One of the ways Melatonin makes you tired is by decreasing your body’s wake signals.
Melatonin is absorbed through the small intestines → portal blood → liver → systemic blood → SCN
Melatonin binds to the MT1 receptor and causes G-protein to be activated
Activated G-protein inhibits adenylyl cyclase which leads to lower cAMP levels
In general, most of the melatonin you ingest is broken down in the Liver by the CYP1A2 enzyme. Supplements that increase the effectiveness of melatonin do so by inhibiting this enzyme and therefore decreasing how much melatonin is broken down into useless metabolites:
Grapefruit extract
Green tea extract
Turmeric (less so)
Curcumin (less so)
I’ve also added medications to the diagram, a few of which also inhibit CYP1A2.
Let me know if I missed anything! There are a few other pathways that involve melatonin but they deserve their own diagram.
One thing i’d add from my own tracking is that melatonin’s effect on wakefulness seems amplified when combined with consistent light exposure control, especially avoiding blue light in the last hour before bed. It’s subtle, but i’ve noticed it shifts the whole balance of how quickly drowsiness sets in
to the diagram, a few of which also inhibit CYP1A2.