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Improvement in facial skin appearance by a cosmetic treatment regimen: A case study in identical twins
P7041
P7025
Impact of oxidative stress on cellular bioenergetics in older aged fibroblasts: Ability of niacinamide to prevent and restore metabolic pathway efficiency and energy production Holly Rovito, MS, Procter and Gamble Beauty, Cincinnati, OH, United States; John Oblong, PhD, Procter and Gamble Beauty, Cincinnati, OH, United States
Improved appearance of facial wrinkles with use of a cosmetic moisturizer containing retinyl propionate, peptides, and niacinamide Rosemarie Osborne, PhD, The Procter and Gamble Company, Cincinnati, OH, United States; Jim Li, MS, The Procter and Gamble Company, Cincinnati, OH, United States; Joseph Kaczvinsky, PhD, The Procter and Gamble Company, Cincinnati, OH, United States; Ziyi Wang, MS, The Procter and Gamble Company, Beijing, China Background: The earliest signs of facial skin aging in women worldwide include fine lines, wrinkles, and bumpy texture. To address the need for skin care products that alleviate these signs of facial skin aging, we evaluated a daily-use facial moisturizer formulation containing a retinyl ester (retinyl propionate), niacinamide and three peptides (Pal-KT, Pal-KTTKS and carnosine). These ingredients have been shown to affect skin health and structure biomarkers in in vitro skin models.
Exposure of human skin to environmental insults, such as UV, triggers numerous biologic processes that include oxidative stress and inflammation, which can lead to dysfunction of cellular processes, ultimately impacting tissue integrity. One of the main effects from oxidative stress on cells is a diminished capacity of cellular bioenergetics, which leads to reduced levels of ATP and NAD+. Blocking the negative effect on cellular metabolism from oxidative stress is a relevant approach to provide protection from the accumulation of microdamage events, leading to photoaging of skin. Human dermal fibroblasts from younger and older aged donors were used to develop an oxidative stress assay that monitors changes in glycolysis and oxidative phosphorylation and the impact of H202. Dose response testing with niacinamide, olive derivative, dill seed extract, and Pal-KTTKS were evaluated for the ability to prevent and restore glycolysis and oxidative phosphorylation. Measures of cellular ATP and NAD+/NADH levels were also quantitated. Under nontoxic conditions, H202 caused a significant reduction in glycolytic levels and oxidative phosphorylation. The decrease in metabolic output correlated with reduced ATP and NAD+ levels. Fibroblasts from older aged donors were found to have a greater sensitivity to H2O2 induced stress than younger aged fibroblasts, showing more rapid decreases in glycolytic rates. An optimized combination of niacinamide, olive derivative, dill seed extract, and Pal-KTTKS showed a doseeresponse effect on the ability to prevent reduction of glycolysis and maintain elevated ATP levels in all cell lines tested and was able to restore glycolysis levels to nonstressed basal levels in older aged fibroblasts. This combination was able to restore glycolysis to prestress basal levels. These findings study show that dermal fibroblasts under oxidative stress conditions undergo a significant decrease in ATP that correlates with reduced glycolysis and oxidative phosphorylation. This effect is transient in nature because there was no significant effect on cell viability and niacinamide was able to restore glycolytic rates to pre-stress basal levels. Older aged fibroblasts showed a heightened sensitivity to oxidative stress response, suggesting that intrinsic aging and cumulative environmental insults negatively impact cellular bioenergetics. The ability of niacinamide to prevent and reverse damage to cellular metabolism is a new insight into understanding its MOA in skin biology. Supported by Procter and Gamble Beauty.
Methods: Two independent double-blinded 12-week facial studies were conducted in the United States (Cincinnati, OH) and China (Xian) with women 35 to 65 years old with moderate to severe facial fine lines, wrinkles, and bumpy texture. The women applied the moisturizer twice daily in a full (China) or split-face (U.S.) randomized study design, with a moisturizer base vehicle as control. Responses were compared to a retinol containing moisturizer. Skin appearance was evaluated at 0, 4, 8, and 12 weeks by digital imaging and either expert grading or image analysis. Grading of subjects for redness and dryness, and barrier (TEWL) measurements were conducted at all time points. Results: In both studies, use of the cosmetic moisturizer formulation significantly improved the appearance of eye area fine lines and wrinkles, and cheek area bumpy texture as compared to vehicle. The improvement was apparent at the earliest time point evaluated (4 weeks) by both expert grading and image analysis, and increased in magnitude for the duration of product use (12 weeks). The level of improvement was comparable to a formulation containing retinol; however, the retinol product produced skin irritation (redness, dryness, and barrier damage) significantly greater than the retinyl propionate-containing moisturizer. The magnitude of improvement was approximately the same between the white (U.S.) and Chinese women for all parameters evaluated. Conclusion: Daily use of a cosmetic moisturizer containing retinyl propionate, peptides, and niacinamide improved the appearance of signs of facial skin aging, such as fine lines, wrinkles, and bumpy texture. One key attribute of uneven cheek area texture is enlarged pores; the finding of improved appearance of texture indicates improved pore appearance also. The finding of comparable improvements between white (U.S.) and Chinese women indicates that daily use of the cosmetic moisturizer formulation can improve facial appearance in women of different races and geographies. 100% is sponsored by Procter and Gamble Beauty.
P6680
P7031 Improved appearance of facial wrinkles with use of a cosmetic moisturizer containing olive derivative, dill seed extract, Pal-KTTKS, and niacinamide James Li, MS, Procter and Gamble, Cincinnati, OH, United States; Joseph Kaczvinsky, PhD, Procter and Gamble, Cincinnati, OH, United States; Marsha Gabbard, Procter and Gamble, Cincinnati, OH, United States; Mary Werner, Procter and Gamble, Cincinnati, OH, United States; Michael Marmor, Procter and Gamble, Cincinnati, OH, United States; Shannon Powers, Procter and Gamble, Cincinnati, OH, United States; William Janson, MS, Procter and Gamble, Cincinnati, OH, United States Background: Fine lines and wrinkles around the eyes are probably the most noticeable and concerning signs of aging among women. Cosmetic products have been shown to produce benefits after several months of use. However, women desire fine lines and wrinkle benefits as soon as after 1 week of product use. To assess the potential benefit after 1 week of product use, we evaluated a daily-use facial moisturizer formulation containing cosmetic ingredients olive derivative (olive oilederived fatty acids modified with PEG-7), dill seed extract, niacinamide, Pal-KTTKS, and glycerin. Methods: The daily-use facial moisturizer formulation was compared to a no treatment control in a 7-day split-face clinical study in Cincinnati, Ohio. The trial was randomized, double-blinded, with a no treatment control. The study was conducted in 60 women, 30 to 70 years old with moderate to distinct wrinkles in the periorbital region. Improvement in wrinkles was measured via computer analysis of digital images for changes in wrinkle area after 1, 3, 5, and 7 days of treatment. Results: Use of the daily facial moisturizer formulation significantly improved the appearance of eye area fine lines and wrinkles after 7 days (P \.01) compared to the untreated control leg. Conclusion: Daily use of a cosmetic moisturizer containing olive derivative, dill seed extract, niacinamide, Pal-KTTKS, and glycerin improved the appearance of facial skin fine lines and wrinkles after 7 days of product use. 100% is sponsored by Procter and Gamble.
AB30
J AM ACAD DERMATOL
Improvement in facial skin appearance by a cosmetic treatment regimen: A case study in identical twins Greg Hillebrand, PhD, Procter and Gamble, Cincinnati, OH, United States; Mary Johnson, Procter and Gamble, Cincinnati, OH, United States; Tammy Wagner, Procter and Gamble, Cincinnati, OH, United States Objective: This study was aimed at measuring and comparing the signs of facial photodamage in a pair of female monozygotic twins and the improvement afforded when one of the twins used a commercially available cosmetic treatment regimen for a period of 10 months. Methods: One pair of healthy monozygotic (‘‘identical’’) twins, age 35, was enrolled. Both live in the same city (Cleveland, OH). At baseline, facial images were captured using a 2D clinical imaging system (VISIA CR) followed by computer image analysis and visual grading for the visible signs of photodamage. Additional measures included facial stratum corneum capacitance, TEWL, color (L*, a*, b*) and sebum secretion. The twin showing more facial skin photodamage at baseline was placed on a daily regimen of cosmetic products designed to treat the signs of photoaging. This regimen consisted of an SPF 30 sunscreen and day/night moisturizers containing niacinamide, antiaging peptides, antioxidants, and retinyl propionate. The regimen also included regular use of a powered facial cleansing brush in combination with an exfoliating cleanser. The twin showing less facial photodamage remained on her normal skin care treatment program and served as control. The twins returned to the test facility for follow-up measures approximately every 3 months for a total of 10 months. Results: At baseline, twin B showed 10% more facial hyperpigmented macules associated with photodamage and an overall darker facial skin complexion (delta L* ¼ 3) compared to her sister (twin A), a visibly noticeable difference. Over the course of the study, twin B, who used the cosmetic treatment regimen, showed a noticeable reduction in hyperpigmented macules as well as increase in forehead and cheek skin lightness. Specifically, she showed a 20% reduction in facial hyperpigmentation and an increase of 4 L* units in skin lightness. As a result, at the end of the 10-month treatment period, twin B showed nearly the same level of facial hyperpigmentation and essentially the same skin color lightness compared to her sister, twin A, who did not change from her normal skin care program. Conclusion: This case study in identical twins helps demonstrate how noticeable improvement in the visible signs of photoaging can be achieved by daily use of a high SPF sunscreen in combination with antiaging moisturizers and exfoliating facial cleansers. 100% of this research was funded by Procter and Gamble.
APRIL 2013
P7025
Impact of oxidative stress on cellular bioenergetics in older aged fibroblasts: Ability of niacinamide to prevent and restore metabolic pathway efficiency and energy production Holly Rovito, MS, Procter and Gamble Beauty, Cincinnati, OH, United States; John Oblong, PhD, Procter and Gamble Beauty, Cincinnati, OH, United States
Improved appearance of facial wrinkles with use of a cosmetic moisturizer containing retinyl propionate, peptides, and niacinamide Rosemarie Osborne, PhD, The Procter and Gamble Company, Cincinnati, OH, United States; Jim Li, MS, The Procter and Gamble Company, Cincinnati, OH, United States; Joseph Kaczvinsky, PhD, The Procter and Gamble Company, Cincinnati, OH, United States; Ziyi Wang, MS, The Procter and Gamble Company, Beijing, China Background: The earliest signs of facial skin aging in women worldwide include fine lines, wrinkles, and bumpy texture. To address the need for skin care products that alleviate these signs of facial skin aging, we evaluated a daily-use facial moisturizer formulation containing a retinyl ester (retinyl propionate), niacinamide and three peptides (Pal-KT, Pal-KTTKS and carnosine). These ingredients have been shown to affect skin health and structure biomarkers in in vitro skin models.
Exposure of human skin to environmental insults, such as UV, triggers numerous biologic processes that include oxidative stress and inflammation, which can lead to dysfunction of cellular processes, ultimately impacting tissue integrity. One of the main effects from oxidative stress on cells is a diminished capacity of cellular bioenergetics, which leads to reduced levels of ATP and NAD+. Blocking the negative effect on cellular metabolism from oxidative stress is a relevant approach to provide protection from the accumulation of microdamage events, leading to photoaging of skin. Human dermal fibroblasts from younger and older aged donors were used to develop an oxidative stress assay that monitors changes in glycolysis and oxidative phosphorylation and the impact of H202. Dose response testing with niacinamide, olive derivative, dill seed extract, and Pal-KTTKS were evaluated for the ability to prevent and restore glycolysis and oxidative phosphorylation. Measures of cellular ATP and NAD+/NADH levels were also quantitated. Under nontoxic conditions, H202 caused a significant reduction in glycolytic levels and oxidative phosphorylation. The decrease in metabolic output correlated with reduced ATP and NAD+ levels. Fibroblasts from older aged donors were found to have a greater sensitivity to H2O2 induced stress than younger aged fibroblasts, showing more rapid decreases in glycolytic rates. An optimized combination of niacinamide, olive derivative, dill seed extract, and Pal-KTTKS showed a doseeresponse effect on the ability to prevent reduction of glycolysis and maintain elevated ATP levels in all cell lines tested and was able to restore glycolysis levels to nonstressed basal levels in older aged fibroblasts. This combination was able to restore glycolysis to prestress basal levels. These findings study show that dermal fibroblasts under oxidative stress conditions undergo a significant decrease in ATP that correlates with reduced glycolysis and oxidative phosphorylation. This effect is transient in nature because there was no significant effect on cell viability and niacinamide was able to restore glycolytic rates to pre-stress basal levels. Older aged fibroblasts showed a heightened sensitivity to oxidative stress response, suggesting that intrinsic aging and cumulative environmental insults negatively impact cellular bioenergetics. The ability of niacinamide to prevent and reverse damage to cellular metabolism is a new insight into understanding its MOA in skin biology. Supported by Procter and Gamble Beauty.
Methods: Two independent double-blinded 12-week facial studies were conducted in the United States (Cincinnati, OH) and China (Xian) with women 35 to 65 years old with moderate to severe facial fine lines, wrinkles, and bumpy texture. The women applied the moisturizer twice daily in a full (China) or split-face (U.S.) randomized study design, with a moisturizer base vehicle as control. Responses were compared to a retinol containing moisturizer. Skin appearance was evaluated at 0, 4, 8, and 12 weeks by digital imaging and either expert grading or image analysis. Grading of subjects for redness and dryness, and barrier (TEWL) measurements were conducted at all time points. Results: In both studies, use of the cosmetic moisturizer formulation significantly improved the appearance of eye area fine lines and wrinkles, and cheek area bumpy texture as compared to vehicle. The improvement was apparent at the earliest time point evaluated (4 weeks) by both expert grading and image analysis, and increased in magnitude for the duration of product use (12 weeks). The level of improvement was comparable to a formulation containing retinol; however, the retinol product produced skin irritation (redness, dryness, and barrier damage) significantly greater than the retinyl propionate-containing moisturizer. The magnitude of improvement was approximately the same between the white (U.S.) and Chinese women for all parameters evaluated. Conclusion: Daily use of a cosmetic moisturizer containing retinyl propionate, peptides, and niacinamide improved the appearance of signs of facial skin aging, such as fine lines, wrinkles, and bumpy texture. One key attribute of uneven cheek area texture is enlarged pores; the finding of improved appearance of texture indicates improved pore appearance also. The finding of comparable improvements between white (U.S.) and Chinese women indicates that daily use of the cosmetic moisturizer formulation can improve facial appearance in women of different races and geographies. 100% is sponsored by Procter and Gamble Beauty.
P6680
P7031 Improved appearance of facial wrinkles with use of a cosmetic moisturizer containing olive derivative, dill seed extract, Pal-KTTKS, and niacinamide James Li, MS, Procter and Gamble, Cincinnati, OH, United States; Joseph Kaczvinsky, PhD, Procter and Gamble, Cincinnati, OH, United States; Marsha Gabbard, Procter and Gamble, Cincinnati, OH, United States; Mary Werner, Procter and Gamble, Cincinnati, OH, United States; Michael Marmor, Procter and Gamble, Cincinnati, OH, United States; Shannon Powers, Procter and Gamble, Cincinnati, OH, United States; William Janson, MS, Procter and Gamble, Cincinnati, OH, United States Background: Fine lines and wrinkles around the eyes are probably the most noticeable and concerning signs of aging among women. Cosmetic products have been shown to produce benefits after several months of use. However, women desire fine lines and wrinkle benefits as soon as after 1 week of product use. To assess the potential benefit after 1 week of product use, we evaluated a daily-use facial moisturizer formulation containing cosmetic ingredients olive derivative (olive oilederived fatty acids modified with PEG-7), dill seed extract, niacinamide, Pal-KTTKS, and glycerin. Methods: The daily-use facial moisturizer formulation was compared to a no treatment control in a 7-day split-face clinical study in Cincinnati, Ohio. The trial was randomized, double-blinded, with a no treatment control. The study was conducted in 60 women, 30 to 70 years old with moderate to distinct wrinkles in the periorbital region. Improvement in wrinkles was measured via computer analysis of digital images for changes in wrinkle area after 1, 3, 5, and 7 days of treatment. Results: Use of the daily facial moisturizer formulation significantly improved the appearance of eye area fine lines and wrinkles after 7 days (P \.01) compared to the untreated control leg. Conclusion: Daily use of a cosmetic moisturizer containing olive derivative, dill seed extract, niacinamide, Pal-KTTKS, and glycerin improved the appearance of facial skin fine lines and wrinkles after 7 days of product use. 100% is sponsored by Procter and Gamble.
AB30
J AM ACAD DERMATOL
Improvement in facial skin appearance by a cosmetic treatment regimen: A case study in identical twins Greg Hillebrand, PhD, Procter and Gamble, Cincinnati, OH, United States; Mary Johnson, Procter and Gamble, Cincinnati, OH, United States; Tammy Wagner, Procter and Gamble, Cincinnati, OH, United States Objective: This study was aimed at measuring and comparing the signs of facial photodamage in a pair of female monozygotic twins and the improvement afforded when one of the twins used a commercially available cosmetic treatment regimen for a period of 10 months. Methods: One pair of healthy monozygotic (‘‘identical’’) twins, age 35, was enrolled. Both live in the same city (Cleveland, OH). At baseline, facial images were captured using a 2D clinical imaging system (VISIA CR) followed by computer image analysis and visual grading for the visible signs of photodamage. Additional measures included facial stratum corneum capacitance, TEWL, color (L*, a*, b*) and sebum secretion. The twin showing more facial skin photodamage at baseline was placed on a daily regimen of cosmetic products designed to treat the signs of photoaging. This regimen consisted of an SPF 30 sunscreen and day/night moisturizers containing niacinamide, antiaging peptides, antioxidants, and retinyl propionate. The regimen also included regular use of a powered facial cleansing brush in combination with an exfoliating cleanser. The twin showing less facial photodamage remained on her normal skin care treatment program and served as control. The twins returned to the test facility for follow-up measures approximately every 3 months for a total of 10 months. Results: At baseline, twin B showed 10% more facial hyperpigmented macules associated with photodamage and an overall darker facial skin complexion (delta L* ¼ 3) compared to her sister (twin A), a visibly noticeable difference. Over the course of the study, twin B, who used the cosmetic treatment regimen, showed a noticeable reduction in hyperpigmented macules as well as increase in forehead and cheek skin lightness. Specifically, she showed a 20% reduction in facial hyperpigmentation and an increase of 4 L* units in skin lightness. As a result, at the end of the 10-month treatment period, twin B showed nearly the same level of facial hyperpigmentation and essentially the same skin color lightness compared to her sister, twin A, who did not change from her normal skin care program. Conclusion: This case study in identical twins helps demonstrate how noticeable improvement in the visible signs of photoaging can be achieved by daily use of a high SPF sunscreen in combination with antiaging moisturizers and exfoliating facial cleansers. 100% of this research was funded by Procter and Gamble.
APRIL 2013