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Antioxidants: Essential Preventative and Corrective Topicals

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Author: 
Jennifer Linder, MD

A review of the most frequently used and beneficial antioxidants. An acquired knowledge of these antioxidants will help clinicians choose those that are most suitable for their patients.

The Benefits of Antioxidants

The daily application of topical antioxidants has many benefits for the skin, chief among them auxiliary protection from exposure to harmful UV radiation, a well-known cause of skin cancer, photodamage, immunosuppression and other harmful outcomes.1-3 Although the body’s inherent defense system triggers an initial protective response when exposed to damaging UV rays, the destructive radical cascade is still instigated by exposure, making supplementation with topical antioxidants critical. Sunscreen use is imperative; however, no sunscreen product shields the skin from all sun-induced damage. A thorough understanding of the types of radicals, their negative effects on the skin and the mechanisms of action for the most common antioxidants will assist the provider in offering recommendations for effective UV protection. A multitude of topical antioxidants, whose efficacy is supported by research, are available. An acquired knowledge of the most frequently utilized and beneficial antioxidants will help the clinician choose those that are most suitable for their patients.

UV Radiation and Radical Oxygen Species (ROS)

Of the three types of UV rays, mid-range UVB (280 nm to 320 nm) and long-wave UVA (320 nm to 400 nm) rays are widely known to be the chief causes of premature photoaging, immune dysfunction and certain skin cancers.4 In particular, UVB rays are believed to affect the skin more adversely, despite UVA rays being more prominent in the sunlight that reaches our skin.5,6 The shortest rays, UVC (200 nm to 280 nm), are currently prevented from reaching the earth’s surface because they are filtered by the ozone layer.

Innumerable environmental factors can impact human skin, but UV rays are the principal cause of the overproduction of reactive oxygen species (ROS), which include hydroxyl radicals, nitric oxide, peroxynitrite, superoxide anions, peroxide, triplet oxygen and singlet oxygen.1,2 Radicals lack an electron balance in their outer shell, which generates highly reactive species; though many types of free radicals exist, ROS are frequently studied because of their known adverse effects on the skin. While the overproduction of ROS can lead to oxidative stress in the skin, causing damage to cellular proteins, DNA and lipids, it is important to note that free radicals also have the potential to be beneficial.1,2

Radicals are necessary to maintain homeostasis at the cellular level. They also assist the human body by generating adenosine triphosphate (ATP) from adenosine diphosphate (ADP) in the mitochondria and oxygenases that perform many regulatory functions.7 Additionally, free radicals play a role in the apoptosis of defective cells.7

Due to the endogenous presence of enzymatic (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and thioredoxin reductase) and non-enzymatic (ascorbate, glutathione, tocopherol and ubiquinol) antioxidants in the tissue, radicals can perform these necessary functions without causing extensive damage to the surrounding cells.7,8 When the body’s systems are functioning properly, free radicals and the antioxidants that work to contain them function symbiotically.9 However, several intrinsic and extrinsic factors — most notably UV radiation — diminish the body’s store of cellular antioxidants while simultaneously increasing the production of ROS, resulting in oxidative damage.7

In order to adequately protect patients’ skin from ROS, topical antioxidant supplementation in addition to daily sunscreen use is becoming the standard of care. A plethora of antioxidant ingredients have demonstrated a capability for decreasing the occurrence of ROS-induced photocarcinogenesis and photoaging.1,10 The following list provides a look at some of the most potent and effective antioxidants currently available:

Resveratrol

AntioxidantsGrapes, berries, peanuts and cocoa are common sources of resveratrol, a widely used topical antioxidant.11-13 Resveratrol’s ability to quench free radicals is irrefutable, as this popular ingredient’s mechanism of action has been evaluated for several years. When applied prior to UV exposure, resveratrol inhibits the production of hydrogen peroxide radicals and lipid peroxidation. Additionally, this antioxidant has demonstrated the ability to suppress nuclear factor kappa B (NF-kB) activation, a key contributor to the formation of malignancies.10,14,15

Green Tea

AntioxidantsNaturally derived from the camellia sinensis plant, green tea contains numerous potent polyphenol antioxidants, the most plentiful of which is epigallocatechin gallate (EGCG). Because of this abundance, many accredit green tea’s antioxidant, anti-inflammatory and protective properties to EGCG.14 Research indicates that when EGCG is applied to the skin prior to or immediately after exposure to UV rays, this powerful antioxidant is capable of correcting cellular damage as well as protecting against further impairment. Specifically, EGCG has the potential to reverse the immunosuppressive consequences of free radicals16 while deterring hydrogen peroxide radicals17 and beginning the breakdown of carcinogenic skin cells.18

Ferulic Acid

AntioxidantsFerulic acid, another polyphenol antioxidant, is naturally derived from botanical sources such as rice bran and tomatoes. Despite not being considered a sunscreen agent, it has demonstrated an aptitude for preventing the production of nitric oxide and lipid peroxidation, as well as UV absorption abilities.19,20 Ferulic acid does not possess the potent scavenging function of other polyphenols like green tea, but research suggests it is highly effective in terms of photoprotection, exceeding even the popular antioxidant idebenone.21,22

Genistein

AntioxidantsA polyphenol derivative of soybeans, the isoflavone genistein effectively increases enzymatic antioxidant activity found naturally in the skin.23 Genistein’s ability to obstruct UV-induced cellular mutation and DNA damage, as well as prevent lipid peroxidation and hydrogen peroxide production, make it an essential component of protective topicals.24,25 Furthermore, in vivo studies indicate that genistein has the capacity to prevent both short- and long-term consequences of exposure to UV radiation, such as erythema, cutaneous carcinomas and visible photoaging.26

Coffea Arabica Extract

AntioxidantsCoffea arabica extract, also known as coffeeberry, is naturally derived from the unripe coffea arabica plant. The mechanism of action of coffea arabica extract in the skin is not entirely understood; however, in vitro studies have shown that the antioxidant is capable of suppressing free radicals.27,28 The antioxidant capabilities of coffea arabica extract could be accredited to its capacity for increasing superoxide dismutase, glutathione reductase and catalase content, all components of the body’s innate enzymatic antioxidant functions.29

Silybin Marianum Fruit Extract

AntioxidantsSilybin is the most active component of silymarin, a potent flavonoid antioxidant that is derived from milk thistle. Research suggests that silymarin has the ability to hinder the peroxidation of lipids as well as the production of nitric oxide and hydrogen peroxide.3 The topical application of silymarin also results in an increase in the endogenous antioxidant glutathione.34 Additionally, silymarin treatment has been identified as an inhibitor of the effects of UV exposure, including immunosuppression and carcinogenesis, as well as a factor in decreasing the damage caused by free radicals.35-37

Caffeine

AntioxidantsIn addition to being a potent antioxidant itself, caffeine is widely believed to be a key element in the antioxidant functions of common topicals such as coffea arabica, cocoa seed extract and green tea.38-40 Studies have shown that caffeine has the ability to diminish free radicals, including peroxyl, hydroxyl, hydrogen peroxide and singlet oxygen.41 Further investigation also indicates that applying caffeine to the skin’s surface may decrease UV-induced skin cancers by increasing cellular apoptosis in damaged keratinocytes that result from exposure to free radicals.39,41

Idebenone

AntioxidantsIdebenone is an engineered analog of coenzyme Q-10 that serves as a potent primary antioxidant. Clinical trials performed on the topical benefits of idebenone suggest an impressively well-rounded radical scavenging capacity when compared to the traditional antioxidant agents alpha lipoic acid, kinetin, tocopherol and ascorbic acid.42 In vivo tests showed a decrease in lipid peroxidation and an inhibition of UVB-induced DNA damage and erythema.42 Further research, however, indicates a lack of photoprotection when compared to other topical antioxidants.43,44

L-ascorbic Acid

AntioxidantsL-ascorbic acid is the only true bioavailable form of vitamin C and the only ingredient that provides all of vitamin C’s topical benefits. Topically applied L-ascorbic acid serves as a multi-functional antioxidant that effectively quenches ROS in the aqueous environment of the skin.45 Because vitamin C is easily oxidized, a product’s proper stabilization is crucial. Encapsulation and anhydrous vehicles are the most effective means of stabilization.46 Products with an aqueous base should have a pH of 3.5 or lower.47 Esterfication is another method of stabilization. Although ester versions of vitamin C, such as ascorbyl palmitate and magnesium ascorbyl phosphate, have shown in clinical studies to provide some of the antioxidant capabilities of vitamin C, they do not provide the collagen synthesis, anti-inflammatory and photoprotective activities.48 Therefore, esterfication is not the preferred method of stabilization.

Glutathione

AntioxidantsGlutathione is part of the body’s endogenous antioxidant system. Many of the commonly used topical antioxidants work by regenerating this essential protective component. Research indicates that glutathione provides primary antioxidant capabilities by neutralizing current and preventing future oxidation.49 In addition, glutathione serves as a co-antioxidant that supports L-ascorbic acid and vitamin E.50 Topically applied glutathione reduces UV-induced erythema to a higher degree than superoxide dismutase, ascorbyl palmitate and tocopherol.51

Protecting Patients from UV Exposure and its Adverse Effects

Research strongly supports the connection between UV radiation and increased ROS production, which simultaneously drains the body’s store of radical-expelling antioxidants. Furthermore, such exposure may adversely impact any topical skincare formulation’s ability to protect against photocarcinogenesis and photoaging.52 Sunscreens are designed to block UV rays from reaching the skin’s surface and to prevent UV-induced damage, but, unfortunately, not all rays can be blocked. An SPF of 15, for instance, protects from 95% of the sun’s rays. In addition, common sunscreen ingredients that are intended to absorb or reflect UV rays are vulnerable to breakdown and free radical formation with prolonged sun exposure.52  

Patient compliance is already a challenge for clinicians, and the revelation that sunscreen can generate a fair number of free radicals has contributed to the complexity by causing unnecessary fear among some patients. But the potential for additional free radical damage from applying sunscreen can easily be avoided. Clinicians can provide their patients with broad-spectrum UVA/UVB sun protection moisturizers that are formulated to include antioxidants, or, alternatively, suggest antioxidant serums to use along with a daily sunscreen. Doing so will help alleviate patients’ concerns while also providing the best defense against dangerous UV radiation. The antioxidants provide an additional layer of protection from the rays that make it past the sunscreen shield and can prevent damage from any generated ROS.

Radicals play a key role in maintaining homeostasis within the body, but it is virtually impossible to avoid contact with UV radiation and other sources of ROS to shield skin from adverse effects. Daily use of topical antioxidants can, however, impede the ensuing diminution of endogenous antioxidants, production of ROS and damage to DNA, cellular proteins and lipids. As illustrated, the variety of antioxidants available provides clinicians and their patients with innumerable options for achieving maximum protection against UV exposure and its destructive effects.

Dr. Linder, a board-certified dermatologist and fellowship-trained Mohs skin cancer surgeon, is a
volunteer Clinical Instructor in the Department of Dermatology at the University of California,
San Francisco. Dr. Linder is currently in private practice in Scottsdale, AZ.

Disclosure: Dr. Linder is Chief Scientific Officer, PCA SKIN, is National Instructor, Dermik Aesthetics (Sculptra), and National Instructor, Allergan Facial Aesthetics.