Melatonin: Countering Chaotic Time Cues

Abstract

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.

Melatonin Content of Human Milk: The Effect of Mode of Delivery

“…Our results show that human milk exhibits a daily rhythm of melatonin concentration similar to other body fluids 15 ; melatonin is more elevated at night than during the day, independent of mode of delivery, under physiological maternal and neonatal conditions. This condition was maintained at the three stages of lactation studied (colostrum, transitional milk, and mature milk).…”

Impact of Melatonin on Skeletal Muscle and Exercise

“…Remarkably, the SCN pathway linked to retinal ganglion cells produces melatonin, an endogenous Zeitgeber able to control vital rhythms during the nighttime, to reduce mitochondrial dysfunctions and chronodisruption [160,161]. In particular, melatonin added in vitro to brain slices stimulated SCN phase via melatonin type-2 receptors and protein kinase C activation [162].…”

Impact of Dim Light at Night on Urinary 6-Sulphatoxymelatonin Concentrations and Sleep in Healthy Humans

“…In our study, illuminance at a level up to five lux significantly reduced melatonin production, albeit the effect was detected only in the second-morning urine and not in the first one, which is generally used as a marker of the suppressive effects of ALAN on melatonin biosynthesis ([ 8 ] for a review). We found the expected continuous decrease of aMT6s during the day, with the highest levels in the first-morning sample, lower in the second-morning sample, and the lowest at the midday urine sample.…”

“…The synthetized hormone is immediately released and serves as a synchronizing signal for different organs in the body. Since high nocturnal melatonin levels reflect the length of the photoperiod, melatonin can transmit information about environmental conditions to the internal milieu of organisms and can serve as a clock and a calendar ([ 7 , 8 ] for a review). Melatonin receptors are present in different organs, including the brain and SCN ([ 9 , 10 ] for a review).…”