High Dose Melatonin Therapy

Laura

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This therapy was recently brought to our attention and there seems to be so many positive things about it, and it is relatively inexpensive, that I thought I would share a few links here to articles about it.







Here's something interesting:
The acute toxicity of melatonin as seen in both animal and human studies is extremely low. Melatonin may cause minor adverse effects, such as headache, insomnia, rash, upset stomach, and nightmares. In animals, an LD50 (lethal dose for 50% of the subjects) could not be established. Even 800 mg/kg bodyweight (high dose) was not lethal.[138] Studies of human subjects given varying doses of melatonin (1–6.6 g/day) for 30–45 days, and followed with an elaborate battery of biochemical tests to detect potential toxicity, have concluded that, aside from drowsiness, all findings were normal at the end of the test period.[139,140]

Melatonin is a ubiquitous natural neurotransmitter-like compound produced primarily by the pineal gland. This agent is involved in numerous aspects of the biological and physiologic regulation of body functions. The role of endogenous melatonin in circadian rhythm disturbances and sleep disorders is well established. Some studies have shown that melatonin may also be effective in breast cancer, fibrocystic breast diseases, and colon cancer. Melatonin has been shown to modify immunity, the stress response, and certain aspects of the aging process; some studies have demonstrated improvements in sleep disturbances and “sundowning” in patients with Alzheimer's disease. The antioxidant role of melatonin may be of potential use for conditions in which oxidative stress is involved in the pathophysiologic processes. The multiplicity of actions and variety of biological effects of melatonin suggest the potential for a range of clinical and wellness-enhancing uses. This review summarizes the physiology of melatonin and discusses the potential therapeutic uses of melatonin.

Melatonin is a widely occurring neurotransmitter-like compound derived primarily from the pineal gland. It is also produced in a number of other areas, for example the gastrointestinal tract.[1–3] Once labeled as a master hormone, it has been found to be involved in numerous aspects of biological and physiologic regulation.
 
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nicklebleu

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Thanks for posting - fascinating stuff!

What I found interesting is that melatonin seems to use the glucose transporter to get inside of the cell. Which could mean that a ketogenic diet could significantly increase the amount of melatonin the cell is able to gobble up, as it doesn’t have to compete with glucose. And at the same time it also means that melatonin could potentially compete with vitamin C absorption into the cell. In that case it probably would be prudent to stagger the doses to minimize them interfering with each other.
 

Mrs. Peel

The Living Force
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Because of extreme light sensitivity and a lot of other eye issues, I do not go outside without sunglasses, nor do I stand by windows unless it is very dim out so I do not get direct sun(light) into my eyes. I was told (and take with a grain of salt but it makes sense) by an energy reader that my body is hardly making melotonin, and to take 3 mg of sublingual melatonin before bed and also another 3 mg time-release tablet to try and keep me asleep throughout the night (I wake up about 5-6 times each night). It doesn't work so I upped the sublingual dose before bed to 5 mg and I still wake up. I already sleep in a dark room, have a humidifier, use earplugs, stay away from electronics, and have tried every sleep trick and supplement known to man. ;-D

Perhaps I should try taking a higher a dose of melatonin at night? Or maybe start taking some during the day also?
 

Gaby

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Or maybe start taking some during the day also?
According to the article Laura posted above, that might be counterproductive.

There is pretty amazing information concerning depression, cancer, etc. but here are some concepts to keep in mind for those with autoimmune diseases:


Melatonin antagonizes several effects of exogenous corticoids: immune depression[28] and hypercatabolism, thymic involution, and adrenal suppression.[29] These findings have led to the suggestion that melatonin might work as an antiadrenocortical or antistress factor.[29] The melatonin/corticoid relationship is significant because chronic hypercortisolemia has been linked to several aspects of aging and age-associated phenomena, including glucose intolerance, atherogenesis, impaired immune function, and cancer.[30]

In addition to high absolute levels of corticoids, disorganization of the normal rhythm of corticoid release is also pathogenic. Corticoids are normally high in the early morning and daytime, and low at night. Properly timed exogenous melatonin may entrain, or reorganize, this critical endocrine rhythm, resulting in long-term systemic benefit. Indeed, the immune-enhancing and anticorticoid effects of melatonin, or putative mediators of melatonin action, appear to depend on nocturnal administration.[28,31] This may represent an integral immune-recovery mechanism by which melatonin acts as a kind of buffer against the harmful effects of stress on immune homeostasis.[28]

Beta-adrenoceptor blockers, which depress melatonin secretion, exert immunosuppressive effects, but only when given in the evening.[32,33] This is when blood melatonin (and the immunoenhancing effect of melatonin) is highest. Exogenous melatonin reverses beta-blocker-induced immunosuppression and enhances immune parameters in animals. A preliminary report of patients with AIDS who took melatonin 20 mg daily in the evening revealed uneven but generally beneficial effects on immune parameters.[34] It has been recommended that the dose be timed not only periodically within each day (at night only) but also periodically within the month, with treatment periods of 3–4 weeks, followed by a week-long “washout” period.[33]

Immunomodulatory effects of melatonin were also observed recently in healthy subjects and patients with bronchial asthma.[35] Melatonin increased production of interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha, indicating the possibility of an adverse effect of exogenous melatonin in patients with asthma. On the other hand, in a model of adjuvant-induced arthritis, both prophylactic and therapeutic melatonin administrations inhibited the inflammatory response.[36] This inhibition was accompanied by enhanced thymocyte proliferation and IL-2 production by melatonin. In another animal study, melatonin was shown to possess both cellular and humoral immunoenhancing effects, and immune responses were augmented even in the absence of previous immunosuppression.[37] Melatonin-receptor immunoreactivity has also been detected in the human eye,[38] the physiologic function of which remains unclear.

Predictably, melatonin-induced corticoid antagonism and immune enhancement may not always be desirable. Melatonin should be used cautiously, if at all, in patients with autoimmune conditions and in those with known or suspected adrenocortical insufficiency. The effects of melatonin on the immune system are complex, occasionally contradictory, and depend on several factors, including the dose of melatonin, the immune status of the animal (as well as its age, sex, and species), the season during which the immune system is studied, circadian rhythm of immunity, pineal gland status, and presence of a stressful condition.[39]

[...]

Studies linking melatonin loss to age-related phenomena and the case for melatonin as an antiaging substance have been highlighted in review articles.[9,129] One proponent of this hypothesis suggests that “the Melatonin Deficiency Syndrome is perhaps the basic mechanism through which aging changes can be explained.”[129] Indeed, some believe that the data thus far support the possibility that supplemental melatonin may be beneficial.[130]

An experimental study found significant declines in plasma melatonin levels in aged ring doves.[131] In addition, the capacity of the animals for ingestion and destruction of Candida albicans and phagocytosis was reduced by aging and restored by exogenous administration of melatonin.

Melatonin levels decline with age in humans,[132] and the nocturnal melatonin peak is almost completely lost.[133] Because of the close reciprocal relation of melatonin and corticoids, this loss of melatonin rhythmicity may be responsible for the pituitary/adrenal axis disinhibition that has been described as a characteristic of aging. The adrenals of elderly humans are apparently hypersensitive to adrenocorticotropic hormone, and midnight corticoid levels (low in youth) are markedly elevated in old age.[134] The effects of melatonin on both the release of corticoids and their peripheral effects, the pathogenic conditioning influence of corticoid excess, and the phasic inhibitory influence of melatonin on the pituitary/adrenal axis have been discussed. Modification of corticoid-related phenomena could explain much of melatonin's apparent antiaging and other beneficial actions.

Despite the evidence linking lowered levels of melatonin with aging, the decline may not be so dramatic in reality. That is why melatonin cannot be unequivocally recognized as a substance that delays aging, although some of its actions may be beneficial to the process of aging.[135]

[...]

ADDED:
Although melatonin is a potential adjunctive agent in the treatment of cancer and immune deficiency, poorly timed administration can produce opposite effects. Melatonin injections given in the morning stimulate tumor growth,[46,148] whereas the same doses in midafternoon have no effect but in the evening have a retarding effect. And although some people with depression may suffer from a “low melatonin syndrome,”[27] melatonin administration that unduly prolongs the nocturnal melatonin rise, or that is given throughout the day, may exacerbate SAD[82] and bipolar and classic depression.[83] Finally, animal studies have shown that moderately large doses of melatonin (equivalent in one study to about 30 mg in adult humans) increased light-induced damage to retinal photoreceptors.[149]
 
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Laura

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I read the NCBI paper carefully and it appears that it is best to start taking the doses in the afternoon, at least, and then take several before bedtime. Like starting with 10 mg at 3 pm, 10 at 6, 10 at 9 pm. Then, the next day, double the dose, and go up to say 50 mg each dose. They say do something like this for 3 or 4 weeks on and then take a week off. But that's for severe things like AIDS, so maybe less severe conditions would require only a week or so? There are a lot of papers listed as sources for that one, but I haven't read them. But it sure seems that a lot of things can get fixed pretty easily this way.
 

Mrs. Peel

The Living Force
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Okay, I have tried CBD and have taken it for a long time but it does not help me sleep. I have even got the CBD with melatonin in it and certain types specifically formulated to help you sleep.

Also, I do have autoimmune issues so perhaps I shouldn't be messing with melatonin at all.
 

Laura

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Okay, I have tried CBD and have taken it for a long time but it does not help me sleep. I have even got the CBD with melatonin in it and certain types specifically formulated to help you sleep.

Also, I do have autoimmune issues so perhaps I shouldn't be messing with melatonin at all.
Well, if it was me, knowing what all you've tried and been through, I would sure try it, but start slow, like I said above.
 

Persej

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For me, if I take more than half a milligram of melatonin I cannot fall asleep. :-/
Maybe I should try another brand.
 

Redrock12

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Took a 4mg tablet the other night and, after two sleepless nights caused by, I suspect, side effects of antibiotics, I fell asleep within a half hour.
fwiw
 

primeaddict

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I have noticed that melatonin reduces blood flow to the brain and for me I get a morning headaches after taking it for more than 3 nights in a row. The other problem I have when taking it is very bazaar dreams. A total suspension of normal dream story lines with a Alice in Wonderland types.

Some of the affects attributed to melatonin could be due to better sleep. Good quality sleep maybe the key factor here and less to do with melatonin.

My experience only not to be used as approval or disapproval of anything.
 

trendsetter37

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I have noticed that melatonin reduces blood flow to the brain and for me I get a morning headaches after taking it for more than 3 nights in a row. The other problem I have when taking it is very bazaar dreams. A total suspension of normal dream story lines with a Alice in Wonderland types.

Some of the affects attributed to melatonin could be due to better sleep. Good quality sleep maybe the key factor here and less to do with melatonin.

My experience only not to be used as approval or disapproval of anything.
I too started getting bad headaches in the mornings after taking melatonin the night before. I'm not prone to headaches so this was alarming enough for me to stop. However, CBD (in the smoked form) has proven VERY beneficial for sleep in my case (was muscle tested to confirm as well) to the point where I wake up actually refreshed.

Regarding melatonin, It's suppose to be a horomone so it may be very specific for whom it will benefit. I know we can't really excrete horomones if too much is taken so I'd make sure to have some sort of bodily feedback loop (whether that be muscle testing or some other diagnostic method) to determine if it's helpful on a case by case basis.
 

primeaddict

The Force is Strong With This One
trendsetter37

I noticed that if I do an aggressive aerobic exercise in the mornings it would clear the headache and improve the circulation to the brain. So it maybe that melatonin reduces blood flow to the brain which induces sleep. A possible explanation for this side affect.

I too have stopped taking it on a regular basis and only take it when I have a few night of poor quality of sleep.

Melatonin is a neurotransmitter and is not a hormone which does reduce its risk of harm.
 

trendsetter37

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Melatonin is a neurotransmitter and is not a hormone which does reduce its risk of harm.
What's your source for this statement? A quick duckduckgo.com search showed the top listings describing it as a horomone.

Melatonin is a hormone that regulates the sleep–wake cycle. It is primarily released by the pineal gland. As a supplement, it is often used for the short-term treatment of trouble sleeping such as from jet lag or shift work. Evidence of benefit, however, is unclear.
Haven't dug any further than that but I'm interested in your viewpoint.
 
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