The robustness of the circadian system decreases with age and in certain diseases, together with a decline in melatonin production, notes the review published in the British Journal of Pharmacology. However, evidence suggests that supplementing the hormone might assist mitigate these effects.
Melatonin supplementation has helped adult insomniacs fall asleep quicker, and realignment in sleep cycles to the normal dark/light pattern in blind people with sleep-wake disorder, reports author, Dr. Nava Zisapel from the George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel.
Prolonged-release melatonin (PRM) has also been shown to lower nocturnal blood pressure (BP) in ‘non-dippers’ (individuals whose BP does not follow the normal night-time reduction). The risk of cardiovascular events is significantly higher in such people.
Additionally, a recent meta-analysis has strengthened previous evidence that melatonin may be effective in improving sleep problems in children with Autistic Spectrum Disorder.
“Clinically meaningful effects of melatonin treatment have been demonstrated in placebo-controlled trials in humans, particularly in disorders associated with diminished or misaligned melatonin rhythms,” explained Zisapel.
“The ability of exogenously administered melatonin to mitigate the loss of the endogenous night signal and improve the restorative value of sleep, represents a promising investigational route for early intervention to promote healthy physical and mental ageing,” he added.
Application in Alzheimer’s?
Melatonin has also attracted attention in the area of Alzheimer’s Disease (AD).
Researchers have identified associations between insomnia and neurodegenerative diseases such as AD. The build-up of beta-amyloid plaque in pre-clinical AD has been correlated with poor sleep quality, while early neuropathological changes at this stage of AD are accompanied by lower melatonin levels.
Scientists have also identified a possible mechanism whereby sleep disruption may reduce the capability of clearing the toxic beta-amyloid plaques, particularly in an area of the brain known as the precuneus. (Activation of the precuneus is involved in the speed of reaction time to a verbal memory task).
One intervention study helped maintain or improve cognitive function in mild-moderate AD patients using 2milligrams/ day (mg/d) of PRM over 6 months. However, randomised controlled trials (RCTs) using the immediate-release form of the supplement, have not demonstrated efficacy.
Nevertheless, the balance of evidence to-date therefore warrant furthers research in this area, suggests Zisapel.
“The ability of melatonin to improve the restorative value of sleep, through its effects on the circadian clock and reduced activation of the precuneus, open new perspectives to the role of clock and sleep disturbances in AD pathophysiology.
“The relationship between these effects, attenuated beta-amyloid overproduction and enhanced clearance of accumulated amyloid to decrease beta-amyloid load in this region, warrant further investigation’ he concludes.
Zisapel is the founder and Chief Scientific Officer of Neurim Pharmaceuticals, the company that developed and produces prolonged release melatonin-Circadin®.
Source: British Journal of Pharmacology
Published online, doi: 10.1111/bph.14116
“New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation”
Author: Nava Zisapel