Thank you so much @Fabnus for sharing this with me.
"Conclusion
Due to the hypnotic and chronobiotic properties of melatonin, its use for the treatment of insomnia has been recommended. Several meta-analyses support such a therapeutic role (Auld et al., 2017; Ferracioli-Oda et al., 2018; Li et al., 2019) Additionally, a number of consensuses concluded that melatonin is the first-line treatment when a hypnotic is indicated in patients over 55 years of age (Wilson et al., 2010; Geoffroy et al., 2019; Palagini et al., 2020; Vecchierini et al., 2020). However, as discussed in this article, clinical studies with 2–5 mg melatonin/day may not be adequate to provide comparison with data on protection against neurodegeneration derived from animal studies. Indeed, studies with doses of 100 mg/day or higher are needed. Melatonin may also be involved in the pathophysiology of other non-motor symptoms in PD, but the current evidence is not convincing enough (Li et al., 2020; Batla et al., 2021) Therefore, more research is needed.
The safety of melatonin is very high and its non-toxicity remarkable. The lethal dose 50 after intraperitoneal injection was 1168 mg/kg (rats) and 1131 mg/kg (mice) but could not be reached after oral administration of melatonin (tested up to 3200 mg/kg in rats or subcutaneous injection of melatonin (tested up to 1600 mg/kg in rats and mice) (Sugden, 1983). There is evidence in dose escalation, phase 1, experiments of the remarkable lack of toxicity of melatonin in humans up to 100 mg (Galley et al., 2014; Andersen et al., 2016). As discussed elsewhere (Cardinali, 2019a), high doses of melatonin have been used in various pathologies without undesirable sequelae, that is, in humans, melatonin has a high safety profile and, in general, is very well tolerated. Currently, the only option for the incumbent physician interested in the use of melatonin as a cytoprotector is the off-label indication of the drug. Therefore, studies on the potential disease-modifying effects of melatonin are warranted. RBD patients may be the first group to target with melatonin. Indeed, melatonin has shown some interesting therapeutic effects in this group, although it must be remarked that high-quality evidence is lacking. Therefore, two birds might be killed with the same tone, as melatonin would offer an immediate clinical benefit in addition to reducing the rate of conversion to PD."
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Have this diagram in my digital files. It is one of the most distinctive illustrations I came across detailing biological effects of a supplement.
If my recall serves me - my iPad died three weeks ago - the paper from which it is drawn was seminal in my appreciation of melatonin. And it may well have been from chartist and if not certainly inspired my the many references thrown up on this molecule.
Unfortunately my spouse can not use melatonin during the work week. Use 20mg on Friday through to Sunday.
The higher doses - probably producing noticeable therapeutic effects - will have to await her retirement.
You are already there - go for it.
P.S: There is much information on escalation of dosage here on HU, put up by chartist.
Yes, that is a great diagram. I was not ready to retire, but thankfully we were somewhat prepared. I hope your spouse is able to alter there work schedule to incorporate as many reasonable protocols as possible.
Thank you for your words of support.
I was using 10 mg of Melatonin quick release for quite some time but my depression was really bad and I stopped. I am not sure if the melatonin contributes to the depression or if I am just depressed regardless.
Based on some advice I just got I am going to try 10 mg quick release an hour before bedtime and 8 mg extended release right before bed (I was advised 10 but all I could find was 4 mg ER tablets).
Indeed it seem like a tricky molecule, as some folks cannot tolerate it.
My spouse got up to 60/70 mg, per night. [10 mg sublingual and 60 mg capsule] But that was during the COVID lock down and she was at home. Now that she is at work the 20mg brings complaints of sleepiness.
Paradoxically she does not nap or complain of sleepiness on the weekends she takes it and is at home.
Chartist has a 1-2-3 Melatonin protocol, you might want to try. For example 10/10/10 mg one hour apart before bed, if my memory serves me right.
Wishing you the best in this new trust.
PS: As for retirement I am trying to line up her ducks by the end of March to spring for the exits by May. Little tight on the scheduling but we will see how it goes.
Complains of sleepiness when she goes to work. It may be the melatonin or could be other factors as the sleepiness complaint sometimes comes when she has not taken melatonin.
Thought it best to leave it out of the work week. Easier to try and figure out why she feels sleepy at times.
Thank you for the reply! Good to know why. Well, when she gets to retirement, she will able to get her melatonin from the sun, and that approach to obtaining melatonin comes without any daytime sleepiness!
We have just started cutting down my husband's 10 mg a night of melatonin to 8, then, 5. based on his neurologist's reading of recent studies and the fact that he is very sleepy during the day. when we started it 3 years ago, it helped immediately with making him sleep through the night (in combo with effexor, Klonepin, and olanzapine.) but the effect of making him sleep all night wore off while he added hydroxyzine and became more sleepy during the day. It seems like his underlying anxiety is always trying to break through. hard to tell!
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