Topical Melatonin Promotes Youthful SkinApril 2018
By Robert Goldfaden and Gary Goldfaden, MD
The impact of a good night’s sleep on maintaining younger-looking skin is often overlooked.
A recent study found that sleep quality strongly affects skin function and aging, concluding that:
“Chronic poor sleep quality is associated with increased signs of intrinsic aging, diminished skin barrier function, and lower satisfaction with appearance.”1
The skin-rejuvenating effects of sleep are partially attributed to the hormone melatonin, which exerts a wide range of anti-aging benefits.2-6
As melatonin output decreases with age,7 many people become more vulnerable to sleep disturbances that fail to adequately repair aging and photodamaged skin.
Research has revealed that topical melatonin, along with additional compounds, restores youthful reparative processes during the night to produce visible and long-lasting improvements in the health and appearance of skin.
Melatoninergic Antioxidative System: Your Skin’s Internal Ultraviolet Defense
Derived from the amino acid tryptophan, melatonin is a hormone produced mainly by the brain’s pineal gland, where it regulates our internal biological clock.8
Melatonin secretion is triggered in response to darkness, and diminished in the presence of light. Over the past decade, accumulating evidence indicates that melatonin offers health-promoting benefits that extend beyond regulating circadian rhythms. For example, it provides significant protection against UV-induced skin aging (photoaging).9
When melatonin attaches to receptors on various skin cells,10,11 it suppresses oxidative stress from sun exposure.4 Melatonin is known to:
- Act as a free-radical scavenger.12 After interacting with free radicals, melatonin is degraded to N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK)—both of which possess antioxidant and anti-inflammatory effects themselves.13,14 This antioxidant cascade is known as melatoninergic antioxidative system of the skin.15
- Activate intracellular antioxidant systems including superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT).16-19
Melatonin’s versatility as a free-radical scavenger attenuates lipid peroxidation, protein oxidation, and DNA damage to promote the survival of healthy skin cells.2,4
Dermal fibroblasts are cells that manufacture collagen and elastin, which are structural proteins that keep skin young, strong, and resilient. When dermal fibroblasts were treated with melatonin before sun exposure, they showed a survival rate of 92.5% compared to just 56% in those untreated.20
By protecting against damage caused by photoaging, melatonin combats a prime culprit behind wrinkles, fine lines, loss of tone, and skin cancer, and is therefore an important ally for retaining a youthful appearance.
Why We Need Topical Melatonin
Melatonin secretion gradually declines over time, increasing our susceptibility to sleep debt that diminishes the skin’s capacity to recover from external insults.21,22
Oral ingestion of melatonin does not always provide optimal skin protection.23 A more effective method is to apply melatonin topically, where it penetrates the stratum corneum and accumulates to initiate nightly repair and renewal.24,25
A review of human studies found that topically applied melatonin safeguards against sun-induced erythema by reducing cell death, DNA damage, and oxidative stress.26
Let’s now take a look at how three other topical agents provide photoprotection, while repairing and regenerating damaged skin.
Ectoin: Natural Skin-Cell Protection
Ectoin is a natural substance found in halophilic bacteria that allows them to withstand harsh environmental stressors such as cold temperatures, sweltering UV rays, and droughts.27,28 Researchers have discovered that ectoin behaves like a sponge to bind and trap water molecules around skin structures, forming large hydration shells that protect against premature cell damage from extrinsic factors.29
In a controlled study, human volunteers with crow’s feet topically applied ectoin or a placebo twice daily for four weeks. Compared to the subjects on placebo, participants in the ectoin-treatment group experienced a mean reduction in wrinkle depth of 32%, deepest wrinkle by 17%, and wrinkle volume by 40%.30
In a double-blind, placebo-controlled trial, topical application of ectoin twice daily for four weeks in 24 women aged 30-60 significantly increased skin elasticity by 82.4% over a placebo.29
Ectoin enhances the skin’s ability to retain moisture, making it visibly softer and smoother. In another double-blind, placebo-controlled trial, a topical cream with ectoin increased skin hydration by up to 200% compared to a placebo after 12 days.29 This increased hydration level of the skin was preserved for the next seven days without treatment, thereby demonstrating the sustained moisturizing effect of Ectoin.
Acetyl Tetrapeptide-22 Stimulates Stress-Responsive Heat-Shock Proteins
The skin relies on heat-shock proteins, which act as a clean-up crew for the cellular damage induced by stressful stimuli.31,32 When inside the cell, heat-shock proteins assist in the recovery of damaged proteins, while degrading others to halt protein aggregates that impair normal cellular processes.33,34
The age-related decline in heat-shock proteins—notably heat-shock protein 70 (HSP70)—diminishes the skin’s natural stress response and accelerates aging.
A novel peptide called acetyl tetrapeptide-22 has been developed to boost HSP70 levels in the skin with or without prior stress, in turn maintaining protein homeostasis and increasing cell viability to slow down aging.35
Coconut Amino-Acid Complex Soothes Sensitive Skin
The combination of coconut amino acids and minerals (potassium and magnesium) has been shown to improve the skin’s moisture barrier and modulate the UV-induced inflammatory response in epidermal keratinocytes and dermal fibroblasts.36 This anti-inflammatory action helps soothe sensitive and irritated skin.
One research team found that coconut amino acid complex reduced the sensation of discomfort from lactic acid in humans with hypersensitive skin. They observed that coconut amino-acid complex decreased the stinging intensity of lactic acid by 46% immediately after topical application, and by 90% after one minute.36
Our skin is under attack from external forces like ultraviolet radiation that create damaging free radicals and oxidative stress, leaving behind a path of wrinkles, age spots, and mutations.
Research shows that topical compounds—including melatonin, ectoin, acetyl tetrapeptide-22, and coconut amino-acid complex—work through distinct and complementary mechanisms to offset the harmful effects of sunlight and enhance nightly repair of damaged skin to enable a younger-looking appearance.
Gary Goldfaden, MD, is a clinical dermatologist and lifetime member of the American Academy of Dermatology. He is the founder of Academy Dermatology in Hollywood, FL, and Cosmesis Skin Care. Dr. Goldfaden is a member of Life Extension®’s Medical Advisory Board. All Cosmesis products are available online.
If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.
- Oyetakin-White P, Suggs A, Koo B, et al. Does poor sleep quality affect skin ageing? Clin Exp Dermatol. 2015;40(1):17-22.
- Reiter RJ, Tan DX, Mayo JC, et al. Melatonin as an antioxidant: biochemical mechanisms and pathophysiological implications in humans. Acta Biochim Pol. 2003;50(4):1129-46.
- Karaaslan C, Suzen S. Antioxidant properties of melatonin and its potential action in diseases. Curr Top Med Chem. 2015;15(9):894-903.
- Kleszczynski K, Fischer TW. Melatonin and human skin aging. Dermatoendocrinol. 2012;4(3):245-52.
- Pandi-Perumal SR, BaHammam AS, Brown GM, et al. Melatonin antioxidative defense: therapeutical implications for aging and neurodegenerative processes. Neurotox Res. 2013;23(3):267-300.
- Kleszczynski K, Hardkop LH, Fischer TW. Differential effects of melatonin as a broad range UV-damage preventive dermato-endocrine regulator. Dermatoendocrinol. 2011;3(1):27-31.
- Hardeland R. Melatonin in aging and disease -multiple consequences of reduced secretion, options and limits of treatment. Aging Dis. 2012;3(2):194-225.
- Masters A, Pandi-Perumal SR, Seixas A, et al. Melatonin, the Hormone of Darkness: From Sleep Promotion to Ebola Treatment. Brain Disord Ther. 2014;4(1).
- Lee KS, Lee WS, Suh SI, et al. Melatonin reduces ultraviolet-B induced cell damages and polyamine levels in human skin fibroblasts in culture. Exp Mol Med. 2003;35(4):263-8.
- Slominski A, Pisarchik A, Zbytek B, et al. Functional activity of serotoninergic and melatoninergic systems expressed in the skin. J Cell Physiol. 2003;196(1):144-53.
- Slominski A, Wortsman J, Tobin DJ. The cutaneous serotoninergic/melatoninergic system: securing a place under the sun. Faseb j. 2005;19(2):176-94.
- Allegra M, Reiter RJ, Tan DX, et al. The chemistry of melatonin’s interaction with reactive species. J Pineal Res. 2003;34(1):1-10.
- Tan DX, Manchester LC, Reiter RJ, et al. Significance of melatonin in antioxidative defense system: reactions and products. Biol Signals Recept. 2000;9(3-4):137-59.
- Mayo JC, Sainz RM, Tan DX, et al. Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophages. J Neuroimmunol. 2005;165(1-2):139-49.
- Slominski AT, Kleszczynski K, Semak I, et al. Local melatoninergic system as the protector of skin integrity. Int J Mol Sci. 2014;15(10):17705-32.
- Esrefoglu M, Seyhan M, Gul M, et al. Potent therapeutic effect of melatonin on aging skin in pinealectomized rats. J Pineal Res. 2005;39(3):231-7.
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- Ryoo YW, Suh SI, Mun KC, et al. The effects of the melatonin on ultraviolet-B irradiated cultured dermal fibroblasts. J Dermatol Sci. 2001;27(3):162-9.
- Iguichi H, Kato KI, Ibayashi H. Age-dependent reduction in serum melatonin concentrations in healthy human subjects. J Clin Endocrinol Metab. 1982;55(1):27-9.
- Magri F, Sarra S, Cinchetti W, et al. Qualitative and quantitative changes of melatonin levels in physiological and pathological aging and in centenarians. J Pineal Res. 2004;36(4):256-61.
- Fischer TW, Slominski A, Zmijewski MA, et al. Melatonin as a major skin protectant: from free radical scavenging to DNA damage repair. Exp Dermatol. 2008;17(9):713-30.
- Bangha E, Lauth D, Kistler GS, et al. Daytime serum levels of melatonin after topical application onto the human skin. Skin Pharmacol. 1997;10(5-6):298-302.
- Fischer TW, Greif C, Fluhr JW, et al. Percutaneous penetration of topically applied melatonin in a cream and an alcoholic solution. Skin Pharmacol Physiol. 2004;17(4):190-4.
- Scheuer C, Pommergaard HC, Rosenberg J, et al. Melatonin’s protective effect against UV radiation: a systematic review of clinical and experimental studies. Photodermatol Photoimmunol Photomed. 2014;30(4):180-8.
- Buenger J, Driller H. Ectoin: an effective natural substance to prevent UVA-induced premature photoaging. Skin Pharmacol Physiol. 2004;17(5):232-7.
- Graf R, Anzali S, Buenger J, et al. The multifunctional role of ectoine as a natural cell protectant. Clin Dermatol. 2008;26(4):326-33.
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- Zhou X, Tron VA, Li G, et al. Heat shock transcription factor-1 regulates heat shock protein-72 expression in human keratinocytes exposed to ultraviolet B light. J Invest Dermatol. 1998;111(2):194-8.
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