RENEW SERUM™ Clinical Study XERIDIAN® CLINICAL SKINCARE® 2 General Discussion The Renew Serum™ is a face and neck product that includes a synergistic combination of alpha & beta hydroxy fruit acids and skin-refinishing enzymes that dramatically enhance skin cell renewal to polish away lines, hyperpigmentation (“age spots,” freckles, etc), uneven texture, and acne blemishes. This formula also contains dual-stabilized forms of l-ascorbic acid (Vitamin C) and centella asiatica extract to correct wrinkles and sagging by stimulating collagen fiber production. The grape seed extract and resveratrol red wine polyphenols in this product combine with superoxide dismutase and peroxidase (super-antioxidant enzymes) to protect the skin against free radical damage. The pH of this formula is kept near 4.0 as hydroxy acids are only effective up to a pH of 4.0 while skin irritation can occur at a pH below 3.5. o Fine Line Resurfacing – The synergistic combination of both Alpha & Beta Hydroxy Acid forms allows them to be supplied in such an effective concentration and yet be gentle enough for daily use. Clinical studies have shown that natural hydroxy acids are up to 4x more gentle than synthetic alternatives at equal concentrations. When combined with Papaya & Pineapple Enzymes this formula can refinish away lines, wrinkles, and uneven texture to reveal a more flawless and radiant complexion without the skin peeling associated with synthetic hydroxy acids products. o Anti-Acne – The epidermal renewing and pore-cleansing properties of hydroxy compounds and botanical enzymes make this an ideal product for use on acne-prone skin to resolve current acne lesions and prevent the formation of future blemishes. o Hyperpigmentation Lightening & Skin Cell Renewing – Alpha & Beta Hydroxy Fruit Acids have been shown in numerous clinical studies to encourage youthful epidermal cell division while resurfacing away older skin cells. This skin renewing property allows them to even out pigmentation over time, especially when combined with the Dual-Stabilized L-Ascorbic Acid (Vitamin C), Kojic Acid (from Mushroom Extract), and Alpha-Arbutin (from Bearberry Extract) to yield a younger, more unblemished complexion. o Skin Energizing – Hydroxy compounds additionally aid in the absorption of Vitamins B3 & B5 through the epidermis to feed mitochondrial organelles, which in turn boosts cellular energy production and stimulates the increased microcirculation needed to bring other vital nutrients to the skin at a more youthful rate. o Anti-Wrinkle – Numerous clinical studies have shown that stabilized forms of L-Ascorbic Acid (Vitamin C) can dramatically enhance collagen synthesis and act as a potent antioxidant against free radicals. Centella Asiatica Extract, magnifies these results by also promoting collagen synthesis as well as guarding the collagen network from degradation. o Antioxidant Protection – In addition to the potent antioxidant activity of Vitamin C, this formula also includes Grape Seed Extract and Resveratrol (a red wine polyphenol) along with Superoxide Dismutase and Peroxidase super-antioxidant enzymes to protect the skin against free radical damage. o Skin Cell Life Extending – The Resveratrol, in this formula is a grape polyphenol that gives red wine much of its antioxidant attributes. Laboratory studies have shown that this compound can greatly extend the lifespan of cells by mimicking the beneficial aspects of caloric restriction and new research is constantly coming out pointing to the implications this has on extending youthful skin cell life. Formula Active Mechanisms Anti-Wrinkle Ingredients L-Ascorbic acid is a water-soluble form of vitamin C chirally shifted left to be more effectively incorporated into the skin, where it can act not only as an essential antioxidant, but also has been shown in clinical studies to stimulate collagen synthesis (which produces visibly tighter and smoother skin over time) as well as lighten hyperpigmentation. It is also a natural free radical scavenger that works synergistically with other antioxidants in the skin. Because pure ascorbic acid is very unstable in aqueous formulas we use dual-stabilized forms of Vitamin C that clinical studies have demonstrated have long-term stability when used in topical products while effectively penetrating the skin to impart its antioxidant and collagen-enhancing benefits. Recently a bright spotlight has been on the extract of Centella Asiatica (a herb native to India) as having powerful antioxidant properties, and clinical tests have demonstrated that it can penetrate deeply into the skin to stimulate collagen synthesis (which in turn promotes skin tightening and a reduction of wrinkle depth). Stabilized Vitamin C Centella Asiatica Extract © 2009 XERIDIAN, LLC 3 Resurfacing Extracts These naturally occurring acids come from a variety of biological sources, most notably fruits, and work to resurface away fine lines, wrinkles, freckles, ‘age spots,’ and blackheads found in the epidermal skin layers. The two most notable alpha hydroxy acids are Glycolic Acid (the most powerful) and Lactic Acid (the most gentle). Combined together they form a powerful combination, and due to their water soluble nature they absorb quickly and deeply through the epidermis to stimulate quicker cell turnover that mimics that of youthful skin. They work to encourage the growth of healthy, newer skin cells that produce a more glowing complexion with continual use. Due to their refinishing properties, AHAs have also been shown to diminish acne appearance in addition to their anti-aging benefits. Beta Hydroxy Acids work perfectly alongside Alpha Hydroxy Acids because their affinity for skin oils allows them to better absorb into pores, where they impart deeper cleansing effects as well as promote quicker skin renewal through different epidermal pathways than alpha hydroxy acids. This makes BHAs perfect for fighting acne development by keeping pores unclogged while helping to erase lines and wrinkles. Papaya and Pineapple Enzymes, like hydroxy acids, have a resurfacing effect on the skin. While AHAs and BHAs loosen epidermal dead cells (primarily composed of keratin), these botanical enzymes will gently dissolve away this keratinized layer as it is being exfoliated. This means that skin peeling is dramatically reduced or altogether eliminated during the resurfacing process. Because these proteolytic (protein dissolving) plant enzymes are so effective at resurfacing skin they have also been shown in clinical studies to have effects on keloid (raised) scars. Antioxidant Compounds Grape Seed Extract contains antioxidants that studies have proven to be 50-times more effective than vitamin E and 20-times more effective than vitamin C in scavenging for free radicals. It also has soothing and reparative properties through its ability to strengthen capillaries, reduce inflammation, and strengthen skin’s defenses against UVB radiation. Resveratrol is a recently discovered polyphenol found in particularly high concentrations in the skins of red grapes and is often attributed to the health benefits of moderate red wine consumption. It is a potent antioxidant that has a particularly beneficial affinity for neutralizing the free radicals most responsible for lipid oxidation. This is thought to be the mechanism that gives red wine its antioxidant and heart health promoting attributes. Recent studies in the laboratory have shown that Resveratrol can greatly extend the lifespan of cell cultures, and while further studies are needed to confirm these results in humans there is strong indication they can have life-extending effects on the youthful functioning of skin cells. Superoxide Dismutase (SOD) is a powerful enzyme complex that helps to counteract the damaging effects of various reactive oxygen species (ROS) and is therefore an extremely useful antioxidant in the skin. Superoxide Dismutase neutralizes the superoxide free radical anion and copious clinical evidence demonstrates that topical application of SOD serves to reduce irritation/inflammation in addition to its antioxidant benefits. Superoxide dismutase in conjunction with Peroxidase is responsible for the scavenging and neutralization of both the Superoxide and Peroxide radicals which contribute to premature aging. They form a powerful duo together because when Superoxide Dismutase neutralizes the superoxide anion it can release peroxide, which is subsequently neutralized by Peroxidase. Hyperpigmentation Lightening & Complexion Evening Alpha-Arbutin is extracted from Bearberries and is a faster, safer approach to skin brightening over synthetic chemicals used in many other products on the market. Alpha-Arbutin minimizes "age spot" and freckle hyperpigmentation by blocking epidermal melanin synthesis via inhibiting enzymatic oxidation of Tyrosine and Dopa in and around skin melanocytes. Kojic Acid is a by-product in the fermentation process of malting rice and can also be extracted from certain species of mushrooms. It is an effective inhibitor of the formation of pigment in plant and animal tissues, and is used in skincare products to even out hyperpigmentation and even skin tone in a similar manner to Alpha-Arbutin but through different mechanisms, making them synergistic with each other in a formula. This is a specially purified extract composed of fermented and hydrolyzed proteins extracted from the Brassicaceae plant family. These botanical proteins have strong skin-lightening functions when absorbed through the epidermis and are very effective in reducing the appearance of "age spots" and freckles. Clinical studies have demonstrated that this extract decreases tyrosinase activity in-vitro, reduces melanin content in ex-vivo skin, significantly reduces skin imperfections. Alpha Hydroxy Acids Beta Hydroxy Acids Resurfacing Enzymes Grape Seed Extract Resveratrol Superoxide Dismutase Peroxidase Alpha-Arbutin Kojic Acid Brassica Napus Extract © 2009 XERIDIAN, LLC 4 Study Participant Demographics There were a total of 16 participants in this study, composed of 9 females and 6 males. The age of these participants ranged from 25 to 74 with a median age of 49 (Figure 1). The participants were asked to stop the use of all other skincare products they may be using for one month prior to the study as well as during the study (except for products that were not “leave-on” such as cleansing or shower products). All participants were given the RENEW SERUM to use twice daily for a ten week period. 6% 13% 19% < 29 30‐39 40‐49 50‐59 24% 13% 60‐69 >70 25% Figure 1: Study Participant Age Range During the initial intake the participants of this study were asked to complete a self-evaluation questionnaire in which they assessed various characteristics of their own skin (Figure 2). Most notably this included a self-evaluation of their basic skin type: oily (characterized by excess sebum production that results in acne, greasy skin, and/or glossy shine), combination (characterized by an oily T-zone around the nose and/or forehead but dry skin elsewhere on the face), normal (characterized by the proper balance of oil production to keep the skin plump, hydrated, and moist but not enough to appear greasy, shiny, or for significant acne development), and dry (characterized by dull, flakey, and/or dehydrated skin that does not have enough sebum oil production to keep the skin moist). 31% 37% Oily Combination Normal Dry 13% 19% Figure 2: Study Participant Skin Type Range Also during intake the tonality of the skin was assessed using a Fitzpatrick Skin Type Scale with one (I) representing very light pigmented skin, two (II) representing medium-light pigmented skin, three (III) representing medium skin, four (IV) representing mediumdark skin pigmentation, and (V) representing dark skin pigmentation. No one in this particular study had a Fitzpatrick Skin Type of VI, which is very dark pigmentation. (Figure 3) 6% 13% 31% I II 13% III IV V 37% Figure 3: Fitzpatrick Skin Type Range © 2009 XERIDIAN, LLC 5 Study Methodology & Results To evaluate changes in skin hydration from ten weeks of twice daily product use a Corneometer® CM 825 was utilized. The measuring principle of this device is based on capacitance measurement of a dielectric medium. Any change in the dielectric constant due to skin surface hydration variation alters the capacitance of a precision measuring capacitor. The design of the measuring head is such that the measurement depth is very small (in the first 10-20 µm of the stratum corneum) and the device can detect even slight changes in the hydration level. The statistical mean results of the study participants are presented in the graph below. 30% 25% 20% 15% To determine an absolute measurement of wrinkle depth a standard Skin-Visiometer® SV 600 was used, which evaluates the topography of the skin surface by light transmission of a thin blue dye silicone. This specially prepared silicone, mixed under a vacuum to avoid bubble formation, permeates even the smallest skin depths to form a micro-cast that is evaluated by a parallel light source and CMOS camera to quantitatively measure the heights and depths of the skin surface area as a negative. The statistical mean results of the study participants are presented in the graph below. 28% 50% 40% 49% 37% 21% 17% 10% 5% 0% Average Percentage Improvement In Skin Hydration Of Subjects As Measur ed With Corneometer® CM 825 Day 70 30% 20% 10% 0% 30% 0% Day 0 (Baseline) Day 35 0% 0% Day 0 (Baseline) Day 35 Day 70 Average Percentage Improvement In Deep Wrinkle Depth As Measured With Skin‐ Visiometer® SV 600 Average Percentage Improvement In Fine Line Depth As Measured With Skin‐ Visiometer® SV 600 To evaluate the topography of the skin and assess subtle changes beyond the scope of the naked eye a UV light evaluation of skin topography was used in line with the Visioscan® VC 98 industry standard protocols of evaluation. This type of skin assessment has implications in the general improvement of the skin (improvements in pore size, texture, roughness, and micro-tension) and provides subsequent validation of other test results. The statistical mean results of the study participants are presented in the graph below. For the purposes of measuring pigmentation and hyperpigmentation in the skin a standard Mexameter® MX 18 was used. The probe emits three specific wavelengths of light reflected by the skin in a receiver and the quantity of light absorbed by the skin can be calculated. To assess melanin pigmentation, it is measured by specific wavelengths chosen to correspond to different absorption rates by the pigments. The statistical mean results of the study participants are presented in the graph below. 40% 35% 30% 25% 20% 15% 10% 5% 0% 39% 29% 32% 21% Average Percentage Improvement In General Skin Topography Average Percentage Improvement In Roughness 0%0% Day 0 (Baseline) Day 35 Day 70 70% 60% 50% 40% 30% 20% 10% 0% 67% 39% Average Percentage Improvement In Pigmentation As Measured With Mexameter® MX 18 0% Day 0 (Baseline) Day 35 Day 70 © 2009 XERIDIAN, LLC 6 Forehead Hyperpigmentation Analysis BEFORE: This study participant has fair skin that is sensitive to sun exposure and is prone to hyperpigmentation. This is especially apparent in the freckles of the upper forehead as well as both sides of the exposed cranial skin. AFTER: After twice daily application of the RENEW SERUM for ten weeks there has been an almost complete removal of hyperpigmentation from all regions of the forehead, with only the faintest trace around the sides near the hairline. The skin texture and tone is uniform. © 2009 XERIDIAN, LLC 7 Side Face Acne Analysis BEFORE: This participant has moderate acne on the cheeks and nose as well as underlying redness from inflammation. There also is light scarring from previous acne. AFTER: After ten weeks of daily use of the RENEW SERUM this study participant has largely resolved her acne. The skin craters and scarring that was previously present during her intake into the study has greatly diminished. The pores on her face have decreased sharply in size and even the redness in the nostril region has subsided. The underlying inflammation in her skin has calmed to create more even tone and color. © 2009 XERIDIAN, LLC 8 Front Face Acne Analysis BEFORE: This is a front face view of the study participant in the previous set of pictures. She has moderate acne that is most apparent in the cheeks and chin, as well as enlarged pores in the T-zone around the nose. Also, underlying redness from inflammation can be seen in all facial areas. AFTER: Virtually all of this participant’s acne has cleared and there has been a significant reduction in pore size over the entire face. The underlying blotchiness and redness from inflammation has lessened, creating more uniform skin tone to accompany the more even skin texture. The craters and small scars from previous acne lesions have also been resurfaced to appear almost unnoticeable. © 2009 XERIDIAN, LLC 9 Mid & Lower Face Skin Analysis BEFORE: This study participant has deep wrinkles extending from the sides of the mouth and pronounced creases in the nasolabial fold skin region that extends from the sides of the nostrils down to the sides of the lips. Years of sun overexposure have created areas of hyperpigmentation on the cheeks, chin, and nose. There is also underlying redness from chronic inflammation, especially on the upper nostrils, cheeks, and chin. AFTER: After ten weeks of twice daily use of the RENEW SERUM the deep wrinkles around the sides of her eyes and the sides of the mouth have significantly filled in and reduced to just shallow lines. Her skin is much tighter and appears especially lifted around the nasolabial folds, which show much less creasing. The hyperpigmentation that was once very apparent on her cheeks, nose, and chin has evened out dramatically. The underlying redness around the upper nostrils, cheeks, and chin has diminished, signifying a decrease in chronic inflammation. © 2009 XERIDIAN, LLC 10 UV Light Analysis of Mid & Lower Face Skin Regions BEFORE: This is the same participant from the previous full face analysis shown under a UV Light Lamp used by dermatologists to assess underlying skin damage by increasing the contrast of skin imperfections. There is clearly a prolific amount of underlying hyperpigmentation in virtually all skin regions of this participant’s face, with the most notable amount in the upper nose and cheeks. Though this is visible in regular daylight to a degree, the full extent of discoloration and hyperpigmentation can be more clearly seen here under this special lighting. AFTER: The resolution in underlying hyperpigmentation in all skin regions of this participant’s face is amazing. After ten weeks of RENEW SERUM use the discoloration from hyperpigmentation has been dramatically improved to bring about a more even complexion. Even the darker pigmented spots on the upper nose and lower peri-orbital region have been significantly lightened. © 2009 XERIDIAN, LLC