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Recall that melatonin displays multiple biological functions, acting as an antioxidant, cytokine, neurotransmitter, and global regulator of the circadian clock, the latter for which it is best known.1-3 At the cutaneous level, melatonin exhibits antioxidant (direct, as a radical scavenger; indirect, through upregulating antioxidant enzymes), anti-inflammatory, photoprotective, tissue regenerative, and cytoprotective activity, particularly in its capacity to preserve mitochondrial function.4-8
Melatonin also protects skin homeostasis,6 and, consequently, is believed to act against carcinogenesis and potentially other deleterious dysfunctions such as hyperproliferative/inflammatory conditions.5 Notably, , further buttressing the critical role that melatonin plays in skin health.5 Melatonin also displays immunomodulatory, thermoregulatory, and antitumor functions.9 The topical application of melatonin has been demonstrated to diminish markers of reactive oxygen species as well as reverse manifestations of cutaneous aging.5
Melatonin is both produced by and metabolized in the skin. The hormone and its metabolites (6-hydroxymelatonin, N1-acetyl-N2-formyl-5-methoxykynuramine [AFMK], N-acetyl-serotonin, and 5-methoxytryptamine) reduce UVB-induced oxidative cell damage in human keratinocytes and melanocytes, and also act as radioprotectors.6
Melatonin has been shown to protect human dermal fibroblasts from UVA- and UVB-induced damage.9 In addition, melatonin and its metabolites have been demonstrated to suppress the growth of cultured human melanomas, and high doses of melatonin used in clinical trials in late metastatic melanoma stages have enhanced the efficacy of or diminished the side effects of chemotherapy/chemo-immunotherapy.9
UVB and melatonin in the lab
In a 2018 hairless mouse study in which animals were irradiated by UVB for 8 weeks, Park et al. showed that melatonin displays anti-wrinkle activity by suppressing reactive oxygen species- and sonic hedgehog-mediated inflammatory proteins. Melatonin also protected against transepidermal water loss and prevented epidermal thickness as well as dermal collagen degradation.10
Also that year, Skobowiat et al. found that the topical application of melatonin and its active derivatives (N1-acetyl-N2-formyl-5-methoxykynurenine and N-acetylserotonin) yielded photoprotective effects pre- and post-UVB treatment in human and porcine skin ex vivo. They concluded that their results justify additional investigation of the clinical applications of melatonin and its metabolites for its potential to exert protective effects against UVB in human subjects.8
Although the preponderance of previous work identifies melatonin as a strong antioxidant, Kocyigit et al. reported in 2018 on new in vitro studies suggesting that melatonin dose-dependently exerts cytotoxic and apoptotic activity on several cell types, including both human epidermoid carcinoma and normal skin fibroblasts. Their findings showed that melatonin exhibited proliferative effects on cancerous and normal cells at low doses and cytotoxic effects at high doses.11
Melatonin as a sunscreen ingredient
Further supporting its use in the topical armamentarium for skin health, melatonin is a key ingredient in a sunscreen formulation, the creation of which was driven by the need to protect the skin of military personnel facing lengthy UV exposure. Specifically, the formulation containing avobenzone, octinoxate, oxybenzone, and titanium dioxide along with melatonin and pumpkin seed oil underwent a preclinical safety evaluation in 2017, as reported by Bora et al. The formulation was found to be nonmutagenic, nontoxic, and safe in animal models and is deemed ready to test for its efficacy in humans.12 Melatonin is also among a host of systemic treatment options for skin lightening.13
Oral and topical melatonin in human studies
In a 2017 study on the impact of melatonin treatment on the skin of former smokers, Sagan et al. assessed oxidative damage to membrane lipids in blood serum and in epidermis exfoliated during microdermabrasion (at baseline, 2 weeks after, and 4 weeks after treatment) in postmenopausal women. Never smokers (n = 44) and former smokers (n = 46) were divided into control, melatonin topical, antioxidant topical, and melatonin oral treatment groups. The investigators found that after only 2 weeks, melatonin oral treatment significantly reversed the elevated serum lipid peroxidation in former smokers. Oral melatonin increased elasticity, moisture, and sebum levels after 4 weeks of treatment and topical melatonin increased sebum level. They concluded that the use of exogenous melatonin reverses the effects of oxidative damage to membrane lipids and ameliorates cutaneous biophysical traits in postmenopausal women who once smoked. The researchers added that melatonin use for all former smokers is warranted and that topically applied melatonin merits consideration for improving the effects of facial microdermabrasion.14
In a systematic literature review in 2017, Scheuer identified 20 studies (4 human and 16 experimental) indicating that melatonin exerts a protective effect against artificial UV-induced erythema when applied pre-exposure.7 Also that year, Scheuer and colleagues conducted randomized, double-blind, placebo-controlled work demonstrating that topical melatonin (12.5%) significantly reduced erythema resulting from natural sunlight, and in a separate randomized, double-blind, placebo-controlled crossover study that the same concentration of a full body application of melatonin exhibited no significant impact on cognition and should be considered safe for dermal application.7 Scheuer added that additional longitudinal research is needed to ascertain effects of topical melatonin usage over time.
Early in 2018, Milani and Sparavigna reported on a randomized, split-face, assessor-blinded, prospective 3-month study of 22 women (mean age 55 years) with moderate to severe facial skin aging; the study was designed to test the efficacy of melatonin-based day and night creams. All of the women completed the proof-of-concept trial in which crow’s feet were found to be significantly diminished on the sides of the face treated with the creams compared with the nontreated skin.
Both well-tolerated melatonin formulations were associated with significant improvements in surface microrelief, skin profilometry, tonicity, and dryness. With marked enhancement of skin hydration and reduction of roughness noted, the investigators concluded that their results supported the notion that the tested melatonin topical formulations yielded antiaging effects.4
Conclusion
The majority of research on the potent hormone melatonin over nearly the last quarter century indicates that this dynamic substance provides multifaceted benefits in performing several biological functions. Topical melatonin is available over the counter. Its expanded use in skin care warrants greater attention as we learn more about this versatile endogenous substance.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients,” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. Write to her at [email protected].
References
1. Zmijewski MA et al. Dermatoendocrinol. 2011 Jan;3(1):3-10.
2. Slominski A et al. Trends Endocrinol Metab. 2008 Jan;19(1):17-24.
3. Slominski A et al. J Cell Physiol. 2003 Jul;196(1):144-53.
4. Milani M et al. Clin Cosmet Investig Dermatol. 2018 Jan 24;11:51-7.
5. Day D et al. J Drugs Dermatol. 2018 Sep 1;17(9):966-9.
6. Slominski AT et al. Cell Mol Life Sci. 2017 Nov;74(21):3913-25.
7. Scheuer C. Dan Med J. 2017 Jun;64(6). pii:B5358.
8. Skobowiat C et al. J Pineal Res. 2018 Sep;65(2):e12501.
9. Slominski AT et al. J Invest Dermatol. 2018 Mar;138(3):490-9.
10. Park EK et al. Int J Mol Sci. 2018 Jul 8;19(7). pii: E1995.
11. Kocyigit A et al. Mutat Res. 2018 May-Jun;829-30:50-60.
12. Bora NS et al. Regul Toxicol Pharmacol. 2017 Oct;89:1-12.
13. Juhasz MLW et al. J Cosmet Dermatol. 2018 Dec;17(6):1144-57.
14. Sagan D et al. Ann Agric Environ Med. 2017 Dec 23;24(4):659-66.
Recall that melatonin displays multiple biological functions, acting as an antioxidant, cytokine, neurotransmitter, and global regulator of the circadian clock, the latter for which it is best known.1-3 At the cutaneous level, melatonin exhibits antioxidant (direct, as a radical scavenger; indirect, through upregulating antioxidant enzymes), anti-inflammatory, photoprotective, tissue regenerative, and cytoprotective activity, particularly in its capacity to preserve mitochondrial function.4-8
Melatonin also protects skin homeostasis,6 and, consequently, is believed to act against carcinogenesis and potentially other deleterious dysfunctions such as hyperproliferative/inflammatory conditions.5 Notably, , further buttressing the critical role that melatonin plays in skin health.5 Melatonin also displays immunomodulatory, thermoregulatory, and antitumor functions.9 The topical application of melatonin has been demonstrated to diminish markers of reactive oxygen species as well as reverse manifestations of cutaneous aging.5
Melatonin is both produced by and metabolized in the skin. The hormone and its metabolites (6-hydroxymelatonin, N1-acetyl-N2-formyl-5-methoxykynuramine [AFMK], N-acetyl-serotonin, and 5-methoxytryptamine) reduce UVB-induced oxidative cell damage in human keratinocytes and melanocytes, and also act as radioprotectors.6
Melatonin has been shown to protect human dermal fibroblasts from UVA- and UVB-induced damage.9 In addition, melatonin and its metabolites have been demonstrated to suppress the growth of cultured human melanomas, and high doses of melatonin used in clinical trials in late metastatic melanoma stages have enhanced the efficacy of or diminished the side effects of chemotherapy/chemo-immunotherapy.9
UVB and melatonin in the lab
In a 2018 hairless mouse study in which animals were irradiated by UVB for 8 weeks, Park et al. showed that melatonin displays anti-wrinkle activity by suppressing reactive oxygen species- and sonic hedgehog-mediated inflammatory proteins. Melatonin also protected against transepidermal water loss and prevented epidermal thickness as well as dermal collagen degradation.10
Also that year, Skobowiat et al. found that the topical application of melatonin and its active derivatives (N1-acetyl-N2-formyl-5-methoxykynurenine and N-acetylserotonin) yielded photoprotective effects pre- and post-UVB treatment in human and porcine skin ex vivo. They concluded that their results justify additional investigation of the clinical applications of melatonin and its metabolites for its potential to exert protective effects against UVB in human subjects.8
Although the preponderance of previous work identifies melatonin as a strong antioxidant, Kocyigit et al. reported in 2018 on new in vitro studies suggesting that melatonin dose-dependently exerts cytotoxic and apoptotic activity on several cell types, including both human epidermoid carcinoma and normal skin fibroblasts. Their findings showed that melatonin exhibited proliferative effects on cancerous and normal cells at low doses and cytotoxic effects at high doses.11
Melatonin as a sunscreen ingredient
Further supporting its use in the topical armamentarium for skin health, melatonin is a key ingredient in a sunscreen formulation, the creation of which was driven by the need to protect the skin of military personnel facing lengthy UV exposure. Specifically, the formulation containing avobenzone, octinoxate, oxybenzone, and titanium dioxide along with melatonin and pumpkin seed oil underwent a preclinical safety evaluation in 2017, as reported by Bora et al. The formulation was found to be nonmutagenic, nontoxic, and safe in animal models and is deemed ready to test for its efficacy in humans.12 Melatonin is also among a host of systemic treatment options for skin lightening.13
Oral and topical melatonin in human studies
In a 2017 study on the impact of melatonin treatment on the skin of former smokers, Sagan et al. assessed oxidative damage to membrane lipids in blood serum and in epidermis exfoliated during microdermabrasion (at baseline, 2 weeks after, and 4 weeks after treatment) in postmenopausal women. Never smokers (n = 44) and former smokers (n = 46) were divided into control, melatonin topical, antioxidant topical, and melatonin oral treatment groups. The investigators found that after only 2 weeks, melatonin oral treatment significantly reversed the elevated serum lipid peroxidation in former smokers. Oral melatonin increased elasticity, moisture, and sebum levels after 4 weeks of treatment and topical melatonin increased sebum level. They concluded that the use of exogenous melatonin reverses the effects of oxidative damage to membrane lipids and ameliorates cutaneous biophysical traits in postmenopausal women who once smoked. The researchers added that melatonin use for all former smokers is warranted and that topically applied melatonin merits consideration for improving the effects of facial microdermabrasion.14
In a systematic literature review in 2017, Scheuer identified 20 studies (4 human and 16 experimental) indicating that melatonin exerts a protective effect against artificial UV-induced erythema when applied pre-exposure.7 Also that year, Scheuer and colleagues conducted randomized, double-blind, placebo-controlled work demonstrating that topical melatonin (12.5%) significantly reduced erythema resulting from natural sunlight, and in a separate randomized, double-blind, placebo-controlled crossover study that the same concentration of a full body application of melatonin exhibited no significant impact on cognition and should be considered safe for dermal application.7 Scheuer added that additional longitudinal research is needed to ascertain effects of topical melatonin usage over time.
Early in 2018, Milani and Sparavigna reported on a randomized, split-face, assessor-blinded, prospective 3-month study of 22 women (mean age 55 years) with moderate to severe facial skin aging; the study was designed to test the efficacy of melatonin-based day and night creams. All of the women completed the proof-of-concept trial in which crow’s feet were found to be significantly diminished on the sides of the face treated with the creams compared with the nontreated skin.
Both well-tolerated melatonin formulations were associated with significant improvements in surface microrelief, skin profilometry, tonicity, and dryness. With marked enhancement of skin hydration and reduction of roughness noted, the investigators concluded that their results supported the notion that the tested melatonin topical formulations yielded antiaging effects.4
Conclusion
The majority of research on the potent hormone melatonin over nearly the last quarter century indicates that this dynamic substance provides multifaceted benefits in performing several biological functions. Topical melatonin is available over the counter. Its expanded use in skin care warrants greater attention as we learn more about this versatile endogenous substance.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients,” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. Write to her at [email protected].
References
1. Zmijewski MA et al. Dermatoendocrinol. 2011 Jan;3(1):3-10.
2. Slominski A et al. Trends Endocrinol Metab. 2008 Jan;19(1):17-24.
3. Slominski A et al. J Cell Physiol. 2003 Jul;196(1):144-53.
4. Milani M et al. Clin Cosmet Investig Dermatol. 2018 Jan 24;11:51-7.
5. Day D et al. J Drugs Dermatol. 2018 Sep 1;17(9):966-9.
6. Slominski AT et al. Cell Mol Life Sci. 2017 Nov;74(21):3913-25.
7. Scheuer C. Dan Med J. 2017 Jun;64(6). pii:B5358.
8. Skobowiat C et al. J Pineal Res. 2018 Sep;65(2):e12501.
9. Slominski AT et al. J Invest Dermatol. 2018 Mar;138(3):490-9.
10. Park EK et al. Int J Mol Sci. 2018 Jul 8;19(7). pii: E1995.
11. Kocyigit A et al. Mutat Res. 2018 May-Jun;829-30:50-60.
12. Bora NS et al. Regul Toxicol Pharmacol. 2017 Oct;89:1-12.
13. Juhasz MLW et al. J Cosmet Dermatol. 2018 Dec;17(6):1144-57.
14. Sagan D et al. Ann Agric Environ Med. 2017 Dec 23;24(4):659-66.
Recall that melatonin displays multiple biological functions, acting as an antioxidant, cytokine, neurotransmitter, and global regulator of the circadian clock, the latter for which it is best known.1-3 At the cutaneous level, melatonin exhibits antioxidant (direct, as a radical scavenger; indirect, through upregulating antioxidant enzymes), anti-inflammatory, photoprotective, tissue regenerative, and cytoprotective activity, particularly in its capacity to preserve mitochondrial function.4-8
Melatonin also protects skin homeostasis,6 and, consequently, is believed to act against carcinogenesis and potentially other deleterious dysfunctions such as hyperproliferative/inflammatory conditions.5 Notably, , further buttressing the critical role that melatonin plays in skin health.5 Melatonin also displays immunomodulatory, thermoregulatory, and antitumor functions.9 The topical application of melatonin has been demonstrated to diminish markers of reactive oxygen species as well as reverse manifestations of cutaneous aging.5
Melatonin is both produced by and metabolized in the skin. The hormone and its metabolites (6-hydroxymelatonin, N1-acetyl-N2-formyl-5-methoxykynuramine [AFMK], N-acetyl-serotonin, and 5-methoxytryptamine) reduce UVB-induced oxidative cell damage in human keratinocytes and melanocytes, and also act as radioprotectors.6
Melatonin has been shown to protect human dermal fibroblasts from UVA- and UVB-induced damage.9 In addition, melatonin and its metabolites have been demonstrated to suppress the growth of cultured human melanomas, and high doses of melatonin used in clinical trials in late metastatic melanoma stages have enhanced the efficacy of or diminished the side effects of chemotherapy/chemo-immunotherapy.9
UVB and melatonin in the lab
In a 2018 hairless mouse study in which animals were irradiated by UVB for 8 weeks, Park et al. showed that melatonin displays anti-wrinkle activity by suppressing reactive oxygen species- and sonic hedgehog-mediated inflammatory proteins. Melatonin also protected against transepidermal water loss and prevented epidermal thickness as well as dermal collagen degradation.10
Also that year, Skobowiat et al. found that the topical application of melatonin and its active derivatives (N1-acetyl-N2-formyl-5-methoxykynurenine and N-acetylserotonin) yielded photoprotective effects pre- and post-UVB treatment in human and porcine skin ex vivo. They concluded that their results justify additional investigation of the clinical applications of melatonin and its metabolites for its potential to exert protective effects against UVB in human subjects.8
Although the preponderance of previous work identifies melatonin as a strong antioxidant, Kocyigit et al. reported in 2018 on new in vitro studies suggesting that melatonin dose-dependently exerts cytotoxic and apoptotic activity on several cell types, including both human epidermoid carcinoma and normal skin fibroblasts. Their findings showed that melatonin exhibited proliferative effects on cancerous and normal cells at low doses and cytotoxic effects at high doses.11
Melatonin as a sunscreen ingredient
Further supporting its use in the topical armamentarium for skin health, melatonin is a key ingredient in a sunscreen formulation, the creation of which was driven by the need to protect the skin of military personnel facing lengthy UV exposure. Specifically, the formulation containing avobenzone, octinoxate, oxybenzone, and titanium dioxide along with melatonin and pumpkin seed oil underwent a preclinical safety evaluation in 2017, as reported by Bora et al. The formulation was found to be nonmutagenic, nontoxic, and safe in animal models and is deemed ready to test for its efficacy in humans.12 Melatonin is also among a host of systemic treatment options for skin lightening.13
Oral and topical melatonin in human studies
In a 2017 study on the impact of melatonin treatment on the skin of former smokers, Sagan et al. assessed oxidative damage to membrane lipids in blood serum and in epidermis exfoliated during microdermabrasion (at baseline, 2 weeks after, and 4 weeks after treatment) in postmenopausal women. Never smokers (n = 44) and former smokers (n = 46) were divided into control, melatonin topical, antioxidant topical, and melatonin oral treatment groups. The investigators found that after only 2 weeks, melatonin oral treatment significantly reversed the elevated serum lipid peroxidation in former smokers. Oral melatonin increased elasticity, moisture, and sebum levels after 4 weeks of treatment and topical melatonin increased sebum level. They concluded that the use of exogenous melatonin reverses the effects of oxidative damage to membrane lipids and ameliorates cutaneous biophysical traits in postmenopausal women who once smoked. The researchers added that melatonin use for all former smokers is warranted and that topically applied melatonin merits consideration for improving the effects of facial microdermabrasion.14
In a systematic literature review in 2017, Scheuer identified 20 studies (4 human and 16 experimental) indicating that melatonin exerts a protective effect against artificial UV-induced erythema when applied pre-exposure.7 Also that year, Scheuer and colleagues conducted randomized, double-blind, placebo-controlled work demonstrating that topical melatonin (12.5%) significantly reduced erythema resulting from natural sunlight, and in a separate randomized, double-blind, placebo-controlled crossover study that the same concentration of a full body application of melatonin exhibited no significant impact on cognition and should be considered safe for dermal application.7 Scheuer added that additional longitudinal research is needed to ascertain effects of topical melatonin usage over time.
Early in 2018, Milani and Sparavigna reported on a randomized, split-face, assessor-blinded, prospective 3-month study of 22 women (mean age 55 years) with moderate to severe facial skin aging; the study was designed to test the efficacy of melatonin-based day and night creams. All of the women completed the proof-of-concept trial in which crow’s feet were found to be significantly diminished on the sides of the face treated with the creams compared with the nontreated skin.
Both well-tolerated melatonin formulations were associated with significant improvements in surface microrelief, skin profilometry, tonicity, and dryness. With marked enhancement of skin hydration and reduction of roughness noted, the investigators concluded that their results supported the notion that the tested melatonin topical formulations yielded antiaging effects.4
Conclusion
The majority of research on the potent hormone melatonin over nearly the last quarter century indicates that this dynamic substance provides multifaceted benefits in performing several biological functions. Topical melatonin is available over the counter. Its expanded use in skin care warrants greater attention as we learn more about this versatile endogenous substance.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients,” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. Write to her at [email protected].
References
1. Zmijewski MA et al. Dermatoendocrinol. 2011 Jan;3(1):3-10.
2. Slominski A et al. Trends Endocrinol Metab. 2008 Jan;19(1):17-24.
3. Slominski A et al. J Cell Physiol. 2003 Jul;196(1):144-53.
4. Milani M et al. Clin Cosmet Investig Dermatol. 2018 Jan 24;11:51-7.
5. Day D et al. J Drugs Dermatol. 2018 Sep 1;17(9):966-9.
6. Slominski AT et al. Cell Mol Life Sci. 2017 Nov;74(21):3913-25.
7. Scheuer C. Dan Med J. 2017 Jun;64(6). pii:B5358.
8. Skobowiat C et al. J Pineal Res. 2018 Sep;65(2):e12501.
9. Slominski AT et al. J Invest Dermatol. 2018 Mar;138(3):490-9.
10. Park EK et al. Int J Mol Sci. 2018 Jul 8;19(7). pii: E1995.
11. Kocyigit A et al. Mutat Res. 2018 May-Jun;829-30:50-60.
12. Bora NS et al. Regul Toxicol Pharmacol. 2017 Oct;89:1-12.
13. Juhasz MLW et al. J Cosmet Dermatol. 2018 Dec;17(6):1144-57.
14. Sagan D et al. Ann Agric Environ Med. 2017 Dec 23;24(4):659-66.
