High Dose Melatonin Therapy

I finished reading "Melatonin: Breakthrough Discoveries That Can Help You Combat Aging, Boost Your Immune System, Reduce Your Risk of Cancer and Heart Disease, Get a Better Night's Sleep" by Russel Reiter. The book was published in the 90s, but I was amazed of how passionate was the author about this topic and how he presents all the research. It really makes you appreciate melatonin!

There's no bio of Russel Reiter, although is briefly mentioned that he was at the University of Rochester prior to his move to the University of Texas. He has published an academic book on Melatonin and the bestseller mentioned above that I'm going to summarize in parts because its trivia is really pretty amazing.

First, Reiter orients us to where exactly is the pineal gland, which is the first gland in your body to be formed and which is clearly distinguishable after 3 weeks of conception:

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The pineal gland produces melatonin which is a very "old" molecule. That is, it has been found in every animal and plant studied to date, from human beings to the most primitive once-celled algae that appeared on the scene more than 3 billion years ago. In each organism's, melatonin's molecular structure is identical. This sameness is a rare occurrence in biology. Humans produce 5 to 10 times more melatonin at night that during the day, a circadian rhythm found in animals as well.

The first experiment involving melatonin, after it was isolated and chemically re-created, was an experiment for skin diseases. Since it turned frog's skin lighter, they wanted to see the effects in humans. They used 200mg and the only side effect was mild sedation.

To test toxicity, they've used in animals the equivalent of injecting half-cup of pure melatonin in humans, and no toxic effects were seen.

Babies produce increasing amounts of melatonin until they are about one year old. Then their nocturnal melatonin levels remain steady until just before puberty, when they decline markedly, a trend that continues for 5 years or so. This suggests a strong tie between melatonin levels and sexual maturity. Children who are late to enter puberty have been found to have higher levels of melatonin.

Then, melatonin continues to decline with age. So it may also trigger senescence. A 70 or 80 year old may have the hormone in amounts so small as to be undetectable.

Melatonin's first link with stimulating the immune system comes from studies done in mice where they were able to fight deadly viruses, their diabetes type I was less severe and adverse effects of chemotherapy were counteracted with the use of melatonin.

Melatonin is an excellent antioxidant, as well as a hormone. In fact, Reiter considers it the most efficient and versatile antioxidant. It is 5 times more effective than glutathione and 500 times more effective than DMSO!!!

Melatonin's protective effect in cancer comes in part from its antioxidant effect. They have done studies where after giving a toxic element to rats, their DNA gets destroyed. Mice who receive melatonin sustained only 1% as much damage. They had given the animals 750 times more of the toxin than melatonin, yet the hormone had offered near total protection!

For this same reason, melatonin protects against radiation. In fact, melatonin was 500 times more effective than DMSO as a radioprotector, and DMSO is already regarded as an excellent radioprotector.

In still the same line, melatonin has proven to protect against cataracts which are considered a result of oxidative stress among other things.

Melatonin's neuroprotective effects might also derive from the fact that the brain is most vulnerable to free radical attack. The brain presents a challenge because it has the blood brain barrier. However, this is not a problem for melatonin which can cross readily the blood brain barrier. They've found melatonin to be protective against free radicals generated by strokes.

In fact, melatonin is both water and fat soluble - a rare occurrence in nature - making it the one antioxidant that can protect all parts of the cell including its fatty membrane, and the one antioxidant that can cross all barriers. Furthermore, once in the body (after an oral dose), you don't have to worry about having the right enzymes or cofactors because it doesn't have to be converted into some other form.

In future posts, we'll see how melatonin's role in hormones, aging, immune system, glucose metabolism, etc. from Reiter's point of view. But I also wanted to mention now that some beneficial effects in animal studies were not seen when they used super high artificial doses of melatonin that your body can't produce. They were seen when a more "normal" range was used though. The scientists speculated that it had to be levels that the body could recognize so to speak. I also wanted to mention now that Reiter suggests a dose range from 0.1mg to 10mg depending on the aim or condition. I forgot the exact figure, but there's an individual difference response to melatonin of about 75%. Those who are very sensitive, will have anxiety and nightmares from taking just even 1 or 2 mg, which is why some suggest to start with 0.5mg or less.
 
Reiter conducted hundreds of experiments involving melatonin, yet melatonin's central role in the body's immune system eluded him for decades. Retrospectively, he thinks this was because melatonin's immune-enhancing effects are more evident when an animal is under stress. That is, melatonin buffers the effects of stress and/or melatonin is able to boost the immune system when people are under extreme stress. During a life-and-death study conducted in mice, those who were subjected to high amounts of stress and were treated with melatonin fared well. In fact, 82% of the mice survived, compared to 6% who only were stressed.

It's not okay to torture humans though, but similar studies revealed similar benefits under "normal" stressful situations. For example, college students who took 20 mg of melatonin while there was a seasonal virus around, were able to produce 250% more salivary IgA, a protein in the saliva that helps protect against colds and upper respiratory infections.

Stress and aging have a number of similar effects on the body. In both instances, there are more stress hormones, the thymus glands shrinks, and the number of immune cells decline. Old people have a deficit of immune system T cells and the T cells they produce are less capable of doing their job. Here's where melatonin helps. There are melatonin receptors on T-helper cells (a subgroup of the T cells), which means melatonin plays a crucial role in regulating that cell. When melatonin docks with its receptor on the T-helper cell, a cascade of events takes place, including the stimulation of cytokine interleukin-4 or IL-4, which then stimulates other immune responses.

Melatonin also stimulates natural killer (NK) cells. Men taking 2 mg of melatonin for 2 months had an average of 240% more NK cells, more than the double of their usual levels. NK cells fights cancer cells and viruses.

Melatonin also stimulates phagocytes which also destroy invaders. Monocytes are types of phagocytes. Trace amounts of melatonin were able to increase the ability of monocytes to destroy skin cancer cells by 73% in test tubes.

Melatonin also stimulates GM-CSF AKA granulocyte-macrophage colony stimulating factor, which sends a stimulatory message to stem cells located in bone marrow, so that white blood cells that fight disease can be produced.

People with AIDS have benefited enormously from melatonin because of its antioxidant and immune stimulating effects. Melatonin also seems to slow down the replication of the HIV because melatonin inhibits nuclear factor kappa-B which is an essential link in the chain of events that leads to cloning of the HIV. NK-kB levels are reduced by as much as 23% during the night- precisely when melatonin is in its highest concentration. Melatonin injections reduced the binding activity of NF-kB by 43%.

Melatonin also preserves muscle mass in people with wasting syndrome or cachexia.

As far as cancer goes, there's literature from the 1800s and 1900s when researchers were using pineal gland extracts to fight cancer. There are reports of partial and even complete responses. The first official study was conducted in 1963 when a Welsh physician used melatonin IV to treat osteogenic sarcoma with success.

It's in cancer research where controversy of the right dose comes to play. A study was conducted using breast cancer cells and melatonin. Despite the initial promising results, the study showed that there was no difference in the rate of growth between the cancer cells that were growing with or without a hundred times more melatonin that present in the human bloodstream. Then it dawned o them that maybe they were using too much melatonin. "Maybe less is more", they thought. "The body produces so little of it, that maybe it works in small quantities". They went back to the lab and repeated their experiments with less melatonin and sure enough. A mere mattering of melatonin backed the growth of the breast cancer cells by 75%!! This finding was unexpected since virtually all anticancer compounds are most effective in high doses. Melatonin apparently works the other way around. They conducted more studies to determine the most effective concentration of melatonin and this is when they found the most remarkable result: Melatonin had the greatest effect in a very particular range - a range that happens to be the amount of melatonin present in the human body. Concentrations above and below that amount had no effect on the cells.

I think the above is crucial in order to relax a bit the urge to megadose. Sometimes a little goes a long way and not the other way around. It will depend on the context, of course. Dosing according to age might be the best way to go, unless you need a PET scan or CT scan, then you might want to increase your dose.
 
And now in this post, we finish with Russel Reiter's research and recommendations.

Melatonin has a direct protective effect on the heart and the circulatory system in general. Evidence shows that the abrupt melatonin fall in the morning and the gradual decline that goes with aging, are hazardous to the heart.

Melatonin reduces oxidative cholesterol. People with severe hypertension had half the night-time melatonin levels of people with moderate hypertension. There is plenty of indirect evidence which shows that melatonin helps regulate blood pressure. It might be through the hormone's action in the hypothalamus, an area which regulates blood pressure, or it might be through melatonin's antioxidant effect.

Melatonin also prevents blood clots. When human blood platelets are incubated in a melatonin solution, the hormone reduces their tendency to clump by as much as 85%. Furthermore, heart arrhythmias, like most heart problems, occurs less frequently at night when melatonin is high.

Reiter also reviews all the sleep medications available today and how they all disrupt the sleeping architecture, that is, a person taking sleeping pills spend less time in phase 3 and 4 and more in phases 1 and 2. Healing and restoration happens in phase 3 and 4. Melatonin as a sleep aider, preserves sleeping architecture in a natural way.

You can also change your melatonin levels by changing your body temperature. Volunteers sitting in a hot bath in the middle of the day experienced about a 2 degree rise in body temperature, and they also had an accompanying rise in their melatonin level.

As far as reproductive hormones go, it was observed in a study how all women had a noticeable drop in melatonin around ovulation. As they neared their menstrual flow, the luteal stage of the menstrual cycle, most women produced significantly more melatonin, almost twice as much as in the first part of the cycle. This is referred as the "luteal surge". As it happens, high levels of melatonin are associated with infertility. Women athletes who train extensively and who don't have menstruations, have melatonin levels twice as high as normal women.

PMS is associated with low melatonin levels. Women with PMS produce less melatonin than other women, especially in the week before menstruation. Afflicted women are recommended to take 1 or 2 mg of melatonin taken at night at mid-cycle and extending until mensuration.

Melatonin levels decline rapidly around menopause. Melatonin levels of women aged 40 to 59 was half that of women in the 20 to 39 age bracket. Follicle stimulating hormone, or FSH, rises sharply just before menopause. The higher a woman's level of FSH, the lower her levels of melatonin. A number of menopausal changes are related to lower levels of melatonin. Rate of hypertension increases around age 48 for women, triglycerides and LDL cholesterol rise too. All these conditions have been linked with low levels of melatonin.

As far as mental health goes, there's data that shows that melatonin has an anti-depressant effect and that suicide victims had far less melatonin in their pineal glands than controls at the autopsy. The difference was especially striking when the deaths occurred at night, the time when melatonin is being actively produced.

People with schizophrenia have unusually low levels of melatonin. Patients who have undergone pinealectomy, exhibit symptoms of schizophrenia.

Melatonin has potent analgesic properties, changing the threshold to pain.

Reiter suggests light therapy during the day in order to maintain healthy melatonin levels, and also decreasing light at night. Back in the 90s, he was already making a big connection between EMFs and less melatonin production as well.

What was also surprising was to learn all the medications that block the production of melatonin: NSAIDs, especially indomethacin which had a complete blockade of the nocturnal increase of melatonin. NSAIDs also increase blood pressure and it might be through their effect on melatonin production. All the common pain relievers had a negative effect on melatonin production.

Beta blockers abolish melatonin production in animals. In fact, they are known to be "pharmacological [drug-induced] pinealectomy". Even ophthalmic beta blockers used for glaucoma can block melatonin production. Reiter suggests using these medications early in the morning.

Calcium channel blockers appear to have the same effect. Nifedipine caused significant reduction in nocturnal levels of melatonin. Verapamil, a common calcium channel blocker didn't have this effect though.

Some antidepressants such as Prozac affect melatonin levels. Vitamin B12 also deplete melatonin supplies. Steroids and tobacco too. In fact, he speculates that tobacco increases the risk of heart disease, cancer and other problems because it decreases melatonin levels. People who drink the equivalent of one or 2 glasses of wine at 7pm had 41% less melatonin at midnight compared with nights when they were given a non-alcoholic drink. Benzodiazepines also interfere with melatonin.

Back in the 90s there was already preliminary research about melatonin's positive effect in autism, epilepsy, and diabetes. This last one was interesting because they have found that diabetics produce significantly less melatonin, in fact, some of them have barely detectable amounts. Those with autonomic neuropathy induced by diabetes had more melatonin during the day than at night. Melatonin prevents diabetes in animal studies. Diabetics who take melatonin often need less diabetes medication.

It's hard to pin down a specific dose for each person because melatonin has a liver metabolism that is very individual. There has been a 35 fold difference in the amount of melatonin that enters the bloodstream in each individual. Those who have lot of melatonin entering the blood might feel anxious and get nightmares. They can take 0.1mg if they can split a pill this much. Others might need a more decent dose.

Melatonin usually has a short life of 30 to 40 minutes. The decline in melatonin levels in your bloodstream will cause your temperature to rise, which your body interprets as a wake-up signal. People who take relatively high doses (10mg), are able to sustain elevated melatonin levels through the night. Others, take a smaller dose of melatonin if they wake up in the middle of the night. Another option is to take a time released melatonin. Nevertheless, the doses that Reiter recommends for people who choose to take melatonin (based on 90s research) are:

Sleep 0.2-10mg
Jet lag 1-10mg
Anti-ageing 0.1-3mg
Shift work 1-5mg
Immune stimulation 2-20mg

The doses that Laura suggested from the other book, looked better. But keep in mind that if there's a virus flying around, you can take 2-20mg to help you fight it off.
 
Vitamin B12 also deplete melatonin supplies. Steroids and tobacco too. In fact, he speculates that tobacco increases the risk of heart disease, cancer and other problems because it decreases melatonin levels. People who drink the equivalent of one or 2 glasses of wine at 7pm had 41% less melatonin at midnight compared with nights when they were given a non-alcoholic drink. Benzodiazepines also interfere with melatonin.
. . .
Melatonin usually has a short life of 30 to 40 minutes. The decline in melatonin levels in your bloodstream will cause your temperature to rise, which your body interprets as a wake-up signal. People who take relatively high doses (10mg), are able to sustain elevated melatonin levels through the night. Others, take a smaller dose of melatonin if they wake up in the middle of the night. Another option is to take a time released melatonin. Nevertheless, the doses that Reiter recommends for people who choose to take melatonin (based on 90s research) are:

Sleep 0.2-10mg
Jet lag 1-10mg
Anti-ageing 0.1-3mg
Shift work 1-5mg
Immune stimulation 2-20mg

The doses that Laura suggested from the other book, looked better. But keep in mind that if there's a virus flying around, you can take 2-20mg to help you fight it off.
Very interesting, thank you Gaby
It looks to me that although the doses that Laura discovered may be better for most people, being a smoker I will try the 10mg amount, rather than the 3mg I have been taking, and see how that works out for me. Was there any indication in Reiters work as to a coorelation between the amount smoked and the amount of melatonin needed to counteract that affect? I suspect it is probably dose dependent, a pack a day smoker would probably need less melatonin to compensate than a two pack a day smoker.
You mention that the research was from the 90's, and the book Laura got that information from was printed in 1996. I think I'll take a boo at PubMed and see what they have that might be more recent.
 
It looks to me that although the doses that Laura discovered may be better for most people, being a smoker I will try the 10mg amount, rather than the 3mg I have been taking, and see how that works out for me. Was there any indication in Reiters work as to a coorelation between the amount smoked and the amount of melatonin needed to counteract that affect? I suspect it is probably dose dependent, a pack a day smoker would probably need less melatonin to compensate than a two pack a day smoker.

Well, 3 mg is not bad. In fact, in the studies they found great benefits with even just traces of melatonin. I think the chart Laura posted is a good guide. There might be specific times when you need more, i.e. fight jet lag or a virus.
 
In this article:

Dr. Sircus mencioned melatonin as a booster for glutathione status

Dr. Julian Whitaker writes, “Alpha lipoic acid also ramps up glutathione synthesis and significantly enhances detoxification, and we use it at the clinic, along with selenium and silymarin, to treat hepatitis and other liver diseases. Recent research suggests that the “sleep hormone” melatonin boosts glutathione status too, by stimulating production of the antioxidant enzyme glutathione peroxidase. We’ve had particularly good success treating patients who are recovering from strokes and those with hepatitis, neurodegenerative disorders such as Parkinson’s disease, and other chronic illnesses—conditions associated with dramatic increases in oxidative stress and depletions in glutathione. IV glutathione isn’t a slam-dunk, and it’s always used in conjunction with hyperbaric oxygen and other therapies, but we’ve seen remarkable improvements, particularly in patients who’d been told that nothing else could be done.”
 
All very interesting! Thanks a lot for the summaries!

I was wondering about melatonin's effect on immunity because if it stimulates the immune system it could actually trigger symptoms in some people. I searched just a little bit about melatonin and autoimmune disease focusing primarily on inflammatory bowel disease and found that it is mostly very beneficial.

I still have to read some more, and there are some articles to which I don't have access, but here's some of what I've found.

Regarding autoimmune diseases in general:


Abstract
Melatonin is the major secretory product of the pineal gland during the night and has multiple activities including the regulation of circadian and seasonal rhythms, and antioxidant and anti-inflammatory effects. It also possesses the ability to modulate immune responses by regulation of the T helper 1/2 balance and cytokine production. Autoimmune diseases, which result from the activation of immune cells by autoantigens released from normal tissues, affect around 5% of the population. Activation of autoantigen-specific immune cells leads to subsequent damage of target tissues by these activated cells. Melatonin therapy has been investigated in several animal models of autoimmune disease, where it has a beneficial effect in a number of models excepting rheumatoid arthritis, and has been evaluated in clinical autoimmune diseases including rheumatoid arthritis and ulcerative colitis. This review summarizes and highlights the role and the modulatory effects of melatonin in several inflammatory autoimmune diseases including multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes mellitus, and inflammatory bowel disease.


Now, focusing more on bowel diseases. This one is about the effects of melatonin on the intestinal flora, but also on oxidative stress, showing that melatonin could be beneficial for bowel diseases. Just keep in mind that it is a study with mice.


Abstract
This study investigated the antioxidant capacity and intestinal bacteria community in a mouse model of DSS-induced colitis. Twenty mice were randomly assigned to two treatments: mice with colitis induced by 5% DSS (DSS group) and mice with colitis induced by 5% DSS that also received melatonin treatment (MEL group). The DSS group showed significantly less antioxidant capability than the MEL group, but the two groups did not differ significantly in terms of diversity index (Shannon and Simpson), bacterial culture abundance (Chao1 and ACE), and coverage (Good's coverage estimator). Bacteroidetes were the most abundant phylum in the DSS group (58.93%), followed by Firmicutes with 31.46% and Proteobacteria with 7.97%. In contrast, Firmicutes were the most abundant in the MEL group (49.48%), followed by Bacteroidetes with 41.63% and Proteobacteria with 7.50%. The results support the use of melatonin for prevention of intestinal bowel disease due to its modulatory effect on antioxidant capability and microbiota in mice with colitis. Melatonin was demonstrated to improve the oxidative stress resistance of mice with colitis and regulate the intestinal microbial flora, thus improving intestinal health.


I don't have access to the full article that comes next, but it looks quite interesting. It's also in Russian, which I don't speak... :rolleyes:


AIM: to provide rationale for and develop treatment regimens using melatonin for inflammatory bowel diseases (IBD).
SUBJECTS AND METHODS: Prior to and 30 days after treatment, colonic mucosal biopsy specimens were studied by electron microscopy in 40 patients with Crohn's disease (CD) and ulcerative colitis (UC) in whom the diagnosis was verified by the examination and morphological study of the colonic mucosa. The patients were divided into 2 groups: 1) traditional pathogenetic therapy; 2) combined therapy using melatonin.
RESULTS: Following 30-day therapy using melatonin, signs of inflammatory infiltration were absent in 77.8% of the patients with CD. Minor inflammatory infiltrates consisting mainly of lymphoid cells and solitary granulocytes persisted in the mucosa and submucosal layer in 44.4% of the CD patients receiving the therapy without melatonin. The surface of columnar cells exhibited villi in 77.8%; however, a brush border failed to form in all cells. One month after therapy using melatonin, the ultrastructure of the colonic mucosa was normal in the patients with UC. Inflammatory infiltration and dystrophy were absent in 88.8% of cases. Small inflammatory infiltrates consisting of lymphocytes were seen in occasional mucosal portions in 50% of the melatonin-untreated patients with UC. There was focal plethora in the vessels.
CONCLUSION: The use of melatonin in combined therapy for IBD considerably improves the results of treatment and promotes a more complete ultrastructural recovery of the colonic mucosa.


Then, I was wondering about the use of melatonin while taking NSAIDs, because these are typically prescribed to people with bowel or pelvic pain to manage pain and inflammation (which is rather unfortunate because NSAIDs are also known for causing problems in the gastro-instestinal tract :-().

Gaby posted this:

What was also surprising was to learn all the medications that block the production of melatonin: NSAIDs, especially indomethacin which had a complete blockade of the nocturnal increase of melatonin. NSAIDs also increase blood pressure and it might be through their effect on melatonin production. All the common pain relievers had a negative effect on melatonin production.

And I've found an article stating that melatonin may be a good option for reducing this unfortunate NSAIDs side-effects. Here's the link where you can download the article in PDF or view it in HTML:


ABSTRACT
Non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely prescribed medicines to treat numerous pathophysiological conditions clinically. However, growing evidence indicates the adverse effects of NSAIDs on the different vital organs, among which gastrointestinal (GI) tract seems to be the utmost target in most of the cases. NSAIDs promote over production of harmful reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the gastric mucosa. These toxic species cause microvascular damage, increasing intestinal permeability, leading to the development of gastric lesions including ulcerations. Several strategies have been proposed to reduce the side effects of NSAIDs on the GI tissue, but most of them have failed to achieve this goal. Identification of an appropriate therapeutic strategy is urgently required. It is our opinion that this novel strategy to target GI damage induced by NSAID should include both anti-inflammatory and antioxidant properties. Under such a circumstance melatonin probably is the best choice for this purpose. Melatonin is a broad spectrum antioxidant and anti-inflammatory molecule. Numerous studies have reported the protective role of melatonin against gastric tissue damages caused by NSAIDs in animals or clinically. However, the underlying molecular mechanisms are not fully clarified. Thus, the present review attempts to gather the available information on this topic to provide a clear understanding on the exact scenario of this aspect.


The whole article is very interesting, although I don't fully understand the technical terms. Basically, it says that melatonin increases ulcer healing, it "scavenges free radicals and inhibits development of gastric ulcer", as well as intestinal permeability. This excerpt is interesting:

Melatonin as an alternative to NSAIDs
[...] In addition to the protective effects of melatonin on gastric injury induced by the NSAIDs, melatonin per se can also decrease inflammatory pain, by inhibiting NO generation and regulating the signalling pathways of NO‑cyclic GMP (156). The analgesic action of melatonin involves several components and diverse pathways including β‑endorphins, GABA receptor, opioid l‑receptors and the nitric oxide (NO)‑ arginine pathway (157-158). Interestingly, due to steric and electronic complementarity, melatonin can directly bind to the active site of COX-1 and COX-2 acting as a natural inhibitor of COX to suppress the inflammatory reaction (158-159). Its application not only reduces the GI tract injury induced by the NSAIDs but also improves the anti-inflammatory effects of NASID.


Finally, I did find some references to at least one patient who experienced a worsening of his Chron's Disease symptoms after taking melatonin and then felt better when he stopped it. So, there's still a possibility that it may not be beneficial for a very small number of people:


Melatonin treatment for CD is rare. We found a single article related to the effects of melatonin (3 mg) in a CD patient [89]. The authors observed disease activation after melatonin treatment in a single previously inactive patient. 24 h after stopping melatonin treatment, the symptoms abated. The authors suggested that melatonin may have activated a number of cytokines (i.e., IL-2 andIL-12) which could have exacerbated the symptoms. This presumption is based on the findings that Th1 and Th17 pathways appear to predominate in the inflamed mucosa of CD patients, whereas Th2 and Th17 factors are abundant in UC [90]. Moreover, it is known that Th1 increases the IFN-γproduction in CD[91], and CD patients exhibit elevated lamina propria IL-12 production as compared to controls [92]. Melatonin promotes a Th1-response by in-creasing IL-12 and IFN-γlevels [93,94]. The observations of Calvo and co-workers [89] require additional studies in a larger population of CD patients.

Very interesting indeed! I hope this is useful to some people with bowel conditions or other autoimmune conditions.
 
I didn’t have any sleeping problems, but because Cs information, I have taken 3mg melatonin a few years ago. But at the time, I was unable to sleep like I used to. So after few days tried, then stopped.

I started again about 23 days ago. I got MZS by Dr. Pierpali brand, 1 tablet containing 3mg melatonin, 8.7mg zinc, 50mcg selenium. This time I didn’t have any problems, after taking 1 tablet per night about one week then now I am taking 2 tablets per night.

one thing I noticed that seeing colors is different.
I have been doing the Prayer of the Soul meditation before going to sleep. after that I do short meditation. Mostly I see purple, white, blue colors together coming and go In my closed eyes vision.
But now, the colors more sharper, sparkling, seems like open up to more, then when I open my eyes, I see same image but it is more beautiful, is like I am seeing whole living Universe.

I have ordered more melatonin 5mg Now Brand. Lot more cheaper than MZS.
 
I did it for 4 days taking 3mg before going to bed. The sleepiness during the day time was building up with each day, so finally I had to stop taking it. I probably should have started with 1mg but I have only 3mg pills. I think, it's also important not to take 5-HTP or Tryptophan during this melatonin protocol since they are both melatonin precursors so one might end up with higher melatonin concentration in the body than expected.
 
I did it for 4 days taking 3mg before going to bed. The sleepiness during the day time was building up with each day, so finally I had to stop taking it. I probably should have started with 1mg but I have only 3mg pills.

My pills are also 3mg, but to avoid the grogginess the next day, I cut them in half, sometimes in 4 pieces even.
 
I experimented with taking 20 mg for about one week and a half, was feeling good, not groggy, had vivid dreams, though lately I've noticed that by taking so much it hadn't any effect on me anymore, so I lowered the dosage to 10 mg, feeling good and continue to have vivid dreams. Also another interesting thing I've noticed is that now I'm more stress resilient than before, unbelievable but it's true.
 
I've been taking 3.8 mg consistently and some days 5.6 mg. It's my third week and I noticed waking up feeling less groggy and overall more energetic in the early morning. I noticed, just as described in the research quoted above, that my PMS symptoms were reduced and overall there is less discomfort. The quality of the dreams are overall more protective and/or more graphic. I have to say that I'm very pleased with my melatonin experiment. I might reduce the dose to 1mg or 1.8mg, but for now, 3.8mg sounds about right for me.
 
I had started a few years ago with 3mg of melatonin, sometimes I woke up groggy depending on the time I went to bed. Once the boxes were finished, I went back down to 1.8mg with magnesium for 3 months but it wasn't enough. So I have been down for a week to 6mg with magnesium malate and I sleep better, I have a lot of graphic dreams, an increase of erotic dreams, I wake up in shape so for the moment it seems to fit me too !
 
Around a decade ago, I started taking 1mg of Melatonin with Magnesium Malate before bed and been taking that consistently for a long time until a few years ago, when I increased the dose up to 3mg and been on that pretty much every night, just to sleep better. What made me change that at that time, I'm not sure exactly. Either stress at work, being around WiFi or changes in my environment (EMF upgrades). All I knew that I wasn't getting much sleep and dreams were rare.

I started experimenting with 10mg three weeks ago, with first two weeks on alternating days (10mg every two days). I slept better. I woke up the next morning each time, feeling super alert after having experienced series of vivid dreams. It took me a while to get used to that. I didn't feel groggy during the day. This past week, I was on 10mg regularly and experienced no changes between regular and alternating days. I'll increase the dosage next week to see any differences. I currently live in high EMF/5G-active environment as well as being around experimental WiFi at work.
 

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