Clinical Evaluation of a Multi-Modal Facial Serum That Addresses Hyaluronic Acid Levels in Skin.

BACKGROUND: Hyaluronic acid (HA), the major glycosaminoglycan present in the human skin, is a key contributor to water retention and mechanical support in skin. The level, size, and functionality of cutaneous HA are known to diminish with age. Topical treatments designed to increase the HA content of skin have been met with limited success. The purpose of this study was to evaluate the tolerance and efficacy of a multi-modal facial serum containing HA, Proxylane (C-Xyloside), purple rice extract, and dipotassium glycyrrhizate in addressing HA levels in skin. METHODS: A 12-week, single center, clinical study was conducted on 59 women with mild to moderate photodamage. Clinical grading to assess the efficacy and tolerability was conducted on the face at baseline and at weeks 4, 8, and 12. Bioinstrumentation measurements were taken, including corneometer, tewameter, ultrasound, and standardized digital imaging. A randomized subset of 20 subjects from the study population had 3 mm punch biopsies collected for quantitative RT-PCR analysis from 2 sites on the face at baseline and week 12. Additionally, a 4-week, single center, clinical study was conducted on the photodamaged forearms of 12 subjects. At both baseline and week 4, a 4 mm punch biopsy was obtained from the subjects' randomized forearms. Biopsy samples were subjected to immunohistochemical staining and analysis of HA content. RESULTS: Statistically-significant improvements in all facial skin attributes (weeks 4, 8, and 12), stratum corneum hydration (week 12), and transepidermal water loss (week 12) were observed. Tolerability was excellent, with no increases in irritation parameters noted. A significant increase of HA content in skin after 4 weeks of treatment was observed. By PCR analysis, there was a significant increase in hyaluronan synthase 2, as well as a significant increase in collagen type 1a1 after 12 weeks of application. CONCLUSION: The findings suggest that this novel topical facial serum is capable of stimulating HA and skin extracellular matrix components, as well as improving skin hydration and skin quality in women with mild to moderate photodamage.

J Drugs Dermatol. 2017;16(9):884-890.

Enhanced efficacy of a topical antioxidants regimen in conjunction with a home-use non-ablative fractional diode laser in photodamaged facial skin.

BACKGROUND: Photodamaged facial skin is characterized by fine lines and wrinkles, mottled pigmentation, and other changes. OBJECTIVE: To evaluate and compare the efficacy and tolerance of a home-use laser device when used alone or in combination with an antioxidant facial treatment for moderate photodamage. METHODS: This was a 49-subject, evaluator-blinded, split-face, randomized, single-center, 24-week, phase-2, study. In phase 1, all subjects were treated on one facial side with test products and a home-use laser device and the other side was treated with laser alone for 12 weeks, followed by a 2-week regression period during which they used only support materials. For phase 2, all subjects were divided into 2 independent treatment groups. For the next 10 weeks, subjects of first group treated the assigned facial side with test products and support materials and the other facial side with only support materials. Subjects in the second group treated their entire face with only support materials. Efficacy and tolerance were assessed by clinical grading, VISIA-CR imaging, and self-assessment questionnaires. RESULTS: The combination of laser and test products improved all photodamage parameters evaluated. CONCLUSION: The test products enhanced and prolonged clinical benefits obtained with the laser alone.

A method for maintaining the clinical results of 4% hydroquinone and 0.025% tretinoin with a cosmeceutical formulation.

Facial dyspigmentation treatment is an unmet need in dermatology with increasing challenges due to the questionable safety of hydroquinone. This research examined a new OTC formulation containing hydroxyphenoxy propionic acid, ellagic acid, yeast extract, and salicylic acid on subjects who previously completed 12 weeks of treatment with 4% hydroquinone and 0.025% retinoic acid. The goal of this study was to evaluate the skin lightening and tolerability profile of a 20-week maintanence therapy with a cosmeceutical formulation during the summer months. 33 healthy subjects ages 25-60 years with moderate facial dyspigmentation defined as a score of 3 on a 5-point scale were enrolled. There was statistically significant improvement at week 20 in terms of even skin tone (P<0.001), spot intensity (P<0.001), spot size (P<0.05) and overall hyperpigmentation (P>=0.002).

Clinical effects of a novel topical composition on persistent redness observed in patients who had been successfully treated with topical or oral therapy for papulopustular rosacea.

Rosacea is a condition most commonly characterized by central facial erythema and pupulopustules. There are highly effective drugs, both oral and topical, for papulopustular disease. At the present time, consistently effective pharmacologic therapy for erythematotelangiectatic rosacea is lacking. Patients whose papulopustular disease has been adequately treated are often still bothered by central facial erythema for which there is no adequate treatment short of laser and light. We present a study utilizing a novel topical composition evaluated for its ability to reduce background erythema remaining after adequate care of papulopustular disease. Patient, investigator and photographic evidence of erythema reduction was seen in 24/25 patients in this 8-week study.

Evaluation of efficacy and tolerance of a nighttime topical antioxidant containing resveratrol, baicalin, and vitamin e for treatment of mild to moderately photodamaged skin.

Resveratrol is an effective anti-aging molecule with diverse biologic activity. It functions as a dual antioxidant that can neutralize free radicals and increase intrinsic antioxidant capacity. Additionally resveratrol increases mitochondrial biogenesis and has anti-inflammatory, anti-diabetic, and anti-cancer activity. In this paper we will focus on the use of topically applied resveratrol using a proprietary blend containing 1% resveratrol, 0.5% baicalin, and 1% vitamin E. This stabilized high concentration formulation demonstrates percutaneous absorption and alterations in gene expression such as hemoxygenase-1 (HO-1), vascular endothelial growth factor (VEGFA), and collagen 3 (COL3A1). Clinical assessment showed a statistically significant improvement in fine lines and wrinkles, skin firmness, skin elasticity, skin laxity, hyperpigmentation, radiance, and skin roughness over baseline in 12 weeks. Ultrasound measurements in the periorbital area showed an average improvement of 18.9% in dermal thickness suggesting significant dermal remodeling. These studies confirm that topical resveratrol, baicalin, and vitamin E are valuable ingredient that can be used for skin rejuvenation.

Complementary clinical effects of topical tightening treatment in conjunction with a radiofrequency procedure.

UNLABELLED: Abstract Background: Skin laxity and cellulite on the buttocks and thighs are two common cosmetic concerns. Skin tightening with radiofrequency (RF) devices has become increasingly popular. OBJECTIVE: The purpose of this study is to evaluate the efficacy and safety of a topical skin laxity tightening agent when used in combination with an RF device. METHODS: A double-blinded, randomized clinical trial enrolled twenty females with mild-to-moderate skin laxity on the posterior thighs/buttocks. Each subject underwent two monthly treatments with an RF source (Alma Accent) to both legs. Subjects were then randomized to apply a topical agent (Skinceuticals Body Tightening Concentrate) twice daily to only one designated thigh/buttock throughout the eight-week duration of the study. All subjects were evaluated for improvement in lifting, skin tone, radiance, firmness/tightness, skin texture, and overall appearance based on photographic evaluation by blinded investigators at 12 weeks following the final RF treatment. RESULTS: A statistically significant improvement was found in the overall appearance on both sides treated with the RF device when compared to baseline. However, the area treated with the topical agent showed a statistically significantly greater degree of improvement than the side where no topical agent was applied. No adverse effects were reported. CONCLUSION: The use of a novel skin tightening agent used after RF procedures is both safe and effective for treatment of skin laxity on the buttocks and thighs. Combined therapy leads to a better result.

Tolerance and efficacy of a product containing ellagic and salicylic acids in reducing hyperpigmentation and dark spots in comparison with 4% hydroquinone.

Hydroquinone (HQ) is the benchmark prescription agent for skin lightening. However, HQ use is recently banned in Europe and in parts of Asia because of potential long-term consequences, including carcinogenesis when orally consumed. This has resulted in development of alternative skin-lightening agents with comparable efficacy to HQ, but better safety profiles. This study examined the skin-lightening ability of a topical product containing 0.5% ellagic acid and 0.1% salicylic acid and compared its efficacy with that of a prescription generic 4% HQ product. Fifty-four multiethnic subjects were randomly assigned to use the topical test formulation or generic 4% HQ twice daily for 12 weeks to evaluate product tolerability and efficacy. Under the conditions of this double-blinded clinical study, the test product demonstrated comparable tolerance and efficacy to that of a benchmark product 4% HQ, as assessed by clinical grading, physical measurement of spot size using image analysis, and questionnaire response analysis. This study suggests that this new product provided comparable skin depigmentation benefit to the benchmark product. In addition, the product appears to have better esthetics (texture, pleasantness to use, skin feel) than the 4% HQ product.

Comparison of clindamycin 1% and benzoyl peroxide 5% gel to a novel composition containing salicylic acid, capryloyl salicylic acid, HEPES, glycolic acid, citric acid, and dioic acid in the treatment of acne vulgaris.

This study evaluated the tolerance and efficacy of 2 facial skin products in subjects with acne using the following acne treatments: 1) treatment A, a combination of salicylic acid, capryloyl salicylic acid, HEPES, glycolic acid, citric acid, and dioic acid, and 2) treatment B (BenzaClin®, clindamycin 1% and benzoyl peroxide 5% gel). The treatment design included the split-face application of treatment A and treatment B and the full-face application of the cleanser, moisturizer, and sunscreen. Data were collected through physician visual assessments, subject irritation questionnaires and assessments, along with clinical photography. Results showed similar tolerance and efficacy for both treatments.

Protective effects of a topical antioxidant complex containing vitamins C and E and ferulic acid against ultraviolet irradiation-induced photodamage in Chinese women.

OBJECTIVE: The objective of the study was to investigate whether a topical antioxidant complex containing vitamins C and E and ferulic acid can protect solar-simulated ultraviolet irradiation (ssUVR)-induced acute photodamage in human skin. METHOD: Twelve healthy female Chinese subjects were enrolled in this study. Four unexposed sites on dorsal skin were marked for the experiment. The products containing antioxidant complex and vehicle were applied onto 2 sites, respectively, for 4 consecutive days. On day 4, the antioxidant complex-treated site, the vehicle-treated site, and the untreated site (positive control) received ssUVR (5 times the minimal erythema dose). The fourth site (negative control) received neither ssUVR nor treatment. Digital photographs were taken, and skin color was measured pre- and postirradiation. Skin biopsies were obtained 24 hours after exposure to ssUVR, for hematoxylin and eosin and immunohistochemical staining. RESULTS: A single, 5 times the minimal erythema dose of ssUVR substantially induced large amounts of sunburn cell formation, thymine dimer formation, overexpression of p53 protein, and depletion of CD1a+ Langerhans cells. The antioxidant complex containing vitamins C and E and ferulic acid conferred significant protection against biological events compared with other irradiated sites. CONCLUSION: A topical antioxidant complex containing vitamins C and E and ferulic acid has potential photoprotective effects against ssUVR-induced acute photodamage in human skin.

Antioxidants and the skin: understanding formulation and efficacy.

Antioxidants are molecules capable of inhibiting the oxidation of other molecules. Although oxidation reactions are essential for life, they can also be damaging. All living organisms maintain complex systems of multiple types of antioxidants to protect their cells from oxidative damage. Antioxidants can also act as pro-oxidants, under certain circumstances. The efficacy and benefit of an antioxidant is, therefore, very much dependent on the delivery of the antioxidant to the organism. Topically applied antioxidants constitute an important group of pharmacologically active agents capable of preventing the occurrence and reducing the severity of UV-induced skin damage and skin aging. Antioxidants protect skin cells against the damaging effects of reactive oxygen species (ROS), such as singlet oxygen, superoxide, peroxyl radicals, hydroxyl radicals, and peroxynitrite. ROS induced oxidative stress in the skin has been linked to cancer, aging, inflammation, and photodamage. This review focuses on antioxidants used in the cosmetic industry for protection of skin, formulation methods used to enhance their efficacy, and methods used to test the efficacy of antioxidants in topical formulations.

Safety and efficacy of two anti-acne/anti-aging treatments in subjects with photodamaged skin and mild to moderate acne vulgaris.

BACKGROUND: Although reliable prevalence data are not available, adult acne is thought to be somewhat common, and it is not unusual for patients to have acne as well as early signs of skin aging. A novel anti-acne/anti-aging formulation (Treatment A) has been developed for daily use by patients to address both signs of skin aging and facial acne vulgaris. The novel, non-prescription formulation includes several ingredients shown to target factors underlying the pathogenesis of acne vulgaris while also addressing multiple components in the pathophysiology of skin aging. METHODS: A blinded, randomized, split-face study was conducted to evaluate and compare the tolerability and efficacy of the novel anti-acne/ anti-aging product in subjects with photodamaged skin and acne vulgaris relative to tretinoin cream 0.025% (Treatment B). All subjects also were given supportive skincare, consisting of a cleanser, moisturizer, and sunscreen. Each treatment was assessed for its effects on subjects' appearance, lesion count reductions, and tolerability. RESULTS: Treatment A produced statistically significantly greater improvements in skin tone evenness, skin tone clarity, and blemishes and blotchiness. There were also statistically greater reductions in total lesion count for acne patients on the side of the face treated with Treatment A compared to Treatment B; Treatment A was also associated with early (day 2) improvement in skin tone evenness and clarity, tactile skin smoothness, and blemishes and blotchiness. Both treatments demonstrated favorable tolerability. CONCLUSION: The novel topical anti-aging/anti-acne therapy (Treatment A) within a comprehensive skin care regimen of cleanser, moisturizer, and sunscreen may maximize efficacy and tolerability and contribute to our armamentarium for treating both photodamage and acne at the same time.

A multicenter, double-blind study to evaluate the efficacy and safety of 2 treatments in participants with mild to moderate acne vulgaris.

Acne treatment regimens have changed due to the recent over-the-counter (OTC) switch of all prescription benzoyl peroxide (BPO) topical preparations. The elimination of prescription single-agent BPO products means that dermatologists must select from a variety of OTC formulations to utilize the time-tested efficacy of BPO in the treatment of mild to moderate acne. Our research compared the efficacy and safety of an OTC BPO 5.5% formulation with lipohydroxy acid and tretinoin cream 0.025% with prescription clindamycin 1%-BPO 5% gel and tretinoin cream 0.025%. Parity was demonstrated between the 2 treatment regimens at 12 weeks.

Comparative evaluation of men's depilatory composition versus razor in black men.

Shaving with razors often is problematic for men with sensitive skin, especially black individuals who are generally prone to developing pseudofolliculitis barbae (PFB). For patients with PFB, physicians often recommend shaving with depilatory creams that chemically remove hair from the skin surface by dissolving keratin. This 1-week, controlled, single-center, split-faced, randomized trial compared shaving with 3 different depilatory compositions to shaving with a manual razor in black men. One depilatory composition was withdrawn during the study because of the high incidence of adverse events. The depilatory compositions produced fewer papules and more irritation immediately after use and to a greater extent than the manual razor; the irritation was transient and more often subjective than objective. In this preliminary study, the result of using depilatory compositions was that the skin looked and felt smoother compared to shaving with a razor. Depilatory products are recommended for patients who develop PFB or are unsatisfied with the results of shaving with a manual razor.

Complementary effects of antioxidants and sunscreens in reducing UV-induced skin damage as demonstrated by skin biomarker expression.

BACKGROUND: UV-exposure of the skin causes oxidative stress, leading to inflammatory reactions and premature skin aging. Sunscreens protect by absorbing or reflecting UV on the skin surface. Antioxidants provide protection by quenching UV-induced reactive oxygen species inside skin. OBJECTIVE: To evaluate the complementary photoprotective benefits of formulas containing either an antioxidant complex of Cassia alata leaf extract or a combination of the antioxidant complex and sunscreens on normal healthy volunteers using biomarkers of skin damage. METHODS: Each formula and a placebo control were applied separately to selected areas on the lower back of 10 individuals for 4 consecutive days. On Day 4, the control and three test sites were exposed to 5 x MED (minimal erythemal dose) of solar-simulated UV-irradiation (UVR). On Day 5, 4-mm punch biopsies were collected from the four exposed sites and a control site (untreated, unexposed) for immunohistochemistry. RESULTS: Exposure to 5 x MED demonstrated significant damage as assessed by thymine dimer formation, MMP-9 and p53 protein expression on untreated exposed skin. The formula containing sunscreens + the antioxidant complex was the most protective, followed by the formula with the antioxidant alone. CONCLUSION: The study demonstrated that a combination of antioxidants and sunscreens complement each other, resulting in superior photoprotection.

Evaluation of a kojic acid, emblica extract, and glycolic acid formulation compared with hydroquinone 4% for skin lightening.

Hydroquinone has been the standard prescription agent for skin lightening; however, its use recently has become controversial. Hydroquinone is banned in Europe and parts of Asia because of potential long-term consequences, including carcinogenesis when orally consumed. These concerns have stimulated research to develop alternative skin lightening agents with efficacy comparable to hydroquinone but with a better safety profile. This double-blind study examined the skin lightening ability of a topical formulation containing kojic acid, emblica extract, and glycolic acid compared with prescription generic hydroquinone cream 4%. Eighty multiethnic participants with mild to moderate facial dyschromia were randomly assigned to use the study product or hydroquinone 4% twice daily for 12 weeks to evaluate product efficacy, tolerability, and safety using investigator assessment, participant assessment, and dermospectrophotometry. Study results demonstrated efficacy parity between the study product and hydroquinone 4%. Thus this novel skin lightening preparation is an alternative to hydroquinone 4% for participants with mild to moderate facial dyschromia.

Dyspigmentation, skin physiology, and a novel approach to skin lightening.

BACKGROUND: Even facial pigmentation is considered a universal sign of youth and beauty in all cultures and at all ages in both men and women. The recent FDA concern about the safety of topical hydroquinone has provided the impetus for research into new pigment lightening alternatives in the cosmetic OTC market. AIM: This research examined a novel hydroxyphenoxy propionic acid, ellagic acid, yeast extract, and salicylic acid formulation applied twice daily compared to the standard prescription combination of 4% hydroquinone cream and 0.025% tretinoin cream applied nightly. METHOD: This single-center investigator-blinded 12 week study enrolled 82 subjects (7 male, 75 female) ages 25-60 years divided into 2 balanced groups of 41 subjects each with one group using a novel hydroxyphenoxy propionic acid, ellagic acid, yeast extract, and salicylic acid formulation applied twice daily compared to the standard prescription combination of 4% hydroquinone cream and 0.025% tretinoin cream applied nightly. RESULTS: Significant tolerability issues arose with the prescription combinations that were not seen with the cosmetic formulation. In terms of ability to even skin tone, decrease spot intensity, decrease spot size, and improve overall pigmentation, both products demonstrated parity. CONCLUSION: This research demonstrated the value of cosmetic formulations as part of a treatment regimen for pigmentation issues.

Tolerability and Efficacy of Retinoic Acid Given after Full-face Peel Treatment of Photodamaged Skin.

OBJECTIVE: All-trans retinoic acid is a well-established topical treatment of photodamaged skin. This study assessed the tolerance and efficacy of all-trans retinoic acid after full-face treatment with a chemical peel. DESIGN: This was a split-face, randomized study. One side of each face was treated with peel and the other side with peel and all-trans retinoic acid (3%). Four treatments were given during the 10-week study period. SETTING: Physician office. PARTICIPANTS: Fifteen female subjects 39 to 55 years of age. MEASUREMENTS: RESULTS were evaluated at Baseline; Weeks 4, 7, and 10; and at a 13-week follow-up visit by dermal grading of visual symptoms of irritation, subjective experiences of irritation, clinical grading of skin condition, and self-assessment questionnaires. RESULTS: Both peel and peel plus all-trans retinoic acid treatments achieved significant improvement in fine lines, radiance, roughness, skin tone clarity, skin tone evenness, and hyperpigmentation appearance. Improvement in wrinkles and firmness was not observed in the peel plus all-trans retinoic acid arm, while pore appearance failed to improve in either treatment arm. Improvement in overall facial appearance was greater in the peel alone arm. Peel alone and the addition of all-trans retinoic acid did not cause dryness, edema, or peeling, and the frequency of peel-induced erythema did not increase with the addition of all-trans retinoic acid. Subject-perceived improvements with the peel treatment did not differ significantly from subject-perceived improvements of the peel plus all-trans retinoic acid treatment. Adverse events requiring intervention or discontinuing treatment were not observed in either treatment arm. CONCLUSION: The addition of all-trans retinoic acid after peel treatment does not significantly enhance peel-induced improvement in photoaging parameters, peel-induced adverse effects, and subject-perceived improvements.

An evaluation of the effect of a topical product containing C-xyloside and blueberry extract on the appearance of type II diabetic skin.

BACKGROUND: Diabetes is a multisystem disease caused by the presence of chronic hyperglycemia, which leads to increased oxidative stress. Many of the changes observed in type II diabetic patients can be traced to the increased production of advanced glycation end products, also known as AGEs. AGEs are produced as a result of a nonenzymatic reaction with glucose interacting with proteins, lipids, and nucleic acids. AGEs are also present in normal skin with advancing age and contribute to the senescence of many body organs, including the skin. AIMS: This research evaluated the effect of a topical product formulation containing blueberry extract, an AGE inhibitor, and C-xyloside, a GAG synthesis stimulator, applied twice daily on the hand, arm, and facial skin of 20 type II diabetic females. Diabetic skin was chosen for evaluation because AGEs are found in increased concentration in diabetic skin, representing a model for accelerated aging. MATERIALS AND METHODS: This single-center study enrolled 20 female type II diabetics aged 55+ years with mild to moderate fine lines, wrinkles, and hyperpigmentation on the face and hands. Subjects used the study product on their face, hand, and inner forearm twice daily for 12 weeks. Ordinal grading on a 4-point scale (0 = none, 1 = mild, 2 =moderate, 3 = severe) of facial fine lines, wrinkles, firmness, radiance, skin tone, skin smoothness, hyperpigmentation, creping, density, sagging, and overall appearance was performed by the investigator at baseline, week 4, week 8, and week 12. Tolerability, subject assessments, digital photography, AGE measurements, skin caliper measurements, and corneometry were also performed at each time point. RESULTS: 19/20 subjects successfully completed the study. The presence of AGEs was documented by skin autofluorescence. The 12-week duration of the study was insufficient to measure a change in skin AGEs, but longer application of the study product might produce different results. No tolerability issues were noted. There was a statistically significant increase in skin caliper measurements on the face (P = 0.004) and arm (P = 0.014) as well as corneometry measurements (P < 0.001) consistent with enhanced moisturization at week 12. The dermatologist investigator also found statistically significant improvement in fine lines (P = 0.01), firmness (P = 0.011), radiance (P < 0.001), skin tone (P = 0.014), skin smoothness (P < 0.001), creping (P < 0.004), and overall appearance (P < 0.001). CONCLUSION: This study examined a topical product containing an AGE inhibitor and a GAG synthesis stimulator designed for the unique needs of diabetic skin.

Clinical tolerance and efficacy of capryloyl salicylic acid peel compared to a glycolic acid peel in subjects with fine lines/wrinkles and hyperpigmented skin.

BACKGROUND: Several chemical agents are currently used to perform superficial peels of the face to reduce facial hyperpigmentation and fine lines/wrinkles. Some of the most commonly used agents are alpha hydroxyl acids, such as glycolic acid (GA), or beta hydroxy acid, such as salicylic acid. AIM: This study aims to compare the efficacy of GA to that of a novel derivative of salicylic acid, capryloyl salicylic acid (LHA). SUBJECTS/METHODS: In a split-face study, 50 female volunteers between the ages of 35 and 60 years with mild to moderate facial hyperpigmentation and fine lines/wrinkles were randomized and LHA or GA peel was applied to one side of the face. Increasing peel concentrations were applied (5-10% LHA or 20-50% GA) based on the tolerance level of the subjects and clinical observations of an expert dermatologist for 12 weeks at biweekly intervals. RESULTS: Of the 44 volunteers who completed the study, at 12 weeks 41% of LHA-treated and 30% of GA-treated subjects demonstrated significant reduction of fine lines/wrinkles compared to baseline. Forty-six percent of LHA-treated subjects and 34% of GA-treated subjects showed significant reduction of hyperpigmentation compared to baseline. LHA treatment was better than GA peels, although there were no statistically significant differences between the two groups. CONCLUSIONS: Five percent to 10% of LHA peel is generally safe and as effective as 20-50% GA peel in reducing facial hyperpigmentation and fine lines/wrinkles.

Protective effects of a topical antioxidant mixture containing vitamin C, ferulic acid, and phloretin against ultraviolet-induced photodamage in human skin.

BACKGROUND: Ultraviolet (UV) irradiation of the skin leads to acute inflammatory reactions, such as erythema, sunburn, and chronic reactions, including premature skin aging and skin cancer. AIM: In this study, the effects of a topical antioxidant mixture consisting of vitamin C, ferulic acid, and phloretin on attenuating the harmful effects of UV irradiation on normal healthy volunteers were studied using biomarkers of skin damage. SUBJECTS/METHODS: Ten subjects (age, 18-60 years; Fitzpatrick skin types II and III) were randomized and treated with antioxidant product or vehicle control on the lower back for four consecutive days. On day 3, the minimal erythema dose (MED) was determined for each subject at a different site on the back. On day 4, the two test sites received solar-simulated UV irradiation 1-5x MED at 1x MED intervals. On day 5, digital images were taken, and 4-mm punch biopsies were collected from the two 5x MED test sites and a control site from each subject for morphology and immunohistochemical studies. RESULTS: UV irradiation significantly increased the erythema of human skin in a linear manner from 1x to 5x MED. As early as 24 h after exposure to 5x MEDs of UV irradiation, there were significant increases in sunburn cell formation, thymine dimer formation, matrix metalloproteinase-9 expression, and p53 protein expression. All these changes were attenuated by the antioxidant composition. UV irradiation also suppressed the amount of CD1a-expressing Langerhans cells, indicating immunosuppressive effects of a single 5x MED dose of UV irradiation. Pretreatment of skin with the antioxidant composition blocked this effect. CONCLUSION: This study confirms the protective role of a unique mixture of antioxidants containing vitamin C, ferulic acid, and phloretin on human skin from the harmful effects of UV irradiation. Phloretin, in addition to being a potent antioxidant, may stabilize and increase the skin availability of topically applied vitamin C and ferulic acid. We propose that antioxidant mixture will complement and synergize with sunscreens in providing photoprotection for human skin.