I have many many articles on melatonin and I have been taking it for 5 years on and off. Today Dale Bredesen posted this re Alzheimers in a group I follow so thought I would share.
Melatonin: A potential nighttime guardian against Alzheimer’s | Molecular Psychiatry
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In the context of the escalating global health challenge posed by Alzheimer’s disease (AD), this comprehensive review considers the potential of melatonin in both preventive and therapeutic capacities. As a naturally occurring hormone and robust antioxidant, accumulating evidence suggests melatonin is a compelling candidate to consider in the context of AD-related pathologies. The review considers several mechanisms, including potential effects on amyloid-beta and pathologic tau burden, antioxidant defense, immune modulation, and regulation of circadian rhythms. Despite its promise, several gaps need to be addressed prior to clinical translation. These include conducting additional randomized clinical trials in patients with or at risk for AD dementia, determining optimal dosage and timing, and further determining potential side effects, particularly of long-term use. This review consolidates existing knowledge, identifies gaps, and suggests directions for future research to better understand the potential of melatonin for neuroprotection and disease mitigation within the landscape of AD.
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The body sees fit to wash melatonin into the brain at high concentrations during the night. There is probably a reason for this.
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For what it’s worth, the 2024 report of the Lancet Commission on Dementia says: “There was no evidence of melatonin efficacy.”
The paper Alzheimer’s disease risk reduction in clinical practice: a priority in the emerging field of preventive neurology also doesn’t mention melatonin.
There is only one ongoing trial of melatonin for neuroprotection: Disease Modifying Potential of 5mg of Melatonin on Cognition and Brain Health in Aging. “The study will examine whether 5mg melatonin (over the counter, OTC) over a 9-month period improves Alzheimer’s disease (AD) biomarkers and cognitive function in two groups of individuals: those with mild cognitive impairment (MCI+) and those who are not (MCI-). AD biomarkers will be measured from cerebrospinal fluid (CSF) obtained from lumbar punctures. Cognitive function will be evaluated with routine neuropsychological tests.” Ending next year. Results in 2026?
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I wonder what dosage they use. It is important to remember that CSF concentrations are much higher (5-20 times) than serum.
I am currently taking around 1.8 grams of melatonin a night. I would not be surprised if 5mg would have a negligable effect.
Melatonin’s effects are likely to be dose dependent.
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I take 720mg of melatonin daily. My introduction to high-dose melatonin began here:
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Do you sleep soundly? I find very early wakening though I have only ever take 3-5mg melatonin but my GP recently suggested I move to a higher dose as I still battle with sleep/nerve pain (I combine the melatonin with full spectrum CBD or high dose PEA which does help). I have an acoustic neuroma treated by Cyberknife 5 years ago and my specialist recomended it. What brand do you use and when do you take it? Did you titrate to that level gradually? Great video!
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Yes, I sleep well. Here’s another resource:
I take 60mg gelcaps, 8 at bedtime (480mg), and 4 more spread throughout the day (another 240mg). Sorry, I misspoke in my original comment, I take on 720mg/day. I take this product:
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A new paper on Melatonin actvating the NRF2 pathway (which I didn’t know about). Paper out of China.
Melatonin prevents glyphosate-induced hepatic lipid accumulation in roosters via activating Nrf2 pathway
Results
Data firstly showed that MET administration markedly improved GLY-induced hepatic injury, as evidenced by normalized liver enzymes and alleviated pathological changes of liver tissues. Moreover, MET supplementation alleviated GLY-induced hepatic lipid accumulation, which was correlated with improved serum and hepatic lipid profiles and normalized expression of lipolysis- and lipogenesis-related proteins. Notably, MET significantly inhibited vital enzymes involved in stimulating oxidative stress. Moreover, MET enhanced GLY-inhibited Nrf2 nuclear transcription and increased the expressions of its downstream target genes HO1 and NQO1. Further studies revealed that MET may interact with Nrf2 to enhance nuclear translocation of Nrf2.
Open Access Paper:
https://www.sciencedirect.com/science/article/abs/pii/S1567576924017028
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Whats interesting in this video is that it confirms that exogenous melatonin wont affect endogenous production (something I have been told in the past). Thats good to know. Last night I doubled my dose from 3 mg to 6 mg and I must say no side effects and I did sleep better. Am going to ask my GP to prescribe 10mg next.
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I am not entirely sure about that, but I take a lot more melatonin where this will have an effect.
It remains, however, that normally I don’t take melatonin until I wake up during the night.
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I wake up at 3 am every night regardless of what I take - including Zolpidem when desperate. I have not tried melatonin at this time however, so I am interested in your comment.
People have sleep cycles. When you wake up at 3am that is because a sleep cycle has just ended with melatonin going down in your blood serum. The odd thing is that a lot of melatonin goes first into the cerebrospinal fluid and then comes from there into the blood.
Ideally what you need is a sleep tracker. With that you can see when the sleep cycles are more easily. Most of them last 90 mins or about that.
The really important thing to understand is that if you wake up at 3am at the end of a sleep cycle and you have the autonomous nervious system in sympathetic mode you have what is called the cortisol awakening response. You won’t then be able to get back to sleep until the next sleep cycle. (also called an ultradian cycle or HPA cycle)
Simplistically you can wait about an hour then take some melatonin gradually over the next 30 mins or so and if you are resting and not reading a phone you are likely to go back to sleep and get a sleep cycle or two extra sleep. That can make a big difference to how you are during the day.
Ideally, however, it is best to work out when the sleep cycles are. I take a very large number of pills even though some of them are 60mg. This is not only to get back to sleep, but to supplement the mitochondrial melatonin throughout the body and resist mitochondrial heteroplasmy.
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When I wake up in the night (3 am or earlier) I take 2-3 gr taurine. It is not a quick acting fix, but It works for me. It is ofc not for everyone. Since taurine comes with other benefits as well, it might be a good option to try.
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Thanks for this info. I am currently exploring higher dose melatonin for non-sleep benefits. I only take 10mg if I wake up early (2-3am) to use the bathroom, which is most nights. I find I am sleepy when I wake up at 6am (my normal non-alarm wakeup time) when I take 10mg of melatonin 3-4 hours earlier (2-3am). The sleepy feeling doesn’t last but is noticeable compared to nights when I slept through the night (didn’t take melatonin). My plan is to ramp up the dose but I worry about increasing the sleepy feeling. What is your experience in building up to and now taking huge doses of melatonin?
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I can’t find where I heard this but one of the researchers/doctors said that if you experience sleepiness that its possible your dose is too low… that there is some threshold above which sleepiness issue disappears.
For my part, I jumped straight to 180mg, and then went from there directly to 720mg, without any sleepiness issues.
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I think daytime sleepiness from taking high-dose melatonin is coincidental.
If you have daytime sleepiness, you probably have other issues.
Melatonin alone does ensure a good night’s sleep.
I can take 1 gram of melatonin first thing in the morning and experience no daytime sleepiness
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I mean I feel sleepy when I wake up, not during the day. The sleepiness fades quickly but is strong when I first wake up if I took 10mg of melatonin at 2 or 3am regardless of sleep duration (which is always about 7 hours). So not coincidental, but also not a large problem. I will try upping the dose to see if that changes anything.
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I understand, but as melatonin only regulates the sleep cycle, a little or a lot of melatonin shouldn’t make any difference.
As John Hemming says, it matters which part of the sleep cycle you are in when you wake up.
Unless you are retired like me, you probably use an alarm or light to wake you up in the morning.
If that is the case, you should try adjusting the time you go to bed up or down 15-30 minutes until you find the sweet spot.
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Hi I have read that melatonin suppresses dopamine. Does anyone have an opinion on that aspect?
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