Dr. Shallenberger is the exact source I went through several years ago. Interesting how megadose melatonin was more effective against protecting from radiation damage from a PET/CT than any other antioxidants. If you are taking doses above 60mg, I would recommend you to Melatonin 60 - Scientific Health Solutions . Dr. Shallenberger personally oversees the purity testing of their melatonin max capsules. I personally take 300mg most nights from this company.
I tried to make my own capusles from powder form, but it is not as efficient nor accurate. Premade capsules from the link are much better.
Also, you have to keep in mind that melatonin levels decline gradually over age which is related to lowered sleep efficacy. So someone who is 60-70 will probably need to supplement with the higher doses of melatonin vs a 20-30 year old who will need smaller doses.
It refers to melatonin stimulating complexes I and IV of the Electron Transport Chain and how a deficiency results in lower ATP production.
3.8 Melatonin
A study in mice has demonstrated that melatonin rescued mitochondria from oxidative stress-induced mitochondrial dysfunction and may prevent subsequent cell death of muscle cells [[132]]. Several in vitro and in vivo studies demonstrate that melatonin affects mitochondria by increasing the activity of the electron transfer system and ATP production, increasing mitochondrial membrane potential and membrane fluidity and by closing the mitochondrial permeability pore [71, 112, 133, 134, 135].
Several small studies measured melatonin levels in critically ill patients. Circadian rhythm of melatonin secretion was disturbed and melatonin secretion low in almost all critically ill patients investigated [136, 137, 138, 139]. Low levels of melatonin were associated with more severe illness in septic patients, but not in patients admitted for coronary syndrome, intoxications, gastrointestinal bleeding, pneumonia or stroke [[136]]. Melatonin supplementation was also found to reduce oxidative stress and inflammation in new-borns with sepsis [[140]]. No published studies were found on the effect of melatonin supplementation on mitochondrial function and clinical outcomes in critically ill patients. However, the study of Mistraletti and co-workers showed a good bioavailability of exogenous melatonin in critically ill patients [[141]].
Earlier in this thread I said I use the biovea brand. Recently I have become concerned at its sugar content (which is not that high, but does mean some sugar). I have therefore tried Carlyle’s 12mg which has mannitol in it. Because mannitol is poorly absorbed the energy from multiple tablets is less.
I am also experimenting with some of the 60mg tablets in the market. There seem to be quite a few providers in the USA.
This seems to be really good value as well as it provides 300 12mg tablets.
Based on your posts, I decided to try a high-dose melatonin regimen back in June of this year.
I normally use NatureBell Melatonin 20 mg, 365 Fast Dissolve Tablets - Natural Strawberry Flavor, mainly because it is cheap. They work sublingually and have a medium dissolve time and use sorbitol as a sweetener,
Do you think there is a significant difference as to which is worse, sorbitol or mannitol?
I take one at bedtime along with a Healthfare Melatonin 60 mg Vegetarian Formula | Non-GMO | Gluten-Free | Unflavored | Made in The US tablet. These are fairly small non-favored tablets.
Usually, I have to get up once in the middle of the night to empty my bladder, and that is the time I take the 20 mg tablet to make a total of 100 mg nightly. I have been on this regimen since June 21st of this year. So far; zero negative effects. Surprisingly it doesn’t produce any daytime drowsiness. Positive effects? Don’t know but I have had no indication of developing any cancers, and that is my main purpose for the larger doses.
@desertshores How many hours between 2nd dose and waking, to get no daytime sleepiness? I’m always dancing with the devil on “is there enough time left” ? My cutoff rule-ish is 330am for a 1mg dose. I’ll then wake between 5am and 7am. I can’t image what a huge dose would do. I did just buy 10mg melatonin tablets, so I may just find out about medium dose effects.
I tried, twice, taking 60mg in the 1am timeframe. Had to write off the following day both times. I didn’t sleep all day, just felt lousy and non-functional.
Right now I am going to bed at 10 pm and getting up at 6 a.m. If I wake up during the night, which is most nights, it is usually between 3 and 4 a.m. When I first started this routine I was using a 1 mg sublingual dose. I ran out of the 1 mg pills and happened to have the 20mg around so I tried that. It made no difference in how I felt. I have been taking high-dose melatonin of 3 or more mg nightly since the 1980s so my body has just become accustomed to it.
Thanks. I’ve been taking melatonin since the 90s. Low doses only. I’m going to see how LDN works (if it ever shows up), and try high dose melatonin of LDN goes bye bye.
I have not reviewed the research. My protocol includes large amounts of melatonin. Hence i am really interested in any research as to why this is wrong, but otherwise that protocol is set.
Sorbitol and mannitol are isomers. They are different metabolically, but i picked the tablets using mannitol as a first one to try. I might get some of the sorbitol ones and see what happens.
I dont know the reasons for this. It could be slow metabolism or that your nervous system is shifted from sympathetic to parasympathetic. It may be worth working out what dose works if any.
What I think happens with sleep cycles is that at the end of a sleep cycle the body either starts up the cortisol awakening response (CAR) or keeps in parasympathetic mode in which people tend to be sleepy. The thing that decides this is melatonin levels. If they are decreasing (remembering melatonin has a shortish half life of around 30 mins, but this will vary) then the body shifts into CAR/Sympathetic mode. I have tried measuring this with the elite HRV and a polar H10 and that tends to agree.
Hence it should not make any difference between taking 1mg of melatonin or say 2mg. There will come a point at which your body cannot metabolise it that quickly and then it will hang around a bit. However, what you could do is to experiment wiith varying doses at that time (3am) and record waking time. I hypothesise that your waking time is defined by a sleep cycle and the metabolism of melatonin.
It would be interesting to have a database of how different people respond to different doses of melatonin at 3-4am in different circumstances. That would be something that would be good data to collect via the rapamycin.news forum. Clearly different people respond in different ways to melatonin. The fact that (IMO) it has an effect via the ultradian cycle (HPA/Sleep Cycles) means it otherwise seems a bit random, but actually isn’t.
I think what happens with megadoses is that a large proportion passes via osmosis (or some other mechanism) into cells and is drawn up into the mitochondria. Hence the rate of metabolism would if measured appear to be particularly high. However, I have not had a mechanism in place to measure this although I would happily run some experiments on megadose pharmokinetics.
It is also important to remember that levels of melatonin in the Cerebrospinal Fliud are much higher than blood serum. A material proportion (may be all) of pineal melatonin is injected directly into the third ventrical of the CSF. That is then used to clean up the brain. Obviously if you have some melatonin in the serum it will get into the CSF, but normally the proportion in the CSF is much higher. This would also imply that the pineal switches off earler than people think and the melatonin supply in blood serum is actually then coming from the pool of melatonin in the CSF. This is why I would suggest that supranormal serum levels are required to have the same effects as normal (young animal) levels in the CSF. A lot of researchers seem to have missed this key aspect of melatonin processing.
@John_Hemming Thanks for the information. I will think about this at length. Clearly the problem is complex. There are many variables at play but melatonin (amount and change) and stress (sympathetic > parasympathetic) are at the heart of it.
Ideally you need to use a sleep tracker and try to spot the sleep cycles which are something around 90 minutes long. My experience is that if I wake and my system is sympathetic mode then getting back to sleep is nigh on impossible until the next cycle. There are things that can be done such as NDSR/Yoga Nidra that encourage your body to switch into parasympathetic state.
If I were you I would keep detailed notes of the outcomes with varying doses of melatonin.
Explains a bit about the CSF being used to wash the brain. I have no idea whether melatonin in CSF is better for getting access to brain cells or melatonin in serum. However, if you take enough melatonin for enough time you can push up the CSF levels. CSF turns over about every 5 hours.
I don’t think melatonin in the CSF metabolises the same way as that in serum. However, some will get absorbed into cells.
In the end, however, as melalonin levels go down all of this goes wrong. Much that it is best to get things to work better and produce more endogenous melatonin, more melatonin as far as my own personal experience is concerned, is a good thing.
Interestingly if I have a slight hangover (which is slight because of use of DHM/Pantethine/Bae) I find I can clear almost all of it with a wodge of melatonin. (as far as I feel which is IMO a key test).
One of my tricks to get back to sleep is to use my sleep tracker to work out when the last sleep cycle ended. That is likely to be when I last woke, but sometimes it isn’t. I then estimate when the next sleep cycle starts and start taking melatonin about 30 minutes before that. I have a partial objective of increasing CSF levels to assist in maintaining melatonin levels. Hence I may take melatonin 30 minutes before my estimated start time, then 15 minutes, then at or around the time. This does not always work and when I am particularly drunk the alcohol rebound can cause an additional problem. However, it works a lot of the time. That also gives me a dose of melatonin that helps with everything else.
Brad Standfield says he only takes small doses of melatonin.
Andrew Huberman says avoid melatonin because it acts to hold back puberty. That it acts to hold back puberty in chidren is I think confirmed. My personal experience is that it makes me less smelly (in terms of body odour) which is symptomatic of it having anti-puberty effects. My sense of smell, however, has not been harmed.
Having taken doses over 30mg for 4 years and mega (strictly deci/hecto) doses for over a year I am not unhappy with the broader effects of everything I do.
For complex reasons I have more recently been really chugging the melatonin with dose one night over a gram (1.077) and on average taking more than 0.5g.
I am wondering whether there are clearly identifiable shifts in biomarkers from this and whether there is anyone in the same dosing territory. I have started dropping it right down to see what that results in terms of biomarkers (If anything can be spotted).
