Melatonin’s Mechanism of Action
Melatonin Is a Naturally Occurring Hormone1
Melatonin Is a Naturally Occurring Hormone1
Melatonin is often called the ‘hormone of darkness’ as its synthesis and release is induced by the dark and inhibited by light.1 It is secreted by the pineal gland, following synthesis from the amino acid tryptophan.1
Melatonin and the Body Clock
Melatonin and the Body Clock
The timing of melatonin secretion is governed by the suprachiasmatic nucleus (SCN) in the hypothalamus – the site of the body’s biological clock.1 The SCN is dependent upon the retina’s perception of light (both natural and domestic): 1-3
- Light stimulates the SCN via central nervous system pathways to inhibit melatonin synthesis and release
- Darkness induces melatonin synthesis and release.
Melatonin begins to be released naturally about 2-3 hours before sleep onset,4 with peak melatonin release occurring between 2am and 4am and decreasing during the latter half of the night.5
Image adapted from Avidan, 20078 with additional information from Foster, 2020.9
DLMO and the Body Clock
DLMO and the Body Clock
The Dim Light Melatonin Onset (DLMO) indicates the time at which endogenous melatonin levels begin to start rising, as the light becomes low.6 This differs by individual and is the characteristic of their 24-hour melatonin curve.6,7 As melatonin levels rise, and provided other cues are favourable, e.g. the sleep environment and zeitgebers, sleep can occur.7 If a person’s DLMO shifts to later than normal, their sleep onset can be delayed.7
Melatonin’s Mechanism of Action
Melatonin’s Mechanism of Action
On release, melatonin activates two membrane-specific receptors, MT1 and MT2, that are involved in the regulation of the circadian rhythm.1,7,10
This contributes to sleep in two ways:
- It has a phase-shifting effect, that is, melatonin changes the timing of the biological clock.4,6,7 If melatonin supplementation is given during the early evening, it triggers the circadian rhythm and counters the effect of light, i.e. it has a chronobiotic effect.4,6
- Via a direct sedative effect,4,5 by a dose-dependent increase in the concentration of the inhibitory neurotransmitter GABA (gamma aminobutyric acid), which helps modulate both REM and NREM sleep.11,12
Melatonin synthesis and mechanism of action
Image adapted from Gurunathan, et al, 20203 with additional content from Wilson, et al, 2019.4
Timing Melatonin
Timing Melatonin
As people have individualised DLMO times, the timing of taking melatonin supplements is critical in optimising sleep onset.14 In the absence of routine DLMO saliva testing, the timing of melatonin dosing, rather than the dose itself, may be varied to reveal the optimal effect.7 Parents/children can be advised to help find their child’s optimal DLMO time by setting a desired ‘end-goal’ bedtime and taking melatonin 30–60 minutes before this new bedtime5 each evening while monitoring the progress of melatonin’s ability to help improve sleep onset.10 Over the course of four weeks, children taking melatonin had an advance in their DLMO.10
UK-AGB-ADA-0019 | Date of preparation: January 2024
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