This month’s Featured Article:

By Ada Polla Tray, Barbara Polla, M.D., and Anne Pouillot

Over the last few years a number of studies have established the essential role of systemic antioxidants—whether consumed orally as foods or in the form of supplements—in the prevention of various diseases related to aging, including cancer. The role of topical antioxidants in the prevention and treatment of skin aging has also been investigated in numerous studies, which conclude that antioxidants represent a significant opportunity for the future of cosmetology. And indeed, during the meeting of the American Academy of Dermatology in Washington D.C. that took place in February 2007, dermatologists and cosmetic experts discussed in detail the role of antioxidants.

This article focuses on a review of oxidants and their role in skin aging, the effectiveness of antioxidants, the contradictory results of some studies and the future of antioxidants, such as preferential use of phytoantioxidants and antioxidants.

Relative oxygen species

Essential to sustain life, oxygen is metabolized in the body by successive reductions that lead to the generation of relative oxygen species (ROS). Some are free radicals, which are defined by the presence of an unpaired electron, whereas others are stable such as hydrogen peroxide.

At low concentrations, ROS are an integral part of physiological processes and have precise and positive functions. However, the production of ROS must be strictly controlled in order to prevent their toxicity. Indeed, in large quantities, ROS are nefarious to organs and cells. To control ROS production, human cells are equipped with a series of endogenous antioxidants, primarily enzymes. However, these endogenous antioxidants are gradually depleted. Thus, exogenous antioxidants—those not produced by the human body—play a key role in the prevention of oxidative damage.

ROS, oxidative stress and skin aging

When the natural balance between oxidants and antioxidants is altered, either by an increase in the production of oxidants or by a decrease in antioxidants, ROS can potentially damage cellular structures. This process is called oxidative stress.

Exposure of the skin to UV rays is the main cause of oxidative stress: UV exposure induces the production of high quantities of ROS. These ROS damage DNA, lipids, intracellular and extracellular proteins, membranes and sugars, resulting in both immediate and long-term detrimental effects. Over time, UV induced DNA lesions lead to the appearance of actinic keratoses and possibly carcinogenesis. UV induced oxidative damage of lipids or lipid peroxidation is responsible for the citrine coloration of the skin. And UV induced protein alterations lead to a progressive deterioration and loss of collagen and elastin.

Most of the clinical signs of accelerated skin aging related to excessive UV exposure can be explained by oxidative stress and prevented by an effective combination of sunscreens and antioxidants. Indeed, it should be noted that sunscreens, whether chemical or physical, play an essential role in the protection against UV exposure. However, despite their importance, sunscreens alone cannot ensure full protection of the skin from sun damage. Even with adequate use of the best sunscreens, UV rays penetrate the skin and create oxidative stress, which can be tackled by antioxidants.

Clinical studies and their contradictions

Several recent clinical studies attempted to compare the effectiveness of various antioxidants, offering contradictory conclusions.

According to the Journal of Cosmetic Derm­atology, Volume 4, Issue 1, in the report titled, “Idebenone: a new antioxidant – Part I. Relative assessment of oxidative stress protection capacity compared to commonly known antioxidants,” McDaniel et al. defined and used a standardized method to characterize and compare the relative total antioxidant activity of ascorbic acid, tocopherol, kinetin, ubiquinone and idebenone. Idebenone was found to have the best score and ascorbic acid the weakest.

In a separate study published in the March 2006 issue of the Journal of Investigative Derma­tology, Tournas et al. compared the effects of an “antioxidant solution” containing ascorbic acid, tocopherol and ferulic acid, with solutions of either ubiquinone, idebenone or kinetin, on the density of sunburn cells. The density of sunburn cells was significantly reduced when the skin was treated with the “antioxidant solution” whereas ubiquinone, idebenone and kinetin offered little or no photoprotection.

The apparent contradictions between these two as well as other studies can be explained by the different methodologies and measurements used. The studies indicate that the tools currently available are insufficient to optimally compare the antioxidant activities of various molecules.

Future approaches: phytoantioxidants

Over the last few years, antioxidants derived from plants or phytoantioxidants have been shown to be effective in the prevention of aging in general, and skin aging in particular. It is interesting to note that plants, like human beings, suffer from UV generated oxidative stress. Plants are, however, unable to protect themselves by moving into the shade or by using sunscreens. Consequently, plants have developed effective antioxidant strategies, including developing a combination of multiple antioxidants, which allow them to protect themselves against the oxidizing stress induced by their environment, in particular UV exposure.

Phytoantioxidants fall into four main groups, namely enzymes, terpens, polyphenols and vitamins. Some of the best known and most studied phytoantioxidants are carotenoids (terpens), flavonoids and anthocyanins (polyphenols). More specifically, we will discuss green tea, grape seeds and tomatoes.

Green tea contains catechins, epicatechin, epicatechin-gallate and epigallocatechin-3-gallate. These antioxidant molecules neutralize ROS. Moreover, epigallocatechin has also been shown to have UVB protective effects on the skin.

Grape seeds contain resveratrol and quercetin. Resveratrol has been shown to prevent UVB damage on the skin. Quercetin protects endogenous antioxidants and therefore allows their continued activity after UV exposure. Quercetin also helps to neutralize excess iron, which is involved in accelerated skin aging.

Tomatoes are rich in lycopene, which is particularly known for its antioxidant and anticarcinogenic properties when consumed orally in large quantities. Lycopene not only neutralizes ROS but is also most effective in scavenging free radicals. Lycopene also reduces lipid peroxidation and prevents UV induced redness.

Synergies among antioxidants

The natural combination of phytochemicals in fruits and vegetables appears to be essential to their antioxidant efficacy. Indeed, the synergistic effects of phytochemicals are vital, as is shown by a diet rich in fruits and vegetables. Thus, no single antioxidant can replace the combination of natural antioxidants present in fruits and plants. Furthermore, phytoantioxidants have distinct molecular masses, polarity and solubility. These differences affect their biological availability and their specific distribution and effects.

Ingesting antioxidants is a key therapeutic method of preventing skin aging. More specifically, the combination of multiple antioxidants at low concentrations and the association of topical and oral administrations seem to represent the most effective approach to skin health. Nonetheless, continued studies on the penetration and effectiveness of plant extracts are essential to confirming their effective use in dermatology and cosmetology.

Ada Polla Tray is the co-creator of the skin care line Alchimie Forever. She holds a master’s from Georgetown University, and a bachelor’s from Harvard University. Tray is on the editorial board of PCI Magazine, a member of the ISPA marketing committee, a contributor to numerous trade magazines and a frequent speaker at Georgetown University and industry conferences. To reach her, visit www.alchimie-forever.com.

Barbara Polla, M.D., is as an expert on heat shock/stress proteins and the oxidants/antioxidants balance. In 1997, Dr. Polla and her husband opened Europe’s first fully-integrated medical spa, Forever Laser Institut, and in 2003, together with her daughter Ada Polla, she created the Alchimie Forever skin care line. Dr. Polla is coauthor of more than 100 scientific articles. She is also a writer in the national and international press and the author of novels and essays.

Anne Pouillot is scientific and technical assistant at Alchimie Forever. She holds a master’s degree in biochemistry with a specialization in plant molecules. Pouillot is involved in the conception and formulation of the company’s products and works closely with its laboratories and manufacturer, and participates in the promotion and commercial development of Alchimie Forever in Europe.