Melatonin: Range of Effects and Therapeutic Applications

Endocrinology Advisor: What are some examples of clinical disorders related to melatonin dysfunction?

Dr Zeitzer: Overproduction of melatonin is most typically associated with pineal teratomas. Loss of or reduced production of melatonin is often secondary to neurologically complete tetraplegia (complete loss of melatonin), use of beta-blockers (partial loss), or nonspecific poor health — especially involving liver function. Bilateral oculosympathoparesis (Horner syndrome) is predictive of a loss of melatonin. There are, however, no specific clinical disorders that are associated with over- or underproduction of melatonin.

Endocrinology Advisor: How is melatonin used to treat these and other disorders?

Dr Zeitzer: Melatonin replacement has thus far not been deemed effective at treating sleep problems in individuals with tetraplegia. Melatonin supplementation may help improve sleep in individuals using beta-blockers. Melatonin supplementation has been used as a treatment for generically poor sleep in older individuals, but with very mixed results.

Endocrinology Advisor: What treatment recommendations would you offer to clinicians regarding therapeutic melatonin use?

Dr Zeitzer: Melatonin is available as both a prescription medication and over-the-counter nutraceutical. Healthy individuals often take melatonin to help with sleep, especially sleep-onset insomnia. In these circumstances, the over-the-counter melatonin is often supraphysiologic in concentration (physiologic dosing is 0.3 mg, and most people take 1-10 mg) and is supplementing normal melatonin concentrations. Few adverse effects, mainly morning grogginess, have been reported at elevated doses of melatonin, and high concentrations of melatonin are thought to be relatively safe. The nutraceutical status of melatonin, however, means that it is not regulated by the United States Food and Drug Administration, and caution should be taken in terms of selecting a respected manufacturer.

Endocrinology Advisor: What should be the focus of future research in this area?

Dr Zeitzer: The mechanism of action of supraphysiologic melatonin administration is unknown, and should be better described so as be used for specific etiologies of sleep disruption.

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

2. Cipolla-Neto J, Amaral FG, Afeche SC, Tan DX, Reiter RJ. Melatonin, energy metabolism, and obesity: a review. J Pineal Res. 2014;56(4):371-381.

3. Ortiz GG, Benítez-King GA, Rosales-Corral SA, Pacheco-Moisés FP, Velázquez-Brizuela IE. Cellular and biochemical actions of melatonin which protect against free radicals: role in neurodegenerative disorders. Curr Neuropharmacol. 2008;6(3):203-214.

4. Seifman MA, Adamides AA, Nguyen PN, et al. Endogenous melatonin increases in cerebrospinal fluid of patients after severe traumatic brain injury and correlates with oxidative stress and metabolic disarray. J Cereb Blood Flow Metab. 2008;28(4):684-696.

5. Bumb JM, Enning F, Mueller JK, et al. Differential melatonin alterations in cerebrospinal fluid and serum of patients with major depressive disorder and bipolar disorder. Compr Psychiatry. 2016;68:34-39.

6. Ángeles-Castellanos M, Ramírez-Gonzalez F, Ubaldo-Reyes L, Rodriguez-Mayoral O, Escobar C. Loss of melatonin daily rhythmicity is asociated with delirium development in hospitalized older adults. Sleep Sci. 2016;9(4):285-288.