Dermatologic Therapy, Vol. 20, 2007, 314–321 Copyright © Blackwell Publishing, Inc.

, 2007
Printed in the United States · All rights reserved
DERMATOLOGIC THERAPY
ISSN 1396-0296

Interaction of vitamins C and

Blackwell Publishing Inc

E as better cosmeceuticals
KAREN E. BURKE
Department of Dermatology, Mount Sinai Medical Center, New York

ABSTRACT: Although many cosmeceutical formulations contain vitamin C and/or vitamin E, very
few are actually effective in topical application. First because there is only a low concentration,
second because the stability is compromised as soon as the product is opened and exposed to air and
light, and third because the form of the molecule (an ester or a mixture of isomers) is not absorbed or
metabolized effectively by the skin.
However, when a stable formulation delivers a high concentration of the nonesterified, optimal
isomer of the antioxidant, vitamins C and E do indeed inhibit the acute ultraviolet (UV) damage of
erythema, sunburn, and tanning as well as chronic UV photoaging and skin cancer. Both are highly
effective depigmenting agents. Topical vitamin C also increases collagen synthesis in both young and
old fibroblasts. Because vitamin C regenerates oxidized vitamin E, the combination in a cosmeceutical
formulation is synergistic – particularly in UV protection.

KEYWORDS: topical antioxidants, UV protection, vitamin C, vitamin E

Introduction bat, and the guinea pig lack the enzyme L-glucono-
gamma-lactone oxidase to synthesize vitamin C. A
Antioxidants provide the mainstay for protection 59-kg goat synthesizes 13 g of vitamin C per day,
against free-radical damage throughout the body. almost 200 times the American Food and Drug
Our skin is the organ that suffers most from the Administration (FDA) requirement (1). Not only
environmental free-radical damage of sunlight, do other animals make hundreds of times the
urban pollution, and cigarette smoke, and this vitamin C we ingest, but also, they synthesize
exposure depletes antioxidants, overwhelming our more than 10 times their normal amount when
natural protective mechanisms. Because our most under stress.
important aqueous- and lipid-phase antioxidants We humans obtain vitamin C solely from our
– vitamins C and E, respectively – can only be diet – citrus fruits, black currants, and red peppers
provided exogenously, it is indeed beneficial to and other leafy green vegetables. Because active
enhance oral supplementation by topical applica- transport from the gastrointestinal tract is limited,
tion for extra protection of the skin. unfortunately even massive oral doses do not
increase the concentration to optimal levels in
the skin.
Vitamin C Exposure to sunlight and environmental pollu-
tion actually depletes vitamin C from the center
Vitamin C (L-ascorbic acid) is the body’s major layers of the skin. Even minimal ultraviolet (UV)
aqueous-phase antioxidant and is vital for life. exposure of 1.6 minimal erythema dose (MED)
Most animals make their own vitamin C; only decreases the level of vitamin C to 70% of the
humans and other primates, the Indian fruit-eating normal level, and exposure to 10 MED decreases
vitamin C to only 54% (2). Exposure to 10 ppm of
ozone in city pollution decreases the level of
Address correspondence and reprint requests to: Karen E. epidermal vitamin C by 55% (3).
Burke, MD, PhD, Rivercourt, 429 East 52nd Street, New York, Thus, enhancing the level of vitamin C in the
New York 10022, or email: [email protected]. skin is of utmost importance and delivery topically

314
 Vitamins C and E

FIG. 1. The molecular structure of L-asorbic acid, L-

ascorbyl-6-palmitate, and magnesium ascorbyl phosphate.
(Diagram provided by Sheldon R. Pinnell, MD, and printed
with his permission.)

as a cosmeceutical can be extremely beneficial. FIG. 2. Levels of vitamin C in porcine skin after once-daily
Indeed, several forms of vitamin C are used in application of 10% L-ascorbic acid (5).
lotions, creams, serums, and patches. However,
active L-ascorbic acid is such an excellent anti-
oxidant that it is inherently unstable, turning brown
as it is oxidized to dihydroascorbic acid when
exposed to air. Therefore the shelf life of most
formulations containing pure vitamin C is short.
To overcome the problem of instability, the
more stable esterified derivatives ascorbyl-6-
palmitate and magnesium ascorbyl phosphate are
often used. (See FIG. 1) However, these derivatives
are not well absorbed (4) and are only minimally
metabolized by the skin to the active, free-acid
form.
To achieve the benefits to the skin with topical
vitamin C, the cosmeceutical product must (i)
contain L-ascorbic acid (ii) in a high enough con-
FIG. 3. Levels of vitamin C in porcine skin after dis-
centration (at least 10%), (iii) be stable, and (iv) be continuing once-daily application of 10% L-ascorbic acid (5).
at an acid pH – less than the pKa (4.2) of vitamin
C. (The optimal pH of a vitamin C formulation is
3.5.) Fortunately, several commercially available
products do meet these criteria. Two stable in the highest skin levels, with maximized con-
formulations are (i) Force C Premium (Helena centration in the skin after 3 days of once-daily
Rubinstein) (not available in the United States), application (5). (See FIG. 2) In fact, levels of
which is packaged so that pure, stable crystals of vitamin C after topical application of 15% serum
L-ascorbic acid are in a separate compartment are a factor of about 27 times that which could
from the lotion vehicle; the user mixes these to ever be attained by even very high oral intake. If
make the active 15% vitamin C lotion, which is topical application is discontinued after skin
stable for about 4–6 weeks; and (ii) SkinCeuticals saturation is achieved, high levels still exist in the
Vitamin C Serum 15% which is a stabilized serum skin for more than 3 days (5). (See FIG. 3)
formulation (now improved as described, below) Vitamin C provides many benefits to the skin –
that maintains activity for 1 to 2 months after most significantly, synthesis of collagen and photo-
opening. protection. Vitamin C is absolutely required for
If the formulation meets the previously men- synthesis of collagen. With no vitamin C, humans
tioned criteria, effective skin levels of vitamin C develop scurvy, which can be lethal. Vitamin C is
can be attained. Topical absorption has been the essential cofactor for the two enzymes required
proved by radioactive labeling studies in pigs. for collagen synthesis: prolyl hydroxylase (to
After treatment with 10% vitamin C cream, 8.2% stabilize the collagen molecule) and lysyl hydro-
was found in the dermis, and 0.7% was in the xylase (to give structural strength cross-linking) (6).
blood (4). Formulations containing 5%, 10%, 15%, Recent research has further demonstrated that
20%, or 25% vitamin C were tested: 20% resulted vitamin C acts directly on DNA to increase the

315
Burke

transcription rate and to stabilize the procollagen (nuclear factor kappa beta), the factor responsible
messenger RNA, thus regulating and maintaining for many preinflammatory cytokines such as tumor
the intercellular amount of collagen (7). necrosis factor alpha (TNF-α), and interleukins
By enhancing collagen synthesis, vitamin C also Il-1, Il-6, and Il-8 (11). In fact, topical vitamin C
has antiaging effects. Studies in vitro compared has been used by dermatologists to treat acne and
newborn with elderly (80–95 years old) fibroblasts rosacea (12) and to decrease erythema after laser
(8). Elderly cells proliferate in vitro at only one- abrasion (13).
fifth of the rate of newborn cells. However, when By directly decreasing inflammation, post-
vitamin C is added to the culture medium, the inflammatory hyperpigmentation is reduced. Also,
elderly cells proliferate better than normal new- vitamin C is itself an excellent depigmentating
born fibroblasts. Even the newborn fibroblasts agent because it inhibits the enzyme tyrosinase
proliferate almost four times better when exposed (14) to decrease melanin production. In the
to vitamin C (8). experience of this author, topical vitamin C (15%)
Not only do fibroblasts increase proliferation in demonstrated clinical lightening of melasma and
the presence of vitamin C, but they also synthe- solar lentigines even after only 2 months of daily
size more collagen. Newborn fibroblasts synthe- application.
size a larger percentage of collagen than elderly Furthermore, Kameyama et al. (15) showed
cells, but again, when elderly cells are exposed to suppression of melanin formation by inhibition of
vitamin C in vitro, they produce more collagen tyrosinase in melanosomes and in melanoma
than the normal, newborn fibroblasts (8). Surpris- cells by magnesium-L-ascorbyl-2 phosphate.
ingly, even newborn cells double the amount of When a 10% magnesium-L-ascorbyl-2 phosphate
collagen synthesized (8). cream was applied to human skin, significant
In contrast to the increased synthesis of col- lightening of melasma and of lentigenes was
lagen, in vitro studies suggest that vitamin C may observed in 19 of 34 patients (15).
inhibit elastin biosynthesis by fibroblasts (9). This All of these proved functions of topical vitamin
may be advantageous in reducing the solar elastosis C contribute to reversal of the appearance of pho-
seen in photodamage. toaging: Photoprotection over many months
Topical vitamin C has also been shown to allows the skin to correct previous photodamage;
enhance collagen production in human skin in the synthesis of collagen and inhibition of MMP-
vivo (10). Postmenopausal women who applied I was proved to decrease wrinkles (10), and the
5% vitamin C to one arm and half of the neck with inhibition of tyrosinase and antiinflammatory activ-
placebo to the other side showed an increase in ity results in depigmenting solar lentigines. As
mRNA of collagens I and III (10). Tissue levels of seen in FIG. 4, after 1 year of once-daily treatment
the inhibitor of metalloproteinase-I (MMP-I) with 15% topical vitamin C, wrinkles were clearly
were also increased, thus decreasing UV-induced reduced and mottled pigmentation resolved. The
collagen breakdown. However, mRNA levels of skin acquired a healthy, more youthful glow.
elastin, fibrillin, and tissue inhibitor of MMP2 Another important action of vitamin C on the
remained unchanged (10). Clinically, a significant skin is that topical vitamin C increases the synthesis
decrease was observed in deep furrows and sub- of several specific lipids of the skin surface (16).
stantiated by silicone replicas. Histology showed Thus, not only does vitamin C help the natural
elastic tissue repair. moisturization of the skin, but it also enhances
Vitamin C has also been proven to be photo- the protective barrier function (Catiel-Higournenc
protective. Vitamin C is itself not a sunscreen et al., L’Oréal Advancer Research Laboratories,
because it does not absorb light in the UV spectrum; Clichy and Aulnay-sous-Bois, France, personal
however, as an antioxidant it deactivates UV- communication).
induced free radicals and decreases UVB erythema
by 52% (4). This protection is confirmed histologi-
cally: Treatment with topical 10% vitamin C Vitamin E
decreases the number of abnormal “sunburn cells”
by 40–60% (4) and reduces UV damage to DNA 8- Natural vitamin E is the most important lipid-
hydroxydeoxyguanosine (8-OHdG) by 62% (4). soluble, membrane-bound antioxidant in plasma,
Vitamin C has further been proven to be anti- membranes, and tissues. Like vitamin C, vitamin
inflammatory. In vitro studies with human cells in E is supplied to the body solely by the diet. Fresh
vitamin C-enriched media demonstrated decreased vegetables, vegetable oils, seeds, cereals, nuts,
activation of the transcription factor NF-κβ some meats, and some dairy products provide

316
 Vitamins C and E

FIG. 4. Correction of photoaging after 1 year of once-daily treatment with 15% Vitamin C Serum (SkinCeuticals). Notice the
improvement of periorbital wrinkles and lightening of solar lentigines. (Photographs provided by SkinCeuticals, Garland, TX,
USA and are printed with their permission.)

vitamin E. In the skin, vitamin E is especially

abundant in the stratum corneum, delivered there
by sebum (17,18). Its concentration is highest at
the lower levels of the stratum corneum, with a
decreasing gradient outward. As the outermost
defense of the body, the stratum corneum is first
to absorb the oxidative stress of sunlight and
pollution. With this exposure, vitamin E is depleted,
so topical application is particularly advanta-
geous. The lipophilic structure makes vitamin E
an especially attractive cosmeceutical for applica- FIG. 5. Molecular structure of tocopherols.
tion and absorption.
Several forms of vitamin E exist in natural
dietary sources. The form found in mammalian formulations because the esters are far more
tissues with by far the greatest biologic activity stable. This ester must be hydrolyzed before there
is pure, nonesterified RRR-α-tocopherol (or D- is any biologic activity, a reaction which readily
α-tocopherol) (19,20), which has three methyl occurs in the stomach after oral ingestion or in
groups on the 6-chromal ring. Humans use cell and organ culture, but is very slow after topical
predominantly α-tocopherol because a specific α- application. The skin has only a limited capacity
tocopherol transfer protein selectively transfers to cleave the esterified forms of vitamin E to the
α-tocopherol into lipoproteins (21). The other active free tocopherol form, so the antioxidant
natural forms are β, γ, and δ, which contain only potential of the esters is minimal (23,24). Further-
one or two methyl groups on the 6-chromal ring more, the all-rac form of vitamin E has been
(See FIG. 5). Relative to the α form, the β, γ, and δ reported to cause allergic contact dermatitis (25)
RRR-tocopherols give only 42%, 72%, and 40%, and erythema multiforme (26) when applied
respectively, of the protection against post-UV topically. No such adverse reaction has been
edema (22). The synthetic form is “dl” or “all-rac,” reported with d-α-tocopherol.
a mixture of eight stereoisomers. These synthetic Although oral vitamin E has been used to treat
isomers are esterified (to acetates and succinates) many dermatologic diseases – including yellow
for use in commercial vitamins and some topical nail syndrome, epidermolysis bullosa, claudication,

317
Burke

FIG. 6. UV-induced pigmentation of Skh:2 mice after

exposure to UV irradiation. Values (means ± SE) are averages FIG. 7. Mean number of tumors ≥ 2 mm in UV-irradiated
of 15 mice in each treatment group. 0, no hyperpigmentation; Skh:2 mice. Beginning 2 weeks before UV exposure, 15 mice
α-tocopherol
4, maximal hyperpigmentation. Eol = topical RRR-α in each treatment group were treated thrice weekly
(blue); Esuc = topical d-αα-tocopheryl succinate (green); throughout the duration of the experiment with vehicle
α-tocopheryl acetate (red).
Eac = oral d-α lotion ( and α-tocopherol (5%) (Eol)
), topical d-α
( ), or topical d-αα-tocopheryl succinate (5%) (Esuc) ( )
≥ 30 minutes before UV exposure. In addition, one group
( ) was fed a diet supplemented with d-αα-tocopheryl acetate
ulcers, and wound healing – the efficacy has not (Eac) (comparable to a human dose of about 600 IU/day).
been convincing because the reports are anecdotal Animals were exposed to UV radiation thrice weekly for 24
rather than placebo-controlled prospective studies weeks, and topical and oral treatments were continued
through and thereafter. Number of tumors ≥ 2 mm on each
with specifically the natural d-α-tocopherol form. mouse was counted, and mean number of tumors per mouse
In a placebo-controlled study of 96 atopic derma- was calculated based on total number of 15 mice in each
titis patients treated with placebo or 400 IU of oral treatment group (28).
vitamin E for 8 months, there was improvement
and sometimes almost remission, in atopic
dermatitis with a 62% decrease in IgE levels (27).
Topical vitamin E may also prove to be effective. As seen in FIG. 7, topical d-α-tocopherol was
There is controversial data about the use of far more effective in protecting against all acute
topical vitamin E in preventing and treating and chronic UV-induced damage than topical d-α -
hypertrophic scars. Again, few controlled studies tocopheryl succinate in mice; oral d-α-tocopheryl
were carried out and the most effective natural acetate was about as effective as topical d-α-
d-α-tocopherol form has rarely been used. tocopherol (28). In other mouse studies, topical
Topical vitamin E has been used effectively to α-tocopheryl succinate and α-tocopheryl acetate
treat melasma and pigmented contact dermatitis, not only failed to inhibit UVB-induced immuno-
as demonstrated in one multiclinical double- suppression and carcinogenesis, but appeared to
blind study (the combination of vitamins E and C enhance carcinogenesis (23). Topical α-tocopheryl
was better). In preventing UV-induced pigmenta- acetate was less effective than α-tocopherol in
tion in mice, oral d-α-tocopheryl acetate and top- protecting against UV-induced erythema in rabbits
ical d-α-tocopherol were equally effective; topical (23) and against UV-induced photoaging in
d-α-tocopheryl succinate was less protective, as mice (37).
shown in FIG. 6 (28). Interestingly, both dL-α- Clinically, topical vitamin E does decrease
tocopherol in lecithin and dL-α-tocopheryl ferulate wrinkles and solar lentigoes of photoaging. Reversal
in lecithin were found to inhibit the enzyme of photoaging was confirmed histologically in
tyrosinase to decrease melanogenesis in human mice: Microscopic examination showed correc-
melanoma cells (29). Both also decreased UV- tion of the UV-induced epidermal hypertrophy,
induced DNA damage as measured by reduced thickened stratum corneum, increased “sunburn
8-OHdG (29). cells” in the basal layer, and disruption of dermal
Even forms of topical vitamin E, which are collagen and elastin after 8 weeks of topical treat-
less metabolically potent than nonesterified d-α- ment (KE Burke, L Ricotti, EG Gross, unpublished
tocopherol, have demonstrated protection from the observation). Further electron microscopic analysis
acute (28,30–33) UV-induced damage of inflamma- confirmed correction of collagen and elastin fiber
tion (erythema, sunburn) and hyperpigmentation damage and demonstrated repair of UV-induced
(tanning) as well as protection from the chronic disruption of the basement membrane anchoring
UV-induced damage of skin cancer (28,32–36). fibrils.

318
 Vitamins C and E

FIG. 8. Minimal erythema dose after application of antioxidants. Skin was pretreated with vehicle, ferulic acid (0.5%), vitamin
C (15%) with vitamin E (1%), and vitamin C + E + ferulic acid and irradiated with solar simulated radiation of 2× × to 10×
× MED.
The increase in MED with topical antioxidant treatment is clearly seen (43). (Diagram provided by Sheldon R. Pinnell, MD, and
printed with his permission.)

Vitamin C with vitamin E Vitamin C with vitamin E and

ferulic acid
In cells, vitamins C and E interact synergistically
to provide antioxidant protection. In membranes, Ferulic acid is a potent antioxidant present in the
vitamin E is oxidized as it quenches peroxyl free cell walls of grains, fruits, and vegetables. Ferulic
radicals. The neighboring, plentiful, intracellular acid alone absorbs some UV and therefore is itself
vitamin C (with its lower redox potential) reduces a weak sunscreen. When mixed with vitamins C
the oxidized vitamin E to regenerate its activity so and E, it stabilizes the formulation and acts syner-
it needs not be replaced in the membrane (38). Oral gistically to double the photoprotection from
vitamin C with E in high doses protects against fourfold to eightfold (42). The increase in MED is
UV-induced erythema in humans (39), whereas clearly seen in FIG. 8. This triple antioxidant
either vitamin alone is ineffective (39). Topical combination has been made into the SkinCeuticals
L-ascorbic acid (15%) with α-tocopherol (1%) product C E Ferulic (with 15% vitamin C, 1% vitamin
gives four-fold protection against UV-induced E, and 0.5% ferulic acid).
erythema, decreasing the number of damaged
“sunburn cells” seen histologically and decreasing
thiamine dimer formation in porcine skin (40), Conclusion
compared to twofold protection for either vita-
min alone. This protection from UV-induced Although sunscreens are mainstay for protecting
erythema (41) by vitamins C and E combined skin from photodamage, they are not enough.
with melatonin was further demonstrated in Recent research shows that individuals only apply
humans. Fortunately, mixing these hydrophilic and about one-fourth of the amount of sunscreen
lipophilic antioxidants in a topical formulation required to achieve the designated SPF (2 mg/cm2,
stabilizes each (40) for a cosmetically attractive giving, for example, only an SPF of 2.3 for a
application. sunscreen designated SPF 30). Furthermore,

319
Burke

although sunscreens reduce UV-induced erythema magnesium 1-ascorbyl-2-phosphate (VC-PMG) on melan-

and thymine dimmer formation, they only block ogenesis in vitro and in vivo. J Am Acad Dermatol 1996: 34:
29 – 33.
about 55% of the free-radical production (43,44). 16. Uchida Y, Behne M, Quiec D, et al. Vitamin C stimulates
Because even once-daily application of correct sphingolipid production and markers of barrier formation
formulations of vitamins C + E provides a reservoir in submerged human keratinocyte cultures. J Invest Dermatol
in the skin for protection not only against post- 2001: 117: 1307–1313.
UV–induced erythema, hyperpigmentation, photo- 17. Podda M, Weber C, Traber MG, Packer L. Simultaneous
determination of tissue tocopherols, tocotrienols, ubiquinols,
aging, and skin cancer, but also against other and ubiquinones. J Lipid Res 1996: 37: 893–901.
free-radical damage, they are indeed a valuable 18. Thiele JJ. Oxidative targets in the stratum corneum: a new
adjunct to frequent sunscreen application. This basis for antioxidative strategies. Skin Pharmacol Appl Skin
protection over time allows repair of prior photo- Physiol 2001: 14: 87–91.
damage, thereby visibly reversing the unattractive 19. Mayer P, Pittermann W, Wallat S. The effects of vitamin E
on the skin. Cosmet Toiletries 1993: 108: 99–109.
appearance of photoaging. 20. Burton GW, Traber MG, Acuff RV, et al. Human plasma and
tissue -tocopherol concentrations in response to supple-
mentation with deuterated natural and synthetic vitamin
E. Am J Clin Nutr 1998: 67: 669–684.
References 21. Azzi A, Breyer I, Feher M, et al. Specific cellular responses
to alpha-tocopherol. J Nutr 2000: 131 (Suppl.): 369–375.
1. Pauling L. How to live longer and feel better. New York: 22. Potokar M, Holtmann W, Werner-Busse A. Effectiveness of
W.H. Freeman, 1987. vitamin E protecting against UV light – comparative testing
2. Shindo Y, Wit E, Han D, Packer L. Dose response effects of of the natural tocopherols on the skin of the hairless
acute ultraviolet irradiation on antioxidants and molecular mouse. Fat Sci Technol 1990: 92: 406–410.
markers of oxidation in murine epidermis and dermis. 23. Gensler HL, Aickin M, Peng YM, Xu M. Importance of the
J Invest Dermatol 1994: 23: 470– 475. form of topical vitamin E for prevention of photocarcino-
3. Thiele JJ, Traber MG, Tsange KG, et al. In vivo exposure to genesis. Nutr Cancer 1996: 26: 183–191.
ozone depletes vitamins C and E and induces lipid peroxi- 24. Beijersbergen van Hanegouwne GMJ, Junginger HE, de
dation in epidermal layers of murine skin. Free Radic Biol Vries H. Hydrolysis of RRR-alpha-tocopheryl acetate
Med 1997: 23: 85 – 91. (vitamin E acetate) in the skin and its UV protecting activity
4. Darr D, Combs S, Dunsten S, et al. Topical vitamin C (an in vivo study with the rat). J Photochem Photobiol B
protects porcine skin from ultraviolet radiation-induced Biol 1995: 29: 4551.
damage. Br J Dermatol 1992: 127: 247–253. 25. Hart M. Vitamin E: a contact sensitizer. Schoch Lett 1990:
5. Pinnell SR, Yang HS, Omar M, et al. Topical 1-ascorbic acid: 40: 48.
percutaneous absorption studies. Dermatol Surg 2001: 27: 26. Saperstein H, Rapaport M, Rietschel RL. Topical vitamin E
137–142. as a cause of erythema multiforme-like eruption. Arch
6. Kivirikko KI, Myllyla R. Post-translational processing of Dermatol 1984: 120: 906 – 908.
procollagens. Ann NY Acad Sci 1985: 460: 187–201. 27. Tsoureli-Nikita E, Hercogova J, Lotti T, Menchini G. Evalua-
7. Tajima S, Pinnell SR. Ascorbic acid preferentially enhances tion of dietary intake of vitamin E in the treatment of atopic
types I and III collagen gene transcription in human skin dermatitis – a study of the clinical course and evaluation of
fibroblasts. J Dermatol Sci 1996: 11: 250–253. the immuno-globulin E serum levels. Int J Derm 2002: 41:
8. Phillips CL, Combs SB, Pinnell SR. Effects of ascorbic acid 146–150.
on proliferation and collagen synthesis in relation to donor 28. Burke KE, Clive J, Combs GF Jr, et al. The effects of topical
age of human dermal fibroblasts. J Invest Dermatol 1994: and oral vitamin E on pigmentation and skin cancer
103: 228 –232. induced by ultraviolet irradiation in Skh: 2 hairless mice.
9. Davidson JM, Luvalle PA, Zoia O, et al. Ascorbate differen- Nutr Cancer 2000: 38: 87–97.
tially regulates elastin and collagen biosynthesis in vascular 29. Ichihashi M, Funasaka Y, Ohashi A, et al. The inhibitory
smooth muscle cells and skin fibroblasts by pretransla- effect of DL-alpha-tocopheryl ferulate in lecithin on
tional mechanisms. J Biol Chem 1997: 272: 345–352. melanogenesis. Anticancer Res 1999: 19: 3769 –3774.
10. Humbert PG, Haftek M, Creidi P, et al. Topical ascorbic acid 30. Trevithick J, Xiong H, Lee S, et al. Topical tocopherol
in photoaged skin. Clinical topographical and ultrastruc- acetate reduces post-UVB, sunburn-associated erythema,
tural evaluation: double-blind study vs. placebo. Exp edema and skin sensitivity in hairless mice. Arch Biochem
Dermatol 2003: 12: 237–244. Biophys 1992: 296: 575–582.
11. Carcamo JM, Pedraza A, Borquez-Ojeda O, Golde DS. 31. Record IR, Dreosti IE, Konstantinopoulos M, Buckley RA.
Vitamin C suppresses TNF alpha-induced NF-kappa B The influence of topical and systemic vitamin E on ultraviolet
activation by inhibiting I Kappa B alpha phosphorylation. light-induced skin damage in hairless mice. Nutr Cancer
Biochem 2002: 41: 12995– 30002. 1991: 16: 219–225.
12. Pinnell SR, interview by Wilma Bergfield. Topical vitamin C. 32. Marenus K, Muizzuddin N, Kasman K, et al. The use of anti-
Dialogues Dermatol Am Acad Derm 1996: 38: 1. oxidants in providing protection from chronic suberythemal
13. Alster T, West TB. Effect of vitamin C on postoperative CO2 UV-B exposure. 16th IFSCC Conference 1990: 1: 24–34.
laser resurfacing erythema. Dermatol Surg 1998: 24: 331–334. 33. Berton TR, Conti CJ, Mitchell DL, et al. The effect of vitamin
14. Maeda K, Fukuda M. Arbutin: mechanism of its depig- E acetate on ultraviolet-induced mouse skin carcinogenesis.
menting action in human melanocyte culture. J Pharmacol Mol Carcinog 1998: 23: 175–184.
Exp Ther 1996: 276: 765–769. 34. Bissett D, Chatterjee R, Hannon D. Protective effect of a
15. Kameyama K, Sakai C, Kondoh S, et al. Inhibitory effect of topically applied antioxidant plus an antiinflammatory agent

320
 Vitamins C and E

against ultraviolet radiation-induced chronic skin damage 40. Lin J, Selim A, Shea C, et al. UV photoprotection by com-
in the hairless mouse. J Soc Cosmet Chem 1992: 43: 85–92. bination topical antioxidants vitamin C and E. J Am Acad
35. Gensler H, Magdaleno M. Topical vitamin E inhibition Dermatol 2003: 48: 866–874.
of immunosuppression and tumorigenesis induced by 41. Dreher F, Gabard B, Schwindt DA, Malbach HI. Topical
ultraviolet irradiation. Nutr Cancer 1991: 15: 97–106. melatonin in combination with vitamins E and C protects
36. Gerrish K, Gensler H. Prevention of photocarcinogenesis by skin from ultraviolet-induced erythema: a human study in
dietary vitamin E. Nutr Cancer 1993: 19: 125–133. vivo. Br J Dermatol 1998: 139: 332–339.
37. Bissett DL, Chatterjee R, Hannon DP. Photoprotective 42. Lin FH, Lin JY, Gupta RD, et al. Ferulic acid stabilizes a
effect of superoxide-scavenging antioxidants against solution of vitamins C and E and doubles its photoprotec-
ultraviolet radiation-induced chronic skin damage in the tion of skin. J Invest Dermatol 2005: 125: 826 – 832.
hairless mouse. Photodermatol Photoimmunol Photomed 43. Wulf HC, Stender IM, Lock-Andersen J. Sunscreens used at
1990: 7: 56 – 62. the beach do not protect against erythema: a new definition
38. Chan AC. Partners in defense, vitamin E and vitamin C. of SPF is proposed. Photodermatol Photoimmunol Photo-
Can J Physiol Pharmacol 1993: 71: 725–731. med 1997: 13: 129–132.
39. Fuchs J, Kern H. Modulation of UV-light-induced skin 44. Haywood R, Wardman P, Sanders R, Linge C. Sunscreens
inflammation by d-α-tocopherol and 1-ascorbic acid: a inadequately protect against ultraviolet A-induced free
clinical study using solar simulated radiation. Free Radic radicals in skin: implications for skin aging and melanoma?
Biol Med 1998: 25: 1006–1012. J Invest Dermatol 2003: 121: 862–868.

321