Antioxidants and Vitamins in

Cosmetics
MARY P. LUPO, MD

osmetics are commercially available products

that are used to improve the appearance of the
skin. Since the late 1980s, consumer demand for
more effective products that more substantively beautify the appearance has resulted in increased basic science research and product development in the cosmetics industry. The result has been more ingredients that
may actually improve not just the appearance of the
skin, but the health of the skin as well. We now have
products that renew, restore, and rejuvenatenot just
cleanse, protect, and moisturize. There is probably no
greater focus of interest currently than the incorporation of vitamins and antioxidants in skin care products.
There are considerable data to suggest the benefits of
such ingredients in cosmetics. This article reviews the
published data that support the usefulness of vitamins
and antioxidants in cosmetics. Our job as dermatologists is to digest and assess the data so we can give
knowledgeable recommendations to our patients.
The ingestion and absorption of vitamins and antioxidants, most importantly through diet, and secondarily through intake of manufactured supplements, is
critical to the health of human beings. The skin is the
largest organ; as our primary external barrier, it is on
the forefront of the battle with external causes of damaging free radicals. Ultraviolet light and environmental
pollutants are known initiators of free radicals. Free
radicals are highly reactive molecules with an unpaired
electron that result in damage to surrounding molecules and tissues. The most significant damage by free
radicals is to biomembranes and to DNA. It is thought
that additional, topical use of vitamins and antioxidants
in cosmetics can better protect and possibly correct the
damage by neutralizing these free radicals. In addition,
some vitamins may be beneficial to the skin because of
other actions such as effects of suppression of pigmentation and bruising, stimulation of collagen production,
refinement of keratinization, or anti-inflammatory effects.
From the Department of Dermatology, Tulane University School of
Medicine, New Orleans, Louisiana, USA.
Address correspondence to Mary P. Lupo, MD, Tulane University
School of Medicine, Department of Dermatology, 145 Robert E. Lee Boulevard, New Orleans, LA 70124 USA.
E-mail address: mplupomd@aol.com.
2001 by Elsevier Science Inc. All rights reserved.
655 Avenue of the Americas, New York, NY 10010

Vitamin A
Vitamin A, its derivatives, and beta-carotene (pro vitamin A) have been popular additives in cosmetics for
years. Dietary sources of beta-carotene include carrots,
tomatoes, and other yellow vegetables. Sources of vitamin A come primarily through animal foods such as
egg yolk and liver. Beta-carotene, as a precursor of
vitamin A, is a potent lipid-soluble antioxidant capable
of quenching singlet oxygen, a highly reactive free radical. Singlet oxygen is capable of inducing DNA damage and of being mutogenic.1,2 Beta-carotene has been
shown to have topical photoprotective effects. It has
been studied on mouse and guinea pig skin and demonstrated to protect against UVA radiation effects.3,4 In
addition, both beta-carotene and vitamin A were found
to be photoprotective by decreasing lipid peroxyl radicals in UV-radiated murine skin.5 Beta-carotene is so
unstable, however, that other forms of vitamin A are
commonly used in cosmetic formulations.
The primary benefit of vitamin A and its derivatives
in cosmetic products has been their ability to normalize
keratinization. The popular derivatives of vitamin A
that are found in cosmetics include vitamin A alcohol
(retinol), vitamin A esters (retinyl palmitate, retinyl
acetate), vitamin A aldehyde (retinal), and tretinoin
(retinoic acid). These are found in various concentrations in cosmetic formulations. The cosmetics benefits
from vitamin A and its derivatives lie in their ability as
retinoids to regulate epithelial cell growth and differentiation. This family of compounds called retinoids
has been shown to have receptor-specific effects on the
skin, resulting in decreased roughness and decreased
facial wrinkling. For many years, in many circles, vitamin A has been called the normalizer. Tretinoin (alltrans-retinoic acid) is considered the most bioactive
retinoid for modulating skin function. For this reason, it
is considered a drug in the United States, available in
higher strengths only by prescription. It is the conversion of the other forms of vitamin A into tretinoin that
affords them any cosmetic benefits to the skin.
Retinyl palmitate, a vitamin A ester, has been added
to cosmetics for years. It has a large molecular weight
and is stable in formulation. It is, however, considered
the least effective topical retinoid. Retinyl palmitate
must be enzymatically converted in the skin first to
0738-081X/01/$see front matter
PII S0738-081X(01)00188-2

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468 LUPO

retinol by cleavage of the ester bond, then the retinol

must be converted by a two-step oxidative process into
the active tretinoin.6 The limitations on enzymatic and
oxidative processes in the skin explain the decreased
effectiveness of both retinyl palmitate and retinol compared with retinoic acid. Nonetheless, there are data to
support some benefit of topical retinyl palmitate on the
skin. It has been found to increase epidermal thickness
in human skin.7 In another study, topical retinyl palmitate administered for fourteen consecutive days on hairless mice resulted in an increase in protein and collagen
as well as DNA content and increased epidermal thickening.8 It is reasonable to assume that other vitamin A
esters, such as retinyl acetate and retinyl proprionate,
may have similar, limited cosmetic benefits for the skin.
Retinal, vitamin A aldehyde, is considered another retinoid of limited efficacy, but has excellent stability in
formulation. Studies have shown responses to include
increased epidermal thickness and increase cellular retinoic acid binding protein II mRNA content.7,9 Confirmation of penetration into the epidermis and dermis in
vitro has been demonstrated on human skin, so there
can be some argument regarding cosmetic efficacy.10
Retinol is currently the vitamin A ingredient of
choice in cosmetics. When stabilized in formula, by
protecting it from breakdown from oxygen and light, it
is a clinically useful addition to skin care products. In
one study, application of retinol to human skin in vivo
resulted in increased epidermal thickness as well as
increased mRNA levels of cellular retinoic acid-binding
proteins and cellular retinol-binding proteins.11 This
reflects the biologic activity of a retinoid.
Consistent with the need for conversion of the retinol
to retinoic acid for activity is that much higher concentrations of retinol were needed to achieve similar results. The investigators concluded in their study that
the retinol was twentyfold less potent than retinoic
acid. Other studies confirmed the requirement of retinol
conversion to retinoic acid to produce retinoid effects.12
Another study similarly demonstrated that retinol enhanced epidermal hyperplasia as well as cellular and
molecular changes with little irritation.7 Retinol was
found to effectively penetrate human skin in vivo and,
in concentrations of 0.25%, induced both cellular and
molecular changes.
Of course the gold standard for retinoid activity on
the skin is all-trans-retinoic acid, or tretinoin. Tretinoin
was first used for acne, and Kligman first noted and
reported its benefits on photoaged skin.1315 When used
on photodamaged skin, tretinoins clinical effects included improvement of wrinkling and roughness, and
lightening of lentigines and melasma.16 18 Objective histologic changes from tretinoin include decreased corneocyte adhesion and epidermal hyperplasia, increased
Langerhan cells, increased collagen, elastin, and angiogenesis.19 Such biological effects on structure and func-

2001;19:467 473

tion explain the appropriate classification of retinoic

acid as a drug at higher concentration.

Vitamin B
Vitamin B is a group of water-soluble nutrients found in
many food sources, especially whole grains and green
leafy vegetables. Panthenol is the alcohol form of pantothenic acid, or vitamin B5. This has been used for
years in hair care products because it functions as a
humectant and increases the water content and improves the elasticity of hair. Humectants can attract
water into the stratum cornium to soften the skin; because of this effect, panthenol is effective as a moisturizer in cosmetics.
Niacinamide (also called nicotinamide), a form of
vitamin B3 (niacin), has been shown to have some
exciting benefits when applied to the skin. Niacinamide
has been shown to have anti-inflammatory properties
that result in improvement of acne.20,21 The pyridine
ring present in niacinamide is believed to be responsible for the anti-inflammatory activity.22 Additional
studies on niacinamides anti-inflammatory effects have
shown suppression of antigen-induced lymphocyte
transformation and inhibition of potassium-iodide-induced inflammation.22,23 Human keratinocytes incubated with niacinamide showed improved barrier function and decreased transepidermal water loss because
of stimulation of ceramide synthesis, which normally
decreases in aging skin.24 Topical niacinamide also
showed benefits for pityriasis rubra pilaris, psoriasis,
isonizid-induced pellagra-like skin eruptions, and rosacea.2528 Like some other topically applied vitamins, B3
prevented immunosuppression and skin cancer in UVirradiated mice.29 Such a finding suggests some photoprotection, perhaps through antioxidant activity. Other
anticarcinogenic actions of niacinamide may include its
ability to act as both a protease inhibitor and a stimulator of DNA repair.30,31

Vitamin C
Vitamin C, ascorbate, a water-soluble vitamin present
in citrus fruits and vegetables, is important because of
its antioxidant actions as well as its function as a cofactor in hydroxylation reactions of collagen production.
Humans are unable to synthesize ascorbate, so dietary
intake is essential. Interest in vitamin C as a cosmetic
ingredient is partly a result of it ability to quench UVinduced free radicals directly, and to regenerate vitamin E, another potent antioxidant.32,33 Vitamin C is also
considered an antiaging ingredient because of its potential to stimulate collagen production.34 There are
three forms commonly available in cosmetics: ascorbyl
palmitate, magnesium ascorbyl phosphate, and
L-ascorbic acid.
Ascorbyl palmitate, a fat-soluble synthetic ester of

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2001;19:467 473

vitamin C, is stable in cosmetic formulas at neutral pH.

Hydrolysis of ascorbyl palmitate yields ascorbic acid
and palmitic acid. Topical ascorbyl palmitate in one
study was found to be thirtyfold more effective than
ascorbic acid as an inhibitor of some of the biochemical
parameters associated with tumor production in mice
skin.35 Ascorbyl palmitate, applied after UV burning,
reduced redness 50% sooner than areas on the same
patient that were left untreated.36 The suspected mechanism is that the ascorbyl palmitate acted as both an
antioxidant and anti-inflammatory agent. Other dermatologic conditions that have inflammation as a component of the disease process, such as psoriasis and asteototic eczema, have shown clinical improvement when
treated with ascorbyl palmitate.37
Another vitamin C derivative found in cosmetics is
magnesium-L-ascorbyl-2-phosphate, which has been
studied for various antioxidant benefits. Magnesium
ascorbyl phosphate was found to protect against UVB
radiation-induced lipid peroxidation in hairless mice.38
The authors found in vitro evidence that magnesium
ascorbyl phosphate crossed the epidermis and is converted to ascorbic acid. In an in vitro study of monolayer human fibroblast cultures, magnesium ascorbyl
phosphate was found to be equivalent to ascorbic acid
in stimulating collagen synthesis and was stable at a
neutral pH.39 Another in vitro study of human skin
fibroblast in culture demonstrated enhanced collagen
synthesis and cell growth.40 Significant also was the
extended stability under various conditions and the
effectiveness over a wide concentration range. Evidence
suggested that cell membrane dephosphorylation converted the magnesium ascorbyl phosphate to ascorbic
acid. Subsequent in vitro study of cultured fibroblast
suggested that magnesium ascorbyl phosphate regulates type I collagen production.41 An in vivo study of
human skin demonstrated a clinical improvement of
melasma and senile freckles when utilizing a 10% magnesium ascorbyl phosphate cream.42 In situ testing
demonstrated absorption into the epidermis. Presence
of vitamin C after 48 hr was measurable but minimal
(1.6%). The ingredient was stable in nonacid solution,
hydrolyzed by phosphatases in the skin to form ascorbic acid, which then inhibited melanin production by
reducing o-quinone. Another ascorbate derivative, 2-0alpha-D-glucopyranosyl-L-ascorbic acid, which is also
stable in solution and at wide pH ranges, also stimulated cultured human skin fibroblasts in vitro, resulting
in increased collagen synthesis.43
L-ascorbic acid is the most bioactive form of vitamin
C and has been found to have numerous benefits for the
skin. This form of vitamin C is water soluble but it must
be formulated at low pH to be stable. In cultured human skin fibroblast, it increases type I and type III
procollagen mRNA.44,45 The measured difference was a
result of increased synthesis of procollagen polypep-

ANTIOXIDANTS AND VITAMINS IN COSMETICS

469

tides. The authors speculated that ascorbic acid may

have affected gene transcription or mRNA degradation.
Another studys results indicated that ascorbic acid
stimulated collagen synthesis in collagen matrix.46 Such
3-D models more closely mimic in vitro conditions. As
an electron donor, L-ascorbic acid is able to function as
an antioxidant. In porcine studies, it was found to be
photoprotective because it reduced sunburn cell formation by both UVB and PUVA exposure.47 The authors
speculate that replenishing the vitamin C that is normally depleted by UV radiation helps protect the skin
from free radical damage. Further study is warranted to
determine optimal concentration and formulations of
ascorbic acid so that it may be a stable formulation
perhaps used as an adjunct to sunscreens for more
complete photoprotection.

Vitamin E
Vitamin E is a lipid-soluble vitamin present in many
food sources, especially soy, nuts, whole-wheat flour,
and oils. Systemically, it is reported to have numerous
health benefits to the eyes and cardiovascular systems
due to its ability to reduce lipid peroxidation.48,49 When
applied topically, numerous cutaneous benefits have
been shown. The primary mechanism of action to justify vitamin Es importance is its potent antioxidant
ability. Because of this ability to quench free radicals,
especially lipid peroxyl radicals, the term protector
has been used to describe the actions of vitamin E and
its derivatives. Several studies show their ability to
reduce UV-radiation-induced erythema and edema,
sunburn cell formation, and lipid peroxidation.50 55
Clinical improvement in the visible signs of skin aging
has been documented with decrease in both skin wrinkling and skin tumor formation.56 60 Multiple studies
have been performed on both tocopherol and its acetyl
ester derivative, tocopherol acetate. While tocopherol is
the primary active form of vitamin E, the vitamin E
esters have also been shown to penetrate the epidermis
when applied topically.61 Like other vitamins, however,
conversion to the more bioactive form is required for
action to occur at the target. Limits on the speed of the
necessary hydrolysis reaction limit bioactivity of the
acetate form of vitamin E. One study found tocopherol
sorbate, a less commonly used vitamin E derivative, to
be photoprotective via its antioxidant actions as well.56
All this data validates the popularity of vitamin E and
its derivatives as antioxidant, rejuvenating ingredients
in cosmetics. Current trends suggest vitamin Es popularity will continue in the future.

Vitamin K
Vitamin K1, phytonadione, is necessary for the hepatic
production of multiple clotting factors. Vitamin K is
supplied to the body primarily in green leafy vegetables

Clinics in Dermatology

470 LUPO

as well as by production by intestinal bacteria. Clinically, it is used to reverse prothrombin deficiency states
such as coumadin intake. Because parental vitamin K
improves prolonged bleeding time, a reasonable rationale that is topical vitamin K to correct and prevent
some of the vascular manifestations of aging. Topical
1% vitamin K used twice daily was found to be effective
in speeding the resolution of bruising as well as decreasing future bruising.62 A similar formulation combined with retinol has been tested and is marketed for
under eye circles.63 Presumably, this is the result of
vitamin Ks ability to prevent and remove extravasated
blood in the skin, as well as retinols ability to correct
certain aspects of photoaging.

Nonvitamin Antioxidants
There is great importance for an intact antioxidant defense system for the skin. Directly exposed to a hostile
pro-oxidative environment, endogenous skin antioxidants can be easily depleted. In addition to research on
antioxidant vitamins, there has also been research into
the efficacy of other antioxidants that can be used topically in cosmetics.
Coenzyme Q, or ubiquinone, is a naturally occurring,
lipid-soluble substance found in high levels in the epidermis. Its presence in most cells in the body, and its
ability to react with reactive oxygen species, has resulted in scrutiny for systemic use for many diseases of
aging, such as heart disease and atherosclerosis.64,65
Like other naturally occurring skin antioxidants, it is
depleted by UV exposure.66 It has also been suggested
that it protects vitamin E present in the skin, which can
further help the skin fight free radical damage.67 These
actions have resulted in recent commercial interest in
Coenzyme Q-10 as a topical ingredient in cosmetics.
Research has suggested antioxidant effects against UV
radiation in cultured skin cells as well as penetration
into the epidermis and dermis in vivo.68 More study
must be done to determine the mechanism of its antioxidant actions in human skin after topical application.
Flavinoids are a family of compounds that are reported to have health benefits systemically via antioxidant action. Recently, there has been an increase in the
use of these polyphenolic compounds in cosmetics. Catechin, a green tea extract, has been tested on murine
skin and found to be protective against photocarcinogenesis.69 Genistein, an isoflavone present in soybeans,
has anticancer properties via inhibition of tyrosine protein kinase (TPK).70 Further study on genistein shows
inhibition of UVB-induced c-fos and c-jun proto-oncogenes, suggesting that topically it may be protective
against photocarcinogenesis.71 Silymarin, another flavinoid derived from the milk thistle plant, has also been
shown to have protective effects against photocarcinogenesis in mice and to inhibit UVB-induced, sunburn,

2001;19:467 473

and apoptotic cell formation.72 Such data suggest a need

for future study and possible incorporation of these and
similar compounds into cosmetic formulation.
Lipoic acid and its redox derivative, dihydrolipoic
acid, have been studied systemically for multiple benefits as a result of potent antioxidant actions.73 It is
widely agreed that lipoic acid scavenges hydroxyl radicals, hypochlorous acid, and singlet oxygen. There is
evidence that it may affect regulatory protein and genes
involved in normal growth and metabolism.74 Lipoic
acid is stable in formulation and evidence suggests
conversion in the skin to dihydrolipoic acid.75 Skin
penetration on hairless mice has been demonstrated.
This suggests probable effectiveness as an ingredient
when applied topically.
Other compounds have shown photoprotective, antioxidant action when applied topically. In one study,
glycolic acid, already a popular antiaging cosmetic ingredient because of its exfoliative actions, was found to
have photoprotective and anti-inflammatory benefits
against UVB irradiation on human skin in vivo.76 Polyamines such as spermine, an epidermal antioxidant,
may also be protective against UV-irradiation-induced
oxidative stress. It is hypothesized that it acts as a metal
chelator.77 This is important because transition metals,
such as iron, can be an important requirement for lipid
peroxidation.78 Another iron chelator, 2-furildioxime,
has been studied for similar benefits and found to improve photoprotection against UVA and UVB irradiation in guinea pigs.79 Topical application of the pineal
hormone melatonin has also shown inhibition of UVradiation-induced erythema in humans.80 The enzymatic epidermal antioxidant, superoxide dismutase,
has also been studied for topical benefits. Due to its
molecular size, significant penetration is unlikely, yet
antioxidant actions after topical application have been
described.4,81 Finally, commonly used food antioxidants, such as butylated hydroxyanisole (BHA) and
butylated hydroxyltoluene (BHT), have been studied.
BHA was found to be involved in the modulation of
collagen synthesis by tumor necrosis factor-alpha in
human dermal fibroblasts.82 BHT has been found to
have protective effects against UV-induced erythema
on rabbit skin and to inhibit lipid peroxidation in
mouse skin.5,83 That there have been so many studies on
so many potential topical antioxidants certainly suggests even more potential product development in the
future.

Conclusions
Vitamins and antioxidants have great popularity as
primary ingredients in cosmetics. There have been considerable scientific data, as well as anecdotal experience, with these more bioactive cosmetics to suggest
definite benefits to consumers. For any ingredient to be

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2001;19:467 473

beneficial it must be stable in production, storage, and

use; be nontoxic to the consumer; and have activity at
the target site once applied. More study is needed to
improve skin penetration of these bioactive cosmetics.
Perhaps there is even a need for instrumentation, like
ionophoresis for example, to enhance delivery into the
skin. Market-driven economics clearly reflect great popularity and apparent satisfaction with antioxidant and
vitamin formulations. Further research and testing can
only enhance our understanding of these cosmetic ingredients actions and benefits, and result in even more
efficacious cosmetic products in the future.

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