Melatonin: Facts, Extrapolations and Clinical Trials

Biomolecules. 2023 Jun 5;13(6):943. doi: 10.3390/biom13060943.


Melatonin is a fascinating molecule that has captured the imagination of many scientists since its discovery in 1958. In recent times, the focus has changed from investigating its natural role as a transducer of biological time for physiological systems to hypothesized roles in virtually all clinical conditions. This goes along with the appearance of extensive literature claiming the (generally) positive benefits of high doses of melatonin in animal models and various clinical situations that would not be receptor-mediated. Based on the assumption that melatonin is safe, high doses have been administered to patients, including the elderly and children, in clinical trials. In this review, we critically review the corresponding literature, including the hypotheses that melatonin acts as a scavenger molecule, in particular in mitochondria, by trying not only to contextualize these interests but also by attempting to separate the wheat from the chaff (or the wishful thinking from the facts). We conclude that most claims remain hypotheses and that the experimental evidence used to promote them is limited and sometimes flawed. Our review will hopefully encourage clinical researchers to reflect on what melatonin can and cannot do and help move the field forward on a solid basis.

Keywords: bacteria; clinical trials; controversies; melatonin; mitochondria; preclinical data; scavenging hypothesis.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Melatonin* / pharmacology
  • Melatonin* / therapeutic use
  • Mitochondria


  • Melatonin

Grants and funding

The work of R.J. was supported by the Agence Nationale de la Recherche (ANR-19-CE16-0025-01 « mitoGPCR », ANR-21-CE18-00XX « alloGLP1R », ANR-20-COV4-0001 « MELATOVID »), the Fondation de la Recherche Médicale (Equipe FRM DEQ20130326503), La Ligue Contre le Cancer N/Ref: RS19/75-127, Plan de Relance 2021 and the Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS).