Editor's Note: Please see a PDF of this article, posted above, to see the images and figures in this article.
Premature skin aging is associated with cellular oxidative stress from various forms of reactive oxygen species (ROS).1 Topical antioxidants have been shown to limit skin damage due to ROS activity.2 Since antioxidants play an important role in modern skin care, DiNardo, Lewis and colleagues2 have proposed a new term, environmental protection factor (EPF), to describe the ability of an antioxidant to protect skin from oxidative stress. Using a multistep protocol of both in vitro and in vivo studies, these investigators found that idebenone had a higher EPF than the common antioxidants vitamin E, kinetin, ubiquinone, vitamin C and lipoic acid.
Idebenone is a bioengineered analog of coenzyme Q10, the naturally occurring respiratory chain antioxidant. Idebenone is an electron transfer, mitochondria-targeted antioxidant3,4 extensively researched for the treatment and prevention of age-related disorders,5,6 including skin aging. Cell biological studies have shown that idebenone protects cellular lipoproteins, cell membranes and DNA from damage caused by oxidative stress. By coupling oxygen to the respiratory chain tightly (with more potency than coenzyme Q10) idebenone prevents the formation of toxic oxygen-based free radicals that cause aging.
Since idebenone has been introduced as a potent ingredient for improving the appearance of aged skin,1,2 its oil-soluble ester, hydroxydecyl ubiquinoyl dipalmitoyl glycerate (idebenone complex), has been synthesized, added to skin care products and evaluated for its ability to improve the appearance of pigmentation, fine lines, wrinkles and overall photodamage, and to inhibit sunburn cell formation after UV irradiation. Skin maximization studies to assess skin tolerance have also been conducted.7
This article will review a study conducted to evaluate the efficacy of skincare products enriched with idebenone complex for the treatment of photodamaged skin in 30 women aged 52.2 ± 7.5 years (mean ± SD) with moderate to severe photodamage of the face, neck, chest neck or arms in a single-center, double-blinded study. Patients had not undergone antiaging or depigmenting treatments (eg, retinoid therapy, peels, laser resurfacing) within the previous 6 months and had no known medical condition that, in the opinion of the investigator or expert grader, would have interfered with the study. Pregnancy, breast feeding, unwillingness to use an acceptable form of birth control, dermatologic conditions that might interfere with evaluation of treated sites, hypersensitivity to cosmetic products, taking medications that might interfere with the study, recent upper-body surgery, participation in another clinical trial within the previous 30 days and noncompliance with the study protocol were grounds for exclusion. All patients provided informed consent prior to treatment. The Independent Investigational Review Board (IIRB), Plantation, FL, approved the study.
The study was conducted at Tennessee Clinical Research Center, Nashville, TN, between March and May 2010. During the initial visit, patients were evaluated by a trained technician (expert grader) for skin roughness; fine lines and wrinkles, particularly around the eyes; dyschromia; poor skin tone, elasticity, radiance and brightness; and overall appearance. Dyschromia refers to aging spots, freckles and discoloration. Freckles were small hyperpigmented spots and aging spots were large, hyperpigmented spots of hormonal or UV origin. Discoloration described areas of skin darker or lighter than surrounding skin and without borders.
Patients were instructed to discontinue their current skin care products and to apply test products twice daily for 8 weeks. Test products included a facial cleanser, skin brightener, eye serum and a moisturizing cream, each containing 0.5% hydroxydecyl ubiquinoyl dipalmitoyl glycerate (idebenone complex). Patients were also instructed to use sunscreen (SPF 30) during daytime hours and a simple soap to cleanse all test sites during the 1-week washout period, to not use other skin treatment products during the study and to avoid exposure to UV radiation via the sun or visits to a tanning salon. Results were documented with digital photography. Patients returned all unused study materials to the study coordinator at this visit.
Physician Evaluation
Severity of each skin attribute was graded on a 5-point ordinal scale (see Table 1) at baseline, 4 weeks and 8 weeks. The percentages of patients achieving various grades of improvement for each attribute at 4 weeks and 8 weeks are shown in Table 2. At 4 weeks, the most frequent 1-grade improvements occurred in fine lines, dyschromia and brightening, indicating that these three attributes are the most likely to improve early during treatment. The most frequent 2-grade improvements were noted in roughness and radiance, suggesting that these two attributes will achieve the greatest improvement in at least some patients early in treatment. At 8 weeks, 6% of subjects achieved 3-grade improvement in tone and radiance while 3% of subjects achieved 3-grade improvement in fine lines and skin elasticity, suggesting that with continued treatment, these four attributes will improve the most (compared to the other attributes) in at least a few patients.
Physician-evaluated 8-week improvements are ranked below, with the attribute achieving the greatest improvement first.
1. Tone = radiance
2. Fine lines = elasticity
3. Overall improvement
4. Brightening
5. Dyschromia
6. Roughness
As for overall improvement (see Figure 1), 1 to 2 grades of improvement were achieved in 62% of patients at 4 weeks and 85% of patients at 8 weeks.
Clinical examples are presented in Figures 2 and 3.
Results so far have been presented as decreases (improvements) in grades assigned to each attribute by physicians.
Data were also evaluated by comparing proportions of subjects at various grade levels for each attribute at 4 and 8 weeks. In Tables 3 and 4 are physician-assigned grades rather than grades of improvement. Differences in proportions were tested for significance by Pearson Chi square analysis.
Tables 2 and 3 show that improvements at 4 and 8 weeks were significant for every attribute studied compared to baseline.
Patient Evaluation
More patients agreed than disagreed that the product provided significant improvement in each attribute (see Table 5). The highest agreement percentages occurred in softness and smoothness (91%); radiance, tone and clarity (84%); and roughness and dryness (81%). The lowest percentages were in firmness, tightness and elasticity (69%) and texture (74%).
Patient-evaluated 8-week improvements are ranked below, with the attribute achieving the greatest improvement first.
1. Softness and smoothness
2. Radiance, tone and clarity
3. Roughness and dryness
4. Fine lines and wrinkles = overall appearance
5. Spots, freckles and discoloration
6. Skin overall health
7. Texture
8. Firmness, tightness and elasticity
Adverse events or effects were not observed.
Discussion
Early studies in non-human models show that idebenone scavenges free radicals, protects mitochondrial membranes against lipid peroxidation, inhibits platelet aggregation, improves vascular disorders and improves brain function.8 It is neither immunogenic nor mutagenic in animal models.3 The long-term safety of idebenone in humans has been established in a two-year multicenter study.5 The capacity of idebenone to protect against oxidative stress has been confirmed by McDaniel and colleagues.2
A major advantage of the idebenone-enriched skin care products is the early improvements observed in all the attributes studied. After 4 and 8 weeks of twice-daily application of idebenone-enriched skin care products, 35% to 66% of patients achieved at least 1 grade of (physician-assessed) improvement in skin attributes at 4 weeks and 53% to 84% achieved at least 1 grade improvement at 8 weeks. The data (see Table 6) show that the percentage of subjects responding to treatment is higher at 8 weeks than at 4 weeks for each skin attribute, suggesting that application beyond 8 weeks will result in responses from even more patients for every attribute. This finding is corroborated by the results of a 12-week study of the same idebenone-enriched skin-care products (submitted).
Patient-evaluated 8-week improvement data show that softness and smoothness improve in the highest percentage of subjects (91%) while firmness, tightness and elasticity improve in the lowest percentage (69%).
In summary, the present study shows that the idebenone-enriched skincare products are effective for the treatment of the cutaneous manifestations of photoaged skin. The encouraging results warrant additional studies with vehicle controls to establish the duration and ultimate level of improvement achievable with this novel formulation.
Skin care products enriched with the new idebenone derivative, idebenone complex (hydroxydecyl ubiquinoyl dipalmitoyl glycerate), are an effective treatment for photodamaged skin.
Dr. Gold and Ms. Biron are with the Tennessee Clinical Research Center in Nashville, TN.
Mr. DiNardo and Mr. Lewis are with PCR Technology Holdings in Richmond, VA.
Disclosure: Dr. Gold is an investigator for Priori. Mr Lewis and Mr DiNardo are the owners of PCR Technology Holdings, LC which formerly owned the exclusive licensing rights to certain idebenone skincare patents worldwide.
Editor's Note: Please see a PDF of this article, posted above, to see the images and figures in this article.
Premature skin aging is associated with cellular oxidative stress from various forms of reactive oxygen species (ROS).1 Topical antioxidants have been shown to limit skin damage due to ROS activity.2 Since antioxidants play an important role in modern skin care, DiNardo, Lewis and colleagues2 have proposed a new term, environmental protection factor (EPF), to describe the ability of an antioxidant to protect skin from oxidative stress. Using a multistep protocol of both in vitro and in vivo studies, these investigators found that idebenone had a higher EPF than the common antioxidants vitamin E, kinetin, ubiquinone, vitamin C and lipoic acid.
Idebenone is a bioengineered analog of coenzyme Q10, the naturally occurring respiratory chain antioxidant. Idebenone is an electron transfer, mitochondria-targeted antioxidant3,4 extensively researched for the treatment and prevention of age-related disorders,5,6 including skin aging. Cell biological studies have shown that idebenone protects cellular lipoproteins, cell membranes and DNA from damage caused by oxidative stress. By coupling oxygen to the respiratory chain tightly (with more potency than coenzyme Q10) idebenone prevents the formation of toxic oxygen-based free radicals that cause aging.
Since idebenone has been introduced as a potent ingredient for improving the appearance of aged skin,1,2 its oil-soluble ester, hydroxydecyl ubiquinoyl dipalmitoyl glycerate (idebenone complex), has been synthesized, added to skin care products and evaluated for its ability to improve the appearance of pigmentation, fine lines, wrinkles and overall photodamage, and to inhibit sunburn cell formation after UV irradiation. Skin maximization studies to assess skin tolerance have also been conducted.7
This article will review a study conducted to evaluate the efficacy of skincare products enriched with idebenone complex for the treatment of photodamaged skin in 30 women aged 52.2 ± 7.5 years (mean ± SD) with moderate to severe photodamage of the face, neck, chest neck or arms in a single-center, double-blinded study. Patients had not undergone antiaging or depigmenting treatments (eg, retinoid therapy, peels, laser resurfacing) within the previous 6 months and had no known medical condition that, in the opinion of the investigator or expert grader, would have interfered with the study. Pregnancy, breast feeding, unwillingness to use an acceptable form of birth control, dermatologic conditions that might interfere with evaluation of treated sites, hypersensitivity to cosmetic products, taking medications that might interfere with the study, recent upper-body surgery, participation in another clinical trial within the previous 30 days and noncompliance with the study protocol were grounds for exclusion. All patients provided informed consent prior to treatment. The Independent Investigational Review Board (IIRB), Plantation, FL, approved the study.
The study was conducted at Tennessee Clinical Research Center, Nashville, TN, between March and May 2010. During the initial visit, patients were evaluated by a trained technician (expert grader) for skin roughness; fine lines and wrinkles, particularly around the eyes; dyschromia; poor skin tone, elasticity, radiance and brightness; and overall appearance. Dyschromia refers to aging spots, freckles and discoloration. Freckles were small hyperpigmented spots and aging spots were large, hyperpigmented spots of hormonal or UV origin. Discoloration described areas of skin darker or lighter than surrounding skin and without borders.
Patients were instructed to discontinue their current skin care products and to apply test products twice daily for 8 weeks. Test products included a facial cleanser, skin brightener, eye serum and a moisturizing cream, each containing 0.5% hydroxydecyl ubiquinoyl dipalmitoyl glycerate (idebenone complex). Patients were also instructed to use sunscreen (SPF 30) during daytime hours and a simple soap to cleanse all test sites during the 1-week washout period, to not use other skin treatment products during the study and to avoid exposure to UV radiation via the sun or visits to a tanning salon. Results were documented with digital photography. Patients returned all unused study materials to the study coordinator at this visit.
Physician Evaluation
Severity of each skin attribute was graded on a 5-point ordinal scale (see Table 1) at baseline, 4 weeks and 8 weeks. The percentages of patients achieving various grades of improvement for each attribute at 4 weeks and 8 weeks are shown in Table 2. At 4 weeks, the most frequent 1-grade improvements occurred in fine lines, dyschromia and brightening, indicating that these three attributes are the most likely to improve early during treatment. The most frequent 2-grade improvements were noted in roughness and radiance, suggesting that these two attributes will achieve the greatest improvement in at least some patients early in treatment. At 8 weeks, 6% of subjects achieved 3-grade improvement in tone and radiance while 3% of subjects achieved 3-grade improvement in fine lines and skin elasticity, suggesting that with continued treatment, these four attributes will improve the most (compared to the other attributes) in at least a few patients.
Physician-evaluated 8-week improvements are ranked below, with the attribute achieving the greatest improvement first.
1. Tone = radiance
2. Fine lines = elasticity
3. Overall improvement
4. Brightening
5. Dyschromia
6. Roughness
As for overall improvement (see Figure 1), 1 to 2 grades of improvement were achieved in 62% of patients at 4 weeks and 85% of patients at 8 weeks.
Clinical examples are presented in Figures 2 and 3.
Results so far have been presented as decreases (improvements) in grades assigned to each attribute by physicians.
Data were also evaluated by comparing proportions of subjects at various grade levels for each attribute at 4 and 8 weeks. In Tables 3 and 4 are physician-assigned grades rather than grades of improvement. Differences in proportions were tested for significance by Pearson Chi square analysis.
Tables 2 and 3 show that improvements at 4 and 8 weeks were significant for every attribute studied compared to baseline.
Patient Evaluation
More patients agreed than disagreed that the product provided significant improvement in each attribute (see Table 5). The highest agreement percentages occurred in softness and smoothness (91%); radiance, tone and clarity (84%); and roughness and dryness (81%). The lowest percentages were in firmness, tightness and elasticity (69%) and texture (74%).
Patient-evaluated 8-week improvements are ranked below, with the attribute achieving the greatest improvement first.
1. Softness and smoothness
2. Radiance, tone and clarity
3. Roughness and dryness
4. Fine lines and wrinkles = overall appearance
5. Spots, freckles and discoloration
6. Skin overall health
7. Texture
8. Firmness, tightness and elasticity
Adverse events or effects were not observed.
Discussion
Early studies in non-human models show that idebenone scavenges free radicals, protects mitochondrial membranes against lipid peroxidation, inhibits platelet aggregation, improves vascular disorders and improves brain function.8 It is neither immunogenic nor mutagenic in animal models.3 The long-term safety of idebenone in humans has been established in a two-year multicenter study.5 The capacity of idebenone to protect against oxidative stress has been confirmed by McDaniel and colleagues.2
A major advantage of the idebenone-enriched skin care products is the early improvements observed in all the attributes studied. After 4 and 8 weeks of twice-daily application of idebenone-enriched skin care products, 35% to 66% of patients achieved at least 1 grade of (physician-assessed) improvement in skin attributes at 4 weeks and 53% to 84% achieved at least 1 grade improvement at 8 weeks. The data (see Table 6) show that the percentage of subjects responding to treatment is higher at 8 weeks than at 4 weeks for each skin attribute, suggesting that application beyond 8 weeks will result in responses from even more patients for every attribute. This finding is corroborated by the results of a 12-week study of the same idebenone-enriched skin-care products (submitted).
Patient-evaluated 8-week improvement data show that softness and smoothness improve in the highest percentage of subjects (91%) while firmness, tightness and elasticity improve in the lowest percentage (69%).
In summary, the present study shows that the idebenone-enriched skincare products are effective for the treatment of the cutaneous manifestations of photoaged skin. The encouraging results warrant additional studies with vehicle controls to establish the duration and ultimate level of improvement achievable with this novel formulation.
Skin care products enriched with the new idebenone derivative, idebenone complex (hydroxydecyl ubiquinoyl dipalmitoyl glycerate), are an effective treatment for photodamaged skin.
Dr. Gold and Ms. Biron are with the Tennessee Clinical Research Center in Nashville, TN.
Mr. DiNardo and Mr. Lewis are with PCR Technology Holdings in Richmond, VA.
Disclosure: Dr. Gold is an investigator for Priori. Mr Lewis and Mr DiNardo are the owners of PCR Technology Holdings, LC which formerly owned the exclusive licensing rights to certain idebenone skincare patents worldwide.
Editor's Note: Please see a PDF of this article, posted above, to see the images and figures in this article.
Premature skin aging is associated with cellular oxidative stress from various forms of reactive oxygen species (ROS).1 Topical antioxidants have been shown to limit skin damage due to ROS activity.2 Since antioxidants play an important role in modern skin care, DiNardo, Lewis and colleagues2 have proposed a new term, environmental protection factor (EPF), to describe the ability of an antioxidant to protect skin from oxidative stress. Using a multistep protocol of both in vitro and in vivo studies, these investigators found that idebenone had a higher EPF than the common antioxidants vitamin E, kinetin, ubiquinone, vitamin C and lipoic acid.
Idebenone is a bioengineered analog of coenzyme Q10, the naturally occurring respiratory chain antioxidant. Idebenone is an electron transfer, mitochondria-targeted antioxidant3,4 extensively researched for the treatment and prevention of age-related disorders,5,6 including skin aging. Cell biological studies have shown that idebenone protects cellular lipoproteins, cell membranes and DNA from damage caused by oxidative stress. By coupling oxygen to the respiratory chain tightly (with more potency than coenzyme Q10) idebenone prevents the formation of toxic oxygen-based free radicals that cause aging.
Since idebenone has been introduced as a potent ingredient for improving the appearance of aged skin,1,2 its oil-soluble ester, hydroxydecyl ubiquinoyl dipalmitoyl glycerate (idebenone complex), has been synthesized, added to skin care products and evaluated for its ability to improve the appearance of pigmentation, fine lines, wrinkles and overall photodamage, and to inhibit sunburn cell formation after UV irradiation. Skin maximization studies to assess skin tolerance have also been conducted.7
This article will review a study conducted to evaluate the efficacy of skincare products enriched with idebenone complex for the treatment of photodamaged skin in 30 women aged 52.2 ± 7.5 years (mean ± SD) with moderate to severe photodamage of the face, neck, chest neck or arms in a single-center, double-blinded study. Patients had not undergone antiaging or depigmenting treatments (eg, retinoid therapy, peels, laser resurfacing) within the previous 6 months and had no known medical condition that, in the opinion of the investigator or expert grader, would have interfered with the study. Pregnancy, breast feeding, unwillingness to use an acceptable form of birth control, dermatologic conditions that might interfere with evaluation of treated sites, hypersensitivity to cosmetic products, taking medications that might interfere with the study, recent upper-body surgery, participation in another clinical trial within the previous 30 days and noncompliance with the study protocol were grounds for exclusion. All patients provided informed consent prior to treatment. The Independent Investigational Review Board (IIRB), Plantation, FL, approved the study.
The study was conducted at Tennessee Clinical Research Center, Nashville, TN, between March and May 2010. During the initial visit, patients were evaluated by a trained technician (expert grader) for skin roughness; fine lines and wrinkles, particularly around the eyes; dyschromia; poor skin tone, elasticity, radiance and brightness; and overall appearance. Dyschromia refers to aging spots, freckles and discoloration. Freckles were small hyperpigmented spots and aging spots were large, hyperpigmented spots of hormonal or UV origin. Discoloration described areas of skin darker or lighter than surrounding skin and without borders.
Patients were instructed to discontinue their current skin care products and to apply test products twice daily for 8 weeks. Test products included a facial cleanser, skin brightener, eye serum and a moisturizing cream, each containing 0.5% hydroxydecyl ubiquinoyl dipalmitoyl glycerate (idebenone complex). Patients were also instructed to use sunscreen (SPF 30) during daytime hours and a simple soap to cleanse all test sites during the 1-week washout period, to not use other skin treatment products during the study and to avoid exposure to UV radiation via the sun or visits to a tanning salon. Results were documented with digital photography. Patients returned all unused study materials to the study coordinator at this visit.
Physician Evaluation
Severity of each skin attribute was graded on a 5-point ordinal scale (see Table 1) at baseline, 4 weeks and 8 weeks. The percentages of patients achieving various grades of improvement for each attribute at 4 weeks and 8 weeks are shown in Table 2. At 4 weeks, the most frequent 1-grade improvements occurred in fine lines, dyschromia and brightening, indicating that these three attributes are the most likely to improve early during treatment. The most frequent 2-grade improvements were noted in roughness and radiance, suggesting that these two attributes will achieve the greatest improvement in at least some patients early in treatment. At 8 weeks, 6% of subjects achieved 3-grade improvement in tone and radiance while 3% of subjects achieved 3-grade improvement in fine lines and skin elasticity, suggesting that with continued treatment, these four attributes will improve the most (compared to the other attributes) in at least a few patients.
Physician-evaluated 8-week improvements are ranked below, with the attribute achieving the greatest improvement first.
1. Tone = radiance
2. Fine lines = elasticity
3. Overall improvement
4. Brightening
5. Dyschromia
6. Roughness
As for overall improvement (see Figure 1), 1 to 2 grades of improvement were achieved in 62% of patients at 4 weeks and 85% of patients at 8 weeks.
Clinical examples are presented in Figures 2 and 3.
Results so far have been presented as decreases (improvements) in grades assigned to each attribute by physicians.
Data were also evaluated by comparing proportions of subjects at various grade levels for each attribute at 4 and 8 weeks. In Tables 3 and 4 are physician-assigned grades rather than grades of improvement. Differences in proportions were tested for significance by Pearson Chi square analysis.
Tables 2 and 3 show that improvements at 4 and 8 weeks were significant for every attribute studied compared to baseline.
Patient Evaluation
More patients agreed than disagreed that the product provided significant improvement in each attribute (see Table 5). The highest agreement percentages occurred in softness and smoothness (91%); radiance, tone and clarity (84%); and roughness and dryness (81%). The lowest percentages were in firmness, tightness and elasticity (69%) and texture (74%).
Patient-evaluated 8-week improvements are ranked below, with the attribute achieving the greatest improvement first.
1. Softness and smoothness
2. Radiance, tone and clarity
3. Roughness and dryness
4. Fine lines and wrinkles = overall appearance
5. Spots, freckles and discoloration
6. Skin overall health
7. Texture
8. Firmness, tightness and elasticity
Adverse events or effects were not observed.
Discussion
Early studies in non-human models show that idebenone scavenges free radicals, protects mitochondrial membranes against lipid peroxidation, inhibits platelet aggregation, improves vascular disorders and improves brain function.8 It is neither immunogenic nor mutagenic in animal models.3 The long-term safety of idebenone in humans has been established in a two-year multicenter study.5 The capacity of idebenone to protect against oxidative stress has been confirmed by McDaniel and colleagues.2
A major advantage of the idebenone-enriched skin care products is the early improvements observed in all the attributes studied. After 4 and 8 weeks of twice-daily application of idebenone-enriched skin care products, 35% to 66% of patients achieved at least 1 grade of (physician-assessed) improvement in skin attributes at 4 weeks and 53% to 84% achieved at least 1 grade improvement at 8 weeks. The data (see Table 6) show that the percentage of subjects responding to treatment is higher at 8 weeks than at 4 weeks for each skin attribute, suggesting that application beyond 8 weeks will result in responses from even more patients for every attribute. This finding is corroborated by the results of a 12-week study of the same idebenone-enriched skin-care products (submitted).
Patient-evaluated 8-week improvement data show that softness and smoothness improve in the highest percentage of subjects (91%) while firmness, tightness and elasticity improve in the lowest percentage (69%).
In summary, the present study shows that the idebenone-enriched skincare products are effective for the treatment of the cutaneous manifestations of photoaged skin. The encouraging results warrant additional studies with vehicle controls to establish the duration and ultimate level of improvement achievable with this novel formulation.
Skin care products enriched with the new idebenone derivative, idebenone complex (hydroxydecyl ubiquinoyl dipalmitoyl glycerate), are an effective treatment for photodamaged skin.
Dr. Gold and Ms. Biron are with the Tennessee Clinical Research Center in Nashville, TN.
Mr. DiNardo and Mr. Lewis are with PCR Technology Holdings in Richmond, VA.
Disclosure: Dr. Gold is an investigator for Priori. Mr Lewis and Mr DiNardo are the owners of PCR Technology Holdings, LC which formerly owned the exclusive licensing rights to certain idebenone skincare patents worldwide.
