Melatonin: Facts, Extrapolations and Clinical Trials

This narrative review by Boutin, Kennaway, and Jockers critically appraises the expanding literature on melatonin, spanning its established role as a transducer of biological time to hypothesized roles in diverse clinical conditions. The authors evaluate evidence for melatonin acting as a scavenger molecule in mitochondria, its purported synthesis in bacteria, and the extrapolation of animal model findings to human clinical situations. The review highlights that experimental evidence for melatonin synthesis in mitochondria, including quantitative aspects and generalization to all mitochondria-containing cells, is still weak. As a key limitation noted by the authors, rigorous toxicity studies in humans at high dosages have not been reported. The review encourages clinical researchers to distinguish established facts from speculative claims and urges restriction of high-dose melatonin use as a precautionary principle.