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A REFRESHER ON ANTIOXIDANTS

First Hypothesized in 1956 by Dr. Denham Harman, the free radical theory of aging is now the most widely accepted theory regarding the etiology of skin aging. Both internal and external oxidative stressors create inflammatory pathways characterized by the formation of free radicals, which are highly reactive molecules with unpaired electrons. Left unchecked, free radicals can cause severe cellular damage to cell membrances, lipids, proteins, and DNA. Free radicals that are known to cause DNA damage, lipid peroxidation, and inflammation are also believed to cause skin aging. Antioxidants are substances that protect cells from endogenous oxidative stress,which is a natural byproduct of cellular energy production. Antioxidants also offer protection from exogenous stressors, such as UV radiation from the sun, air pollution, cigarette smoke, ozone, and even oxygen itself. The damage accumulation theory of aging suggests that a lifetime buildup of damage caused by unchecked free radicals is a primary mechanism leading to the manifestations of aging. The almost universal acceptance of both the free radical theory and the damage accumulation theory helps explain the intense interest of modern medicine in the capacities of antioxidants. By scavenging and eliminating free radicals, antioxidants balance and thwart the deleterious effects of the free radical-mediated inflammatory pathways promoted by oxidative stress.

How Antioxidants Work
Several antioxidants are used as ingredients in topical skin care formulations, including vitamins C and E, lycopene, grape seed extract, green tea, coenzyme Q10, and alpha-lipoic acid. Each offers distinct advantages, but they all pose similar challenges in terms of harnessing their potency in topical products.

Vitamin C. Although there is a dearth of research evaluating the effects of ascorbic acid (vitamin C) on wrinkles, one such study has garnered a good deal of attention. The topical application of Cellex C serum for 3 months was shown to reduce the size of wrinkles in a study of 19 patients (Arch. Otolaryngol. Head Neck Surg. This study was not blinded, as a significant percentage of the participants experienced stinging on the treated side of the face. Vitamin C is known to play an important role for the skin: It has been shown to increase collagen synthesis in neonatal and adult fibroblasts when added to the culture medium.

Topical vitamin C preparations have proven to be disappointing, however. Most preparations are unstable upon exposure to UV light and air, which renders them useless. Also, most topical vitamin C products, even the stable ones, fail to penetrate the stratum corneum.

Vitamin E. The topical application of a tocopherol (vitamin E) has been shown to confer significant protection against UV-induced damage to animal skin.
Although immunostimulatory and anti-inflammatory effects have been ascribed to vitamin E, several studies have cited adverse reactions to topical vitamin E. A sun protection factor of 3 topical application of vitamin E, which is believed to have the capacity to marginally absorb light (Cosmet. Dermatol.) It appears likely, however, that vitamin E requires the interaction of other antioxidants to provide any photoprotective effect.

Coenzyme Q10. A powerful antioxidant that combats free radical stress and assists in energy production, coenzyme Q10 is found in all cells. By inhibiting lipid peroxidation in plasma membrances thus limiting free radical formation coenzyme Q10 is believed to prevent oxidative stress-induced apoptosis.
Coenzyme Q10 plays an important role in the energy-producing adenosine triphosphate pathways present in the mitochondria of each cell in the body. Energy production is an important component of cellular metabolism that is thought to diminish in efficiency with age. Coincidentally, levels of coenzyme Q10 also decline with age. Supplementation with this coenzyme is believed to have potential to stem the decline in energy production associated with senescence and illness. A preponderance of clinical work with coenzyme Q10 has evaluated its systemic administration. However, topical coenzyme Q10 has been shown to penetrate the viable layers of the epidermis and lower the level of oxidation, measured by weak photon emission, and reduce wrinkle depth. In the same study, the coenzyme suppressed expression of collagenase in human fibroblasts following UVA irradiation. These results suggest that topical coenzyme Q10 may effective in preventing the deleterious effects of ultraviolet radiation exposure.

Grape seed extract. By inducing vascular endothelial growth factor expression in keratinocytes, grape seed extract in one study appeared to exhibit the potential to confer beneficial results in dermal wound healing and related skin problems.

In human volunteers, topical application of grape seed extract has been shown to enhance the sun protection factor. Data suggest that grape seed extract is a significantly more potent scavenger of free radicals than either vitamin C or E. The bioflavonoids in grape seed extract appear to promote the body`s ability to absorb vitamins, creating a symbiotic atmosphere for other nutrients.

Green Tea. Green tea is included in various skin care products because of the purported antioxidant and anti-inflammatory effects of polyphenols that occur naturally in the green tea leaf. The polyphenols have been shown to modulate the biochemical pathways important in cell proliferation, inflammatory responses, and responses, and responses of tumor promoters.

Oral consumption of green tea has actually been shown to increase green tea phenol levels in skin as indicated by tapestripping analysis. Numerous studies support continuing interest in and use of green tea.

Unfortunately, when high levels of green tea are placed in a moisturizing vehicle, the cream often turns brown. One company(Topix) has avoided this problem by making their cream brown to begin with.

Lipoic acid. Water and lipid-soluble lipoic acid is a potent antioxidant and a promising option in the treatment of aging skin.. It is believed to be effective in treating inflammatory diseases, and may slow the pace of skin aging.

Lipoic acid is absorbed in a stable form. After entrance into cells, however, it is immediately converted to its byproduct, dihydrolipoic acid, which has a stronger antioxidative effect. The topical application of 3% lipoic acid in a lecithin base on human skin has been shown to decrease erythema caused by UVB twice as fast as lecithin base alone. This suggests that lipoic acid could potentially reduce the effects of photoaging or even thwart carcinogenesis.

Lipoic acid is another in the long line of antioxidants that show promise, but lack double-blind clinical trials showing their efficacy in available products. Lipoic acid can be irritating to those with sensitive skin.

Lycopene. Naturally present in human blood and tissues, lycopene is a non-provitamin A carotenoid. It is best known as the pigment primarily responsible for the characteristic red color of tomatoes.

Lycopene is now drawing attention for its potential potency as an antioxidant. Lycopene may play a role in reducing oxidative damage to tissues, as suggested by a study in which a 31%-46% decrease in skin lycopene concentration was observed following a single intense exposure (three times the minimal erythema does) of solar simulated light on a small area of the volar arm.

In a separate study of oral consumption of lycopene, both lycopene and B-carotene failed to confer photoprotective effects to human dermal fibroblasts. Their stability was enhanced, however, by the presence of vitamin E, which contributed to the suppression of metalloproteinase-1 mRNA expression. This suggests that to deliver the benefits of lycopense in topical products, it may be necessary to combine the carotenoid with other antioxidant active ingredients. The literature is rife with evidence of the efficacy of ingested lycopene, but there is a paucity of double-blind, case-control studies evaluating the efficacy of topical products.

Measuring Efficacy
Millions of people are likely aware of many of the topical antioxidants currently marketed, given how popular the use of “antiaging” cosmeceuticals containing such ingredients has become. Most consumers are clueless, however, as to how to rate the effectiveness of such formulations, as scant scientific date exist on the wide range of skin care products that contain highly touted antioxidants.

Until now, there have been no standard methods for comparing the relative efficacy of different antioxidants in a fashion readily accessible to consumers.
Pharma Cosmetix Research, a cosmeceutical research and development company, has produced a protocol of in vitro and in vivo studies designed specifically to address the need to standardize efficacy measurement of topical antioxidants. In much the same way that the sun protection factor provides a measuring stick enabling the user to estimate the level of UV protection to expect from a sunscreen product, Pharma Cosmetix Research’s environmental protection factor (EPF) is designed to provide the product user with an estimate of the level of oxidative / environmental stress protection to expect from an antioxidant skin care product.
In all of the antioxidant efficacy protocols, each antioxidant substance is scored, and the results are totaled for each antioxidant on an equal weighted basis. The over all total score for each antioxidant reflects the overall stress protection capacity, or EPF, of the antioxidant.
The bottom line is that EPF is to antioxidant environmental protection efficacy what SPF is to sunscreen UV protection efficacy. Consumers will now have a simple way to rate antioxidant strength and compare the efficacy of topical antioxidant cosmeceutical products.





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