Effects of melatonin supplementation on eating habits and appetite-regulating hormones: a systematic review of randomized controlled clinical and preclinical trials.

Melatonin is a hormone involved in appetite regulation and food intake. Circadian chronorrupture caused by its absence has been associated with excessive food consumption, and there is evidence that exogenous melatonin supplementation can restore homeostasis. Therefore, the aim of this systematic review was to synthesize evidence from randomized controlled clinical and preclinical trials that evaluated the effects of exogenous melatonin supplementation on eating habits and appetite-regulating hormones. The protocol was registered in PROSPERO (number 42020175809). Medline, Scopus, Web of Science and Cochrane Library were systematically searched from January 2020 to February 2021. Of 3.695 articles identified, 2 clinical and 13 preclinical trials (n = 15) met the inclusion criteria. The outcomes were total food intake, calories, macronutrients, cholesterol intake, leptin and ghrelin levels. Interventions ranged from 28 to 336 days and dose of melatonin varied between 0.2 µg/mL of drinking water and 10 mg/day. Clinical trials were conducted with healthy adults, and preclinical trials with rodents and dogs. Of the 15 articles, five assessed food intake and leptin, four assessed food intake only, five assessed leptin only, and one assessed leptin and ghrelin serum levels. The majority of the articles were judged as having low risk of bias. Although findings are heterogeneous and do not allow a robust conclusion, this review adds to the growing body of evidence suggesting that exogenous melatonin may be a potential therapeutic agent against endocrine-metabolic disorders. This reversal is not necessarily associated with changes in food consumption, signaling that melatonin's metabolic effects may occur independently of energy intake. Further studies, especially with humans, are needed provide more evidences for melatonin supplementation in clinical practice, as well as to understand its role on eating habits and appetite-regulating hormones.