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Skin and antioxidants

Article  in  Journal of Cosmetic and Laser Therapy · February 2013

DOI: 10.3109/14764172.2012.758380 · Source: PubMed


17 1,797

3 authors:

Borut Poljšak Raja Gosnak Dahmane

University of Ljubljana University of Ljubljana


Aleksandar Godic
University Hospital Lewisham, London, United Kingdom


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Skin and antioxidants


1University of Ljubljana, Faculty of Health Studies, Zdravstvena pot 5, 1000 Ljubljana,
Slovenia, and 2University of Ljubljana, Faculty of Medicine,Vrazov trg 2, 1000 Ljubljana, Slovenia
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It is estimated that total sun exposure occurs non-intentionally in three quarters of our lifetimes. Our skin is exposed to
majority of UV radiation during outdoor activities, e.g. walking, practicing sports, running, hiking, etc. and not when we
are intentionally exposed to the sun on the beach. We rarely use sunscreens during those activities, or at least not as much
and as regular as we should and are commonly prone to acute and chronic sun damage of the skin. The only protection
of our skin is endogenous (synthesis of melanin and enzymatic antioxidants) and exogenous (antioxidants, which we con-
sume from the food, like vitamins A, C, E, etc.). UV-induced photoaging of the skin becomes clinically evident with age,
when endogenous antioxidative mechanisms and repair processes are not effective any more and actinic damage to the skin
prevails. At this point it would be reasonable to ingest additional antioxidants and/or to apply them on the skin in topical
preparations. We review endogenous and exogenous skin protection with antioxidants.
For personal use only.

Key Words: aging, antioxidants, photoaging, skin

ubiquinol-10, lycopene, ß-carotene, lutein, zeaxan-
More than 50.000 papers appear in Medline when a thin and alpha-carotene (4). In general, surface of
keyword “oxidative stress” is typed, but not all are the skin, the epidermis, contains higher concentra-
related to the skin. Skin aging is a consequence of tions of antioxidants than the dermis (5). Alpha-
two overlapping mechanisms, intrinsic and extrinsic tocopherol is the most prominent antioxidant in the
(UV-exposure, smoking) (1,2). It seems that oxida- lipophilic compartments while vitamin C and GSH
tive damage is the major cause and single most have the highest abundance in the cytosol. Hydrophilic
important contributor of skin aging. Not only that non-enzymatic antioxidants, including L-ascorbic
the free radical production increases with age but the acid, GSH and uric acid are predominant antioxi-
ability of human skin cells to repair DNA damage dants in the human skin compared on an equivalent
steadily reduces with years and the antioxidative molar basis (6). Their overall dermal and epidermal
defense becomes less effective (Figure 1). concentration is more than 10- to 100-fold greater
The skin contains a pool of protective antioxi- than those found for vitamin E or ubiquinol. Kera-
dants. It includes enzymatic antioxidants such as tinocytes and skin fibroblasts contain milimolar levels
glutathione peroxidase, superoxide dismutase and of GSH, α-tocopherol, ascorbate, and DNA repair
catalase, and nonenzymatic low-molecular-weight enzymes. The stratum corneum (SC) was found to
antioxidants such as vitamin E isoforms, vitamin C, contain both hydrophilic and lipophilic antioxidants.
glutathione (GSH), uric acid, and ubiquinol (3). Vitamins C and E (both αγ and α-tocopherol) as well
Other potent antioxidants, which are in the skin, are as GSH and uric acid were found to be present in
ascorbate, uric acid, carotenoids and sulphydrils. the SC (7,8). Surprisingly, they were not distributed
Water-soluble antioxidants in plasma are glucose, evenly, but in gradient fashion, with low concentra-
pyruvate, uric acid, ascorbic acid, bilirubin and tions in the outer layers, which increase toward the
glutathione, and lipid-soluble are alpha-tocopherol, deeper layers of the SC.

Correspondence: Aleksandar Godic, MD, PhD, Faculty of Medicine, Vrazov trg 2, 1000 Ljubljana, Slovenia. Tel: ⫹ 386-51-415-678. E-mail: aleksandar.

(Received 2 September 2012 ; accepted 3 December 2012 )

ISSN 1476-4172 print/ISSN 1476-4180 online © 2013 Informa UK, Ltd.
DOI: 10.3109/14764172.2012.758380
2 B. Poljsak et al.

Cause: Consequence:

Intrinsic free radical formation Premature skin aging

Clinical signs of the aging skin
Increased oxidative stress
Inflammatory reactions
Oxidative Skin aging Immunosupression
stress Depleated cutaneous antioxidants
Oxidised proteins, DNA and lipids
Premalignant and malignant skin lesion

Extrinsic free radical formation

Figure 1. Causes and consequences of skin aging.

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Exogenous antioxidants – compounds Recommended daily intake

derived from the diet The Dietary Reference Intake (DRI) is a system of
Most important preventive mechanisms against ROS- nutrition recommendations from the Institute
induced damage are antioxidative enzymes, non-en- of Medicine (IOM) of the U.S. National Academy of
zymatic compounds, and repair processes, but they Sciences. The DRI system is used by both the United
are less effective with aging. It would be rational at States and Canada and is intended for the general
this point to ingest additional antioxidants or to apply public and health professionals. The Reference Daily
them on the skin in topical preparations. The identi- Intake or Recommended Daily Intake (RDI) is the
fication of free radical reactions as promoters of the daily intake level of a nutrient that is considered to
For personal use only.

aging process implies that interventions, which limit be sufficient to meet the requirements of 97–98% of
their production or inhibit their interactions, reduce healthy individuals in every demographic in the
the disease pathogenesis and consequently rate of United States (where it was developed, but has since
aging. Dietary antioxidants play a major role in main- been adopted in other countries). The DRI values
taining the homeostasis of the oxidative balance. Vita- are not currently used in nutrition labeling, where
min C (ascorbic acid), vitamin E (tocopherol), the older Reference Daily Intakes (RDAs) are still
beta-carotene and other micronutrients such as caro- used. The reference values, collectively called the
tenoids, polyphenols and selenium have been evalu- Dietary Reference Intakes (DRIs), include the Rec-
ated as antioxidant constituents in the human diet. It ommended Dietary Allowance (RDA), the Adequate
is important to obtain many different water and lipid Intake (AI), the Tolerable Upper Intake Level (UL),
soluble antioxidants by intake of different kinds of and the Estimated Average Requirement (EAR). A
fruits and vegetables since all antioxidants work in requirement is defined as the lowest continuing
synergy. Thiols, which are associated with membrane intake level of a nutrient that, for a specified indica-
proteins, may also be important antioxidants. Tocoph- tor of adequacy, will maintain a defined level of
erols and tocotrienols (vitamin E) and ascorbic acid nutriture in an individual (11) (Table I).
(vitamin C) as well as the carotenoids exhibit their Tolerable upper intake levels (UL) were devel-
antioxidative properties through reacting with free oped to caution against excessive intake of nutrients
radicals, notably peroxyl radicals, and with singlet (like vitamin A) that can be harmful in large amounts.
molecular oxygen (1O2). RRR-alpha-tocopherol is The exaggerated intake of antioxidant(s) could cause
the major peroxyl radical scavenger in biological lipid antioxidative stress (12) and alter the complex sys-
phases such as membranes or low-density lipopro- tem of endogenous antioxidative defense of cells or
teins (LDL). L-Ascorbate is present in aqueous com- alter the necrosis or apoptosis pathways. UL is the
partments (e.g. cytosol, plasma, and other body highest level of consumption that is considered safe
fluids) and can reduce the tocopheroxyl radical; it is according to current data. It is recommended that
also important cofactor in hydroxylations. Carote- intake of certain nutrients should be from food
noids, notably beta-carotene and lycopene as well as source only to prevent adverse effects.
oxycarotenoids (e.g. zeaxanthin and lutein), exert
antioxidative functions in lipid phases by free-radical
Topical application and safety risk assessment
or 1O2 quenching (9).
of vitamins A, C, and E
Many studies on usage of different antioxidants
or combinations of them with phytochemicals were Vitamins A, C and E are most frequently used anti-
performed in order to find evidence against ROS- oxidants in skin-care products and authors of the
induced skin damage (10). paper decided to present the summary of their risk
J Cosmet Laser Ther Downloaded from by on 02/18/13
For personal use only.

Table I. Recommended daily intakes.

Intakes recommended Tolerable upper intake Concentration in Over dosage (mg or μg/d),
Nutrient Recommended daily intake*** (**) by the FAO/WHO level (UL) foods (mg/100 g) side-effects and warnings Significant sources

Vitamin A 600 μg 600 μg 3 000 μg Extremely high doses turkey, carrot juice,
5 000 International Unit (IU) (⬎ 9 000 mg) can cause dry, pumpkin
Recommended Dietary Allowance* scaly skin, fatigue, nausea,
Male: 1000 (μg)a loss of appetite, bone and
Female: 800 (μg)a joint pains and headaches.
Vitamin A is not
recommended for pregnant
women. Excess vitamin A
may cause birth defects.
However, an adequate
supply of vitamin A is still
required because of its
essential role in embryonic
Vitamin C 75 mg 30 mg 2 000 mg 10–170 No impacts of over dose have Orange juice, grapefruit
(ascorbic acid) Recommended Dietary Allowance* been proven so far. juice, peaches, bell
Male: 60 mg Cooking may destroy vitamin pepper, citrus fruit.
Female: 60 mg C in fruits and vegetables.
Supplements containing
bioflavonoids increase
adsorption and availability
of vitamin C. Smokers
require a larger dietary
intake of vitamin C than
non-smokers, on account of
oxidative stress in their body
caused by toxins in cigarette
smoke and generally lower
blood levels.
Vitamin E 10 mg 1 000 mg 0.2–10 Doses larger than 1 000 mg fortified cereals, tomato
(tocopherol) Recommended Dietary cause blood clotting, which paste, sunflower seeds,
Allowance* results in increased fish, meat, leafy
Male:10 (mg)b likelihood of haemorrhage vegetables
Female: 8 (mg)b in some individuals.
Selenium 35 μg 400 μg 1–150* Doses larger than 200 μg can Brazil nuts, rockfish, yellow
55 μg**** μg/100 g be toxic. fin tuna, dairy products,
50 μg***** Fatigue, skin disorders, potato, rice
dizziness, nausea, vomiting,
anxiety and hair loss.
Zinc 15 mg 40 mg Doses larger than 25 mg may oysters, fortified cereals,
cause anaemia and copper baked beans
Skin and antioxidants

4 B. Poljsak et al.

and nut butters, legumes (such as

clams), organ meats (such as beef
assessment, what might be of special interest for der-

soybeans, lentils, navy beans, and

liver, kidneys, and heart), nuts
matologists and other medical professionals. From the

seafood (such as oysters, squid,

red meats, fish, chicken liver,

lobster, mussels, crab, and

Significant sources
Elmore’s Final report (13) of the safety assessment of
L-Ascorbic Acid, Calcium Ascorbate, Magnesium
Ascorbate, Magnesium Ascorbyl Phosphate, Sodium

*Subcommittee on the Tenth Edition of the RDAs, Food and Nutrition Board, National Research Council (1989). “Recommended Dietary Allowances”, 10th Ed. National Academy Press, Washington, DC.
Ascorbate, and Sodium Ascorbyl Phosphate as used

***Values on labels are stated Daily Reference values (DRV) of Recommended Daily Intake (RDI). The RDI is a renewed value referring to the old Recommended Dietary Allowance (RDA).
in cosmetics it can be concluded that they function

in cosmetic formulations primarily as antioxidants.

Ascorbic Acid is used as an antioxidant and pH

****Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes: Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academy Press, Washington, DC, 2000.
adjuster in a large variety of cosmetic formulations,
over 3/4 of which were hair dyes and colors at con-
Over dosage (mg or μg/d), side-effects

centrations between 0.3 and 0.6%. For other uses, the

Nausea, vomiting, abdominal pain,

performance, skin pigmentation.

reported concentrations were either very low (⬍ 0.01%)

Abdominal pain, nausea, cramps,
diarrhea, metallic taste in the

irritability, and lowered work

diarrhea, vomiting and liver

or in the 5–10% range. Ascorbic Acid is generally rec-

mouth, fatigue, headache,
and warnings

ognized as safe (GRAS) substance for use as a chem-

ical preservative in foods and as a nutrient and/or
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dietary supplement. Ascorbic Acid was a photopro-

tectant in clinical human UV studies at doses well
above the minimal erythema dose (MED). One prob-

lem of vitamin C is in its instability in various topical

products, as vitamin C is prone to oxidation, and may
*****Dietary reference intakes, Food and Nutrition Boards Institute of Medicine, National Academy Press, Washington, D.C., 1997–2004.

lose its efficacy this way. For effective topical applica-

foods (mg/100 g)
Concentration in

tion, vitamin C has to be non-esterified, acidic and

**Amounts for other age and gender groups, pregnant women, lactating women, and breastfeeding infants may be much different.

optimally at 20% concentration (14).

Safety and risk assessment of tocopherol and its
compounds were published in Int J Toxicol by Zondlo
For personal use only.

in 2002. Tocopheryl Acetate, Tocopherol, and

Tocopheryl Linoleate are used in 2673 formulations,
Tolerable upper intake

generally at concentrations of up to 36%, 5%, and

2%, respectively, although Tocopheryl Acetate is
10 000 mg
level (UL)
45 mg

100% of vitamin E oil (15). Tocopherol, Tocopheryl

Acetate, Tocopheryl Linoleate, and Tocopheryl Suc-
cinate were all absorbed in human skin. Tocopherol
is a natural component of cell membranes thought
to protect against oxidative damage. Tocopherol,
Tocopheryl Acetate, and Tocopheryl Succinate each
Intakes recommended
by the FAO/WHO

were reported to protect against ultraviolet radiation-

induced skin damage. These ingredients are generally
not toxic in animal feeding studies, although very
high doses (ⱖ 2 g/kg/day) have hemorrhagic activity.
These ingredients are generally not irritating or sen-
sitizing to skin or irritating to eyes, although a
Tocopheryl Acetate did produce sensitization in one
Recommended daily intake*** (**)

animal test, and Tocophersolan was a slight eye irri-

tant in an animal test (15). According to Burke (14),
for effective topical application, vitamin E must
be the non-esterified isomer d-alpha-tocopherol at
1 250 mg
14 mg

2–5% concentration. Skin penetration experiments

showed that 55% of the topically applied α-tocopherol
accumulated in full thickness of the skin after 24
hours (16). Tocopherol acetate is very often used
antioxidant in sunscreen products.

Vitamin A derivatives are used as anti-aging ingre-

Table 1. (Continued).


dients in cosmetics. Vitamin A is absorbed through

the skin, increases the rate of epidermal keratinocytes

turnover and collagen production, and consequently

leads to more youthful appearance of the skin (17).


Topical retinoids remain the mainstay therapy of the


photoaged skin, and their efficacy can be noticed

Skin and antioxidants 5

clinically, evaluated histologically, and measured supplements. None of the major clinical studies,
biochemically. Their regular use might also prevent which used mortality or morbidity as an end point,
photoaging (18). Available topical retinoids include proved positive effects of supplementation with oral
tretinoin (Retin-A®), adapalene (Differen®), and antioxidants such as vitamin C, vitamin E or β-
tazarotene (Tazorac®) and over-the-counter Retinol® carotene. Some recent studies showed that therapy
and Retinol-A®.These drugs are derivatives of vitamin with antioxidants has no effect and can even increases
A which might have anti-aging properties (19). mortality (23–33). The intake of only one antioxidant
could alter the complex system of endogenous anti-
oxidative defence of cells or necrosis or apoptosis
pathways. It is wrong to search the »redox magic bul-
It is important to pretreat the skin with antioxidants let« among different compounds with increased redox
before sun exposure. Human studies have convinc- potential. Better approach is to focus on detailed
ingly demonstrated pronounced photoprotective understanding of the complex redox system of human
effects of ‘natural’ and synthetic antioxidants when cells and to investigate the synergistic effects of dif-
applied topically before UVR exposure. No significant ferent antioxidants on total oxidative stress. There are
protective effect of melatonin and antioxidants (vita- other methods to decrease oxidative stress, e.g. pre-
J Cosmet Laser Ther Downloaded from by on 02/18/13

mins E and C), when applied either alone or in com- vention of free radical formation at first instance
bination, were observed when antioxidants were (10). We have to realize that usage of synthetic vita-
applied after UVR exposure even after multiple min supplements is not an alternative to regular con-
attempts. UVR-induced skin damage starts rapidly, sumption of fruits and vegetables. It is quite possible
and antioxidants effectively prevent such damage only that many antioxidants are still undiscovered; fur-
when present in relevant concentrations, at the site of thermore the combination of antioxidants in fruits
damage, and during the oxidative stress (20). Treat- and vegetables cause their reciprocal regeneration
ment of the skin with antioxidants after the UVR dam- and consecutively intensifies their defense from free
age might cause additional harmful effects on cell radicals. However, deficiency of vitamins B-12, folic
cycle control and apoptosis process. The photoprotec- acid, B-6, C or E, or iron or zinc appears to mimic
For personal use only.

tive effects of antioxidants are significant when applied radiation damage of DNA by causing single- and
in distinct mixtures and in appropriate vehicles. Usage double-strand breaks, oxidative lesions or both. Evi-
of topically applied creams/ointments with such com- dence is accumulating that a multivitamin/mineral
binations may improve antioxidative capacity of the supplement could improve the health of specific
skin due to sustained antioxidative synergism. UVA- populations, e.g. poor, young, obese, elderly and
induced skin alterations are believed to be largely people exposed to increased ROS from the environ-
determined by oxidative processes, and topical admin- ment, but the lack of sufficient double-blind, multi-
istration of antioxidants might be particularly promis- centric studies does not permit recommendations on
ing (21). However, delivery of topically applied systemic usage of antioxidants. Nevertheless, antiox-
antioxidants through the skin is hard since they must idant-rich diets with fruits and vegetables can be
penetrate through the epidermal barrier to reach its recommended without any risk. It is important to
site of action and they are very unstable, what makes mention that antioxidants as dietary supplements
them difficult to formulate. Antioxidants like tocoph- can protect in conditions of elevated oxidative stress
erols, vitamin C, and flavonoids are now being added and that they could be therapeutically effective in
as protective agents to the skin creams. However, their those individuals. On the other hand, presented evi-
ability to penetrate deep into the skin is limited, and dences show that synthetic antioxidant supplements
their amount in the dermis might be raised by cannot protect appropriately or entirely against oxi-
consuming them with the diet. dative stress in situations where it is not increased
Usage of topical antioxidants is favored among and that their usage to prevent diseases or slow aging
dermatologists because of their broad biologic activ- is controversial.
ity. Many are not only antioxidants but also possess
anti-inflammatory and anti-carcinogenic activities,
and thus have many potential benefits. In general,
topical antioxidants exert their effects by down- A wide variety of antioxidants or other phytochemi-
regulating free-radicals-mediated pathways that cals, such as licopene, coenzyme Q, glutathione, car-
damage skin (22). nosine, selenium, zinc, bioflavonoids, green tea
Endogenous oxidative stress could be influenced polyphenols, grape seed proanthocyanidins, resvera-
in two ways: by preventing ROS formation or by trol, silymarin, genistein, and others have been
quenching ROS with antioxidants. Results of epide- reported to possess substantial protective effects on
miological studies on healthy volunteers, who were UV-induced skin inflammation, oxidative stress and
treated with oral antioxidants, are inconclusive and DNA damage.
even contradictory: from no effect to proven either In order to determine oxidative stress in individu-
beneficial or harmful effect of oral antioxidant als, both, the ROS potential as well as the antioxidative
6 B. Poljsak et al.

defense potential should be measured in blood or 7. Thiele J, Traber MG, Packer L. Depletion of human stratum
cytosol. Numerous in vitro antioxidational potential corneum vitamin E: an early and sensitive in vivo marker of
UV induced photo-oxidation. J Invest Dermatol. 1998;110:
determinations exist that are easy to perform and 756–761.
largely used in screening. It is important to recognize 8. Weber SU, Thiele JJ, Cross CE, Packer L. Vitamin C, uric
oxidative imbalance in individuals early in order to acid, and glutathione gradients in murine stratum corneum
prevent the long term oxidative and antioxidative and their susceptibility to ozone exposure. J Invest Dermatol.
stresses (12). These requirements should be consid- 1999;113:1128–1132.
9. Sies H, Stahl W, Sundquist AR. Antioxidant functions of vitamins.
ered when determining individuals’ oxidative status Vitamins E and C, beta-carotene, and other carotenoids. Ann N
before begining or ending the therapy with antioxi- Y Acad Sci. 1992;30:7–20.
dants. Even better approach would be to monitor in 10. Poljsak B. Strategies for reducing or preventing the generation
vivo the oxidative stress in skin cells. Several tech- of oxidative stress. Oxid Med Cell Longev. 2011;2011:
niques exist to assess oxidative stress in the skin and 194586.
11. Institute of Medicine, Food and Nutrition Board. Dietary Refer-
many methods are currently under development, e.g. ence Intakes: Vitamin C, Vitamin E, Selenium, and Carotenoids.
electron spin resonance, fluorescence probes, cyclic Washington, DC: National Academy Press; 2000.
voltammetry, but they are not routinely used (10). 12. Poljsak B, Milisav I. The neglected significance of “antioxida-
From the consumers point of view, they would be tive stress”. Oxid Med Cell Longev. 2012;2012:480895.
J Cosmet Laser Ther Downloaded from by on 02/18/13

interested in the information regarding antioxidative 13. Elmore AR. Final report of the safety assessment of L-Ascorbic
Acid, Calcium Ascorbate, Magnesium Ascorbate, Magnesium
potential of skin products. Ascorbyl Phosphate, Sodium Ascorbate, and Sodium Ascorbyl
There is no widely accepted and standardized Phosphate as used in cosmetics. Int J Toxicol. 2005;24:
method to evaluate antioxidative capacity of skin- 51–111.
care products, like SPF rating system in sunscreens. 14. Burke KE. Photodamage of the skin: protection and reversal
ORAC (Oxygen Radical Absorbance Capacity) and with topical antioxidants. J Cosmet Dermatol. 2004;3:
ABEL-RAC (Analysis By Emitted Light-Relative 15. Zondlo FM. Final report on the safety assessment of Tocopherol,
Antioxidant Capacity) are both accepted worldwide Tocopheryl Acetate,Tocopheryl Linoleate,Tocopheryl Linoleate/
as a standard measure of the antioxidative capacity Oleate, Tocopheryl Nicotinate, Tocopheryl Succinate, Dioleyl
of foods, and a similar rating system could be devel- Tocopheryl Methylsilanol, Potassium Ascorbyl Tocopheryl
For personal use only.

oped for the antioxidative capacity of skin-care prod- Phosphate, and Tocophersolan. Int J Toxicol. 2002;3:51–116.
16. Ainbinder D, Touitou E. Skin photodamage prevention: state
ucts (34). Although many methods already exist for of the art and new prospects. In: Farage MA, Miller KW,
evaluation of skin-care cosmetic antioxidative capac- Maibach HI, editors. Textbook of aging skin. Berlin:
ity, e.g. indirect spectorphotometric determination of Springer-Verlag; 2010.
a free radical DPPH or ABTS (34–36), they are not 17. Kafi R, Kwak HS, Schumacher WE, Cho S, Hanft VN,
commercially available for skin-care products found Hamilton TA, et al. Improvement of naturally aged skin with
vitamin A (retinol). Arch Dermatol. 2007;143:606–612.
on the market. The standardization and evaluation of 18. Serri R, Iorizzo M. Cosmeceuticals: focus on topical retinoids
antioxidative potential of skin-care products could in photoaging. Clin Dermatol. 2008;26:633–635.
help consumers to choose products with effective 19. Helfrich YR, Sachs DL, Voorhees JJ. Overview of skin aging
antioxidative properties. and photoaging. Dermatol Nurs. 2008;20:177–183.
20. Dreher F, Denig N, Gabard B, Schwindt DA, Maibach HI.
Effect of topical antioxidants on UV-induced erythema
Disclosures of interest: Authors have no financial and formation when administered after exposure. Dermatology.
conflict of interests to disclose. The authors alone are
21. Dreher F, Maibach H. Protective effects of topical antioxidants
responsible for the content and writing of the paper. in humans. Curr Probl Dermatol. 2001;29:157–164.
22. Farris P. Idebenone, green tea, and Coffeeberry extract: new and
innovative antioxidants. Dermatol Ther. 2007;20:322–329.
23. Omenn GS, Goodman GE, Thornquist MD, Balmes J,
Cullen MR, Glass A, et al. Effects of a combination of beta
1. Dahmane R, Poljsak B. Free radicals and intrinsic skin aging: carotene and vitamin A on lung cancer and cardiovascular
basic principles. Health Med. 2011;5:1647–1654. disease. N Engl J Med. 1996;334:1150–1155.
2. Poljšak B, Dahmane R. Free radicals and extrinsic skin aging. 24. Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Antioxi-
Dermatol Res Pract. 2012;2012:135206. dant supplements for prevention of gastrointestinal cancers:
3. Shindo Y, Witt E, Packer L. Antioxidant defense mechanisms in a systematic review and meta-analysis. Lancet. 2004;36:
murine epidermis and dermis and their responses to ultraviolet 1219–1228.
light. J Invest Dermatol. 1993;100:260–265. 25. Miller ER, Pastor-Barriuso R, Dalal D, Riemersma R, Appel
4. Poljsak B. Skin aging, free radicals and antioxidants. New LJ, Guallar E. Meta-analysis: high-dosage vitamin E supple-
York: NovaScience Publishing; 2011. mentation may increase all-cause mortality. Ann Intern Med.
5. Shindo Y, Witt E, Han D, Tzeng B, Aziz T, Nguyen L, et al. 2005;142:37–46.
Recovery of antioxidants and reduction in lipid hydroperoxi- 26. Heart Protection Study Collaborative Group. MRC/BHF Heart
des in murine epidermis and dermis after acute ultraviolet Protection Study of antioxidant vitamin supplementation in
radiation exposure. Photodermatol Photoimmunol Photomed. 20,536 high-risk individuals: a randomised placebo-controlled
1994;10:183–191. trial. Lancet. 2002;360:23–33.
6. Thiele J, Barland CO, Ghadially R, Elias P. Permeability and 27. Age-Related Eye Disease Study Research Group. A randomized,
antioxidant barriers in aged skin. In: Gilchrest B, Krutmann placebo-controlled, clinical trial of high-dose supplementation
J, editors. Skin aging. Berlin: Springer-Verlag; 2006. with vitamins C and E and beta carotene for age-related cataract
Skin and antioxidants 7

and vision loss: AREDS report no. 9. Arch Ophthalmol. 32. Bardia A, Tleyjeh IM, Cerhan JR, Sood AK, Limburg PJ,
2001;119:1439–1452. Erwin PJ, et al. Efficacy of antioxidant supplementation in
28. Mursu J, Robien K, Harnack LJ, Park K, Jacobs DR Jr. Dietary reducing primary cancer incidence and mortality: systematic
supplements and mortality rate in older women: the Iowa Wom- review and meta-analysis. Mayo Clin Proc. 2008;83:23–34.
en’s Health Study. Arch Intern Med. 2011;171:1625–1633. 33. Lawenda BD, Kelly KM, Ladas EJ, Sagar SM, Vickers A,
29. Klein EA, Thompson IM Jr, Tangen CM, Crowley JJ, Lucia Blumberg JB. Should supplemental antioxidant administra-
MS, Goodman PJ, et al. Vitamin E and the risk of prostate tion be avoided during chemotherapy and radiation therapy?
cancer: the Selenium and Vitamin E Cancer Prevention Trial J Natl Cancer Inst. 2008;100:773–783.
(SELECT). JAMA. 2011;306: 1549–1556. 34. Palmer DM, Kitchin JS. Oxidative damage, skin aging, antioxi-
30. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud dants and a novel antioxidant rating system. J Drugs Dermatol.
C. Antioxidant supplements for prevention of mortality in 2010;9:11–15.
healthy participants and patients with various diseases. 35. Brand-Williams W, Cuvelier ME, Barset C. Use of a free rad-
Cochrane Database Syst Rev. 2008;2:CD007176. ical method to evaluate antioxidant activity. Lebensm-Wiss
31. Hercberg S, Ezzedine K, Guinot C, Preziosi P, Galan P, Bertrais U-Technol. 1995;28:25–30.
S, et al. Antioxidant supplementation increases the risk of skin 36. Ratz-Lyko A, Arct J, Pytkowska K. Methods for evaluation of
cancers in women but not in men. J Nutr. 2007;137: cosmetic antioxidant capacity. Skin Res Technol. 2012;18:
2098–2105. 421–430.
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