Melatonin megadoses?

Thank you very much for your detailed reply!

Here is a nice interview with Dr. Reiter, a melatonin specialist at the University of Texas. Watch the first 1 minute to hear his credentials. He’s clearly a big deal in Melatonin. Show notes below.

Show Notes
-How Dr. Reiter got into melatonin research [1:23]
-What melatonin does in the body [3:28]
-How blue light inhibits melatonin production [7:05]
-How melatonin is passed to the fetus and newborn [12:00]
-The anticancer benefits of melatonin [15:25]
-How pharmaceutical drugs suppress melatonin production [18:40]
-When should melatonin be taken during the day? [22:47]
-Does taking melatonin affect natural production? [24:36]
-Older people need more melatonin [29:20]
-How melatonin can reduce the impact of Covid-19 [31:15]
-The impact of alcohol and caffeine on melatonin production [34:45]
-Melatonin acts as an antiviral [37:24]
-How sunlight helps with the production of melatonin [44:35]
-Melatonin can reduce the likelihood of metastasis [50:45]

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What is the best extended-release melatonin brand at a reasonable price?

Some notes from the video in the comment above https://youtu.be/YU9QUbsqrcQ:

  1. Melatonin levels are both an internal clock and an internal calendar, the latter because of the changing amount of light in different seasons.

  2. You should take Melatonin at the same time very night.

  3. Avoid blue light at night, and avoid light during the night.

  4. Retinas have a set of photoreceptors (not cones or rods) that affect the internal clock.

  5. Fire light, candle light, and moon light have no blue.

  6. Night lights should be red, yellow, orange.

  7. Melatonin helps set the biological clock of a developing fetus. Nursing children for 3-4 months and maybe as long as 5-6 months do not produce melatonin – they get it from nursing. Babies who do not nurse do not receive this melatonin. Some have speculated that SIDS could have a correlation with melatonin, but this has not been studied.

  8. Melatonin is one of the most powerful anti-cancer hormones and it is also an antioxidant.

  9. Most cancers are age-related. As you age you produce less melatonin. Melatonin suppresses tumor growth and cancer growth.

  10. Melatonin is part of your body’s repair and regeneration process.

  11. Melatonin should be more widely used because of the misuse of light.

  12. We could reduce some negative age-related effects on health through the use of melatonin.

  13. Animal studies show that cancer, neuro-degenerative diseases are inhibited by melatonin.

  14. People fighting cancer may want to take melatonin during the day as well as night, because it leaves the body quickly.

  15. Melatonin can also help sepsis.

  16. Does taking Melatonin reduce your body’s ability to produce Melatonin? Melatonin in the body is produced in the pineal glad. This Melatonin is controlled by the nervous system and not by endocrine feedback. Therefore, there is no evidence of this.

  17. Blind people have lower rates of certain cancers. This could have to do with their high levels of melatonin.

  18. Melatonin levels drop as we age. If you take 75 year olds and separate them by health level, those who are more healthy have more melatonin. Could be one way or the other, but there is the correlation.

  19. How much do you take at night? Started with 3-5 mg as a young person. To defer aging, a 45 year old person might take 10mg. But others more. He is reluctant to say how much he takes because he doesn’t want to make a recommendation. But he does take 100mg nightly “for a very specific reason.” It is also very anti-viral. He wants to impede the likelihood that he’ll get COVID. If not for COVID he would be taking less. Probably 30-50mg/night as an 85 year old.

  20. Six clinical trials on Melatonin and COVID were currently being conducted when the video was made. They have all shown it helps: reduce either the severity of the infection, duration of hospitalization, necessity for tracheal intubation, decreased mortality.

  21. Melatonin is cheaper than aspirin.

  22. Older people have lower melatonin. They also tend to take more prescription medications. Some of these reduce melatonin levels.

  23. Does alcohol affect melatonin? Yes, particular if late in the day or evening. Also coffee.

  24. Women are delaying child-bearing. This leads to some negative effects in the children. Melatonin seems to help protect against this. Women in late reproductive periods should take melatonin, also helps preserve the reproductive system.

  25. There is very little evidence that it ever has negative effects.

  26. Melatonin is an anti-viral generally, even against the common cold. Zika, Ebola. Up-regulates the immune system.

  27. Ebola: WHO says any reasonable treatment should be used to help if it helps. Melatonin can help.

  28. Blue-blocker glasses: are these helpful? One or two studies say maybe. Often they’re not wrap-around. If you’re going to wear them they should be like goggles. Avoid blue light in the the evening by any means. But they are so-so as a help.

  29. Astronauts change the wavelengths of the light on the space stations. Light is a drug that impacts our physiology.

  30. Oxidative stress is a great pressure on the body.

  31. Infrared light from the sun has an effect on melatonin in the body. This has high permeability. It impacts cells directly.

  32. Melatonin is produced in the pineal gland. It is also produced in the body, in cells, but it is never released into the blood.

  33. Infrared light has impacts on melatonin synthesis in the cells.

  34. Sunlight changes during the day: In the early morning hours we’re getting mostly infrared. Later UV. In late afternoon back to infra-red. The infrared actually helps repair skin damage, so morning and evening sun help the skin to repair what is caused by the midday UV.

  35. So melatonin is also produced during the day – not in the blood but in the cell.

  36. Cancer cells produce less melatonin than normal cells. Warberger Effect. They are deficient in the way of protecting themselves with melatonin.

  37. Melatonin reduces the effect of metastasis. It has actions that suggest it would be anti-metastatic.

  38. Melatonin is absorbed from the blood by the cell and by the mitochondria. Supplemental melatonin encourages in-cell production of melatonin.

  39. Can infrared light from devices also encourage the body to produce melatonin? Probably, it is the light that does it.

  40. The evidence regrind stroke and heart attack – those cells don’t regenerate or don’t do it very well. Aspirin is often chewed to get it in the blood quickly. This doctor would immediately load up on melatonin if he had a heart attack. What dose? 100mg perhaps several times over that next 24 hours. Not a recommendation.

  41. Melatonin is not magical. It is just a good wholesome molecule that evolved to help cells operate at a maximum level. Benefits greatly outweigh the risks.

  42. Some say 120-150mg a day. Is that too much? Different cancers, comorbidities may suggest different amounts. But…

  43. You can’t overdose on melatonin.

  44. The optimal dose is hard to decide upon. The double-blind studies have not been done. But don’t be afraid of taking too much.

  45. Are there any side effects that might suggest an overdose? Sleepy? Dizzy? This is hard to quantify. There could be some unique metabolic issues for some people in some times where Melatonin might not be recommended.

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This has been discussed months ago

Reiter takes 180mg per day, review Shallenberger paper/discussion.

Shallenberger’s slides and paper have been posted more than one time on this forum

And a link to a PDF copy of Reiter’s medical book {NOT his consumer book] has been posted.

Yes, I see the thread is quite long. Do you disapprove of me sharing more information on the subject? I thought these details might be helpful for some people.

Also, Shallenberger’s paper and slides explicitly recommend a particular brand of melatonin from a specific company. That made me hesitant to trust his recommendation. Dr. Reiter does not make any such recommendation, so I trust his conclusions more.

As it happens, they do align! All the better.

Mentions the brand he uses That is NOT the only brand that is 60mg per capsules size. There are other brands mfg/sold in 60mg capsules

FWIW
I personally know Frank since the early 80’s. I was the person that organized the first German Medical Ozone Training Course (done in English) in Heidelberg.

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The persuasion is really strong that high dose melatonin is snake oil.
If I wanted to make money by selling snake oil, I would do what he does.

(i.e see all his statements like “prevent cardiovascular disease”), there’s a reason why that’s not allowed, if it’s not true, it’s fraud and he’s lucky he is not on the radar of the FDA.

"Do you disapprove of me sharing more information on the subject? "
Absolutely not, I for one am not interested in rummaging around trying to find an old thread. The content of this site has grown to be quite large. When some new reason comes up to discuss things in an old thread, it is fine by me.

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The video I watched of Dr. Reiter was persuasive to me. Also, he did repeat many of the claims by Dr. S.

It sounds like high dose melatonin is inexpensive and almost impossible to overdo. It does not stop your body from making its own melatonin and does do something that your pineal glad melatonin does not do: it travels through your bloodstream into your cells where it supplements the natural melatonin that cells make for themselves as an antioxidant.

This appears to be the primary benefit of supplemented high doses of melatonin — not to regulate sleep but to help regenerate and repair the inner machinery and especially the mitochondria of your cells.

I’m going to give it a go and we’ll see what happens. I’m taking 60mg tonight for the first time. I’ll report back a few times to share my experience, particularly as regards daytime grogginess and sleepiness (two supposed side effects that some experience), and as regards sleep quality.

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If you find something that seems “too good to be true”, it probably is. Also please be careful, and consider why you are doing this. What are you really trying to get out of it? Can’t you get that from something else.
High dose melatonin will certainly not increase happiness.

I got rid of my weighted blanket. I felt like I was being slowly crushed every night. Not trying that again.

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I’m surprised people can get away with such high doses of melatonin without feeling groggy. Even just 5mg makes me tired well into the next day. It’s a relaxing feeling at least.

I find it quite useful as a “stress buffer”, so for example if I exercise a lot of am cutting calories, I can get away with higher doses without as much sedation.

The research is certainly promising.

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Timing is key, not only against the circadian cycle, but also against ultradian cycles.

Way way higher than 180

Tg2576 mice receiving ~66.66 mg/kg daily starting at age 4 months showed a significant reduction in Aβ levels in brain tissues, as well as lowered abnormal nitration of proteins [362]. Importantly, Tg2576 mice receiving ~266.66 mg/kg daily starting at age 4 months produced the most impressive results where the brains of mice terminated at 15.5 months not only exhibited a dramatic decline in oligomeric Aβ40, but also a significant increase in soluble monomeric Aβ40. A noticeable decreasing trend in Aβ42 was observed in treated compared to untreated mice at the same age [361]. When Tg2576 mice from two separate experiments were administered ~266.66 mg/kg melatonin in drinking water daily starting at age 4 months until termination at 15.5 months, survival was significantly increased in treated compared to untreated mice [361,362]. Melatonin treatment at ~266.66 mg/kg daily in drinking water was able to reduce mortality in Tg2576 mice to levels observed in wild-type mice [361] (Table 2). Consequently, the effective translation of melatonin doses between animals and humans becomes the primary consideration when designing the dosage for clinical trials.

Table 3. Calculations of three HEDs converted from animal doses using different adjustments that account for differences in (A) Metabolic rates by scaling to the ¾-power; (B) Bioavailability; (C) Bioavailability that is enhanced by solubility and/or formulation.

Study Design/Total Daily Dose/Duration/Ref. Results (A) HED Daily Total (mg/kg) Scaled to Mb3/4 (B) Dose (A) Adjusted by Bioavailability (C) Dose (A) Adjusted by Enhanced Bioavailability
2 mg/mL in drinking water, Tg2576 AD mice/266.66 mg/kg/11.5 mos starting at 4 mos old/[361,362] Striking reductions in Aβ aggregates at all ages during treatment; dramatic extension of survival of AD mice to levels similar to wild types. 2499 mg (35.7 mg/kg) 4831 mg (69 mg/kg) 10,621 mg (151.73 mg/kg)
0.5 mg/mL in drinking water, Tg2576 AD mice/66.66 mg/kg/11.5 mos starting at 4 mos old/[362] Striking reductions in Aβ levels in brain tissues of treated mice at 8, 9.5, 11, and 15.5 months. 625 mg (8.928 mg/kg) 1208 mg (17.26 mg/kg) 2656 mg (37.94 mg/kg)
0.016 mg/mL in drinking water, Tg2576 AD mice/2.13 mg/kg/10 wks starting at age 14 mos old/[363] Failed to reduce brain Aβ levels, unable to reverse oxidative damage. 19.96 mg (0.285 mg/kg) 38.58 mg (0.55 mg/kg) 84.83 mg (1.21 mg/kg)
10 mg/kg in drinking water, healthy, normal C57BL/6J mice/14 days after tauopathy initiation/[366] Reduced memory impairment, tau hyperphosphorylation, ROS, and neuroinflammation. 96.23 mg (1.375 mg/kg) 186.0 mg (2.66 mg/kg) 408.98 mg (5.84 mg/kg)
40 ppm in food pellets, healthy, normal B6C3F1 mice/7.2 mg/kg/11 weeks different age groups/[364] Significant reduction in Aβ peptides in brain cortex tissues: 57% in Aβ40 and 73% in Aβ42; increased melatonin levels in cerebral cortex in all 3 treated age groups (12 > 6 > 27 mos) compared to untreated. 69.29 mg (0.99 mg/kg) 133.94 mg (1.91 mg/kg) Not applicable
10 mg/kg IP injection, C57BL/6J mice treated with Aβ1-42 peptide/daily IP injections for 3 wks/[365] Reversed Aβ1-42-induced synaptic disorder, memory deficit; prevented Aβ1-42-induced apoptosis, neurodegeneration, and tau phosphorylation. 98.55 mg (1.41 mg/kg) 486.15 mg (6.95 mg/kg) Not applicable
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Based on the info in this thread, I have increased my Melatonin dose to 20 mg extended release. I feel so much more rested in the AM. I was a skeptic.

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I was surprised also. John Hemming’s report of his personal usage inspired me to take a closer look at the literature. Because melatonin has many anti-cancer properties I was interested in increasing my dose. I just assumed that taking high doses would induce daytime sleepiness. That is not the case. I have experienced zero daytime sleepiness from taking doses of 60 to 100 mg at night. The number of adverse events associated with taking high-dose melatonin is very small.

“Beyond its sleep and chronobiotic properties, melatonin is a potent antioxidant9 and has the ability to cross the blood-brain barrier,10 with suggested anti-amyloid properties. Due to this, melatonin has been increasingly investigated in many varying conditions, including cancer, cardiometabolic conditions and neurodegenerative diseases at higher doses, where there is less documentation of its safety. Doses ranging from 30 to 100 mg are being suggested or tested for effectiveness in a range of conditions and ages, including ocular ischaemic syndrome”

“In supporting the anti-cancer effect of melatonin, its efficacy in reducing the incidence of cancer has been proven through animal studies and clinical trials”

“Safety of higher doses of melatonin in adults: A systematic review and meta-analysis”

https://onlinelibrary.wiley.com/doi/full/10.1111/jpi.12782

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I’m back up to 40mg time released melatonin and on days off if I wake up too early or in the middle of the night I’ll take an additional 80mg bulk powder. I’m currently doing shift work from 06:30-19:00 so sleep can be a bit challenging. When I was taking high doses before I thought it was causing hair shedding but apparently it was a coincidence because I don’t have that problem this time around.
I was wondering if anyone has read that melatonin can help menopause by lowering FSH/LH? I had run across that info years ago but haven’t been able to confirm if it’s true. My menopausal symptoms seem greatly improved with a high enough dose of melatonin -although it could be placebo.

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I dont know about any specific reasearch about menopause. However, the body generates melatonin in the mitochondria to handle oxidative stress. Exogenous melatonin will top up the mitochondrial melatonin.

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Very cheap for 50grams

This makes taking 1g per day possible… That said kids overdose on it so maybe try 200 to 400 mg at first. I’ve definitely done 300mg at once before

More broadly this may be THE way to ameliorate Adderall neurotoxicity (socially important in a world of shrinking AGI timelines)

It’s also worth using it while taking an ION panel to see effects on 8 oxo g