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Found in various plant and animal species, including humans, melatonin (N-acetyl-5-methoxytryptamine) is best known for its daily fluctuations in circulating levels that regulate circadian rhythms. But this ancient serotonin derivative, stimulated by beta-adrenergic receptors, is the primary neuroendocrine product of the pineal gland (discovered as such in 1917) in humans and a dynamic compound with diverse roles in human health levels of which decrease with age.1,2 Over the last quarter of a century, we have arrived at a much greater understanding of the varied biological functions of this highly lipophilic hormone, which is now recognized as the strongest endogenous antioxidant, particularly potent against hydroxyl radicals, the most harmful of reactive oxygen species, and known to protect mitochondria and DNA from direct oxidative harm.2-4 Directly or via its circadian impact, melatonin also affects skin as well as core body temperature.1 This column is a . Next month’s column will address some more of the activities of this dynamic hormone while concentrating on the interaction of melatonin and ultraviolet radiation.
Early studies
In the mid-1990s, Bangha et al. performed several studies in healthy human volunteers that demonstrated that topically applied melatonin suppressed UVB-induced erythema (with one study showing pre- and posttreatment as effective and a subsequent one showing only pretreatment as effective), and also found that melatonin appears to have the potential to accumulate in the stratum corneum with extended release into the blood system through cutaneous delivery.5-7
A randomized, double-blind study by Dreher et al. in 12 healthy adults (6 women and 6 men, all white, aged 29-49 years) considered the short-term photoprotective effects of topically applied vitamin C, vitamin E, and melatonin, alone or in combination, 30 minutes after UV exposure. A dose-dependent photoprotective effect was associated with melatonin, and photoprotective properties were enhanced when melatonin in was combined with vitamins C and E.8
The following year, Dreher et al. evaluated the short-term photoprotective effects of the same compounds in a randomized, double-blind, placebo-controlled human study. Each antioxidant was topically applied alone or in combination after UV exposure in a single application (immediately or 30 minutes after UV exposure) or in multiple applications 30 minutes, 1 hour, and 2 hours after UV exposure (totaling three applications). Interestingly, no photoprotective effects were seen. The researchers concluded that given the speed of cutaneous damage from UV radiation, antioxidants likely must be delivered at the appropriate site in sufficient doses at the outset of and during active oxidative harm.9
In 2004, Fischer et al. conducted a clinical study of 15 healthy volunteers to test the skin penetration activity of melatonin 0.01% in a cream and 0.01% and 0.03% in a solution. During a 24-hour period, researchers obtained blood samples for melatonin measurement prior to application at 9 a.m. as well as 1, 4, 8, and 24 hours after application. Preapplication serum melatonin levels ranged from 0.6 to 15.9 pg/mL. The mean serum value 24 hours later after application of the 0.01% melatonin cream was 9.0 pg/mL. For the 0.01% solution group, the mean melatonin level was 12.7 pg/mL 24 hours after application. Melatonin levels also substantially rose just 1 and 8 hours later in the 0.03% solution group, with cumulative melatonin measured as 7.1 pg/mL in the 0.01% cream group, 8.6 pg/mL in the 0.01% solution participants, and 15.7 pg/mL in the 0.03% group. The investigators concluded that as a strong lipophilic compound melatonin penetrates the skin with serum blood levels increasing in a dose- and galenic-dependent manner without prompting spikes above the physiological range.10
Wound healing and atopic dermatitis
In 2006, Sener et al. reported that topically applied and systemically administered melatonin was successful as a pressure ulcer treatment in rats.11 Four years later, in a study using a chronic wound model in rats with pinealectomy that suppressed basal melatonin, Ozler et al. found that systemic and topical melatonin treatment were equally effective in imparting wound healing effects.12
A study in mice conducted by Kim et al. at around the same time showed that topically applied melatonin, by reducing total IgE in serum and interleukin-4 and interferon-gamma production by activated CD4(+) T cells, inhibits atopic dermatitis–like skin lesion development engendered by 2,4-dinitrofluorobenzene (DNFB) treatment in NC/Nga mice.13
More recently, Abbaszadeh et al. have suggested that melatonin has the potential to enhance the therapeutic ratio in radiation oncology, and to be more effective at reducing skin damage in this setting when used in optimal and non-toxic doses.2
Pigmentation disorders
Melatonin and serotonin are thought to have potential to ameliorate or attenuate the spread of vitiligo.1 In addition, melatonin appears to have potential in the realm of hyperpigmentation treatment. Investigators have found that the combination of topical melatonin 5% and a daily dose of 3 g of oral melatonin over 120 days significantly reduces Melasma Area Severity Index scores in comparison to placebo; the improvement is attributed primarily to the use of topical melatonin.14,15
Androgenetic alopecia
In 2018, Hatem et al. designed nanostructured lipid carriers to better deliver melatonin in antioxidant oils to treat androgenic alopecia. They found that the carriers achieved a sustained release of 6 hours and raised the skin deposition of melatonin 4.5-fold in the stratum corneum, 7-fold in the epidermis, and 6.8-fold in the dermis compared with a melatonin solution. The nanostructured lipid carriers also improved on clinical results, compared to the melatonin formula, by increasing hair density and thickness and reducing hair loss in patients with androgenic alopecia.16
Conclusion
Studies in humans have shown that through systemic administration and, particularly, topical application. Demonstrated to be safe and effective, topically applied melatonin appears to warrant serious consideration as a skin-protective, anti-aging tool in the dermatologic armamentarium.
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 dermnews@mdedge.com.
References
1. Slominski AT et al. J Invest Dermatol. 2018 Mar;138(3):490-9.
2. Abbaszadeh A et al. J Biomed Phys Eng. 2017 Jun;7(2):127-136.
3. Fischer T et al. Hautarzt. 1999 Jan;50(1):5-11.
4. Scheuer C. Dan Med J. 2017 Jun;64(6). pii:B5358.
5. Bangha E et al. Arch Dermatol Res. 1996 Aug;288(9):522-6.
6. Bangha E et al. Dermatology. 1997;195(3):248-52.
7. Bangha E et al. Skin Pharmacol. 1997;10(5-6):298-302.
8. Dreher F et al. Br J Dermatol. 1998 Aug;139(2):332-9.
9. Dreher F et al. Dermatology. 1999;198(1):52-5.
10. Fischer TW et al. Skin Pharmacol Physiol. 2004 Jul-Aug;17(4):190-4.
11. Sener G et al. J Pineal Res. 2006 Apr;40(3):280-7.
12. Ozler M et al. Scand J Clin Lab Invest. 2010 Oct;70(6):447-52.
13. Kim TH et al. J Pineal Res. 2009 Nov;47(4):324-9.
14. Juhasz MLW et al. J Cosmet Dermatol. 2018 Dec;17(6):1144-57.
15. Hamadi SA, Mohammed MM, Aljaf AN, et al. The role of topical and oral melatonin in management of melasma patients. J Arab Univ Basic Appl Sci. 2009;8:30‐42.
16. Hatem S et al. Expert Opin Drug Deliv. 2018 Oct;15(10):927-35.
Found in various plant and animal species, including humans, melatonin (N-acetyl-5-methoxytryptamine) is best known for its daily fluctuations in circulating levels that regulate circadian rhythms. But this ancient serotonin derivative, stimulated by beta-adrenergic receptors, is the primary neuroendocrine product of the pineal gland (discovered as such in 1917) in humans and a dynamic compound with diverse roles in human health levels of which decrease with age.1,2 Over the last quarter of a century, we have arrived at a much greater understanding of the varied biological functions of this highly lipophilic hormone, which is now recognized as the strongest endogenous antioxidant, particularly potent against hydroxyl radicals, the most harmful of reactive oxygen species, and known to protect mitochondria and DNA from direct oxidative harm.2-4 Directly or via its circadian impact, melatonin also affects skin as well as core body temperature.1 This column is a . Next month’s column will address some more of the activities of this dynamic hormone while concentrating on the interaction of melatonin and ultraviolet radiation.
Early studies
In the mid-1990s, Bangha et al. performed several studies in healthy human volunteers that demonstrated that topically applied melatonin suppressed UVB-induced erythema (with one study showing pre- and posttreatment as effective and a subsequent one showing only pretreatment as effective), and also found that melatonin appears to have the potential to accumulate in the stratum corneum with extended release into the blood system through cutaneous delivery.5-7
A randomized, double-blind study by Dreher et al. in 12 healthy adults (6 women and 6 men, all white, aged 29-49 years) considered the short-term photoprotective effects of topically applied vitamin C, vitamin E, and melatonin, alone or in combination, 30 minutes after UV exposure. A dose-dependent photoprotective effect was associated with melatonin, and photoprotective properties were enhanced when melatonin in was combined with vitamins C and E.8
The following year, Dreher et al. evaluated the short-term photoprotective effects of the same compounds in a randomized, double-blind, placebo-controlled human study. Each antioxidant was topically applied alone or in combination after UV exposure in a single application (immediately or 30 minutes after UV exposure) or in multiple applications 30 minutes, 1 hour, and 2 hours after UV exposure (totaling three applications). Interestingly, no photoprotective effects were seen. The researchers concluded that given the speed of cutaneous damage from UV radiation, antioxidants likely must be delivered at the appropriate site in sufficient doses at the outset of and during active oxidative harm.9
In 2004, Fischer et al. conducted a clinical study of 15 healthy volunteers to test the skin penetration activity of melatonin 0.01% in a cream and 0.01% and 0.03% in a solution. During a 24-hour period, researchers obtained blood samples for melatonin measurement prior to application at 9 a.m. as well as 1, 4, 8, and 24 hours after application. Preapplication serum melatonin levels ranged from 0.6 to 15.9 pg/mL. The mean serum value 24 hours later after application of the 0.01% melatonin cream was 9.0 pg/mL. For the 0.01% solution group, the mean melatonin level was 12.7 pg/mL 24 hours after application. Melatonin levels also substantially rose just 1 and 8 hours later in the 0.03% solution group, with cumulative melatonin measured as 7.1 pg/mL in the 0.01% cream group, 8.6 pg/mL in the 0.01% solution participants, and 15.7 pg/mL in the 0.03% group. The investigators concluded that as a strong lipophilic compound melatonin penetrates the skin with serum blood levels increasing in a dose- and galenic-dependent manner without prompting spikes above the physiological range.10
Wound healing and atopic dermatitis
In 2006, Sener et al. reported that topically applied and systemically administered melatonin was successful as a pressure ulcer treatment in rats.11 Four years later, in a study using a chronic wound model in rats with pinealectomy that suppressed basal melatonin, Ozler et al. found that systemic and topical melatonin treatment were equally effective in imparting wound healing effects.12
A study in mice conducted by Kim et al. at around the same time showed that topically applied melatonin, by reducing total IgE in serum and interleukin-4 and interferon-gamma production by activated CD4(+) T cells, inhibits atopic dermatitis–like skin lesion development engendered by 2,4-dinitrofluorobenzene (DNFB) treatment in NC/Nga mice.13
More recently, Abbaszadeh et al. have suggested that melatonin has the potential to enhance the therapeutic ratio in radiation oncology, and to be more effective at reducing skin damage in this setting when used in optimal and non-toxic doses.2
Pigmentation disorders
Melatonin and serotonin are thought to have potential to ameliorate or attenuate the spread of vitiligo.1 In addition, melatonin appears to have potential in the realm of hyperpigmentation treatment. Investigators have found that the combination of topical melatonin 5% and a daily dose of 3 g of oral melatonin over 120 days significantly reduces Melasma Area Severity Index scores in comparison to placebo; the improvement is attributed primarily to the use of topical melatonin.14,15
Androgenetic alopecia
In 2018, Hatem et al. designed nanostructured lipid carriers to better deliver melatonin in antioxidant oils to treat androgenic alopecia. They found that the carriers achieved a sustained release of 6 hours and raised the skin deposition of melatonin 4.5-fold in the stratum corneum, 7-fold in the epidermis, and 6.8-fold in the dermis compared with a melatonin solution. The nanostructured lipid carriers also improved on clinical results, compared to the melatonin formula, by increasing hair density and thickness and reducing hair loss in patients with androgenic alopecia.16
Conclusion
Studies in humans have shown that through systemic administration and, particularly, topical application. Demonstrated to be safe and effective, topically applied melatonin appears to warrant serious consideration as a skin-protective, anti-aging tool in the dermatologic armamentarium.
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 dermnews@mdedge.com.
References
1. Slominski AT et al. J Invest Dermatol. 2018 Mar;138(3):490-9.
2. Abbaszadeh A et al. J Biomed Phys Eng. 2017 Jun;7(2):127-136.
3. Fischer T et al. Hautarzt. 1999 Jan;50(1):5-11.
4. Scheuer C. Dan Med J. 2017 Jun;64(6). pii:B5358.
5. Bangha E et al. Arch Dermatol Res. 1996 Aug;288(9):522-6.
6. Bangha E et al. Dermatology. 1997;195(3):248-52.
7. Bangha E et al. Skin Pharmacol. 1997;10(5-6):298-302.
8. Dreher F et al. Br J Dermatol. 1998 Aug;139(2):332-9.
9. Dreher F et al. Dermatology. 1999;198(1):52-5.
10. Fischer TW et al. Skin Pharmacol Physiol. 2004 Jul-Aug;17(4):190-4.
11. Sener G et al. J Pineal Res. 2006 Apr;40(3):280-7.
12. Ozler M et al. Scand J Clin Lab Invest. 2010 Oct;70(6):447-52.
13. Kim TH et al. J Pineal Res. 2009 Nov;47(4):324-9.
14. Juhasz MLW et al. J Cosmet Dermatol. 2018 Dec;17(6):1144-57.
15. Hamadi SA, Mohammed MM, Aljaf AN, et al. The role of topical and oral melatonin in management of melasma patients. J Arab Univ Basic Appl Sci. 2009;8:30‐42.
16. Hatem S et al. Expert Opin Drug Deliv. 2018 Oct;15(10):927-35.
Found in various plant and animal species, including humans, melatonin (N-acetyl-5-methoxytryptamine) is best known for its daily fluctuations in circulating levels that regulate circadian rhythms. But this ancient serotonin derivative, stimulated by beta-adrenergic receptors, is the primary neuroendocrine product of the pineal gland (discovered as such in 1917) in humans and a dynamic compound with diverse roles in human health levels of which decrease with age.1,2 Over the last quarter of a century, we have arrived at a much greater understanding of the varied biological functions of this highly lipophilic hormone, which is now recognized as the strongest endogenous antioxidant, particularly potent against hydroxyl radicals, the most harmful of reactive oxygen species, and known to protect mitochondria and DNA from direct oxidative harm.2-4 Directly or via its circadian impact, melatonin also affects skin as well as core body temperature.1 This column is a . Next month’s column will address some more of the activities of this dynamic hormone while concentrating on the interaction of melatonin and ultraviolet radiation.
Early studies
In the mid-1990s, Bangha et al. performed several studies in healthy human volunteers that demonstrated that topically applied melatonin suppressed UVB-induced erythema (with one study showing pre- and posttreatment as effective and a subsequent one showing only pretreatment as effective), and also found that melatonin appears to have the potential to accumulate in the stratum corneum with extended release into the blood system through cutaneous delivery.5-7
A randomized, double-blind study by Dreher et al. in 12 healthy adults (6 women and 6 men, all white, aged 29-49 years) considered the short-term photoprotective effects of topically applied vitamin C, vitamin E, and melatonin, alone or in combination, 30 minutes after UV exposure. A dose-dependent photoprotective effect was associated with melatonin, and photoprotective properties were enhanced when melatonin in was combined with vitamins C and E.8
The following year, Dreher et al. evaluated the short-term photoprotective effects of the same compounds in a randomized, double-blind, placebo-controlled human study. Each antioxidant was topically applied alone or in combination after UV exposure in a single application (immediately or 30 minutes after UV exposure) or in multiple applications 30 minutes, 1 hour, and 2 hours after UV exposure (totaling three applications). Interestingly, no photoprotective effects were seen. The researchers concluded that given the speed of cutaneous damage from UV radiation, antioxidants likely must be delivered at the appropriate site in sufficient doses at the outset of and during active oxidative harm.9
In 2004, Fischer et al. conducted a clinical study of 15 healthy volunteers to test the skin penetration activity of melatonin 0.01% in a cream and 0.01% and 0.03% in a solution. During a 24-hour period, researchers obtained blood samples for melatonin measurement prior to application at 9 a.m. as well as 1, 4, 8, and 24 hours after application. Preapplication serum melatonin levels ranged from 0.6 to 15.9 pg/mL. The mean serum value 24 hours later after application of the 0.01% melatonin cream was 9.0 pg/mL. For the 0.01% solution group, the mean melatonin level was 12.7 pg/mL 24 hours after application. Melatonin levels also substantially rose just 1 and 8 hours later in the 0.03% solution group, with cumulative melatonin measured as 7.1 pg/mL in the 0.01% cream group, 8.6 pg/mL in the 0.01% solution participants, and 15.7 pg/mL in the 0.03% group. The investigators concluded that as a strong lipophilic compound melatonin penetrates the skin with serum blood levels increasing in a dose- and galenic-dependent manner without prompting spikes above the physiological range.10
Wound healing and atopic dermatitis
In 2006, Sener et al. reported that topically applied and systemically administered melatonin was successful as a pressure ulcer treatment in rats.11 Four years later, in a study using a chronic wound model in rats with pinealectomy that suppressed basal melatonin, Ozler et al. found that systemic and topical melatonin treatment were equally effective in imparting wound healing effects.12
A study in mice conducted by Kim et al. at around the same time showed that topically applied melatonin, by reducing total IgE in serum and interleukin-4 and interferon-gamma production by activated CD4(+) T cells, inhibits atopic dermatitis–like skin lesion development engendered by 2,4-dinitrofluorobenzene (DNFB) treatment in NC/Nga mice.13
More recently, Abbaszadeh et al. have suggested that melatonin has the potential to enhance the therapeutic ratio in radiation oncology, and to be more effective at reducing skin damage in this setting when used in optimal and non-toxic doses.2
Pigmentation disorders
Melatonin and serotonin are thought to have potential to ameliorate or attenuate the spread of vitiligo.1 In addition, melatonin appears to have potential in the realm of hyperpigmentation treatment. Investigators have found that the combination of topical melatonin 5% and a daily dose of 3 g of oral melatonin over 120 days significantly reduces Melasma Area Severity Index scores in comparison to placebo; the improvement is attributed primarily to the use of topical melatonin.14,15
Androgenetic alopecia
In 2018, Hatem et al. designed nanostructured lipid carriers to better deliver melatonin in antioxidant oils to treat androgenic alopecia. They found that the carriers achieved a sustained release of 6 hours and raised the skin deposition of melatonin 4.5-fold in the stratum corneum, 7-fold in the epidermis, and 6.8-fold in the dermis compared with a melatonin solution. The nanostructured lipid carriers also improved on clinical results, compared to the melatonin formula, by increasing hair density and thickness and reducing hair loss in patients with androgenic alopecia.16
Conclusion
Studies in humans have shown that through systemic administration and, particularly, topical application. Demonstrated to be safe and effective, topically applied melatonin appears to warrant serious consideration as a skin-protective, anti-aging tool in the dermatologic armamentarium.
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 dermnews@mdedge.com.
References
1. Slominski AT et al. J Invest Dermatol. 2018 Mar;138(3):490-9.
2. Abbaszadeh A et al. J Biomed Phys Eng. 2017 Jun;7(2):127-136.
3. Fischer T et al. Hautarzt. 1999 Jan;50(1):5-11.
4. Scheuer C. Dan Med J. 2017 Jun;64(6). pii:B5358.
5. Bangha E et al. Arch Dermatol Res. 1996 Aug;288(9):522-6.
6. Bangha E et al. Dermatology. 1997;195(3):248-52.
7. Bangha E et al. Skin Pharmacol. 1997;10(5-6):298-302.
8. Dreher F et al. Br J Dermatol. 1998 Aug;139(2):332-9.
9. Dreher F et al. Dermatology. 1999;198(1):52-5.
10. Fischer TW et al. Skin Pharmacol Physiol. 2004 Jul-Aug;17(4):190-4.
11. Sener G et al. J Pineal Res. 2006 Apr;40(3):280-7.
12. Ozler M et al. Scand J Clin Lab Invest. 2010 Oct;70(6):447-52.
13. Kim TH et al. J Pineal Res. 2009 Nov;47(4):324-9.
14. Juhasz MLW et al. J Cosmet Dermatol. 2018 Dec;17(6):1144-57.
15. Hamadi SA, Mohammed MM, Aljaf AN, et al. The role of topical and oral melatonin in management of melasma patients. J Arab Univ Basic Appl Sci. 2009;8:30‐42.
16. Hatem S et al. Expert Opin Drug Deliv. 2018 Oct;15(10):927-35.