Kinetin and the skin

Kinetin (N6-furfuryladenine or 6-furfurylaminopurine) is a plant cytokinin or phytohormone that promotes cell division, delays senescence in plants, and is reputed to aid in the restoration of skin barrier function and, possibly, in reducing the signs and symptoms of rosacea (Clin. Exp. Dermatol. 2007;32:693-5; Plant Sci. 1999;148:37-45).

Kinetin is believed to develop in cellular DNA as a product of the oxidative, secondary modification of DNA (Plant Sci. 1999;148:37-45). In 1955, it became the first cytokinin isolated from DNA (from herring sperm) as an artifactual rearrangement product of the autoclaving process (J. Cosmet. Dermatol. 2007;6:243-9; Int. J. Biol. Macromol. 2007;40:182-92).

It has since been found to be present in human urine as well as DNA freshly extracted from human cells (Int. J. Biol. Macromol. 2007;40:182-92). The preponderance of amassed experimental evidence suggests that endogenous kinetin acts in vitro and in vivo as a potent antioxidant (Plant Sci. 1999;148:37-45). Currently, it is used as an anti-aging agent in various cosmetic products (J. Cosmet. Dermatol. 2007;6:243-9; J. Cosmet. Dermatol. 2010;9:218-25). Synthetic kinetin is thought to have the capacity to neutralize free radicals as well as limit the damage to DNA and fibroblasts (Photochem. Photobiol. 2012;88:748-52).

In vitro results

Olsen et al. demonstrated in vitro in 1999 that kinetin dose-dependently protected DNA against oxidative damage mediated by the Fenton reaction, and noted that kinetin had previously been linked to anti-aging activity in plants, fruit flies, and human cells in culture (Biochem. Biophys. Res. Commun. 1999;265:499-502). The following year, Verbeke et al. showed in vitro that kinetin potently inhibited damage caused by oxidation and glycoxidation (Biochem. Biophys. Res. Commun. 2000;276:1265-70).

In 2006, Vicanova et al. analyzed the effects of active ingredients from topical and systemic skin care formulations in vitro, finding that kinetin affected the upper dermis by enhancing deposits of fibrillin-1 and elastin fibers as well as their organization perpendicular to the dermal-epidermal junction. In the epidermis, kinetin stimulated keratinocyte production. Further, the investigators noted that the combination of topically applied kinetin with Imedeen Time Perfection ingredients (i.e., BioMarine Complex, grape seed extract, tomato extract, and vitamin C) supplemented systemically into culture medium yielded complementary benefits to dermal and epidermal development (Ann. N.Y. Acad. Sci. 2006;1067:337-42).

It is worth noting that in a study by Tournas et al. published the same month, investigators found that the topical application of a combination of vitamins C and E and ferulic acid yielded photoprotection to pig skin at 5 times the minimal erythema dose (MED) while individual antioxidants to which it was compared (i.e., coenzyme Q10, idebenone, and kinetin) delivered no photoprotective effects (J. Invest. Dermatol. 2006;126:1185-7). Nevertheless, Barciszewski et al. have observed that kinetin is the first stable secondary DNA damage product characterized by well defined cytokinin and anti-aging activity, with data showing that it has delayed human cellular aging in culture (Int. J. Biol. Macromol. 2007;40:182-92).

Rosacea

In 2007, Wu et al. performed a 12-week open-label study in 15 women and 3 men (aged 30-67 years) to ascertain the tolerability and efficacy of kinetin 0.1% lotion in the treatment of mild to moderate facial rosacea. Patients (17 of whom completed the study) applied the lotion twice daily, also daily applying an SPF 30 sunscreen. By week 4, significant improvements were observed in the reduction of skin roughness and mottled hyperpigmentation. Subject assessments at each 4-week interval after baseline and after 12 weeks revealed that kinetin 0.1% was well tolerated and effective for mild to moderate inflammatory rosacea (Clin. Exp. Dermatol. 2007;32:693-5).

Anti-aging

A 2002 study by J.L. McCullough and G.D. Weinstein represented the first evidence of the efficacy of topical kinetin in human beings, with twice-daily application for 24 weeks found to ameliorate skin texture, color, and blotchiness while diminishing rhytides and transepidermal water loss (J. Cosmet. Dermatol. 2002;15:29-32).

Two years later, T. Kimura and K. Doi showed that topical administration of kinetin improved the texture, wrinkling, and pigmentation of aged skin of hairless descendants of Mexican hairless dogs, resulting in notable depigmentation and rejuvenation after 100 days of treatment (Rejuvenation Res. 2004;7:32-9).In 2007, Chiu et al. conducted a randomized, double-blind, placebo-controlled, split-face comparative study in 52 Taiwanese subjects aged 30-60 years (90% of whom were female, all of whom had Fitzpatrick skin types II, III, or IV) to evaluate the clinical anti-aging effects and efficacy differences between kinetin plus niacinamide (kinetin 0.03%, niacinamide 4%) and niacinamide 4% alone versus vehicle placebo.

In the combination group, significant and sustained decreases were observed in counts of spots, pores, wrinkles, and evenness as well as persistent reductions in erythema index at weeks 8 and 12. At week 12, stratum corneum hydration status also was significantly enhanced in this group. In the niacinamide-only group, pore and evenness counts were significantly decreased at week 8, with declines in wrinkle counts emerging at week 12. The investigators concluded that kinetin and niacinamide display synergistic and dynamic anti-aging effects, showing substantial potential as topical anti-aging cosmeceutical agents (J. Cosmet. Dermatol. 2007;6:243-9).

However, Levin et al. noted in 2010 that while the effects of kinetin have been established in plants and its antioxidant properties have been displayed in vitro, the anti-aging effects and clinical efficacy ascribed to kinetin have been based on limited evidence, with no studies extant on the percutaneous absorption of kinetin. They added that research elucidating the mechanisms through which kinetin appears to improve skin barrier function, texture, and pigmentation also are lacking (J. Clin. Aesthet. Dermatol. 2010;3:22-41).

In 2012, Campos et al. assessed the effects on hydration, viscoelastic characteristics, and photoprotection of cosmetic preparations containing a dispersion of liposome with magnesium ascorbyl phosphate, alpha-lipoic acid, and kinetin. They observed that the formulation protected hairless mouse skin barrier function against UV harm. After 4 weeks of application on human skin, the combination product was found to have improved moisturization of the stratum corneum, also delivering hydration effects to deeper skin layers. The researchers concluded that the cosmetic formulation containing kinetin shows promise as a cutaneous anti-aging product (Photochem. Photobiol. 2012;88:748-52).

Conclusion

While some experimental and clinical results appear to suggest an anti-aging effect exerted by topically applied kinetin, much more research – particularly randomized controlled and comparison studies – are needed to provide a clearer picture as to the mechanisms and appropriate role of kinetin in the dermatologic armamentarium.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy,Topix Pharmaceuticals, and Unilever.

Kinetin (N6-furfuryladenine or 6-furfurylaminopurine) is a plant cytokinin or phytohormone that promotes cell division, delays senescence in plants, and is reputed to aid in the restoration of skin barrier function and, possibly, in reducing the signs and symptoms of rosacea (Clin. Exp. Dermatol. 2007;32:693-5; Plant Sci. 1999;148:37-45).

Kinetin is believed to develop in cellular DNA as a product of the oxidative, secondary modification of DNA (Plant Sci. 1999;148:37-45). In 1955, it became the first cytokinin isolated from DNA (from herring sperm) as an artifactual rearrangement product of the autoclaving process (J. Cosmet. Dermatol. 2007;6:243-9; Int. J. Biol. Macromol. 2007;40:182-92).

It has since been found to be present in human urine as well as DNA freshly extracted from human cells (Int. J. Biol. Macromol. 2007;40:182-92). The preponderance of amassed experimental evidence suggests that endogenous kinetin acts in vitro and in vivo as a potent antioxidant (Plant Sci. 1999;148:37-45). Currently, it is used as an anti-aging agent in various cosmetic products (J. Cosmet. Dermatol. 2007;6:243-9; J. Cosmet. Dermatol. 2010;9:218-25). Synthetic kinetin is thought to have the capacity to neutralize free radicals as well as limit the damage to DNA and fibroblasts (Photochem. Photobiol. 2012;88:748-52).

In vitro results

Olsen et al. demonstrated in vitro in 1999 that kinetin dose-dependently protected DNA against oxidative damage mediated by the Fenton reaction, and noted that kinetin had previously been linked to anti-aging activity in plants, fruit flies, and human cells in culture (Biochem. Biophys. Res. Commun. 1999;265:499-502). The following year, Verbeke et al. showed in vitro that kinetin potently inhibited damage caused by oxidation and glycoxidation (Biochem. Biophys. Res. Commun. 2000;276:1265-70).

In 2006, Vicanova et al. analyzed the effects of active ingredients from topical and systemic skin care formulations in vitro, finding that kinetin affected the upper dermis by enhancing deposits of fibrillin-1 and elastin fibers as well as their organization perpendicular to the dermal-epidermal junction. In the epidermis, kinetin stimulated keratinocyte production. Further, the investigators noted that the combination of topically applied kinetin with Imedeen Time Perfection ingredients (i.e., BioMarine Complex, grape seed extract, tomato extract, and vitamin C) supplemented systemically into culture medium yielded complementary benefits to dermal and epidermal development (Ann. N.Y. Acad. Sci. 2006;1067:337-42).

It is worth noting that in a study by Tournas et al. published the same month, investigators found that the topical application of a combination of vitamins C and E and ferulic acid yielded photoprotection to pig skin at 5 times the minimal erythema dose (MED) while individual antioxidants to which it was compared (i.e., coenzyme Q10, idebenone, and kinetin) delivered no photoprotective effects (J. Invest. Dermatol. 2006;126:1185-7). Nevertheless, Barciszewski et al. have observed that kinetin is the first stable secondary DNA damage product characterized by well defined cytokinin and anti-aging activity, with data showing that it has delayed human cellular aging in culture (Int. J. Biol. Macromol. 2007;40:182-92).

Rosacea

In 2007, Wu et al. performed a 12-week open-label study in 15 women and 3 men (aged 30-67 years) to ascertain the tolerability and efficacy of kinetin 0.1% lotion in the treatment of mild to moderate facial rosacea. Patients (17 of whom completed the study) applied the lotion twice daily, also daily applying an SPF 30 sunscreen. By week 4, significant improvements were observed in the reduction of skin roughness and mottled hyperpigmentation. Subject assessments at each 4-week interval after baseline and after 12 weeks revealed that kinetin 0.1% was well tolerated and effective for mild to moderate inflammatory rosacea (Clin. Exp. Dermatol. 2007;32:693-5).

Anti-aging

A 2002 study by J.L. McCullough and G.D. Weinstein represented the first evidence of the efficacy of topical kinetin in human beings, with twice-daily application for 24 weeks found to ameliorate skin texture, color, and blotchiness while diminishing rhytides and transepidermal water loss (J. Cosmet. Dermatol. 2002;15:29-32).

Two years later, T. Kimura and K. Doi showed that topical administration of kinetin improved the texture, wrinkling, and pigmentation of aged skin of hairless descendants of Mexican hairless dogs, resulting in notable depigmentation and rejuvenation after 100 days of treatment (Rejuvenation Res. 2004;7:32-9).In 2007, Chiu et al. conducted a randomized, double-blind, placebo-controlled, split-face comparative study in 52 Taiwanese subjects aged 30-60 years (90% of whom were female, all of whom had Fitzpatrick skin types II, III, or IV) to evaluate the clinical anti-aging effects and efficacy differences between kinetin plus niacinamide (kinetin 0.03%, niacinamide 4%) and niacinamide 4% alone versus vehicle placebo.

In the combination group, significant and sustained decreases were observed in counts of spots, pores, wrinkles, and evenness as well as persistent reductions in erythema index at weeks 8 and 12. At week 12, stratum corneum hydration status also was significantly enhanced in this group. In the niacinamide-only group, pore and evenness counts were significantly decreased at week 8, with declines in wrinkle counts emerging at week 12. The investigators concluded that kinetin and niacinamide display synergistic and dynamic anti-aging effects, showing substantial potential as topical anti-aging cosmeceutical agents (J. Cosmet. Dermatol. 2007;6:243-9).

However, Levin et al. noted in 2010 that while the effects of kinetin have been established in plants and its antioxidant properties have been displayed in vitro, the anti-aging effects and clinical efficacy ascribed to kinetin have been based on limited evidence, with no studies extant on the percutaneous absorption of kinetin. They added that research elucidating the mechanisms through which kinetin appears to improve skin barrier function, texture, and pigmentation also are lacking (J. Clin. Aesthet. Dermatol. 2010;3:22-41).

In 2012, Campos et al. assessed the effects on hydration, viscoelastic characteristics, and photoprotection of cosmetic preparations containing a dispersion of liposome with magnesium ascorbyl phosphate, alpha-lipoic acid, and kinetin. They observed that the formulation protected hairless mouse skin barrier function against UV harm. After 4 weeks of application on human skin, the combination product was found to have improved moisturization of the stratum corneum, also delivering hydration effects to deeper skin layers. The researchers concluded that the cosmetic formulation containing kinetin shows promise as a cutaneous anti-aging product (Photochem. Photobiol. 2012;88:748-52).

Conclusion

While some experimental and clinical results appear to suggest an anti-aging effect exerted by topically applied kinetin, much more research – particularly randomized controlled and comparison studies – are needed to provide a clearer picture as to the mechanisms and appropriate role of kinetin in the dermatologic armamentarium.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy,Topix Pharmaceuticals, and Unilever.

Kinetin (N6-furfuryladenine or 6-furfurylaminopurine) is a plant cytokinin or phytohormone that promotes cell division, delays senescence in plants, and is reputed to aid in the restoration of skin barrier function and, possibly, in reducing the signs and symptoms of rosacea (Clin. Exp. Dermatol. 2007;32:693-5; Plant Sci. 1999;148:37-45).

Kinetin is believed to develop in cellular DNA as a product of the oxidative, secondary modification of DNA (Plant Sci. 1999;148:37-45). In 1955, it became the first cytokinin isolated from DNA (from herring sperm) as an artifactual rearrangement product of the autoclaving process (J. Cosmet. Dermatol. 2007;6:243-9; Int. J. Biol. Macromol. 2007;40:182-92).

It has since been found to be present in human urine as well as DNA freshly extracted from human cells (Int. J. Biol. Macromol. 2007;40:182-92). The preponderance of amassed experimental evidence suggests that endogenous kinetin acts in vitro and in vivo as a potent antioxidant (Plant Sci. 1999;148:37-45). Currently, it is used as an anti-aging agent in various cosmetic products (J. Cosmet. Dermatol. 2007;6:243-9; J. Cosmet. Dermatol. 2010;9:218-25). Synthetic kinetin is thought to have the capacity to neutralize free radicals as well as limit the damage to DNA and fibroblasts (Photochem. Photobiol. 2012;88:748-52).

In vitro results

Olsen et al. demonstrated in vitro in 1999 that kinetin dose-dependently protected DNA against oxidative damage mediated by the Fenton reaction, and noted that kinetin had previously been linked to anti-aging activity in plants, fruit flies, and human cells in culture (Biochem. Biophys. Res. Commun. 1999;265:499-502). The following year, Verbeke et al. showed in vitro that kinetin potently inhibited damage caused by oxidation and glycoxidation (Biochem. Biophys. Res. Commun. 2000;276:1265-70).

In 2006, Vicanova et al. analyzed the effects of active ingredients from topical and systemic skin care formulations in vitro, finding that kinetin affected the upper dermis by enhancing deposits of fibrillin-1 and elastin fibers as well as their organization perpendicular to the dermal-epidermal junction. In the epidermis, kinetin stimulated keratinocyte production. Further, the investigators noted that the combination of topically applied kinetin with Imedeen Time Perfection ingredients (i.e., BioMarine Complex, grape seed extract, tomato extract, and vitamin C) supplemented systemically into culture medium yielded complementary benefits to dermal and epidermal development (Ann. N.Y. Acad. Sci. 2006;1067:337-42).

It is worth noting that in a study by Tournas et al. published the same month, investigators found that the topical application of a combination of vitamins C and E and ferulic acid yielded photoprotection to pig skin at 5 times the minimal erythema dose (MED) while individual antioxidants to which it was compared (i.e., coenzyme Q10, idebenone, and kinetin) delivered no photoprotective effects (J. Invest. Dermatol. 2006;126:1185-7). Nevertheless, Barciszewski et al. have observed that kinetin is the first stable secondary DNA damage product characterized by well defined cytokinin and anti-aging activity, with data showing that it has delayed human cellular aging in culture (Int. J. Biol. Macromol. 2007;40:182-92).

Rosacea

In 2007, Wu et al. performed a 12-week open-label study in 15 women and 3 men (aged 30-67 years) to ascertain the tolerability and efficacy of kinetin 0.1% lotion in the treatment of mild to moderate facial rosacea. Patients (17 of whom completed the study) applied the lotion twice daily, also daily applying an SPF 30 sunscreen. By week 4, significant improvements were observed in the reduction of skin roughness and mottled hyperpigmentation. Subject assessments at each 4-week interval after baseline and after 12 weeks revealed that kinetin 0.1% was well tolerated and effective for mild to moderate inflammatory rosacea (Clin. Exp. Dermatol. 2007;32:693-5).

Anti-aging

A 2002 study by J.L. McCullough and G.D. Weinstein represented the first evidence of the efficacy of topical kinetin in human beings, with twice-daily application for 24 weeks found to ameliorate skin texture, color, and blotchiness while diminishing rhytides and transepidermal water loss (J. Cosmet. Dermatol. 2002;15:29-32).

Two years later, T. Kimura and K. Doi showed that topical administration of kinetin improved the texture, wrinkling, and pigmentation of aged skin of hairless descendants of Mexican hairless dogs, resulting in notable depigmentation and rejuvenation after 100 days of treatment (Rejuvenation Res. 2004;7:32-9).In 2007, Chiu et al. conducted a randomized, double-blind, placebo-controlled, split-face comparative study in 52 Taiwanese subjects aged 30-60 years (90% of whom were female, all of whom had Fitzpatrick skin types II, III, or IV) to evaluate the clinical anti-aging effects and efficacy differences between kinetin plus niacinamide (kinetin 0.03%, niacinamide 4%) and niacinamide 4% alone versus vehicle placebo.

In the combination group, significant and sustained decreases were observed in counts of spots, pores, wrinkles, and evenness as well as persistent reductions in erythema index at weeks 8 and 12. At week 12, stratum corneum hydration status also was significantly enhanced in this group. In the niacinamide-only group, pore and evenness counts were significantly decreased at week 8, with declines in wrinkle counts emerging at week 12. The investigators concluded that kinetin and niacinamide display synergistic and dynamic anti-aging effects, showing substantial potential as topical anti-aging cosmeceutical agents (J. Cosmet. Dermatol. 2007;6:243-9).

However, Levin et al. noted in 2010 that while the effects of kinetin have been established in plants and its antioxidant properties have been displayed in vitro, the anti-aging effects and clinical efficacy ascribed to kinetin have been based on limited evidence, with no studies extant on the percutaneous absorption of kinetin. They added that research elucidating the mechanisms through which kinetin appears to improve skin barrier function, texture, and pigmentation also are lacking (J. Clin. Aesthet. Dermatol. 2010;3:22-41).

In 2012, Campos et al. assessed the effects on hydration, viscoelastic characteristics, and photoprotection of cosmetic preparations containing a dispersion of liposome with magnesium ascorbyl phosphate, alpha-lipoic acid, and kinetin. They observed that the formulation protected hairless mouse skin barrier function against UV harm. After 4 weeks of application on human skin, the combination product was found to have improved moisturization of the stratum corneum, also delivering hydration effects to deeper skin layers. The researchers concluded that the cosmetic formulation containing kinetin shows promise as a cutaneous anti-aging product (Photochem. Photobiol. 2012;88:748-52).

Conclusion

While some experimental and clinical results appear to suggest an anti-aging effect exerted by topically applied kinetin, much more research – particularly randomized controlled and comparison studies – are needed to provide a clearer picture as to the mechanisms and appropriate role of kinetin in the dermatologic armamentarium.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy,Topix Pharmaceuticals, and Unilever.