High Dose Melatonin Therapy

A study came out this month showing how melatonin helps reduce endothelial dysfunction induced by ox-LDL, i.e. oxidised LDL lipoprotein particles which are the ones that cause plaque buildup in the arteries.

It does so by reducing both mitochondrial dysfunction and endoplasmic reticulum stress (a transport system that is involved in the synthesis and folding of proteins) and also activates the JNK/Mff signaling pathway. This pathway is activated by a number of stress stimuli and plays important roles in "development, apoptosis, cell growth, inflammatory, and immune responses."

Melatonin Attenuates ox-LDL-Induced Endothelial Dysfunction by Reducing ER Stress and Inhibiting JNK/Mff Signaling

These results demonstrate that ox-LDL induces ER stress and mitochondrial dysfunction and activates the JNK/Mff signaling pathway, thereby contributing to endothelial dysfunction. Moreover, melatonin inhibited JNK/Mff signaling and sustained ER homeostasis and mitochondrial function, thereby protecting endothelial cells against ox-LDL-induced damage.
I'm still reading through this thread, so maybe this will have been touched on already, but man I'm confused by all the language and terminology. I'm interested in trying out melatonin; I'm not having any sleep issues or anything, I'm pretty healthy and not on any medication so I'm less worried about myself, rather, I'd like to try to talk to my father about taking it with me. He's been not doing well in his battle with depression, and is currently taking medication for it, what I'm not sure, and while most things online say there isn't much risk in taking melatonin while on anti-depressive medication, I'd much rather he not be taking them at all, but it's also a difficult conversation to have because of where he's at in his fight with it, and how he feels it's the only thing that stopped the really terrible thoughts he was having. Of course the C's say to stay away from them period, and to me that's a no-brainer, however I already had my run in with SSRI's when I was a young teenager, so I've already lived through the deal with the devil and fortunately realized quick enough that his deal sucked.

Anyway, what else interested me for my father is that he was also diagnosed with diabetes a few years ago. I know as I'm typing all this how I'm the one who seems to care more about it all than he does, because he hasn't changed his eating habits, he eats way too late at night, cookies when he thinks no one is looking.. and I thought, well, the medication is only taking any energy he might have away, so he's left to just wilt away with no strength to fight back, and I thought I remembered reading somewhere that trying to reset his circadian rhythm could ease some of what he might be going through. He doesn't have issues sleeping that I'm aware of, actually because of the SSRI's he takes frequent naps, and you can tell his energy is just gone. I don't know, there are a lot of variables at play, but when I started reading this thread and saw this posted by Chu about melatonin and diabetes...

"Melatonin: Countering Chaotic Time Cues published" in Frontiers in Endocrinology in 2019 highlights the research for right timing of dosage and also some concerns in people who are genetically predisposed to develop metabolic syndrome with high doses of melatonin (carriers of a gene variant), especially if they take melatonin during the day. The rest sounds pretty interesting. Again, dosage is not widely discussed except briefly for a cancer study where they used 300mg of melatonin.

It seems to point to evening/night time dosage of melatonin, except in shift workers where the circadian rhythm might need to be manipulated with artificial light/darkness exposure+ melatonin.

The Entero-Insular Axis and Diabetes

The importance of rhythms to the entero-insular axis was also evident early on, with variations in glucose tolerance and insulin sensitivity (166). The subject has been very recently reviewed (161). The circadian, SCN-driven nature of these rhythms is now well established alongside the “masking” effects of mealtimes, meal content and other external inputs (167, 168). Triacylglycerol (TAG) has a particularly marked circadian rhythm in constant routine (167). During both simulated and real shift work, standard meals taken at inappropriate times at night—biological night when melatonin secretion is high-lead to evidence of insulin resistance/glucose intolerance and higher TAG, both risk factors for heart disease (167, 169). This is therefore one possible mechanism underlying the epidemiological data showing higher risk of these major diseases.

Circadian re-adaptation in real shift workers resolves some metabolic risk factors (169) (and see Gibbs M, Hampton SH, Morgan L, Arendt J. Effect of shift schedule on offshore shift workers' circadian rhythms and health, 2004. RR318 - Effect of shift schedule on offshore shiftworkers'...). So there is good reason to use the chronobiotic properties of melatonin (and timed light exposure) to manipulate circadian phase. It remains to be determined to what extent central and peripheral oscillators remain in synchrony/coupled in these circumstances.

Melatonin clearly influences glucose concentrations- pinealectomy leads to increased glucose in nocturnal rats (170). In MT1 and MT2 receptor knockout mice the SCN-driven glucose rhythm is abolished independently of peripheral oscillators in muscle, adipose tissue and liver (171). In humans in one study, the decrease in glucose tolerance from morning to evening was mostly influenced by the endogenous circadian system compared to the sleep-wake cycle. However, in apparent contrast to pinealectomy effects in animals, melatonin administered during day time just prior to a glucose tolerance test in healthy adults clearly impaired glucose tolerance both in the morning and the evening (172, 173), an effect that was dependent on a common gain-of-function variant of the melatonin receptor gene MTNR1B151 (see below). Melatonin may also acutely decrease insulin secretion in cultured human islets (174). Thus, some controversy exists in the literature especially when comparing results in nocturnal rodents with diurnal humans with both beneficial and detrimental effects of melatonin reported. It is intriguing to note that the rare condition 'familial insulin resistance' or Rabden-Mendenhall syndrome is associated with pineal hyperplasia (175, 176).

In view of pre-existing associations of the pineal and melatonin with metabolic function the discovery of related MT1 and MT2 receptor variants aroused enormous interest. A common variant in MTNR1B—MTNR1B rs10830963 is associated with increased risk of type 2 diabetes, increased fasting plasma glucose levels and impaired early insulin secretion (177, 178). Moreover, late dinner, associated with elevated melatonin concentrations (as in night shift workers, above), impaired glucose tolerance in “gain of function” MTNR1B risk allele carriers but not in non-carriers. These data suggest that circulating melatonin is related to the development of Type 2 Diabetes, in a deleterious sense. Of course sleep restriction is also associated with impaired glucose tolerance, increased risk of metabolic syndrome and/or diabetes (179, 180). So that the usefulness of melatonin to address sleep problems may well increase risk of metabolic abnormalities. Some controversies have arisen and have been reviewed (181). The question is not solved.

well, I'm having understanding it in layperson terms. Does melatonin help with diabetes? or make it worse? Maybe I'm also tired :-(
well, I'm having understanding it in layperson terms. Does melatonin help with diabetes? or make it worse? Maybe I'm also tired
Keep in mind these studies were done with people eating a standard diet, which is normally high in carbohydrates. If a person is diabetic I would exhort them to change to a low-carb diet, and to avoid eating carbohydrates later in the day (when as the article says carbohydrate metabolism becomes less efficient). Berberine/Metformin also helps the body balance blood sugar and even changes the microbiome in ways. Check out this post in the dedicated thread for it:

If you're not eating carbs, much less carbs later in the day, I wouldn't worry about melatonin having adverse effects on blood sugar levels personally. There's other things much more important that I diabetic should look into. :-)
Thanks @whitecoast I'll give it a read as well! My diet personally isn't also the best, and while I probably know a little more than my dad I'm definitely not anywhere close to being able to give decent advice to him in that regard, so I've also got some reading up to do on that and maybe I can get us both going in a better direction.
Probably one of the best all-around books on diet is Primal Body: Primal Mind by Nora Gedgaudas. Other books talk more specifically about other details, like Wheat Belly, The Plant Paradox, The Vegetarian Myth, and others thrown around in the Diet subforum.
Hi Pearce,
I'd like to try to talk to my father about taking it with me. He's been not doing well in his battle with depression, and is currently taking medication for it, what I'm not sure, and while most things online say there isn't much risk in taking melatonin while on anti-depressive medication, I'd much rather he not be taking them at all, but it's also a difficult conversation to have because of where he's at in his fight with it, and how he feels it's the only thing that stopped the really terrible thoughts he was having.

Anyway, what else interested me for my father is that he was also diagnosed with diabetes a few years ago. I know as I'm typing all this how I'm the one who seems to care more about it all than he does, because he hasn't changed his eating habits, he eats way too late at night, cookies when he thinks no one is looking.. and I thought, well, the medication is only taking any energy he might have away, so he's left to just wilt away with no strength to fight back, and I thought I remembered reading somewhere that trying to reset his circadian rhythm could ease some of what he might be going through.
I understand your good intentions to help your father, but in this case it is very complicated considering that the greatest effort has to come from his part, and changing habits is the most advisable to do. Apart from medication, has he tried an alternative psychological therapy?

Now, what does seem to be positive about melatonin taken at the right time and in the right amount is that it could be very helpful in depression problems. Referring to the Melatonin-Diabetes relationship, this is what Walter Pierpaoli writes in his book The Melatonin Miracle:

Although we have our doubts about the insulin resistance theory of obesity, we do appreciate the very real dangers of insuline resistance. We believe that melatonin may actually help prevent insulin resistance from ocurring in the first place, and thus may help to preventthe occurrence of noninsulin-dependent diabetes. Insulin resistance is a concern in and of itself because high levels of insulin are known to accelerate hardening of the arteries. We also think that melatonin may provide other benefits to people who already have develpoed the disease.

We base our recommendations on studies that have shown that people with diabetes produce less melatonin. We think that there may be a connection here; that the onset of diabetes may be influenced by the lower melatonin levels that occur as the pineal begins to wear out. Consider this: We know that melatonin helps to keep our hormones in balance, and that when melatonin production declines, our hormone levels may be disrupted. For example, during sleep, in addition to melatonin, we produce many other hormones, including growth hormone. Growth hormone can raise blood sugar levels, thereby promoting insulin resistance and diabetes. Melatonin helps to regulate the production of growth hormone. By normalizing growth hormone levels, it may help keep blood sugar levels in check and prevent diabetes.

Melatonin may also help to prevent diabetes in another important way, by regulating the production of corticosteroids. As discussed above, these stress hormones are released when we are upset, angry, or frightened. Cortisol increases the production of glucose, which in turn, raises blood sugar levels. This raise in blood sugar levels helps to rev the body up for action, and is part of our primitive flight or fight response. If we have run across a savannah to escape a predator, all this blood sugar is put to good use, if, however, we are sitting at our desks or in our living rooms, producing corticosteroids because we are mad at boss, or coworker, or relative, the blood sugar is superfluous and unhealthy. It just sits in our bloodstream until it is broken down by insulin. Interestingly, studies have found that diabetics have higher than normal levels of corticosteroids , which makes it more difficult for them to control their blood sugar. By controlling corticosteroids production and its subsequent risen blood sugar, melatonin may help us avoid developing the internal hormonal environment that may trigger diabetes.

In any case, I hope you will find the best way to help your father.

He's seeing a therapist, I don't know how often or really any details, but I know it's been over a year since he started and she put him on the ssri meds, and I told him then all the dangers of it, I just feel like now he's lost all his strength, and I'm not sure if I've been showing that I care and am concerned enough. Basically I haven't really spoken to him much about it at all since then. So that's where I want to start, by bringing him new info to show him the work I've done on his behalf, that I DO care and am here for him, and that now it's his turn to make stronger efforts.

I know to temper my anticipation about it, he may not change anything at all. Then I can say at least I tried my best, and it definitely won't hurt me along the way to gain some new information and knowledge so it's a win-win regardless. I love him and don't delude myself into thinking I can do the fighting for him, but I do want to help him fight in any way I can
Hi everyone, This post could be under other health topics also, but I'll start with the Melatonin thread. I had covid in December 2020. The first part was like a normal bad cold or flu that seemed to resolve after 5 days... mild congestion, headache, fatigue, swollen glands, fever of 100 or less (oh and loss of smell). Symptoms started on Monday and seemed mostly improved by Friday night. Saturday I was still resting, by Sunday night I had developed shortness of breath. No cough or phlegm to speak of, but I was desperate to find a help that didn't involve the ER because I wasn't able to breathe. My neighbor is a naturopath who generously brought me an oxygen concentrator at 10pm along with homeopathics for breathing and anxiety. She also gave me a nebulizer, which I used to nebulize a home made formula of iodine, food grade hydrogen peroxide, and saline. This helped my breathing finally...it took me about a week to recover my normal breathing capacity. The following week, I went to work as normal. Friday night I gathered with a few friends and stupidly had a few drinks. By Sunday night I was ill again, unable to breathe, and having fits of vomiting and diarrhea throughout the night. The nebulizer formula no longer worked and I was using oxygen all the time. I was shaking, blue, and felt numbness and tingling in my limbs. I had my husband chatting online with a friend for support, and she suggested melatonin based on research. I had never taken melatonin and was worried it would really knock me out and felt like I might die in my sleep for lack of oxygen. Finally I took 10mg of melatonin and in 20 minutes I was able to take the first deep breath in over 24 hours. I continued to take the melatonin based on a protocol by Doris Loh, an independent medical researcher. I was taking about 100mg/day spread throughout the day. It took about 6 months for me to really regain my health and I still occasionally get shortness of breath. Doris Loh's research shows that taking melatonin and ascorbic acid together prevent oxidative damage in the same tissues that are damaged by spike proteins. I watched hours of her videos while convelescing. I also read other research supporting even larger doses being safely and successfully used for cancer, so I wasn't concerned about taking 50 -100mg/day. I still take 10mg of melatonin along with 1000mg of liposomal ascorbic acid every night before bed. Just as a little bit of background info, I am an acupuncturist and have studied some functional nutrition. Before, during, and after my illness, I was also taking vitamin D, zinc, NAC, quercitin, alpha lipoic acid, chinese herbals, osha root, lomatium, propolis, fresh ginger tea (this helped a lot), liposomal ascorbic acid, sodium ascorbate, Potent vitamin C powder from Perque... and probably more that I can't remember. I had also taken HCQ and Ivermectin from frontline docs during the second round of this illness, but I think it was much too late in the process to make much difference. That is all I have time to write right now, but I will try to check in in case this info wasn't clear and anyone has questions or concerns. Thanks for listening.


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Some interesting excerpts from From The Magic of Melatonin by Dr. Jan-Dirk Fauteck:

Melatonin is an uncommonly effective antioxidant, so its reduction due to the exposure to light at night may have multiple negative health consequences related to the accumulation of oxidatively damaged molecules.

The drop in melatonin with aging seems to be related to many debilitating changes associated with advanced age, for example, skin deterioration, cataracts, cardiovascular disease, cancer, and neurodegeneration.

In addition to its sleep-aiding effect, melatonin protects our body against free radicals as a potent antioxidant and ensures a quality of life and mental fitness—even in old age. It strengthens our immune system, lowers blood pressure and cholesterol levels, and can help prevent heart disease. Recent studies also demonstrate its excellent effectiveness in the treatment of cancer, diabetes, migraine, chronic pain, eye disease, and infertility, among others. Therefore, melatonin is a true force multiplier for our health.

The choked melatonin production also disrupts processes of cell division and repair, which increases the risk of tumor formation.

Other places in the body where melatonin is produced during the day are the digestive tract, blood platelets, retina, testes or ovaries, spinal cord, lymphocytes, and skin. The melatonin that is also produced in daylight has especially local effects, for example, in its effect as an antioxidant. To what extent and whether the melatonin produced here affects the melatonin production in the pineal gland at night, and thus also functions as a superimposed timer, is still the subject of investigations.

During the day, very little melatonin is produced, and intensive production begins only in the evening. At around 11 p.m., the “sleep” level rises to eight times the daily rate. This is the signal for the command “night operation” to the organs, and the brain then stores important information from the day to long-term memory.

Besides melatonin, the hormone cortisol (produced in the adrenal gland) plays a key role in our circadian rhythm. Between 4 and 5 a.m., it rises continually, reaching its peak at 8:30 a.m. As the day progresses, cortisol levels drop until they reach their lowest level at midnight.

In addition to this receptor-dependent effect, melatonin also acts as a free radical scavenger independent of a receptor and protects the cells against damage resulting from oxidative stress (i.e., stroke or heart attack), UV rays, X-rays, or anemia (Reiter et al. 2014a). Also, the results of the receptor-independent effect of melatonin in animals apply equally in humans.

In addition to the pineal gland, other cells of our body have the ability to produce melatonin, especially in their mitochondria, the so-called power plants of the cell. The melatonin produced in this way is not released into the blood, as from the pineal organ, but acts directly on the spot. This often makes it impossible to prove how much melatonin is produced in these cells. Studies have shown that the mitochondria play an essential role in cell death (e.g., Juszczak and Drewa 2016, Letra-Vilela et al. 2016). Melatonin protects these cell organelles from attack by free radicals,

The protective qualities and positive effects of melatonin extend to all of our cells, regardless of whether the melatonin was formed on the spot, originated from the pineal gland, or was ingested as a supplement. For example, melatonin has the ability to reduce the toxic effects of chemotherapy, while also increasing the effectiveness of such treatment. Ongoing studies also provide the first promising results of melatonin in the fight against cancer. Melatonin, according to a study on its effect on prostate cancer, can positively influence or prevent the spread of tumor cells (Kiss and Ghosh 2016).

Free radicals damage our cells, cause diseases, and accelerate our aging process. As an antioxidant, melatonin acts against the destructive potential of free radicals and protects us from cataracts, stomach ulcers, Alzheimer’s disease, Parkinson’s disease, cancer, and AIDS, among others.

has been shown that melatonin is more potent in controlling free radicals than vitamin C and vitamin E (Reiter et al. 2014a)! The reason is that vitamin C does not reach the brain immediately, while melatonin penetrates very quickly and everywhere in every cell. The importance of this effect cannot be emphasized enough, as more than one hundred diseases of our time are associated with oxidative stress.

Numerous studies demonstrate the high antioxidant activity of melatonin in the fight against free radicals: in the treatment of cancer, cardiovascular diseases (e.g., myocardial infarction and stroke), metabolic diseases (e.g., Diabetes), inflammation, and apoptosis—programmed cell death, which is particularly important in chemotherapy. Furthermore, taken in a sufficient amount, melatonin is a very safe medication without any side effects (Reiter et al. 2016).

Melatonin is the star among the so-called body-specific antioxidants, which can protect you against cataracts, stomach ulcers, and even cancer. Numerous studies have already been carried out with amazing results. Melatonin protects against free radicals, which are released during a stroke and can damage the brain much more than the stroke itself! In addition, it has been demonstrated that melatonin protects against radiation (e.g., X-rays).

However, what is certain is that melatonin can also reduce blood pressure and reduce the risk of diabetes.

If you want to regulate your circadian rhythm by taking melatonin, you will be more likely to succeed by taking it regularly, in low dosage, and one or two hours before sleeping. In this case, it is a chronotherapy.

For example, if you want to use melatonin as an effective free radical scavenger following an acute medical incident such as a stroke, then you should be advised to take it immediately after the incident occurs and not wait for a certain time of day.

Older people with a melatonin deficiency often suffer from high blood pressure, which can lead to a stroke, diseases of the coronary arteries, and high cholesterol. Here, too, melatonin helps maintain healthy blood pressure by its antioxidant effect, not only against harmful cholesterol deposits, but also positively in regard to the cardiovascular system.

Heart attack and stroke are events of acute vessel occlusion. Melatonin has a great vasodilating ability and supports the circulation of blood with its regulating effect. It also protects the heart muscle, as well as the brain, from further damage as a perfect counteragent of free radicals. Recent studies also demonstrate its anti-inflammatory properties, which are particularly effective in the fight against atherosclerosis and associated hereditary diseases (Favero et al. 2014).

Melatonin also plays an important role in the synthesis, secretion, and effects of insulin. As a strong chronobiotic, melatonin is responsible for important metabolic processes. If the melatonin fluctuations are disturbed, this can lead not only to insomnia, but also to insulin resistance, glucose intolerance, and a marked circadian disorganization with further consequences, resulting in obesity and diabetes. This is the result of a study that also concluded that therapy with melatonin benefits the health of the whole body (Cipolla-Neto et al. 2014).

For some time now, researchers have been observing the relationship between sleep disorders and obesity. In people who sleep fewer than four hours, the body secretes the hunger-inducing hormone ghrelin and produces less leptin, a hunger-suppressing hormone. In short, sufficient sleep also leads to balanced eating habits and a healthy body. Evidence that melatonin has a positive effect on body weight and metabolism is increasing.

Studies with shift workers and the elderly have shown that sleep disturbances, melatonin deficiency, and metabolic disorders are related. However, recent studies also demonstrate that melatonin is able to modulate the synthesis and secretion of insulin, to protect the cells producing insulin from overload, thereby counteracting the development of type 2 diabetes (Peschke et al. 2015, Tuomi et al. 2016).

However, if melatonin is produced less—for example, due to the use of sleeping pills, beta-blockers, alcohol, nocturnal light, or increasing age—this leads to long-term insulin resistance and type 2 diabetes. The reason is that melatonin acts on specific receptors on the pancreas, which is responsible for the release of insulin, thus preventing insulin from being released at night. However, if too little melatonin is produced for the reasons mentioned, a vicious cycle is set in motion. Through the release of insulin even at night, the blood glucose level drops, and we get hungry. The nightly walk to the refrigerator is then preprogrammed. A further consequence of melatonin deficiency is that the body accustoms itself to the permanently increased insulin and is resistant, even during the day, which often leads to diabetes with all its accompanying symptoms.

Beta-blockers, which are used as blood pressure agents, are among the handful of drugs that affect melatonin formation. As their name suggests, they block the beta-receptor, which is important in starting melatonin production. Additional drugs that affect sleep are benzodiazepines, or antidepressants. They stimulate sleep but suppress the body’s melatonin release. In other words, by taking a sleeping pill, you block the production of your own sleep regulator.

Studies with aspirin have shown that it can also partly suppress melatonin release (Murphy et al. 1994). Many patients in the studies report problems during and after sleep. Long-term use, especially in the evening, prevents melatonin from protecting you from numerous diseases by acting as a free radical scavenger. Paracetamol, when administered in the evening, has been shown to inhibit melatonin formation to the same extent as ibuprofen and aspirin. If, on the other hand, these products are taken early during the day, they have almost no effect on the production of nocturnal melatonin.

The positive effects of melatonin have been proven many times, not only for healthy sleep and a controlled day-night rhythm, but also for epilepsy, jetlag, diabetes (especially type 2), neuropsychiatric disorders (e.g., Alzheimer’s and Parkinson’s), and even in acute events (e.g., stroke and heart attack). Melatonin relieves stress, pain, and metabolic disturbances, and it increases blood circulation, which has already achieved good success, particularly in the elderly. In cancer treatment, it promotes the efficacy of chemo-and radiation therapy, while simultaneously reducing their negative side effects (Emet et al. 2016).

Inadequate melatonin also affects the liver and the work that is usually done at night. The result is insulin resistance, which can lead to diabetes. In addition, the urge to urinate at night remains as strong as during the day. Because of the lack of melatonin, a special hormone that inhibits urine production (antidiuretic hormone, ADH) is missing.

If melatonin is used as a tablet or capsule, about 30 to 40 percent of the melatonin is absorbed. After about twenty-five minutes, half of the melatonin taken as a pill is already broken down, so there is no longer any significant melatonin after approximately 2.5 hours.

In the case of supporting therapies, such as those for a stroke or myocardial infarction, higher dosages are required. In the earlier studies, quantities of up to 50 mg and more were used successfully as an immediate measure, and specifically as a fast-release form of melatonin. The administration took place immediately after the occurrence of the event, independent of the time of day. It is also advisable to use higher doses for concurrent therapy in tumor patients. Whether these are to be administered in the evening is still controversial but very likely. In the case of radiation therapy, doses of 15 mg need to be administered shortly before the treatment.

Extremely high doses administered in animal experiments show the following: Melatonin is absolutely nontoxic. Melatonin is by no means carcinogenic, but rather has a positive effect in the fight against cancer. Melatonin has no negative effect on the fetus.

How healthy is a short nap during the day? In science, the opinions are divided. There are short “naps,” “power napping,” or a sleep phase of up to 45 minutes at certain times of the day. They do not influence the circadian rhythm, since they have a completely different sleep structure. They are even health promoting, as a recent study has found (Kallistratos 2015).

Nonetheless, it is not recommended to take a nap every day. Some feel even tired after the short sleep and do not even get into gear at all. Others sleep too long and have difficulties with falling asleep in the evening.

Melatonin and Light Even a small, early evening dose of melatonin in a fast-release dosage form improves the consistency of the internal clock and the biological daily rhythm during the winter so that mood improves significantly. Light therapy has also proven to be a useful form of treatment. Used in the morning, the light not only reduces the morning melatonin, but also improves the entire rhythm.

Melatonin as an Effective Painkiller

This leads to the conclusion that a lack of melatonin can lead to nocturnal pain or even pain during the day. In some patients, the frequency of headaches was significantly reduced with the help of melatonin (Srinivasan et al. 2012). There are many mechanisms that may be responsible for the positive effect of melatonin. On one hand, there is an anti-inflammatory effect. On the other hand, it inhibits the excessive release of dopamine, stabilizes the cell membrane, and promotes the release of GABA—the most important neurotransmitter of the brain. In addition, melatonin acts as a protector against free radicals and regulates the vascular nerves and thus the blood flow (Srinivasan et al. 2012).

Melatonin: The Body-Borne Pain Medication Numerous studies deal with the relationship between melatonin and pain. Findings suggest that melatonin is not only the hormone that helps guide our innate circadian rhythm and our biological twenty-four-hour clock, but also serves as a regulator for pain signals. The hormone acts indirectly on the so-called opioid receptors. These are the same receptors on which many painkillers act (Ambriz-Tututi et al. 2009; Danilov and Kurganova 2016).

Melatonin is produced not only in the pineal gland, but also in the retina. Melatonin has many important functions, including the control of the eye pigmentation and thus the regulation of the amount of light that reaches the photoreceptors of the eye. In addition, melatonin protects the outermost leaf of the retina, or retinal pigment epithelium, from oxidative damage.

The British Journal of Ophthalmology recently published an alarming relationship between aging eyes and melatonin production. Measurements show that after the age of 45, fewer sunrays reach the inner eye. This is the result of the slight yellowing of the eyepiece lens and the narrowing of the pupil. For this reason, fewer light particles reach the most important cells in the retina that measure the day-night rhythm to regulate our internal clock. Studies show that changes in the aging eye lead to a series of typical eye diseases in which the cause cannot be found in the eye itself. The consequences of worsening visual power include cognitive deficits (especially memory capacity), insomnia, depression, and prolonged response times. A correlation between this change in the eye and a disturbed melatonin production is therefore always emphasized.

Recently, a study focused on the interplay of circadian rhythm, oxidative stress, and AMD (Fanjul-Moles and López-Riquelme 2016). Even if further studies are required, the results of this study showed that a disturbed circadian rhythm seems to contribute to degenerative processes in the retina that are responsible for the death of cells. Melatonin with its high potency as an antioxidant can help to prevent the destruction of cells by free radicals and thus delay the progress of the disease and to protect the retina. Whether melatonin acts only as a radical scavenger or there are also receptor-mediated effects is still the subject of research.

Research has shown that photoreceptors can also be lost by oxidative stress from glaucoma. Melatonin can be effective by reducing pressure in the eyes as well as protecting the photoreceptors from free radicals.

Melatonin has been shown to be effective in the regulation of blood pressure. Studies in Pechanova et al. 2014 have shown that the oral administration of melatonin reduces both high blood pressure and associated vascular reactivity. This effect results from the fact that the hormone has a relaxing effect on the vessels and acts as a potent free radical scavenger, since these free radicals have a negative influence on blood pressure (Sánchez-Barceló et al. 2010).

In the case of a heart attack, an acute vascular occlusion occurs. The tissue supplied by this vessel suffers from an oxygen deficiency and is damaged. The primary goal of therapy is, therefore, to restore the blood or oxygen supply within a very short amount of time. However, as soon as the oxygen supply necessary for life returns, further oxidative damage occurs to the already-attacked tissue due to the influx of oxygen. This is referred to as a reperfusion injury.

These damages can be significantly mitigated, if not prevented, by administering higher doses of melatonin. Early studies show that melatonin can significantly reduce the extent of cell damage in these situations thanks to its antioxidant and anti-inflammatory effect (Pei et al. 2016, Ozsoy et al. 2016). In order to achieve this effect, though, melatonin must be given immediately after the occlusion of the vessel, irrespective of the time of day.

Numerous studies have shown that melatonin has a positive effect not just in prevention (Pei et al. 2002), but also in acute stroke treatment (Watson et al. 2016). Its antioxidative potency is often documented and could significantly help in the event of stroke in order to alleviate further damage in the brain (Andrabi et al. 2015). In order to prevent a stroke, melatonin should be taken long-term in the evening. When the stroke has occurred, it is important to immediately give higher doses of melatonin, as in myocardial infarction, regardless of the time of day.

The cells in the digestive tract produce four hundred times as much melatonin as the pineal gland. However, this melatonin is not primarily released into the blood, but presumably acts directly on the spot. It, therefore, does not have the characteristic of a timer, as melatonin produced in the pineal gland during the night does. Although the exact function of melatonin in the digestive tract is not yet known, melatonin protects against ulcers of the gastric mucosa thanks to its antioxidant properties. Whether receptor-mediated mechanisms of action play a role here is still the subject of intensive research, but very probable. Scientists have already found out that bacteria in our gut reacts to melatonin. They also follow a circadian rhythm adapted to our natural rhythm. As soon as the bacteria notice that melatonin is multiplied, they begin to heat up and become active. What exactly this behavior means is not yet known. However, what is certain is that the intestinal microbes react to our sleep-wake cycles and thus definitely change their behavior (Paulose et al. 2016)

In the case of gastroesophageal reflux syndrome, in which increased gastric acid is pushed into the esophagus, melatonin significantly reduces the oxidative damage of the mucous membrane and thus also the pain symptoms. Scientists suspect that melatonin serves as universal protection of the stomach lining from the salicylic acid that is contained not only in many foodstuffs, but also in anti-inflammatory and fever-reducing painkillers and for protection against Helicobacter bacteria—which play a superordinate and disease-causing role in gastritis (Vaughn et al. 2014).

The loss of each glycemic control and the increase in glucose in the blood are typical complications that occur in type 2 diabetes and are usually caused by an insulin deficiency, often caused by a lack of function of the beta cells. Melatonin can improve the function of beta cells and support the release of insulin throughout the day. Melatonin supplementation can thus be a hopeful therapy for those affected (Sharma et al. 2015).

Various studies have shown that melatonin may affect the release of insulin and the blood glucose level (Owino et al. 2016). In rats that were diagnosed with type 2 diabetes, melatonin provided protection from hyperlipidemia (an increase in cholesterol) and hyperglycemia. In mice, there was an improvement in insulin resistance and glucose metabolism. In another study with postmenopausal women, it was found that melatonin improves glucose tolerance and insulin sensitivity in older women.

As a natural killer, melatonin plays an important role in the function of cells: it inhibits the uncontrolled proliferation of cells, thus reducing tumor growth, and can even prevent tumor formation by activating the lymphocytes (Zamfir Chiru et al. 2014). Melatonin also protects against common toxic consequences of chemotherapy or radiation, such as nausea and vomiting, low blood pressure, and lack of strength by stimulating the immune system (Seely et al. 2012). Melatonin also relieves inflammation of the oral mucosa, reduces harmful effects on the heart, and helps to reduce blood glucose and insufficient numbers of blood platelets after chemotherapy (Lissoni 2002).

Melatonin plays an important role in the fight against cancer, not only as a potent antioxidant. Many studies have shown that melatonin has a direct influence on various malignant tumors. It can affect tumor growth in some types of breast cancer by directly reducing the cell division rate. In addition, it also affects the activity of estrogens on these cells, which play an important role in breast cancer. Melatonin also reduces the aggressiveness of the tumor and the side effects of radiotherapy and chemotherapy (Sánchez-Barceló et al. 2012). Recently, scientists have shown that melatonin can also prevent cell migration and invasion. This protects our body from the spread of lethal tumor cells into new tissue (Gonçalves et al. 2016b). Melatonin can also positively influence the tumor weight and thus tumor size, a prerequisite required by many therapists before any chemotherapy or surgery is performed (Ma et al. 2015).

Recently, a study showed that melatonin not only inhibits the growth of breast cancer cells, but also the new formation and growth of blood vessels (angiogenesis). This is an important finding, because these vessels provide the tumor with oxygen and nutrients and thus contribute to its growth. Melatonin also reduces uncontrolled cell division, the so-called telomerase activity, and the uncontrolled spread of cancer cells into other tissues. Increased telomerase activity allows the tumor cell to constantly divide and penetrate into other tissues. Melatonin is one of the few substances that can reduce this activity, especially in tumor cells, thus reducing the formation of metastases. What is also underlined in the study is that melatonin supports programmed cell death or apoptosis, alleviates the serious side effects of chemotherapeutic agents, and simultaneously increases the efficacy of chemotherapy and radiation therapy. The authors of the study conclude that its broad spectrum of effects makes melatonin a treatment agent that can achieve very positive effects in breast cancer treatment (Nooshinfar et al. 2017).

As a pretreatment of chemotherapy or radiotherapy, melatonin can significantly sensitize breast cancer cells, according to a recent study. Melatonin reduces the activity and expression of certain proteins by about 50 percent, thereby reducing the amount of bioactive estrogens that promote tumor growth (Alonso-González et al. 2016). Melatonin also demonstrated excellent efficacy after breast cancer surgeries and improved patient sleep quality—an important effect for the regeneration phase and the healing process of women (Madsen et al. 2016b).
(Altair) What additions can be made to our vaccination protocol to better handle mRNA vaccines?

(L) Well, we just got one suggestion: heat would be very useful. I suppose there are other ways to apply heat than far infrared. Is heat in general beneficial?

A: Yes.

Q: (L) So it's not just infrared. Okay. We can do some research on that. That's...

A: Take more melatonin.

Q: (L) Take more melatonin?

(Gaby) It's an antiviral.

(L) Don't take too much, but you can take more. Okay, now Sid has a series of questions:

It is rather interesting this answer from the Cass: melatonin, after far infrared and heat in general.
Here is an article by Mercola in French and a video in English Sunlight: Optimize Health and Immunity (Light Therapy and Melatonin) by Roger Seheult that can teach us some really interesting things.

In a nutshell:
"The vast majority, 95%, of your body's melatonin is produced inside your mitochondria in response to the sun's near infrared radiation. Only 5% of melatonin is produced in your pineal gland at night.

Your mitochondria produce ATP, your body's energy currency. Reactive oxygen species (ROS) are a by-product of this ATP production. They are responsible for oxidative stress.

Melatonin eliminates the DROs that damage your mitochondria. Provided you sleep well and get plenty of sunlight during the day, your mitochondria will be bathed in melatonin, thus reducing oxidative stress."


Melatonin is produced in response to sun exposure

To summarise the main finding before diving in, the vast majority of melatonin produced by your body, 95%, is actually generated inside your mitochondria in response to the sun's near infrared radiation. Only 5% of melatonin is produced in your pineal gland.

It is important to note that melatonin supplements, contrary to what you might expect, do not end up in your mitochondria where they are most needed to mitigate the damage caused by oxidative stress produced by the electron transport chain.
Melatonin has also been shown to be an important component of treatment for COVID, reducing the incidence of thrombosis and sepsis, and mortality. As Dr Roger Seheult notes, evidence suggests that sun exposure can help combat a number of respiratory infections, including IVCOD, and melatonin production in your mitochondria appears to be a key component.

Dr Roger Seheult looks at a number of pieces of evidence showing that rates of COVID around the world correlate with the solar index, or amount of sunlight beaming down on the area. The rates of positive cases are also correlated with blood levels of vitamin D. Higher blood levels correlate with a lower incidence of VaDOC and higher survival rates for hospitalised patients.

In short, vitamin D is more than likely a marker or substitute for sun exposure. But any benefits are probably due to factors other than vitamin D itself. As Dr Roger Seheult has noted, some studies of the effect of giving vitamin D to patients treated for severe VaDOC have found no benefit, even at very high doses.
In addition, research into UVA levels and COVID mortality rates found that areas of the US, UK and Italy with higher UVA also had lower COVID mortality rates. Vitamin D does not increase in response to UVA (only UVB). So something in the sun, other than vitamin D, must have a beneficial impact.

They hypothesised that nitric oxide, produced in response to UVA, might be the key, as nitric oxide has been shown to limit SARS-CoV-2 replication in vitro as well as normalise your blood pressure.

But while it's true that nitric oxide increases in response to sunlight (particularly UVA and near-infrared), Dr Roger Seheult believes that the main mechanism at work here is melatonin. This is because it is produced in response to the infrared spectrum, which makes up a much larger part of the solar spectrum than ultraviolet, and it acts at whatever angle the radiation hits the Earth.

Melatonin and sunlight are intimately linked
It is likely that near-infrared (NIR) photons stimulate the subcellular synthesis of melatonin in your mitochondria by activating cyclic adenosine monophosphate (cAMP) or NF-kB, or alternatively by stimulating the stem cells in your bone marrow. However, if you fail to expose your skin to enough near-infrared sunlight, your mitochondria will have severely depleted melatonin levels that cannot be compensated for by supplementation.

The role of melatonin in COVID
Okay, so what does this have to do with the treatment of VaDOC? For that, we need to delve into the biology a bit. Angiotensin 2 is a pro-oxidant that is converted to angiotensin 1-7, an antioxidant, by the enzyme ACE2. ACE2 is the same enzyme as the SARS-CoV-2 Spike protein that binds to enter the cell.

Angiotensin 2 raises blood pressure, while angiotensin 1-7 lowers it by relaxing your vascular system. If you have high levels of angiotensin 2, you will have more DRO in the cell, which, as mentioned, is detrimental, as it damages the machinery of the cell. Angiotensin 1-7, on the other hand, will decrease the DRO in the cell.

The problem with COVID is that when the virus binds to the cell, it deactivates the enzyme ACE2 (because the Spike protein is now bound to it). Thus, angiotensin 2 increases, angiotensin 1-7 decreases and the conversion of angiotensin 2 to angiotensin 1-7 cannot take place.

As a result, DRO increases uncontrollably inside the cell. SARS-CoV-2 infection also increases the production of white blood cells, which also increases DRO. The end result of this high oxidative stress is the formation of blood clots, which in turn leads to hypoxaemia.

Melatonin can break this destructive cycle by removing DROs and protecting your mitochondria from destruction. As Dr Roger Seheult has noted, if you don't get enough sleep at night and sunlight during the day, your mitochondria are essentially running 'hot' due to inflammation. Melatonin is the coolant that dampens the DRO in your mitochondria.

If your mitochondria are already stressed and you are contracting COVID, the additional stress can send you over the edge. If your melatonin system is working well, because you sleep well and get plenty of sunlight, you are more likely to fight off the infection without it becoming serious.

Seed oils increase your risk of COVID and sunburn
This may not seem like a big deal, but it is. Linoleic acid (LA) makes up the bulk (about 60-80%) of the omega 6 fatty acids you consume, and is a major contributor to almost all chronic diseases. While once thought to be an essential fatty acid, when consumed in excessive amounts, LA actually acts as a metabolic poison.

Optimise your health with reasonable sun exposure
Basically, what "Melatonin in the Mitochondria" has discovered is that melatonin is an ideal target for fighting mitochondrial-related diseases and cancer because it has easy access to your mitochondria and is synthesised there, where oxidative stress occurs. By reprogramming faulty glucose metabolism, melatonin can optimise mitochondrial function and inhibit cancer growth.

Remember that taking melatonin supplements will not result in increased mitochondrial melatonin production. It has to be produced close to your mitochondria and not swim up from your pineal gland. Thus, oral supplementation does not replace going outside during the day.

If you take it during the day, you're tricking your body into thinking it's nighttime, which could cause you problems. As far as we know, the best way to increase mitochondrial melatonin is to optimise your NIR exposure through regular sun exposure.

Interestingly, spending time in nature is another way to increase your IR exposure, as most green plants and trees reflect IR. This is probably why walks in the forest are so beneficial.

Together, exposure to sunlight during the day and staying in the dark at night will ensure that your mitochondria are bathed (day and night) in melatonin which reduces harmful DROs. So, as Dr Roger Seheult suggests, try to spend more time outdoors, especially if you are ill (whether it's COVID or any other respiratory infection) or fighting a chronic disease.
L'« hormone maîtresse » pour traiter le COVID

There is still nothing new under the sun, except the sun, because the sun...shine. 🤠
After this reading, one may wonder what could happen to our mitochondria, if some event in the near or distant future darkens the sky.
In the meantime, enjoy your tan!
After this reading, one may wonder what could happen to our mitochondria, if some event in the near or distant future darkens the sky.

This brings to mind people with seasonal affective disorder (SAD). This from the Mayo Clinic:
Light therapy is a way to treat seasonal affective disorder (SAD) and certain other conditions by exposure to artificial light. SAD is a type of depression that occurs at a certain time each year, usually in the fall or winter.

During light therapy, you sit or work near a device called a light therapy box. The box gives off bright light that mimics natural outdoor light.

Light therapy is thought to affect brain chemicals linked to mood and sleep, easing SAD symptoms. Using a light therapy box may also help with other types of depression, sleep disorders and other conditions. Light therapy is also known as bright light therapy or phototherapy.

Not really a fan of the Mayo Clinic, but finding an artificial light that comes as close as possible to natural sunlight would seem like a good alternative if the skies darken for extended periods of time - sort of like central Ohio most of the time (with rain)! :-P The Clinic is recommending full spectrum light:
The only requirement is sunshine–specifically ultraviolet B rays," according to Mayo Clinic website. And just as people need vitamin D to thrive, so do plants. It makes sense, therefore, that full-spectrum light bulbs–those used in light therapy to treat Season Affective Disorder–could be used to help plants grow.
But as explained in the previous post -
This is because it is produced in response to the infrared spectrum, which makes up a much larger part of the solar spectrum than ultraviolet, and it acts at whatever angle the radiation hits the Earth.
- it would seem that IR is the light one should use for supplemental exposure. I suppose if one doesn't get enough UV light due to skies darkened for months on end by volcanic ash (UV rays penetrate clouds but ash?) one must rely on Vit D3 supplements. That's assuming one can still breathe the available air. Really hope we all can avoid such a fate.

Looks like UV light gets absorbed in volcanic eruptions:
Emission rates of volcanic gases, and their relative abundances, provide valuable insights into the magma dynamics that drive volcanic activity (e.g., Malinconico Jr, 1979; Sutton et al., 2001; Oppenheimer et al., 2003; Caltabiano et al., 2004). Sulfur dioxide is the most commonly measured of these gases due to its low background atmospheric concentration and strong spectral ultraviolet absorption features (Platt et al., 2018).
There are two different radiative transfer corrections required, namely for “multiple scattering” and “light dilution” (Bobrowski et al., 2010; Kern et al., 2010). These phenomena are caused by photons interacting with molecules and particles in the air, causing them to scatter elastically (Rayleigh) or inelastically (Raman) (Figure 1). Multiple scattering occurs in volcanic plumes where large amounts of ash, water vapor or aerosol are present. With more of these particles, photons passing through a plume have a greater chance of scattering, increasing their travel distance inside the plume relative to the idealized linear path, allowing more absorption to occur. Conversely, the path length could decrease when photons cannot penetrate the center of the plume due to high opacity.
And no doubt the electric grid will be working just fine during any dramatic earth changes . . . 🥶
@Pearce ,
The best thing you can do for your dad is to help him get and keep his glycemy at the required limit. Sometimes you might need to be very patient and creative but also firm and supportive because the diabetic mind is nothing that you can imagine when the sugar is out of control.
Does he have a meal +exercise plan per day that corresponds to the diabetes medicine? If not he needs to get one, and you can actually do that for him if there is no diabetes nurse to do it.
Start implementing the blood sugar level strip testing. Does he have a device? If not you buy him one. He needs to test thee times a day in thefirst month to find out what foods give most and biggest sugar spikes.After that he needs to test twice a day for six months. The values are graphed and averaged and as a function of this average the treatment is prescribed. My husband does that himself and gives the spreadsheet to the diabetis doctor.
Look, I am really sorry to see you so concerned...but diabetes is not a disease,is a condition, which means that the person being in that condition or having that condition needs to live in a specific way. My husband has diabetes type 1. The foods we eat both are in majority the ones that go in his diet. That seems to workok as otherwise he gets very unhappy /snappy/grumpy or even panicked about food. It might be that your dad might not even need medication for depression and his moods to rather be produced by the blood sugar imbalance.
It is tough to be alone and have this condition.
All the best of courage and strength!
I don’t know if Melatonin helps me to sleep better or not, because I am always no problems with fall sleep.
But still, I have been taking melatonin every night for some years so far.
And today about 2pm, I have taken 10mg melatonin with blueberries, but, it didn’t make me want to go sleep. So, I am going to experiment this new ideas.

Melatonin is a natural anti-inflammatory that strengthens the immune system, including the liver’s personalized immune system. If the liver is sluggish and stagnant and loses its ability to create melatonin, taking supplemental melatonin can reignite the liver’s capacity to start up again. That’s right: while medical research and science associate melatonin production with the brain, it’s also one of the liver’s hormone functions to create and secrete it.

Melatonin can also act as a powerful antioxidant when taken at the same time as you eat foods that are high in antioxidants such as wild blueberries, raspberries, leafy greens, apples, sweet potato or cherries just to name a few. This combination of Melatonin and antioxidant rich foods can help stop oxidation of toxic heavy metals in the brain and helps protect the brain from Alzheimer’s, dementia, and brain tumors. The nutrients in these foods also bind onto the melatonin and make it more easily accepted by the brain and body and enhancing its medicinal sleep effects and ability to help with stress relief.

You can refer to Medical Medium Cleanse To Heal for specific supplement and dosage recommendations, including melatonin, for over 200 symptoms and conditions.
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I havnt fully read the thread yet but i wanted to ask :

I am taking 10mg of melatonin each night, i didnt fell asleep the first night, how long before it start to take effect?
I remember a transcript of the cassiopaean where the C said that someone wasnt sleeping because he were adjusting to the melatonin.
So i guess I have the same problem. So how long usually does it start to take effect around 10mg?
Hi Romain512,
from my own experience of taking melatonin in high doses i'd recommended to lower the dose to 4-5 mg unless of course you're not trying to use it as a therapy against some serious health conditions. It depends from person to person how long it takes for them to adjust to the melatonin.

It may take a few days to a week. My suggestion will be to avoid from late afternoon onwards coffee and other neuronal excitatory drinks, supplements and so on. Before going to sleep avoid watching TV, using other technological devices emanating blue light and finally be sure to sleep in a dark room since the melatonin is most effective in a dark environment.

Just a few thoughts.
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