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A powerful endogenous antioxidant found most abundantly in mammalian tissues, especially brain and skeletal muscle tissue, carnosine is a dipeptide of alanine and histidine.1,2,3,4,5.
Carnosine was first isolated in 1900 by the Russian scientist Gulewitsch as a substance extracted from muscle tissue.6,4. L-carnosine (beta-alanyl-L-histidine) is the synthetic version identical to the natural form alpha-alanyl-L-histidine.7 Carnosine has long been reputed to confer immunomodulating, wound healing, antiglycating, and antineoplastic effects.2 Several reports have shown that carnosine can accelerate the healing of surface skin wounds and burns.4,8
Wound healing
An early study by Nagai et al. in 1986 on carnosine in wound healing showed that rats treated locally with carnosine exhibited greater tensile skin strength at an incision site after hydrocortisone had been administered to hinder healing. The investigators concluded that carnosine bolsters wound healing by stimulating early effusion by histamine and of collagen biosynthesis by beta-alanine. They also found that the compound significantly augmented granulation inhibited by cortisone, mitomycin C, 5-fluorouracil, and bleomycin.9
Studies by Fitzpatrick and Fisher in the early 1980s revealed that carnosine acts as a histidine reserve in relation to histamine production during trauma, suggesting a role for carnosine in wound healing.10,11
In 2012, Ansurudeen et al. examined the effects of carnosine in wound healing in a diabetic mouse model. Carnosine was applied locally and injected daily, yielding significant amelioration in wound healing, with analysis revealing elevated expression of growth factors and cytokines implicated in wound healing. The investigators also observed that carnosine supported cell viability in the presence of high glucose in human dermal fibroblasts and microvascular endothelial cells in vitro.2
Other findings with implications for cutaneous therapy
In 2006, Babizhayev reported that the L-carnosine-related peptidomimetic N-acetylcarnosine (N-acetyl-beta-alanyl-L-histidine) can act as a timed-release (carrier) stable version of L-carnosine in cosmetic preparations, including lubricants.6 Babizhayev et al. have since claimed that they have developed a technology using imidazole-containing dipeptide-based compounds (including L-carnosine and derivatives) that enhances protein hydration in photoaged skin.12,13,14
A double-blind comparative study conducted by Dieamant et al. in 2008 in 124 volunteers with sensitive skin aimed to evaluate the therapeutic potential of the combination of the antioxidant L-carnosine and neuromodulatory Rhodiola rosea. For 28 days, the groups of 62 received twice-daily applications of the 1% combination formulation or placebo. Skin barrier function (reduction of transepidermal water loss) improved in the treatment group, and favorable subjective responses regarding skin dryness were reported. Discomfort after the stinging test was also reduced. In vitro results showed that the release of proopiomelanocortin peptides was spurred by treatment, with the elevated levels of neuropeptides and cytokines produced by keratinocytes exposed to UV radiation returning to normal.15
Two years later, Renner et al. showed that carnosine hindered tumor growth in vivo in an NIH3T3-HER2/neu mouse model. They contended that this naturally occurring dipeptide warrants increased consideration and study for its potential as an anticancer agent.16
In 2012, Federici et al. conducted a randomized, evaluator-blinded, controlled comparative trial over 1month to assess the efficacy of twice-daily topical urea 5% with arginine and carnosine (Ureadin Rx) as compared with twice-daily application of a glycerol-based emollient topical product (Dexeryl) in treating xerosis in 40 type 2 diabetes patients (40-75 years of age). Use of the carnosine-containing formulation yielded significantly greater hydration and an 89% decline in Dryness Areas Severity Index (DASI) scores, compared with baseline. The DASI score after 4 weeks of treatment was much lower in the treatment group than the control group. The Visual Analog Scale (VAS) score was also significantly higher in the Ureadin group than the Dexeryl group. The investigators concluded that the topical application of a urea 5%, arginine, and carnosine cream enhances skin hydration and relieves dryness in type 2 diabetic patients in comparison with a control glycerol-based emollient formulation.17
Antiaging potential
In 1993, Reeve et al. showed that dietary or topically applied carnosine potentiated the contact hypersensitivity reaction in hairless mice and prevented the systemic inhibition of this reaction after dorsal skin exposure to UVB. Carnosine was found to also prevent the systemic suppression provoked by the topical application of a lotion containing cis-urocanic acid.3
Carnosine was a key active ingredient in antiaging products evaluated by Kaczvinsky et al. in 2009 in two double-blind, randomized, controlled, split-face studies. The researchers used the Fast Optical in vivo Topometry of Human Skin (FOITS) technique to measure changes in periorbital wrinkles in the two studies in women between the ages of 30 and 70 years old (study 1, n = 42; study 2, n = 35). They reported that 4 weeks of treatment with the test products, which contained niacinamide, the peptides Pal-KT and Pal-KTTKS, and carnosine, ameliorated periorbital skin, enhancing smoothness and diminishing larger wrinkle depth.18
In 2012, Babizhayev et al. conducted a 4-month randomized, double-blind, controlled study with 42 subjects to evaluate the effects on skin aging of oral nonhydrolyzed carnosine (Can-C Plus formulation). Skin parameters exhibited a consistent and significant improvement during 3 months of supplementation in the treatment group, compared with the placebo group, with overall skin appearance enhanced and fine lines diminished based on visual inspection. There were no reports of adverse effects. The investigators concluded that supplementation with nonhydrolyzed carnosine or carcinine in patented oral formulations has potential as an agent for antiaging purposes.19
Two years later, Emanuele et al. conducted an experimental double-blind irradiation study to compare a complex novel topical product (TPF50) consisting of three active ingredients (traditional physical sunscreens, SPF 50; a liposome-encapsulated DNA repair enzymes complex – photolyase, endonuclease, and 8-oxoguanine glycosylase [OGG1]; and a robust antioxidant complex containing carnosine, arazine, and ergothionine) to available DNA repair and antioxidant and growth factor topical products. They found that the new topical agent was the most effective product in reducing three molecular markers (cyclobutane pyrimidine dimers, protein carbonylation, and 8-oxo-7,8-dihydro-2’-deoxyguanosine) in human skin biopsies. The researchers concluded that the carnosine-containing formulation enhances the genomic and proteomic integrity of skin cells after continual UV exposure, suggesting its potential efficacy in lowering the risk of UV-induced cutaneous aging and nonmelanoma skin cancer.20
Conclusion
Carnosine is an intriguing compound with well-documented antioxidant and wound healing activity. While more research is necessary to determine its wider applications in dermatology, recent work in formulating topical products to impart antiaging effects appears to show promise.
References
1. Nutr. Res. Pract. 2011;5:421-8.
2. Amino Acids 2012;43:127-34.
4. Mol. Aspects Med. 1992;13:379-444.
5. Am. J. Ther. 2012;19:e69-89.
7. J. Cosmet. Dermatol. 2004;3:26-34.
8. Nihon Yakurigaku Zasshi. 1992;100:165-72.
12. Int. J. Cosmet. Sci. 2011;33:1-16.
13. Crit. Rev. Ther. Drug Carrier Syst. 2011;28:203-53.
14. Crit. Rev. Ther. Drug Carrier Syst. 2010;27:85-154.
15. J. Cosmet. Dermatol. 2008;7:112-9.
18. J. Cosmet. Dermatol. 2009;8:228-33.
19. J. Dermatolog. Treat. 2012;23:345-84.
20. J. Drugs Dermatol. 2014;13:309-14.
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.
A powerful endogenous antioxidant found most abundantly in mammalian tissues, especially brain and skeletal muscle tissue, carnosine is a dipeptide of alanine and histidine.1,2,3,4,5.
Carnosine was first isolated in 1900 by the Russian scientist Gulewitsch as a substance extracted from muscle tissue.6,4. L-carnosine (beta-alanyl-L-histidine) is the synthetic version identical to the natural form alpha-alanyl-L-histidine.7 Carnosine has long been reputed to confer immunomodulating, wound healing, antiglycating, and antineoplastic effects.2 Several reports have shown that carnosine can accelerate the healing of surface skin wounds and burns.4,8
Wound healing
An early study by Nagai et al. in 1986 on carnosine in wound healing showed that rats treated locally with carnosine exhibited greater tensile skin strength at an incision site after hydrocortisone had been administered to hinder healing. The investigators concluded that carnosine bolsters wound healing by stimulating early effusion by histamine and of collagen biosynthesis by beta-alanine. They also found that the compound significantly augmented granulation inhibited by cortisone, mitomycin C, 5-fluorouracil, and bleomycin.9
Studies by Fitzpatrick and Fisher in the early 1980s revealed that carnosine acts as a histidine reserve in relation to histamine production during trauma, suggesting a role for carnosine in wound healing.10,11
In 2012, Ansurudeen et al. examined the effects of carnosine in wound healing in a diabetic mouse model. Carnosine was applied locally and injected daily, yielding significant amelioration in wound healing, with analysis revealing elevated expression of growth factors and cytokines implicated in wound healing. The investigators also observed that carnosine supported cell viability in the presence of high glucose in human dermal fibroblasts and microvascular endothelial cells in vitro.2
Other findings with implications for cutaneous therapy
In 2006, Babizhayev reported that the L-carnosine-related peptidomimetic N-acetylcarnosine (N-acetyl-beta-alanyl-L-histidine) can act as a timed-release (carrier) stable version of L-carnosine in cosmetic preparations, including lubricants.6 Babizhayev et al. have since claimed that they have developed a technology using imidazole-containing dipeptide-based compounds (including L-carnosine and derivatives) that enhances protein hydration in photoaged skin.12,13,14
A double-blind comparative study conducted by Dieamant et al. in 2008 in 124 volunteers with sensitive skin aimed to evaluate the therapeutic potential of the combination of the antioxidant L-carnosine and neuromodulatory Rhodiola rosea. For 28 days, the groups of 62 received twice-daily applications of the 1% combination formulation or placebo. Skin barrier function (reduction of transepidermal water loss) improved in the treatment group, and favorable subjective responses regarding skin dryness were reported. Discomfort after the stinging test was also reduced. In vitro results showed that the release of proopiomelanocortin peptides was spurred by treatment, with the elevated levels of neuropeptides and cytokines produced by keratinocytes exposed to UV radiation returning to normal.15
Two years later, Renner et al. showed that carnosine hindered tumor growth in vivo in an NIH3T3-HER2/neu mouse model. They contended that this naturally occurring dipeptide warrants increased consideration and study for its potential as an anticancer agent.16
In 2012, Federici et al. conducted a randomized, evaluator-blinded, controlled comparative trial over 1month to assess the efficacy of twice-daily topical urea 5% with arginine and carnosine (Ureadin Rx) as compared with twice-daily application of a glycerol-based emollient topical product (Dexeryl) in treating xerosis in 40 type 2 diabetes patients (40-75 years of age). Use of the carnosine-containing formulation yielded significantly greater hydration and an 89% decline in Dryness Areas Severity Index (DASI) scores, compared with baseline. The DASI score after 4 weeks of treatment was much lower in the treatment group than the control group. The Visual Analog Scale (VAS) score was also significantly higher in the Ureadin group than the Dexeryl group. The investigators concluded that the topical application of a urea 5%, arginine, and carnosine cream enhances skin hydration and relieves dryness in type 2 diabetic patients in comparison with a control glycerol-based emollient formulation.17
Antiaging potential
In 1993, Reeve et al. showed that dietary or topically applied carnosine potentiated the contact hypersensitivity reaction in hairless mice and prevented the systemic inhibition of this reaction after dorsal skin exposure to UVB. Carnosine was found to also prevent the systemic suppression provoked by the topical application of a lotion containing cis-urocanic acid.3
Carnosine was a key active ingredient in antiaging products evaluated by Kaczvinsky et al. in 2009 in two double-blind, randomized, controlled, split-face studies. The researchers used the Fast Optical in vivo Topometry of Human Skin (FOITS) technique to measure changes in periorbital wrinkles in the two studies in women between the ages of 30 and 70 years old (study 1, n = 42; study 2, n = 35). They reported that 4 weeks of treatment with the test products, which contained niacinamide, the peptides Pal-KT and Pal-KTTKS, and carnosine, ameliorated periorbital skin, enhancing smoothness and diminishing larger wrinkle depth.18
In 2012, Babizhayev et al. conducted a 4-month randomized, double-blind, controlled study with 42 subjects to evaluate the effects on skin aging of oral nonhydrolyzed carnosine (Can-C Plus formulation). Skin parameters exhibited a consistent and significant improvement during 3 months of supplementation in the treatment group, compared with the placebo group, with overall skin appearance enhanced and fine lines diminished based on visual inspection. There were no reports of adverse effects. The investigators concluded that supplementation with nonhydrolyzed carnosine or carcinine in patented oral formulations has potential as an agent for antiaging purposes.19
Two years later, Emanuele et al. conducted an experimental double-blind irradiation study to compare a complex novel topical product (TPF50) consisting of three active ingredients (traditional physical sunscreens, SPF 50; a liposome-encapsulated DNA repair enzymes complex – photolyase, endonuclease, and 8-oxoguanine glycosylase [OGG1]; and a robust antioxidant complex containing carnosine, arazine, and ergothionine) to available DNA repair and antioxidant and growth factor topical products. They found that the new topical agent was the most effective product in reducing three molecular markers (cyclobutane pyrimidine dimers, protein carbonylation, and 8-oxo-7,8-dihydro-2’-deoxyguanosine) in human skin biopsies. The researchers concluded that the carnosine-containing formulation enhances the genomic and proteomic integrity of skin cells after continual UV exposure, suggesting its potential efficacy in lowering the risk of UV-induced cutaneous aging and nonmelanoma skin cancer.20
Conclusion
Carnosine is an intriguing compound with well-documented antioxidant and wound healing activity. While more research is necessary to determine its wider applications in dermatology, recent work in formulating topical products to impart antiaging effects appears to show promise.
References
1. Nutr. Res. Pract. 2011;5:421-8.
2. Amino Acids 2012;43:127-34.
4. Mol. Aspects Med. 1992;13:379-444.
5. Am. J. Ther. 2012;19:e69-89.
7. J. Cosmet. Dermatol. 2004;3:26-34.
8. Nihon Yakurigaku Zasshi. 1992;100:165-72.
12. Int. J. Cosmet. Sci. 2011;33:1-16.
13. Crit. Rev. Ther. Drug Carrier Syst. 2011;28:203-53.
14. Crit. Rev. Ther. Drug Carrier Syst. 2010;27:85-154.
15. J. Cosmet. Dermatol. 2008;7:112-9.
18. J. Cosmet. Dermatol. 2009;8:228-33.
19. J. Dermatolog. Treat. 2012;23:345-84.
20. J. Drugs Dermatol. 2014;13:309-14.
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.
A powerful endogenous antioxidant found most abundantly in mammalian tissues, especially brain and skeletal muscle tissue, carnosine is a dipeptide of alanine and histidine.1,2,3,4,5.
Carnosine was first isolated in 1900 by the Russian scientist Gulewitsch as a substance extracted from muscle tissue.6,4. L-carnosine (beta-alanyl-L-histidine) is the synthetic version identical to the natural form alpha-alanyl-L-histidine.7 Carnosine has long been reputed to confer immunomodulating, wound healing, antiglycating, and antineoplastic effects.2 Several reports have shown that carnosine can accelerate the healing of surface skin wounds and burns.4,8
Wound healing
An early study by Nagai et al. in 1986 on carnosine in wound healing showed that rats treated locally with carnosine exhibited greater tensile skin strength at an incision site after hydrocortisone had been administered to hinder healing. The investigators concluded that carnosine bolsters wound healing by stimulating early effusion by histamine and of collagen biosynthesis by beta-alanine. They also found that the compound significantly augmented granulation inhibited by cortisone, mitomycin C, 5-fluorouracil, and bleomycin.9
Studies by Fitzpatrick and Fisher in the early 1980s revealed that carnosine acts as a histidine reserve in relation to histamine production during trauma, suggesting a role for carnosine in wound healing.10,11
In 2012, Ansurudeen et al. examined the effects of carnosine in wound healing in a diabetic mouse model. Carnosine was applied locally and injected daily, yielding significant amelioration in wound healing, with analysis revealing elevated expression of growth factors and cytokines implicated in wound healing. The investigators also observed that carnosine supported cell viability in the presence of high glucose in human dermal fibroblasts and microvascular endothelial cells in vitro.2
Other findings with implications for cutaneous therapy
In 2006, Babizhayev reported that the L-carnosine-related peptidomimetic N-acetylcarnosine (N-acetyl-beta-alanyl-L-histidine) can act as a timed-release (carrier) stable version of L-carnosine in cosmetic preparations, including lubricants.6 Babizhayev et al. have since claimed that they have developed a technology using imidazole-containing dipeptide-based compounds (including L-carnosine and derivatives) that enhances protein hydration in photoaged skin.12,13,14
A double-blind comparative study conducted by Dieamant et al. in 2008 in 124 volunteers with sensitive skin aimed to evaluate the therapeutic potential of the combination of the antioxidant L-carnosine and neuromodulatory Rhodiola rosea. For 28 days, the groups of 62 received twice-daily applications of the 1% combination formulation or placebo. Skin barrier function (reduction of transepidermal water loss) improved in the treatment group, and favorable subjective responses regarding skin dryness were reported. Discomfort after the stinging test was also reduced. In vitro results showed that the release of proopiomelanocortin peptides was spurred by treatment, with the elevated levels of neuropeptides and cytokines produced by keratinocytes exposed to UV radiation returning to normal.15
Two years later, Renner et al. showed that carnosine hindered tumor growth in vivo in an NIH3T3-HER2/neu mouse model. They contended that this naturally occurring dipeptide warrants increased consideration and study for its potential as an anticancer agent.16
In 2012, Federici et al. conducted a randomized, evaluator-blinded, controlled comparative trial over 1month to assess the efficacy of twice-daily topical urea 5% with arginine and carnosine (Ureadin Rx) as compared with twice-daily application of a glycerol-based emollient topical product (Dexeryl) in treating xerosis in 40 type 2 diabetes patients (40-75 years of age). Use of the carnosine-containing formulation yielded significantly greater hydration and an 89% decline in Dryness Areas Severity Index (DASI) scores, compared with baseline. The DASI score after 4 weeks of treatment was much lower in the treatment group than the control group. The Visual Analog Scale (VAS) score was also significantly higher in the Ureadin group than the Dexeryl group. The investigators concluded that the topical application of a urea 5%, arginine, and carnosine cream enhances skin hydration and relieves dryness in type 2 diabetic patients in comparison with a control glycerol-based emollient formulation.17
Antiaging potential
In 1993, Reeve et al. showed that dietary or topically applied carnosine potentiated the contact hypersensitivity reaction in hairless mice and prevented the systemic inhibition of this reaction after dorsal skin exposure to UVB. Carnosine was found to also prevent the systemic suppression provoked by the topical application of a lotion containing cis-urocanic acid.3
Carnosine was a key active ingredient in antiaging products evaluated by Kaczvinsky et al. in 2009 in two double-blind, randomized, controlled, split-face studies. The researchers used the Fast Optical in vivo Topometry of Human Skin (FOITS) technique to measure changes in periorbital wrinkles in the two studies in women between the ages of 30 and 70 years old (study 1, n = 42; study 2, n = 35). They reported that 4 weeks of treatment with the test products, which contained niacinamide, the peptides Pal-KT and Pal-KTTKS, and carnosine, ameliorated periorbital skin, enhancing smoothness and diminishing larger wrinkle depth.18
In 2012, Babizhayev et al. conducted a 4-month randomized, double-blind, controlled study with 42 subjects to evaluate the effects on skin aging of oral nonhydrolyzed carnosine (Can-C Plus formulation). Skin parameters exhibited a consistent and significant improvement during 3 months of supplementation in the treatment group, compared with the placebo group, with overall skin appearance enhanced and fine lines diminished based on visual inspection. There were no reports of adverse effects. The investigators concluded that supplementation with nonhydrolyzed carnosine or carcinine in patented oral formulations has potential as an agent for antiaging purposes.19
Two years later, Emanuele et al. conducted an experimental double-blind irradiation study to compare a complex novel topical product (TPF50) consisting of three active ingredients (traditional physical sunscreens, SPF 50; a liposome-encapsulated DNA repair enzymes complex – photolyase, endonuclease, and 8-oxoguanine glycosylase [OGG1]; and a robust antioxidant complex containing carnosine, arazine, and ergothionine) to available DNA repair and antioxidant and growth factor topical products. They found that the new topical agent was the most effective product in reducing three molecular markers (cyclobutane pyrimidine dimers, protein carbonylation, and 8-oxo-7,8-dihydro-2’-deoxyguanosine) in human skin biopsies. The researchers concluded that the carnosine-containing formulation enhances the genomic and proteomic integrity of skin cells after continual UV exposure, suggesting its potential efficacy in lowering the risk of UV-induced cutaneous aging and nonmelanoma skin cancer.20
Conclusion
Carnosine is an intriguing compound with well-documented antioxidant and wound healing activity. While more research is necessary to determine its wider applications in dermatology, recent work in formulating topical products to impart antiaging effects appears to show promise.
References
1. Nutr. Res. Pract. 2011;5:421-8.
2. Amino Acids 2012;43:127-34.
4. Mol. Aspects Med. 1992;13:379-444.
5. Am. J. Ther. 2012;19:e69-89.
7. J. Cosmet. Dermatol. 2004;3:26-34.
8. Nihon Yakurigaku Zasshi. 1992;100:165-72.
12. Int. J. Cosmet. Sci. 2011;33:1-16.
13. Crit. Rev. Ther. Drug Carrier Syst. 2011;28:203-53.
14. Crit. Rev. Ther. Drug Carrier Syst. 2010;27:85-154.
15. J. Cosmet. Dermatol. 2008;7:112-9.
18. J. Cosmet. Dermatol. 2009;8:228-33.
19. J. Dermatolog. Treat. 2012;23:345-84.
20. J. Drugs Dermatol. 2014;13:309-14.
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.
