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Skin Antioksidan
Skin Antioksidan
Introduction
More than 50.000 papers appear in Medline when a
keyword oxidative stress is typed, but not all are
related to the skin. Skin aging is a consequence of
two overlapping mechanisms, intrinsic and extrinsic
(UV-exposure, smoking) (1,2). It seems that oxidative damage is the major cause and single most
important contributor of skin aging. Not only that
the free radical production increases with age but the
ability of human skin cells to repair DNA damage
steadily reduces with years and the antioxidative
defense becomes less effective (Figure 1).
The skin contains a pool of protective antioxidants. It includes enzymatic antioxidants such as
glutathione peroxidase, superoxide dismutase and
catalase, and nonenzymatic low-molecular-weight
antioxidants such as vitamin E isoforms, vitamin C,
glutathione (GSH), uric acid, and ubiquinol (3).
Other potent antioxidants, which are in the skin, are
ascorbate, uric acid, carotenoids and sulphydrils.
Water-soluble antioxidants in plasma are glucose,
pyruvate, uric acid, ascorbic acid, bilirubin and
glutathione, and lipid-soluble are alpha-tocopherol,
ubiquinol-10, lycopene, -carotene, lutein, zeaxanthin and alpha-carotene (4). In general, surface of
the skin, the epidermis, contains higher concentrations of antioxidants than the dermis (5). Alphatocopherol is the most prominent antioxidant in the
lipophilic compartments while vitamin C and GSH
have the highest abundance in the cytosol. Hydrophilic
non-enzymatic antioxidants, including L-ascorbic
acid, GSH and uric acid are predominant antioxidants in the human skin compared on an equivalent
molar basis (6). Their overall dermal and epidermal
concentration is more than 10- to 100-fold greater
than those found for vitamin E or ubiquinol. Keratinocytes and skin fibroblasts contain milimolar levels
of GSH, -tocopherol, ascorbate, and DNA repair
enzymes. The stratum corneum (SC) was found to
contain both hydrophilic and lipophilic antioxidants.
Vitamins C and E (both and -tocopherol) as well
as GSH and uric acid were found to be present in
the SC (7,8). Surprisingly, they were not distributed
evenly, but in gradient fashion, with low concentrations in the outer layers, which increase toward the
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.
godic@gmail.com
(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
108
B. Poljsak et al.
Cause:
Consequence:
Oxidative
stress
Skin aging
600 g
5 000 International Unit (IU)
Recommended Dietary Allowance*
Male: 1000 (g)a
Female: 800 (g)a
75 mg
Recommended Dietary Allowance*
Male: 60 mg
Female: 60 mg
10 mg
35 g
55 g****
50 g*****
15 mg
Nutrient
Vitamin A
Vitamin C
(ascorbic acid)
Vitamin E
(tocopherol)
Selenium
Zinc
30 mg
600 g
Intakes recommended
by the FAO/WHO
40 mg
1 000 mg
Recommended Dietary
Allowance*
Male:10 (mg)b
Female: 8 (mg)b
400 g
2 000 mg
3 000 g
1150*
g/100 g
0.210
10170
Concentration in
foods (mg/100 g)
Extremely high doses
( 9 000 mg) can cause dry,
scaly skin, fatigue, nausea,
loss of appetite, bone and
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
development.
No impacts of over dose have
been proven so far.
Cooking may destroy vitamin
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.
Doses larger than 1 000 mg
cause blood clotting, which
results in increased
likelihood of haemorrhage
in some individuals.
Doses larger than 200 g can
be toxic.
Fatigue, skin disorders,
dizziness, nausea, vomiting,
anxiety and hair loss.
Doses larger than 25 mg may
cause anaemia and copper
deficiency.
(Continued)
Significant sources
equivalents.
equivalents.
b-tocopherol
aRetinol
10 000 mg
1 250 mg
Copper
*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.
**Amounts for other age and gender groups, pregnant women, lactating women, and breastfeeding infants may be much different.
***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).
****Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes: Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academy Press, Washington, DC, 2000.
*****Dietary reference intakes, Food and Nutrition Boards Institute of Medicine, National Academy Press, Washington, D.C., 19972004.
Nutrient
Table 1. (Continued).
Intakes recommended
by the FAO/WHO
Concentration in
foods (mg/100 g)
B. Poljsak et al.
Significant sources
110
assessment, what might be of special interest for dermatologists and other medical professionals. From the
Elmores Final report (13) of the safety assessment of
L-Ascorbic Acid, Calcium Ascorbate, Magnesium
Ascorbate, Magnesium Ascorbyl Phosphate, Sodium
Ascorbate, and Sodium Ascorbyl Phosphate as used
in cosmetics it can be concluded that they function
in cosmetic formulations primarily as antioxidants.
Ascorbic Acid is used as an antioxidant and pH
adjuster in a large variety of cosmetic formulations,
over 3/4 of which were hair dyes and colors at concentrations between 0.3 and 0.6%. For other uses, the
reported concentrations were either very low ( 0.01%)
or in the 510% range. Ascorbic Acid is generally recognized as safe (GRAS) substance for use as a chemical preservative in foods and as a nutrient and/or
dietary supplement. Ascorbic Acid was a photoprotectant in clinical human UV studies at doses well
above the minimal erythema dose (MED). One problem of vitamin C is in its instability in various topical
products, as vitamin C is prone to oxidation, and may
lose its efficacy this way. For effective topical application, vitamin C has to be non-esterified, acidic and
optimally at 20% concentration (14).
Safety and risk assessment of tocopherol and its
compounds were published in Int J Toxicol by Zondlo
in 2002. Tocopheryl Acetate, Tocopherol, and
Tocopheryl Linoleate are used in 2673 formulations,
generally at concentrations of up to 36%, 5%, and
2%, respectively, although Tocopheryl Acetate is
100% of vitamin E oil (15). Tocopherol, Tocopheryl
Acetate, Tocopheryl Linoleate, and Tocopheryl Succinate 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
were reported to protect against ultraviolet radiationinduced skin damage. These ingredients are generally
not toxic in animal feeding studies, although very
high doses ( 2 g/kg/day) have hemorrhagic activity.
These ingredients are generally not irritating or sensitizing to skin or irritating to eyes, although a
Tocopheryl Acetate did produce sensitization in one
animal test, and Tocophersolan was a slight eye irritant 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
25% concentration. Skin penetration experiments
showed that 55% of the topically applied -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 ingredients 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
111
112
B. Poljsak et al.
References
1. Dahmane R, Poljsak B. Free radicals and intrinsic skin aging:
basic principles. Health Med. 2011;5:16471654.
2. Poljak B, Dahmane R. Free radicals and extrinsic skin aging.
Dermatol Res Pract. 2012;2012:135206.
3. Shindo Y, Witt E, Packer L. Antioxidant defense mechanisms in
murine epidermis and dermis and their responses to ultraviolet
light. J Invest Dermatol. 1993;100:260265.
4. Poljsak B. Skin aging, free radicals and antioxidants. New
York: NovaScience Publishing; 2011.
5. Shindo Y, Witt E, Han D, Tzeng B, Aziz T, Nguyen L, et al.
Recovery of antioxidants and reduction in lipid hydroperoxides in murine epidermis and dermis after acute ultraviolet
radiation exposure. Photodermatol Photoimmunol Photomed.
1994;10:183191.
6. Thiele J, Barland CO, Ghadially R, Elias P. Permeability and
antioxidant barriers in aged skin. In: Gilchrest B, Krutmann
J, editors. Skin aging. Berlin: Springer-Verlag; 2006.
28.
29.
30.
31.
113
32. Bardia A, Tleyjeh IM, Cerhan JR, Sood AK, Limburg PJ,
Erwin PJ, et al. Efficacy of antioxidant supplementation in
reducing primary cancer incidence and mortality: systematic
review and meta-analysis. Mayo Clin Proc. 2008;83:2334.
33. Lawenda BD, Kelly KM, Ladas EJ, Sagar SM, Vickers A,
Blumberg JB. Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy?
J Natl Cancer Inst. 2008;100:773783.
34. Palmer DM, Kitchin JS. Oxidative damage, skin aging, antioxidants and a novel antioxidant rating system. J Drugs Dermatol.
2010;9:1115.
35. Brand-Williams W, Cuvelier ME, Barset C. Use of a free radical method to evaluate antioxidant activity. Lebensm-Wiss
U-Technol. 1995;28:2530.
36. Ratz-Lyko A, Arct J, Pytkowska K. Methods for evaluation of
cosmetic antioxidant capacity. Skin Res Technol. 2012;18:
421430.
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