One thousand and one nights of melatonin
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oxidative stress
circadian rhythm

How to Cite

Saavedra-López, H. F. ., García-Pérez, M. J., & Arteaga-Díaz, J. M. . (2022). One thousand and one nights of melatonin. Revista Colombiana De Endocrinología, Diabetes &Amp; Metabolismo, 8(4).


Background: Melatonin was first introduced in 1958 by dermatologist Aaron Lerner from a bovine pineal gland. Around 1970 was discovered its role in the regulation of the circadian rhythm and sleep-wake states, a role on which most clinical studies have focused. Its synthesis occurs from tryptophan through hydroxylation and acetylation processes,
later converted into melatonin. Since its discovery, multiple effects have been raised, all based on its effects as a regulator of oxidative stress; that is why clinical studies show that the supplementation of this hormone, in addition to regulating the circadian rhythm, has possible effects in the management of chronic non-communicable diseases
Objective: To report new evidence about the physiological and biochemical mechanisms of melatonin and discuss its possible therapeutic use.
Methodology: Literature review in the PubMed and Scopus database using the MeSH terms: “melatonin”; "circadian clocks"; "circadian rhythm"; "Cancer"; “oxidative stress”.
Results: There is great bibliographic evidence about the history of melatonin and its possible metabolic effects, which goes in line with its role as a regulator of the circadian rhythm, through the sleep-wake and light-dark states.
Conclusions: Melatonin can serve as an adjuvant in the management of chronic diseases such as cancer, obesity, fatty liver disease, mucositis and in the management of critically ill patients.
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Claustrat B, Leston J. Melatonin: Physiological effects in humans. Neurochirurgie. 2015;61(2-3):77-84. DOI:

Illnait-Ferrer J. Melatonina: actualidad de una hormona olvidada Melatonin: the actuality of a forgotten hormone. Rev Cenic Cienc Biol. 2012;43(3).

Pérez-Beltrán CF, Díaz-Greene EJ, Rodríguez-Weber FL. Melatonina y su utilidad en la práctica diaria. Med Interna Mex. 2014;30(4).

Poza JJ, Pujol M, Ortega-Albás JJ, Romero O. Melatonin in sleep disorders. Neurol Engl Ed. 2020;36(9). DOI:

Ganguly S, Coon SL, Klein DC. Control of melatonin synthesis in the mammalian pineal gland: the critical role of serotonin acetylation. Cell Tissue Res. 2002;309(1):127-37. DOI:

Amaral FG, Cipolla-Neto J. A brief review about melatonin, a pineal hormone. Arch Endocrinol Metab. 2018;62(4):472-9. DOI:

Bhattacharya S, Patel KK, Dehari D, Agrawal AK, Singh S. Melatonin and its ubiquitous anticancer effects. Mol Cell Biochem. 2019;462(1):133-55. DOI:

Cipolla-Neto J, Amaral FG. Melatonin as a hormone: new physiological and clinical insights. Endocr Rev. 2018;39(6):990-1028. DOI:

Dacey DM, Liao HW, Peterson BB, Robinson FR, Smith VC, Pokorny J, et al. Melanopsin-expressing ganglion cells in primate retina signal colour and irradiance and project to the LGN. Nature. 2005;433(7027):749-54. DOI:

Freedman MS, Lucas RJ, Soni B, von Schantz M, Muñoz M, David-Gray Z, et al. Regulation of mammalian circadian behavior by non-rod, non-cone, ocular photoreceptors. Science. 1999;284(5413):502-4. DOI:

Zaidi FH, Hull JT, Peirson SN, Wulff K, Aeschbach D, Gooley JJ, et al. Short-wavelength light sensitivity of circadian, pupillary, and visual awareness in humans lacking an outer retina. Curr Biol. 2007;17(24):2122-8. DOI:

Panda S, Provencio I, Tu DC, Pires SS, Rollag MD, Castrucci AM, et al. Melanopsin is required for non-image-forming photic responses in blind mice. Science. 2003;301(5632):525-7. DOI:

Gooley JJ, Lu J, Fischer D, Saper CB. A broad role for melanopsin in nonvisual photoreception. J Neurosci. 2003;23(18):7093-106. DOI:

Hattar S, Liao HW, Takao M, Berson DM, Yau KW. Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science. 2002;295(5557):1065-70. DOI:

Cajochen C, Jud C, Münch M, Kobialka S, Wirz?Justice A, Albrecht U. Evening exposure to blue light stimulates the expression of the clock gene PER2 in humans. Eur J Neurosci. 2006;23(4):1082-6. DOI:

Acuña-Castroviejo D, Escames G, Venegas C, Díaz-Casado ME, Lima-Cabello E, López LC, et al. Extrapineal melatonin: sources, regulation, and potential functions. Cell Mol Life Sci. 2014;71(16):2997-3025. DOI:

Boutin JA, Jockers R. Melatonin controversies, an update. J Pineal Res. 2021;70(2):e12702. DOI:

Gamble KL, Berry R, Frank SJ, Young ME. Circadian clock control of endocrine factors. Nat Rev Endocrinol. 2014;10(8):466-75. DOI:

Mohawk JA, Green CB, Takahashi JS. Central and peripheral circadian clocks in mammals. Annu Rev Neurosci. 2012;35:445-62. DOI:

Harfmann BD, Schroder EA, Esser KA. Circadian rhythms, the molecular clock, and skeletal muscle. J Biol Rhythms. 2015;30(2):84-94. DOI:

Mason IC, Qian J, Adler GK, Scheer FA. Impact of circadian disruption on glucose metabolism: implications for type 2 diabetes. Diabetología. 2020;63(3):462-72. DOI:

Jagannath A, Taylor L, Wakaf Z, Vasudevan SR, Foster RG. The genetics of circadian rhythms, sleep and health. Hum Mol Genet. 2017;26(R2):R128-38. DOI:

Drew JE, Williams LM, Hannah LT, Barrett P, Abramovich DR, Morgan PJ. Melatonin receptors in the human fetal kidney: 2-(125I) iodomelatonin binding sites correlated with expression of Mel1a and Mel1b receptor genes. J Endocrinol. 1998;156(2):261-8. DOI:

Brydon L, Petit L, Delagrange P, Strosberg AD, Jockers R. Functional expression of MT2 (Mel1b) melatonin receptors in human PAZ6 adipocytes. Endocrinology. 2001;142(10):4264-71. DOI:

Zibolka J, Bazwinsky?Wutschke I, Mühlbauer E, Peschke E. Distribution and density of melatonin receptors in human main pancreatic islet cell types. J Pineal Res. 2018;65(1):e12480. DOI:

Torres-Farfan C, Richter HG, Rojas-García P, Vergara M, Forcelledo ML, Valladares LE, et al. MT1 Melatonin receptor in the primate adrenal gland: inhibition of adrenocorticotropin-stimulated cortisol production by melatonin. J Clin Endocrinol Metab. 2003;88(1):450-8. DOI:

Dubocovich ML, Yun K, Al?Ghoul WM, Benloucif S, Masana MI. Selective MT2 melatonin receptor antagonists block melatonin?mediated phase advances of circadian rhythms. FASEB J. 1998;12(12):1211-20. DOI:

Lewy AJ. Clinical applications of melatonin in circadian disorders. Dialogues Clin Neurosci. 2003;5(4):399. DOI:

Lewy AJ, Ahmed S, Jackson JML, Sack RL. Melatonin shifts human orcadian rhythms according to a phase-response curve. Chronobiol Int. 1992;9(5):380-92. DOI:

Wajid F, Poolacherla R, Mim FK, Bangash A, Rutkofsky IH. Therapeutic potential of melatonin as a chronobiotic and cytoprotective agent in diabetes mellitus. J Diabetes Metab Disord. 2020;1-29. DOI:

Raygan F, Ostadmohammadi V, Bahmani F, Reiter RJ, Asemi Z. Melatonin administration lowers biomarkers of oxidative stress and cardio-metabolic risk in type 2 diabetic patients with coronary heart disease: a randomized, double-blind, placebo-controlled trial. Clin Nutr. 2019;38(1):191-6. DOI:

K?dziora?Kornatowska K, Szewczyk?Golec K, Kozakiewicz M, Pawluk H, Czuczejko J, Kornatowski T, et al. Melatonin improves oxidative stress parameters measured in the blood of elderly type 2 diabetic patients. J Pineal Res. 2009;46(3):333-7. DOI:

Ortiz-Franco M, Planells E, Quintero B, Acuña-Castroviejo D, Rusanova I, Escames G, et al. Effect of melatonin supplementation on antioxidant status and DNA damage in high intensity trained athletes. Int J Sports Med. 2017;38(14):1117-25. DOI:

Cardinali DP, Escames G, Acuña-Castroviejo D, Ortiz F, Fernández-Gil B, Guerra-Librero A, et al. Melatonin-induced oncostasis, mechanisms and clinical relevance. J Integr Oncol. 2016;S1(006):1-25. DOI:

Lauritzen ES, Kampmann U, Smedegaard SB, Støy J. Effects of daily administration of melatonin before bedtime on fasting insulin, glucose and insulin sensitivity in healthy adults and patients with metabolic diseases. A systematic review and meta?analysis. Clin Endocrinol (Oxf). 2021;95(5):691-701. DOI:

Malaguarnera R, Ledda C, Filippello A, Frasca F, Francavilla VC, Ramaci T, et al. Thyroid Cancer and Circadian Clock Disruption. Cancers. 2020;12(11):3109. DOI:

Reiter RJ, Tan DX, Galano A. Melatonin: exceeding expectations. Physiology. 2014;29(5):325-33. DOI:

Lozano A, Marruecos J, Rubió J, Farré N, Gómez-Millán J, Morera R, et al. Randomized placebo-controlled phase II trial of high-dose melatonin mucoadhesive oral gel for the prevention and treatment of oral mucositis in patients with head and neck cancer undergoing radiation therapy concurrent with systemic treatment. Clin Transl Oncol. 2021;23(9):1801-10. DOI:

Rayyan YM, Tayyem RF. Non-alcoholic fatty liver disease and associated dietary and lifestyle risk factors. Diabetes Metab Syndr Clin Res Rev. 2018;12(4):569-75. DOI:

Porter-Starr KN, Orenduff M, McDonald SR, Mulder H, Sloane R, Pieper CF, et al. Influence of weight reduction and enhanced protein intake on biomarkers of inflammation in older adults with obesity. J Nutr Gerontol Geriatr. 2019;38(1):33-49. DOI:

Szewczyk-Golec K, Rajewski P, Gackowski M, Mila-Kierzenkowska C, Weso?owski R, Sutkowy P, et al. Melatonin supplementation lowers oxidative stress and regulates adipokines in obese patients on a calorie-restricted diet. Oxid Med Cell Longev. 2017;2017. DOI:

Chojnacki C, Walecka-Kapica E, Klupinska G, Pawlowicz M, Blonska A, Chojnacki J. Effects of fluoxetine and melatonin on mood, sleep quality and body mass index in postmenopausal women. J Physiol Pharmacol. 2015;66(5):665-71.

Mansoori A, Salimi Z, Hosseini SA, Hormoznejad R, Jafarirad S, Bahrami M, et al. The effect of melatonin supplementation on liver indices in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis of randomized clinical trials. Complement Ther Med. 2020;52:102398. DOI:

Bahrami M, Cheraghpour M, Jafarirad S, Alavinejad P, Asadi F, Hekmatdoost A, et al. The effect of melatonin on treatment of patients with non-alcoholic fatty liver disease: a randomized double blind clinical trial. Complement Ther Med. 2020;52:102452. DOI:

Gandolfi JV, Di Bernardo APA, Chanes DAV, Martin DF, Joles VB, Amendola CP, et al. The effects of melatonin supplementation on sleep quality and assessment of the serum melatonin in ICU patients: A randomized controlled trial. Crit Care Med. 2020;48(12):e1286-93. DOI:

Khaing K, Nair BR. Melatonin for delirium prevention in hospitalized patients: A systematic review and meta-analysis. J Psychiatr Res. 2020;133:181-90. DOI:

Rodríguez-Rubio M, Figueira JC, Acuña-Castroviejo D, Borobia AM, Escames G, de la Oliva P. A phase II, single-center, double-blind, randomized placebo-controlled trial to explore the efficacy and safety of intravenous melatonin in patients with COVID-19 admitted to the intensive care unit (MelCOVID study): a structured summary of a study protocol for a randomized controlled trial. Trials. 2020;21(1):1-3. DOI:

Ziaei A, Davoodian P, Dadvand H, Safa O, Hassanipour S, Omidi M, et al. Evaluation of the efficacy and safety of Melatonin in moderately ill patients with COVID-19: A structured summary of a study protocol for a randomized controlled trial. Trials. 2020;21(1):1-3. DOI:

Paul MA, Gray G, Kenny G, Pigeau RA. Impact of melatonin, zaleplon, zopiclone, and temazepam on psychomotor performance. Aviat Space Environ Med. 2003;74(12):1263-70.

Suhner A, Schlagenhauf P, Tschopp A, Hauri-Bionda R, Friedrich-Koch A, Steffen R. Impact of melatonin on driving performance. J Travel Med. 1998;5(1):7-13. DOI:

Andersen LP, Gögenur I, Rosenberg J, Reiter RJ. The safety of melatonin in humans. Clin Drug Investig. 2016;36(3):169-75. DOI:

Nordlund JJ, Lerner AB. The effects of oral melatonin on skin color and on the release of pituitary hormones. J Clin Endocrinol Metab. 1977;45(4):768-74. DOI:

Shaw KM, Stern GM, Sandler M. Melatonin and parkinsonism. The Lancet. 1973;301(7797):271. DOI:

Lyseng-Williamson KA. Melatonin prolonged release. Drugs Aging. 2012;29(11):911-23. DOI:

Invima. Listado de registros sanitarios vigentes de medicamentos con principio activo [Internet]. 2021. Disponible en:

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