Melatonin supplementation in the management of obesity and obesity-associated disorders: A review of physiological mechanisms and clinical applications

Pharmacol Res. 2021 Jan:163:105254. doi: 10.1016/j.phrs.2020.105254. Epub 2020 Oct 17.


Despite the evolving advances in clinical approaches to obesity and its inherent comorbidities, the therapeutic challenge persists. Among several pharmacological tools already investigated, recent studies suggest that melatonin supplementation could be an efficient therapeutic approach in the context of obesity. In the present review, we have amalgamated the evidence so far available on physiological effects of melatonin supplementation in obesity therapies, addressing its effects upon neuroendocrine systems, cardiometabolic biomarkers and body composition. Most studies herein appraised employed melatonin supplementation at dosages ranging from 1 to 20 mg/day, and most studies followed up participants for periods from 3 weeks to 12 months. Overall, it was observed that melatonin plays an important role in glycaemic homeostasis, in addition to modulation of white adipose tissue activity and lipid metabolism, and mitochondrial activity. Additionally, melatonin increases brown adipose tissue volume and activity, and its antioxidant and anti-inflammatory properties have also been demonstrated. There appears to be a role for melatonin in adiposity reduction; however, several questions remain unanswered, for example melatonin baseline levels in obesity, and whether any seeming hypomelatonaemia or melatonin irresponsiveness could be clarifying factors. Supplementation dosage studies and more thorough clinical trials are needed to ascertain not only the relevance of such findings but also the efficacy of melatonin supplementation.

Keywords: Endocrinology; Melatonin; Obesity; Obesity therapy; Weight loss.

Publication types

  • Review

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Animals
  • Antioxidants / administration & dosage*
  • Dietary Supplements*
  • Glucose / metabolism
  • Humans
  • Insulin Resistance
  • Lipid Metabolism / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Melatonin / administration & dosage*
  • Mitochondria / metabolism
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Obesity / drug therapy*
  • Oxidative Stress / drug effects


  • Antioxidants
  • Glucose
  • Melatonin