(Warning: relatively hot take and also not medical advice.)
Firstly, there’s a major underlying confounder effect here which is the untracked severity of insomnia and it’s correlation with the prescription of melatonin. If these are majorly coupled it could amount to most of the effect?
Secondly, here’s a model and a tip for melatonin use as most US over the top pills I’ve seen are around 10mg which is way too much. I’ll start with the basic mental model for why and then say the underlying thing we see.
TL;DR:
If you want to be on the safe side don’t take more than 3mg of it per night. (You’re probably gonna be fine anyway due to the confounder effects of long-term insomnia having higher correlation with long-term melatonin use but who knows how that trend actually looks like.)
Model:
There’s a model for sleep which I quite like from Uri Alon (I think it’s from him at least) and it is mainly as the circadian rhythm and sleep mechanism as a base layer signal for your other bodily systems to sync to.
The reasoning goes a bit like: Which is the most stable cycle that we could stabilise to? Well we have a day rhythm that is coupled to 24 hours a day each day, very stable compared to most other signals. That’s the circadian rhythm which is maintained by your system’s sleep.
What sleep does is that it is a reset period for the biological version of this as it sends out a bunch of low-range stable signals that are saying “hey gather around let’s coordinate, the time is approximately night time.” These brain signals don’t happen in non-sleep and so they are easy to check.
Melatonin is one of the main molecules for regulating this pattern and you actually don’t need more than 0.3 mg (remember bioavaliability here) to double your existing amount that you already have in the body. Most over the counter medicine is around 10mg which is way too much. Imagine that you change one of the baseline signals of your base regulatory system and just bloop it the fuck out of the stratosphere for a concentrated period once everyday. The half life of melatonin is also something like 25-50 minutes so it decays pretty quickly as well which means that the curve ends up looking like the following:
If you don’t do this then your more natural curve looks something more like this:
So if you stratosphere your melatonin with 10 mg then your REM sleep will be fine but the sensitivity to your MT2 receptor will be a bit fucked which means worse deep sleep (which is important for your cardiovascular system!). Hence you will fall asleep but with worse deep sleep (Haven’t checked if this is true but this could probably be checked pretty easily experimentally).
The bioavaliability of melatonin varies between 10 and 30% so if you aim for approximately your own intragenous generation of melatonin you should take 10 to 3x the amount existent in the system. For my own optimal sleep that is 0.5 mg of melatonin but that’s because my own system already works pretty well and I just need a smaller nudge. The area under the curve part of the model is also a good reason to take slow release melatonin as it better approximates your normal melatonin curve.
(I need to get back to work lol but hopefully this helps a bit)
(Warning: relatively hot take and also not medical advice.)
Firstly, there’s a major underlying confounder effect here which is the untracked severity of insomnia and it’s correlation with the prescription of melatonin. If these are majorly coupled it could amount to most of the effect?
Secondly, here’s a model and a tip for melatonin use as most US over the top pills I’ve seen are around 10mg which is way too much. I’ll start with the basic mental model for why and then say the underlying thing we see.
TL;DR:
If you want to be on the safe side don’t take more than 3mg of it per night. (You’re probably gonna be fine anyway due to the confounder effects of long-term insomnia having higher correlation with long-term melatonin use but who knows how that trend actually looks like.)
Model:
There’s a model for sleep which I quite like from Uri Alon (I think it’s from him at least) and it is mainly as the circadian rhythm and sleep mechanism as a base layer signal for your other bodily systems to sync to.
The reasoning goes a bit like: Which is the most stable cycle that we could stabilise to? Well we have a day rhythm that is coupled to 24 hours a day each day, very stable compared to most other signals. That’s the circadian rhythm which is maintained by your system’s sleep.
What sleep does is that it is a reset period for the biological version of this as it sends out a bunch of low-range stable signals that are saying “hey gather around let’s coordinate, the time is approximately night time.” These brain signals don’t happen in non-sleep and so they are easy to check.
Melatonin is one of the main molecules for regulating this pattern and you actually don’t need more than 0.3 mg (remember bioavaliability here) to double your existing amount that you already have in the body. Most over the counter medicine is around 10mg which is way too much. Imagine that you change one of the baseline signals of your base regulatory system and just bloop it the fuck out of the stratosphere for a concentrated period once everyday. The half life of melatonin is also something like 25-50 minutes so it decays pretty quickly as well which means that the curve ends up looking like the following:
If you don’t do this then your more natural curve looks something more like this:
Section 3 of the following talk about a desentisation of the MT2 part of melatonin as something that happens quite quickly: https://www.sciencedirect.com/topics/neuroscience/melatonin-receptor
So if you stratosphere your melatonin with 10 mg then your REM sleep will be fine but the sensitivity to your MT2 receptor will be a bit fucked which means worse deep sleep (which is important for your cardiovascular system!). Hence you will fall asleep but with worse deep sleep (Haven’t checked if this is true but this could probably be checked pretty easily experimentally).
The bioavaliability of melatonin varies between 10 and 30% so if you aim for approximately your own intragenous generation of melatonin you should take 10 to 3x the amount existent in the system. For my own optimal sleep that is 0.5 mg of melatonin but that’s because my own system already works pretty well and I just need a smaller nudge. The area under the curve part of the model is also a good reason to take slow release melatonin as it better approximates your normal melatonin curve.
(I need to get back to work lol but hopefully this helps a bit)