Melatonin: Countering Chaotic Time Cues

Last year melatonin was 60 years old, or at least its discovery was 60 years ago. The molecule itself may well be almost as old as life itself. So it is time to take yet another perspective on our understanding of its functions, effects and clinical uses. This is not a formal review—there is already a multitude of systematic reviews, narrative reviews, meta-analyses and even reviews of reviews. In view of the extraordinary variety of effects attributed to melatonin in the last 25 years, it is more of an attempt to sort out some areas where a consensus opinion exists, and where placebo controlled, randomized, clinical trials have confirmed early observations on therapeutic uses. The current upsurge of concern about the multiple health problems associated with disturbed circadian rhythms has generated interest in related therapeutic interventions, of which melatonin is one. The present text will consider the physiological role of endogenous melatonin, and the mostly pharmacological effects of exogenous treatment, on the assumption that normal circulating concentrations represent endogenous pineal production. It will concentrate mainly on the most researched, and accepted area of therapeutic use and potential use of melatonin—its undoubted ability to realign circadian rhythms and sleep—since this is the author's bias. It will touch briefly upon some other systems with prominent rhythmic attributes including certain cancers, the cardiovascular system, the entero-insular axis and metabolism together with the use of melatonin to assess circadian status. Many of the ills of the developed world relate to deranged rhythms—and everything is rhythmic unless proved otherwise.