Melatonin megadoses?

Apart from when I am drinking I aim to take melatonin normally around 1.5 grams during the night not before going to bed. I like to get my initial period of sleep purely endogenously.

When I am drinking I tend to take 200mg of melatonin to reduce the harm from acetaldehyde. I accelerate its conversion to acetate, but there remains an issue with acetaldehyde anyway.

Several sleep doctors have told me that melatonin should not be taken after 11 p.m. to avoid disrupting the circadian rhythm. Apparently, this hasn’t been an issue for you? In general, melatonin is recommended specifically for recovering from jet lag, so that warning seems quite logical. However, if your own internal production kicks in at the right time, then perhaps external melatonin doesn’t disrupt your sleep pattern.

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I tend to take it after about 2am when I wake in the night. (apart from when drinking)

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Meta-analyses on the topic: Inflammation: https://sciencedirect.com/science/article/abs/pii/S0889159121000386… https://sciencedirect.com/science/article/abs/pii/S2405457724002213…

Cardiometabolic risk factors: https://sciencedirect.com/science/article/abs/pii/S0261561417314243…

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I think melatonin holds back puberty by preventing mtDNA damage which is why children have v high melatonin levels. I am still taking 1.5g per night.

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Have you seen any differences/changes in biomarkers since you started taking such high doses of melatonin, John? 1.5 grams surely is a high dose.

Because I try a large number of interventions it is difficult to pin any outcome on any one intervention. I do keep detailed records and I would think I have been over 1.5 grams for about 6 months and over a gram for a year.

Obviously I aim to improve my health in the round and I am happy that I am doing that. Melatonin I think assisted originally in losing weight (130kg->85kg), reduced inflammation and body odour. The reason I take so much is to prevent ROS from Complex 1 and Complex 3 (and any others, but those are the main sources) from damaging the mitochondrial DNA which is stored in the mitochondria.

I am also having interventions designed to improve the average quality of mtDNA.

The problem with this is that I am taking it based upon the published papers, but measuring the effects on mtDNA is hard.

There is a dynamic equilibrium in the body with some enzymes repairing mtDNA, some ROS damaging it and mitophagy operating at least in theory to improve the average, by getting rid of the worst.

One thought I had was that high dose melatonin is often used to deal with incurable cancers. Hence taking it would be likely to assist in preventing cancer. I cannot, however, prove that it has done this.

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Thanks a lot, John. Your reasoning does make sense to me. I’ve also increased my melatonin dose the past months.
Having said that, I just ran into this study. Now, it’s clearly in vitro, may not translate to in vivo research, and most in vivo studies of course suggest melatonin has (strong) antioxidant capacities. Plus: to reach 2.5 µM concentration of melatonin at the cellular level would require extremely high oral doses. Still it made me wonder for a moment with regard to taking very high doses. What are your thoughts on this, if you don’t mind me asking?

The role of mitochondrial complex III in melatonin induced ROS production in cultured mesangial cells

Have you discussed these anywhere on the forum, if I may ask?

This is the Rapamycin forum. One of the interventions is Rapamycin which through mitophagy increases the average quality of mtDNA. My view is the main initial driver of development and aging is changes to mtDNA. Hence anti aging interventions are things to resist this. Most of the forum topics discuss this in different aspects.

Other people have other mechanistic theories of aging. However, there are interventions which are generally believed to work.

I am not sure 2.5 microMolar is that hard to hit as cells tend to have levels in the microMolar range anyway at time.

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That’s a very far fetched hypothesis that is not reasonable IMO. We don’t see children experiencing early puberty after being exposed to even massive mtDNA damage such as from chemotherapy, radiation exposure or genetic mtDNA mutation disorders.

Endocrine features of primary mitochondrial diseases - PMC.

By contrast, a recent study also found a high incidence of precocious puberty among girls with mitochondrial disease. Among 140 girls with evidence of mitochondrial disease on muscle biopsy, 10 (7.1%) were diagnosed with central precocious puberty, much higher than the general prevalence of 55.9 per 100 000 girls [56:black_small_square::black_small_square:]. There was no association between precocious puberty and neurologic symptoms, specific enzyme defects, disease onset, or disease severity, and brain MRI was normal in all.

Dr. Greger continues doing god’s work with his video series on supplementing, and this time he tackles melatonin. Short version, he appears not to be a fan of supplementing with melatonin for a variety of reasons.

Melatonin Supplements for Sleep and Anti-Aging?

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Melatonin is a molecule that has complex effects. Personally I don’t take it until I have slept for a few hours. I have woken during the night for perhaps 50 years and I use melatonin to extend sleep. The timing is quite critical, however.

I currently aim to have 1.62 grams when not drinking and 1.82 grams when drinking. If I am drinking I take 200mg of melatonin before starting. I suggest people are cautious about this as if you are not used to it it may make you go to sleep.

After all the talk here about the potential health benefits of melatonin, I began taking it 2-3 hours before bed (it’s when I take all of my nighttime pills in order not to drink water right before sleep!).

Upon reading your comment that you like to fall asleep endogenously, I felt I should double check that there is no potential harm I’m causing by taking it prior to falling asleep. I’m taking sustained release 5mg.

Probably ok. I prefer to know how my endogenous systems are working

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Wow it really seems like a double edged sword when it comes to these rodent lifespan studies.

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I have been learning about Melatonin from DR. Russel Reiter- who is a world- class expert on Melatonin and wrote 1,600 papers on this subject. I also listened to podcasts with Dr.John Lieurance, Deanna Minich and some others. These Melatonin experts are convinced about it’s positive effect on mitochondria, detoxification, treatment and prevention of certain infections (Covid and others), being a strong antioxidant and antiaging among other positive characteristics. There is a lot of information about effect of Melatonin on prevention and even treatment of dementia.

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In the end if the melatonin protects the mitochondria they are more able to function properly and they they ensure the cells have the ATP and acetyl-CoA that enables them to properly function.

The medical establishment is against melatonin supplementation, but there are solid arguments on all the points raised by people such as Dr Greger.

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I’ve taken 2000+mg a day for almost a year now. I feel great.

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Could you please explain your reasoning for taking such a high dose of Melatonin. Do you take the whole amount at the same time or in divided doses? Thank you!

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