col-
lagen synthesis,- enhance wound strength, promote gran-
ulation tissue formation, increase the size of regenerated
dermis, and stabilize the dennoepidermal junctionb3
. Reasoning that photodamaged skin may be akin to a
chronic wound, Fitzpatrick and Rostan tested the efficacy
of a cytokine cocktail derived from neonatal foreskin
fibroblasts on 14 healthy adults.63 The subjects applied
the gel twice daily for a period of 60 days. The formula-
tion, named TNS Recovery Complex (SkinMedica, Carls-
had, CA, USA), is composed of seven cytokines in a lipid-
based penetration enhancer gel. The cytokines include
vascular endothelial growth factor, hepatocyte growth
factor, platelet-derived growth factor A, interleukins 6
and 8, granulocyte colony-stimulating factor, and TGF-
81.
Eleven of the 14 patients showed signs of improvement
in skin texture and visibility of wrinkles in at least one of
four facial areas.studied (Figure 6). Overall, there was
8.6% improvement, with the periorbital area showing the
most significant change (12.2%). There was also a statis-
tically significant improvement in texture (14.1%) and
wrinkle depth as measured by optical profilometry
(36.2%). Histologically, &ere was an increase of 30% in
epidermal thickness, whereas there was a 37% increase in
grent zone collagen (Figure 7). Evaluation of elastic tissue
ROKHSAR ET AL: REVIEW OF PHOTOREJUVENATlON 1173,
0
showed a decrease in amorphous clumping of elastic fibeipl
with increased numbers of fine branching fibers. PI
dr
A multicenter, double-blind, vehicle-controlled, splg-
face study involving 255 patients with moderate to seve&
facial photodamage was conducted using TNS Recovery
Complex topical growth factors twice daily for 90 days
and no treatment for 90 days. Clinical evaluation showffl
a reduction in dyspigmentation, improvement in skin tekk
ture, and decreased wrinkling on the active side versus the
placebo side. These findings were further supported by
optical profdometry and biopsy results. Grenz zone coUa-
gen was increased more than 30% on the growth factor
side, whereas the placebo side showed only a 4% increase.
These clinical and histologic results were maintained dur-
ingthe 90-day follow-up period as well.
Combined Use of Cosmeceuticals and
Nonablative Laser Therapy
Overall, the results achieved using nonablative laser ther-
apy to treat photodamage have been subtle but nevertheless
well received by patients. Improvements in skin texture and
pigmentation have given enough visible changes to satisfy
many patients, if not the majority of those treated. The
degree of improvement in texture is very similar to that
which has been achieved with topical retinoids, vitamin C,
growth factors, and possibly alpha-hydroxy acids. The
mechanism of action of lasers in inducing textural changes
is most likely through cytokiie-mediated collagen remod-
eling and resuucturing of the superficial dermis. It is inter-
esting that histologic studies have shown degrees of new
grenz zone colla\genwith laser rejuvenation similar to those
with treatment using topical retinoids, vitamin C, or
growth factors. However, the improvement seen in
dyschromia associated with photodamage and actinically
induced telangiectasia is clearly superior with laser treat-
ment. At this time, there are no controlled studies combii-
ing the use of cosmeceuticals with laser rejuvenation, but
anecdotal comments, as well as theoretic considerations,
suggest that the use of properly chosen cosmeceuticals in
conjnnction with laser therapy can result in enhanced
results and maintenance of the improvement seen. All of
the cosmeceutical agents discussed in this amcle can be
used simultaneously if the physician and patient so desire.
When the results are subtle, all elfdrts to reasonably
enhance the overall end points may be considered. It is oui
recommendation that selected topical cosmeceuticils be
used in conjunction with nonablalive photorejuvenation.
To evaluate combination therapy approaches, we
should consider two different but typical patients seeking
treatment. Patient 1 is a patient with mild to moderate
dyschromia and mild to moderate textural changes; Such
a patient will'typicallyhave uneven brown patchy i~lgment
'-
of the forehead and mid- to lateral cheeks; trztural
changes of the cheeks, under the eyes, of the midforthead,

>fuseof topical growth facton NNS Recovery Complex, SkinMedica,
and of the perioral areas; and possibly some telangiectasia
of the mid- to lateral cheeks and nasal alae. Patient 2 will
have primarily textural changes, rhytids, and few telang-
iectasia. In such a patient, the lines and textural changes
In both of these patients, we'look at specific cosmeceu-
ticals and lasers to be used in the preoperative, postopera-
tive, and maintenance phases. . may be used as a gel, lotion, or light peel performed res-
In patient 1,improvement in dyschromia (both pigment
and vascular) will make the biggest difference in clinical
Oermatol Surg 3 7:9 Part 2:SeptembepOS
\
hl
Treatment during the preoperative period is almost
entirely through the use of cosmeceuticals. Retinoids may
be particularly useful because they have been shown to
normalize pigment and improve texture. If retinol is to be
used, multiple applications eachday will boost the
response. It will also be beneficial to use an alpha-
hydroxy acid because Kligman has reported that an
alpha-hydroxy acid will boost the response of retinoids in
improving texture and ~igment.~lThe alpha-hydroxy acid
peatedly. ' ' .
Whether vitamin C is useful in this stage is debatable.
Io the two clinical studies cited in this article, one showed
benefit for dyschromia, whereas one did not. \ita.min C,
however, would definitely add some further antiaxidant
protection for the skin and does have the potential to
 at01 Surg 31:9 Part 2:September 2005
I Figure 7. Biopsies of photodamaged skin show a significantincrease i ln grenz zone collagen after 90days of topical growth factor used twice
daily. The average increase in thickness was 3 7 % (hematoxylin+orin; x 100 original magnification).
stimulate new collagen and improve dyspigmentation. If it
is tobe used, it should be applied in the morning before a
sunscreen is applied.
Growth factors have definitely been shown to decrease
dyspigmentation and improve skin texture and should be
applied each evening.
This "preoperativen phase may be a period of several
months while the patient contemplates having laser proce-
dures, or it may be just a few days between consultation
and treatment. In either case, the same regimen would be
used.
The postoperative period is defined for this article as
the period of treatment extending to 90 days after the final
treatment. The primary adjustment during this period
would be to decrease the use of retinoids and alpha-
hydroxy acid products because of their potential to irri-
ROKHSAR ET AL: REVIEW OF PHOTOREJUVENATION 1175-1
->
II!
tate,inflame, and peel the skin. The use of growth factors
should be increased to twice a day to enhance wound heal-
ing. If vitamin C is not already part of the regimen, it
should be added during this phase (Table 2).
The best devices to use in this p a t b t are the IPL and
the Vbeam or the Fraxel. The IPL can be targeted toward
the brown pigment and the Vbeam toward the vascular
ectasia. The Fraxel targets both..Treatment sessions with
the IPL and Vbeam are generally performed once a month
for three to six treatments. Treatments with the Fraxel are
generally performed weekly for three to six treatments.
Once this active treatment phase has passed, the patient
should be placed on a maintenance regimen. Basically, this
would involve returning to the preoperative rigimen,
although the alpha-hydroxy acid may be dropped if the
dysduomia has normalized.
1176 ROKHSAR ET AL: REVIEW OF PHOTOREJWENAlTON Dermatol Surg 31:9 part 2:~eptembeZi005
riI
-4
\,
Table 2. Adjunctive Use of Cosmeceuticalswith Rejuvenative Procedures, ;1 I

Timeline Patient 1 Patient 2 GI

Clinical findings: Clinical findings:
Dyschrornia, vascular ectasia, Textural changes, fine and deep
textural changes lines, mild telangiectasia
Preoperatively Retinol0.3% bid to tid Retinol0.3% bid to tid (Jl
[JI
AHA qd Vitamin Cq am
Vitamin C? q am TNS growth factors qd to bid
TNS growth factors qd
Operatively to Vitamin C q am Vitamin C q am
90 days TNS growth factors bid TNS growth factors bid
postoperatively
Treatment IPL, Vbeam or Fraxel Fraxel, bol~ouch,Smoothbeam or
Er:glass, plus Vbeam, IPL or
long-pulsed 532 nm laser
Maintenance Retinol0.3% qd Retin010.3~hqd
Vitamin C q am- Vitamin Cq am
TNS growth factors q am TNS growth factors q am
AHA = alpha-hydroxy ackl; TNS = TNS Recovery Complex.

The second patient, without dyschromia, would be Conclusions

treated during the preoperative phase with agents that may
help stimulate new collagen. The two agents that have The popularity of noninvasive treatment of photoaging
been most successful in this area are growth factors and through the use of cosmeceuticals and lasers speaks clearly
retinoids. Use of growth factors on a nv~ce-dallybasis that these approaches can be very successful when care is
appears to be more effective than once daily, possibly taken to construct a treatment regimen based on an under-
because more active agents are flooding the skin surface standing of the goals of each component. It is also very
and therefore more may penetrate to a level of activity.
Retinol should be used in a concentration of 0.3 to 0.6%
Table 3. Cosmeceutical Formulation S~ecifia
as the alcohol but in different concentrations for the
esthers (Table 3). Ktamin C defmitely has value as an anti- Chemistry Concentration, % PH
oxidant and a stimulant of new collagen. Alpha-hydroxy
Vitamin C
acid products may help revitalize the epidermis and L-Ascorbicacid" 10 <4
improve elasticity and collagen, leading to improvement in Axorbyl palmitate" 20
fine lines and texture. L-Axorbicacid in 10
The postoperative period would be similar to that for anhydrous silicone'
patient 1. If growth factors have been used twice daily, Tetrahexyldecyl axorbate' 5-10
that regimen would continue. Vitamin C would be used Alpha-hydroxy acid
each night, and retinoids and alpha-hydroxy acid products Glycolic acid OTC 10 > 3.5
would be minimized. Treatment 15-25 2.5-3.5
The lasers to be used for treatment would be the infrared Peels 30-50
lasers targeting tissue water: CoolTouch (1,320 nm), Lactic acid 12-25 2.5-4.0
Smoothbeam (Candela, Boston, MA, USA) (1,450 nm) and ~eer&-50
Retinol
Er:glass lasers (1,540 nm), or the Fraxel laser (1,550 nm). Retinol a l c ~ h o l ' ~ ~ ~ 2 0.3
The Vbeam or other vascular lasers (pulsed 532 nm, or Retinyl palmitate rl
IPL) could be used during the same treatment session to ~etin~l'acetate 0.254.5
target unwanted telangiectasia. Usually, treatment sessions Retinaldehyde 0.254.5
are performed monthly and three to SIX sessions are neces- Growth factors
sary. The Fraxel laser is used weekly to monthly for three TGF-Pa 2.5-20 mglcc
to six sessions. VEGF
The maintenance period would involve using growth PDGF
factors once a day, vitamin C once a day, and retinoids OTC= over the counter; PDGF = plateletderlved growth factor; rGF I tram.
once daily. forming growth factw; VEGF = vawular endmhelial growth factor.

&orrant for the patient to have a realistic goal of what
can be achieved with this approach and the treatment time
cqded to see results.
When assessing the patient, it is important to identify
h e specific aspects of photoaging that bother the patient
and then to select treatment modalities that will target
those specific pathologies. When dyspigmentation is the
primary complaint, retinol, growth factors, and alpha-
hydroxy acids would be the primary cosmeceuticals to use,
plus possibly vitamin C. The best lasers to treat dyschro-
mia would be the Fraxel or IF'L. When vascular ectasia is
the primary complaint, there is no cosmeceutical approach
available. Laser treatment would include use of the Vbeam
or IPL. When textural changes or rhytids are the chief con-
cern, retinol, vitamin C, and growth factors would be the
cosmeceutical approach and use of a midinfrared laser-
Fraxel, Smoothbeam, CoolTouch, or &:glass-would be
indicated.
In general, when using those agents that each have a
mild tb modest efficacy, expectations need to be realistic.
However, it is our impression that far greater success is
achieved by the use of a program that not only combines
multiple cosmeceutical agents but also takes advantage of
toaging the distinct benefits of the nonablative lasers discussed.
:clearlv
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T l i s article presents a nice summary of the t w o phases of anti-
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was a rapid m n h o d of inducing skin rejuvenation through the
ablative thermal destruction of t h e epidermis a n d dermis t o
induce collagen r e m o d e h g . M o r e recently, nonablarive light
sources, such as intense pulsed light, have entered the treatment
arena, with collagen remodeling induced m o r e slowly with
repeated treatments. N o w d e r m a s u g w n s must look beyond the
treatment realm and into the maintenance realm. H o w does the
patient slow t h e aging process a n d maintain the appearance
Dermatol Surg 3 1:9 part 2 : ~ e p t e m b e & O 5
%.
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immediately following a surgical rejuvenative procedure? At tbis
point in time, the maintenance phase is dominated b y the use of
cosmeceuticals t o include sunscreens, retinoids, vitamins,
hydroxy adds, a n d growth factors. Each of these substances w n -
f m a uniquc benefit t o t h e skin. T h e challenge is formulating t h e
active such that i t delivers efficacy and cpcourages patient com-
pliance. Patients should be required +enter t h e maintenance
phase a h e r a surgical procedure rather than relying o n a second
surgical procedure in t h e coming years t o again rejuvenate the
skin. T h e treatment phase and tlie maintenance phase should
always b e part of t h e dermatologic surgery algorithm.
ZOEDIANADRAELOS, MD
. High Point, NC