This is topic melatonin and perimenopause in forum Medical Questions at LymeNet Flash.

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Posted by Ruth Ruth (Member # 11059) on :
Tree gave a reference to melatonin on another thread and I checked out the Wikipedia entry for it.

Of great interest to myself, and perhaps other women in this stage of life, was the research on melatonin in perimenopause.

Wikipedia states:
Recent research has concluded that melatonin supplementation in perimenopausal women produces a highly significant improvement in thyroid function and gonadotropin levels, as well as restoring fertility and menstruation and preventing the depression associated with the menopause.[32]
32. Bellipanni G, DI Marzo F, Blasi F, Di Marzo A (2005). "Effects of melatonin in perimenopausal and menopausal women: our personal experience.". Ann N Y Acad Sci 1057 (Dec): 393-402. PMID 16399909.

Improved thyroid function sounds good for everyone.

Here's the full abstract from the Annals of the New York Academy of Sciences:
The purpose of this clinical trial on possible effects of nocturnal MEL administration in perimenopausal women was to find if MEL by itself modifies levels of hormones and produces changes of any kind, independently of age (42-62 years of age) and the stage of the menstrual cycle.

It is accepted that a close link exists between the pineal gland, MEL, and human reproduction and that a relationship exists between adenohypophyseal and steroid hormones and MEL during the ovarian cycle, perimenopause, and menopause.

Subjects took a daily dose of 3 mg synthetic melatonin or a placebo for 6 months. Levels of melatonin were determined from five daily saliva samples taken at fixed times.

Hormone levels were determined from blood samples three times over the 6-month period. Our results indicate that a cause-effect relationship between the decline of nocturnal levels of MEL and onset of menopause may exist.

The follow up controls show that MEL abrogates hormonal, menopause-related neurovegetative disturbances and restores menstrual cyclicity and fertility in perimenopausal or menopausal women. At present we assert that the six-month treatment with MEL produced a remarkable and highly significant improvement of thyroid function, positive changes of gonadotropins towards more juvenile levels, and abrogation of menopause-related depression.

Does that mean a 62-year-old menopausal woman got her cycles/fertility back?
Posted by northstar (Member # 7911) on :
Does that mean a ........ menopausal woman got her cycles/fertility back?

According to one case study (me) !

I have taken 3 mg sublingual for 13 years. Started 2 years before menopause, and 10 years pre-lyme metldown (but there were hints of it in there).

I have taken it throughout lyme.

Still menopausal (!)....thank heavens!

Posted by Ruth Ruth (Member # 11059) on :
I'm happy if you are happy.

Do you think the lyme would be a reason that your (single person) case study might not be representative of how it would affect a generally healthy female person? [Smile]

I'm not really trying to make a doctrine here, but it was fun to imagine the shock!
Posted by treepatrol (Member # 4117) on :
I want to warn you guys the first few days when I took this melatonin I had what I would say was a Herxiemer reaction. with a few different twists added in.
Normal herx was acheing,tired sore,fever slightly.
Twists were hangover in morning slight headache when first waking,felt agitated,wierd similar sore joints wrist, ankle, adrenals felt kicked up.

But as the day prgressed I felt really pretty goood then refreshed.
This happpened the fiorst week then it was like I adapted to it?

I now only take it maybe 2 3 times a week as needed for sleep and just natural cleanup of free radicals.
Posted by clairenotes (Member # 10392) on :
This reminds me of something learned in yoga. Ancient (and modern) yogis practiced inverted poses, which were said to stimulate a substance held in the pineal gland, referred to as "the nectar of life" and thought to have significant health benefits.

I have suspected that the substance was melatonin. Yoga is known for its' rejuevenating effects, and I have read that women who practice yoga regularly claim that the shift into menopause was not much of an event, barely felt.

Though this does not answer any questions directly about the possibility of reversing menopause, in my own case study, I have found that a more youthful appearance is one side-effect of melatonin, in addition to helping with sleep, which was my original reason for taking it. This also seems true for my husband. Certainly not a terrible thing to live with [Smile] .

Posted by GiGi (Member # 259) on :
"In the pineal gland the melatonin is produced in the peroxisome, in the neurons dopamine and norepinephrine, etc. It is here, where mercury and other toxic metal attach and disable the cell from doing its work. Other researchers have focused on the mitochondria and other cell organelles, which in our experience are damaged much later."

I am not sure if you are aware that melatonin is used in the metal detox process.

You might want to google "melatonin mercury toxicity" to get a different angle of it all.

Take care.
Posted by Ruth Ruth (Member # 11059) on :
Thanks GiGi.

I looked and found enough to get me started thinking.
Posted by Truthfinder (Member # 8512) on :
I have a strange love/hate relationship with Melatonin.

I feel like I should be taking it on a regular basis, from things Gigi has spoken about, and also from reading Marnie's posts, and other posts like this one.

HOWEVER!! Not only do I experience a "hangover" effect similar to what Tree talked about, but I also find that when I take Melatonin, I often wake up even earlier than usual, which is not good in my case. I only sleep about 4.5 hours at night anyway.

I have no idea why this happens with the Melatonin.

I have not "needed" Melatonin for sleep for several months because I often take a dose of a homeopathic remedy right before bed, and this has not only helped make me sleepy, but given me the best and longest sleep that I have experienced in years. Sometimes I actually sleep more than 6 hours!

So far, I have not "mixed" the Melatonin with the homeopathic remedy at night before bed. I am not sure it would be beneficial to do so. I'm sort of in "uncharted waters" at this point.


[ 11. April 2007, 08:01 AM: Message edited by: Truthfinder ]
Posted by clairenotes (Member # 10392) on :
Something may still need to be balanced. Maybe due to the presence of metals or pathogens? I used to have this exact symptom and the only thing I have done differently that I can think of is reduce pathogens and toxins (metals).

Melatonin often comes in peppermint-flavored tablets to hold under the tongue. Have to be careful not to negate your homeopathic if you do decide to take it again or look for a non-peppermint type.

Posted by GiGi (Member # 259) on :
Whether you take melatonin or any other detox agent or killing agent, vitamins and minerals and other supplements, the mop-up agents should be a dominant part of your program. So should a strong liver support. And do google mercury and melatonin. All of us are exposed and have been exposed most days of our lives to heavy metals. It's our world today. It is in the food chain - no matter what you eat. Plus remains in the teeth and in the air we breeth depending where you are.

We all have heard of the "possible"
contributors to autism. Some of these children are also being treated with melatonin (in the alternative field).

If you wake up in the middle of the night when you want to stay asleep, look up the biological clock I posted the other day. In many of us, the liver is screeming for support around that time of night and it keeps us from getting a good night's sleep.

I suspect that's the hangover = toxins on the loose that need to be attended to by mop-ups: chlorella, Destroxin, cholestyramine, lots and lots of fiber (see the "fruit veggie smoothie" I posted about recently), pectin, apples, apples with skin, chitosan, etc, etc.

Take care.
Posted by treepatrol (Member # 4117) on :
Furthermore, we demonstrated that these effects are reduced and/or reversed by the pineal indoleamine melatonin. A 24-h exposure to 50 mg/L mercury induced significant cell cytotoxicity in neuroblastoma cells.

Treatment of cells with melatonin before administration of mercury greatly reduced the mercury-induced cytotoxicity.Mercury treatment of cells produced another as yet undocumented phenomenon, that of inducing oxidative stress, as measured by the loss of reduced GSH from cells.

This was a rapid process, requiring only 30 min of exposure to mercury. Similarly, pretreating the cells with melatonin or premixing mercury and melatonin before administration protected cells from the mercury-induced oxidative stress. Melatonin's mechanism of action is at present unclear; however, melatonin is known to bind heavy metals (Limson et al., 1998) and to increase intracellular GSH levels through an up-regulation of GSH-synthesizing enzymes (Todoroki et al., 1998).

It is thus possible to speculate on two mechanisms for melatonin's antioxidant action, namely, (a) melatonin as a chelating agent binding mercury, thus eliminating its cytotoxic properties, or (b) melatonin causing production of increased levels of intracellular antioxidants such as GSH(Todoroki et al., 1998). It is further not excluded that both these mechanisms could be operating simultaneously.

The release of both Ab 1-40 and Ab 1-42 into the culture medium was increased by exposure of SHSY5Y cells to mercury. Melatonin preincubation resulted in a significant decrease in Ab release. The mercury induced increase in Ab release may be caused through mercury's deleterious action on essential kinase enzymes involved in the a-secretase pathway of APP metabolism.

The result could be that cells are pushed toward the b-secretase pathway of APP metabolism, resulting in an increase in Ab release. Mercury has previously been shown to be a potent inhibitor of enzymes, especially those containing sulfhydryl groups (Edstrom and Mattsson, 1976).

Protein kinase C activity in vitro and in brain tissue is markedly reduced in a concentration-dependent manner by mercury (Rajanna et al.,1995).Phorbolester binding to protein kinase C is also inhibited by micromolar concentrations of mercury(Rajanna et al., 1995).

It is thus possible that increased levels of mercury reduce protein kinase C-mediated a-secretase activity with the consequence of increased Ab formation because protein kinase C mediates activation of the a-secretase pathway.

Mercury induces both Ab production and oxidative stress; thus, the chelation of mercury by melatonin could shift the APP metabolism back toward the a secretase pathway, reducing Ab production and the concomitant oxidative stress-inducing effects of mercury and Ab.

Ab Fibrillogenesis is also inhibited by melatonin, thereby potentially reducing the toxic buildup of Ab 1-40 and Ab 1-42 fibrils (Pappolla et al.,1998).

Furthermore, melatonin has been shown to reduce the release of soluble APP from cells in culture and to reduce the levels of APP mRNA and other housekeeping protein mRNAs (Song and Lahiri, 1997).

These data suggest that melatonin may be involved in metabolic mechanisms regulating APP and other essential cellular protein production, over and above its antioxidant capacity.

In a similar fashion mercury induced an increase in tau phosphorylation as compared with untreated cells. Melatonin treatment was able to protect cells from the mercury- induced tau hyperphosphorylation.

Mercury's influence on tau phosphorylation remains unclear; however, it may be an indirect effect via oxidative stress and Ab production. Both Ab and oxidative stress have been shown to influence tau phosphorylation (Busciglio et al., 1995; Takashima et al., 1996).

It is speculated that Ab's action is through the activation of glycogen synthase kinase-3 concomitant with an inhibition of phosphatidylinositol 3-hydroxykinase (Busciglio et al., 1995; Takashima et al., 1996). Phosphatidylinositol 3-hydroxykinase has further been shown to regulate glycogen synthase kinase-3 negatively via activation of protein kinase B and its pathway (Burgering and Coffer, 1995; Cross et al., 1995).

Mercury could thus exert an effect within this pathway not unlike that in the a secretase pathway of APP metabolism.

In conclusion, our data suggest that inorganic mercury could be involved in some of the pathophysiological aspects of AD. The pineal indoleamine melatonin is able to counteract, at least in part, these effects and needs further investigation as a potential therapeutic agent.




Melatonin: The pineal hormone that helps to regulate the sleep/wake cycle, melatonin is also an anti-oxidant. It is relatively unique among natural anti-oxidants in that it is a terminal antioxidant: once oxidized, it cannot be reduced36. This characteristic means that melatonin cannot participate in destructive redox cycling, where an oxidized compound is reduced by oxidizing another compound. One study has found that neurons are protected from mercury damage by hormonal levels of melatonin37.

Melatonin is also concentrated in the mitochondria and protects them from oxidative damage.38 Aside from its anti-oxidant properties, melatonin helps to regulate the sleep/wake cycle, which is often seriously deranged in autistic children. Its long-term use in institutionalized children has established its safety39.

Doses of up to 0.1 mg/kg at bedtime should be adequate to help with sleep disturbances. Some clinicians have noted that smaller doses of melatonin (0.3 mg in adults) are just as effective for sleep and may cause fewer problems with nightmares and/or night terrors. A sustained release form of melatonin is currently under development and should help with those children who awaken four to six hours after the dose of melatonin. 13

Mercury Detoxification of Autistic Children: Consensus Position Paper - Part 3Mercola



8) Heavy Metals Can Disrupt Sleep The Cycle
The Melatonin hormone controls the sleep/no sleep states. If Melatonin is on in the day, one will feels tired. If it is off at night, one cannot sleep (it should be the other way around).

Too much noradrenaline (NA) at night can also inhibit the sleep state. A chemical called SAMe reduces the level of NA at night; yet mercury, lead, arsenic, cadmium and a variety of other chemicals can bind to SAMe and make it less affective at reducing the night-time NA. If this is the case, supplementing with SAMe, available from health food stores, can help one sleep.

In our example case, George's Melatonin was off at night, and on during the day, which is the opposite of what one would want.

Those with mercury induced autoimmune problems can worsen from Melatonin supplements, and therefore Melatonin supplementation is not recommended for people with mercury issues.

ME> Problems get worse because of ??? just mercury getting out or is this a herx???
How Mercury Can Cause CFS/FMS



These results provide strong experimental evidence that mercury toxicity may be involved in Alzheimer's development, the authors suggested. Melatonin, on the other hand, shows a marked potential to neutralize this toxic-induced pathology, by boosting antioxidant defense and binding to heavy metals.





At first glance, you wouldn't think there was a connection between a hormone that modulates your sleep patterns and your body's natural defense against the effects of lead toxicity. But melatonin, secreted by the pineal gland in the brain, may actually act as a type of natural "antidote" against some of the damaging effects of lead poisoning mediated by oxidative stress.

"One of the major concepts on the mechanisms of Pb (lead) toxicity is its ability to generate reactive oxygen species," notes a new study appearing in the Journal of Biochemical Molecular Toxicology.

In response to lead exposure, free radicals quickly multiply and break down the cell's natural antioxidant defenses, eventually damaging cell membranes, proteins, and DNA. Stores of zinc and copper inside the cell, crucial components of this antioxidant system, may also plunge. At the same time, the body's ability to synthesize hemoglobin - the blood's life-giving "porter" that carries its precious cargo of oxygen to surrounding tissues - becomes significantly stymied.

Researchers conducted an experiment to see if melatonin could help to block this destructive toxic cascade. They found that in laboratory rodents exposed to lead, melatonin reduced lipid peroxidation - free radical damage to fats that serve as critical structural components of the cell membrane - by over one-third, as evidenced in liver tissue. Melatonin also reduced the lead-induced drop in levels of the powerful antioxidant glutathione by over 65%.

What's more, while rodents exposed to lead showed severely suppressed levels of powerful antioxidant enzymes such as glutathione reductase and superoxide dismutase by over 50%, melatonin treatment effectively restored these protective enzymes to near normal, pre-exposure status. In fact, laboratory rodents that received melatonin while being exposed to lead produced nearly the same amount of hemoglobin as healthy rats that had not been exposed to the toxin.

What gives melatonin its one-two punch against lead toxicity? "The prophylactic action of melatonin against lead-induced changes might be associated with two mechanisms," the study concluded. "First, protection of antioxidant capacity in cells, and second, its ability to scavenge hydroxyl radical directly due to its structural features."

Previous studies have reported that melatonin can quench the highly toxic hydroxyl and peroxyl free radicals even more effectively than powerful antixoxidants like glutathione or Vitamin E.

Source: El-Missiry MA. Prophylactic effect of melatonin on lead-induced inhibition of heme biosynthesis and deterioration of antioxidant systems in male rats. J Biochem Molecular Toxicology 2000;14(1):57-62.




A recent study provides additional clinical evidence that practitioners can achieve improved patient outcomes by working with the body's natural wisdom, rather than against it.

By reestablishing the body's natural circadian rhythm of melatonin, a powerful regulatory "sleep" hormone produced in the pineal gland of the brain, practitioners can help patients free themselves from long-term dependence on benzodiazepines, the potentially addictive prescription drugs commonly used to treat insomnia.

In a double-blind placebo-controlled study appearing in the Archives of Internal Medicine, Tel Aviv University researchers report that elderly patients who receive a nightly dose (2 mg) of controlled-release melatonin are much more successful at weaning themselves off medications such as alprazolam, oxazepam, brotizolam, and lorzepam. After six weeks of melatonin therapy, 14 out of 18 patients were able to completely discontinue their benzodiazepine treatment. Only 4 of 16 patients in the control group were able to do so. When patients from the control group were later provided the same melatonin treatment, however, an additional 6 patients were able to end their dependence on benzodiazepines, raising the success rate to 63%.

Ironically, benzodiazepines themselves seem to cause or worsen the problem they attempt to treat. "Long-term benzodiazepine therapy may impair the endogenous melatonin rhythm, which may in turn induce or aggravate sleep disturbances," the researchers noted.

Patients who had their melatonin natural circadian rhythm improved by therapy also showed improved sleep quality, even after quitting their use of benzodiazepines. A six-month follow-up revealed that 79% of the patients who quit using benzodiazepines with melatonin therapy still remained off the drugs. Other clinical studies have shown that patients taking melatonin do not develop tolerance, and experience no withdrawal when therapy is discontinued, unlike patients treated with benzodiazepines.

In an accompanying editorial, Harold J. Bursztajn, M.D., of Harvard Medical School applauded the study's findings and described melatonin therapy as an alternative that "integrates good clinical care with effective risk management." According to Bursztajn, by avoiding the dream-suppressing effects of sedatives, practitioners can also better approach the affective conditions, such as chronic bereavement, depression, and stress disorders, that can cause or worsen insomia among the elderly.

NOTE: The Melatonin Profile is an important diagnostic tool to help physicians successfully utilize this powerful new clinical approach for treating insomnia and benzodiazepine dependence. This noninvasive salivary analysis evaluates melatonin activity over the complete light-dark cycle, clearly revealing any disrupted secretion patterns and providing practitioners with a sound clinical basis for developing and monitoring treatment protocols. Assessment is an important first step in identifying imbalanced circadian rhythm and for individualiing therapeutic interventions.

Source: Garfinkel D, Zisapel N, Wainstein J, Laudon M. Facilitation of benzodiazepine discontinuation by melatonin: a new clinical approach. Arch Intern Med 1999;159:2456-2460.

Bursztajn HJ. Melatonin therapy: from benzodiazepine-dependent insomnia to authenticity and autonomy [editorial]. Arch Intern Med 1999;159(8):2393-95.






Free radicals seem to have a hard time getting over their loss of an electron. In large numbers, these unstable molecules wreak metabolic havoc in the human body, attacking DNA, protein, and lipid components of healthy cells. Eventually this assault can lead to cell breakdown and death, accelerated aging, and degenerative disease.

The human body may have a powerful natural ally against free radical activity, however, in the form of melatonin, a circadian hormone produced by the pineal gland in the brain. Researchers have discovered that by blocking free radical damage, melatonin significantly reduces pancreatic injury in laboratory rodents with experimentally-induced acute pancreatitis. This increased protection was evidenced by lower rates of lipid peroxidation and reduced edema in both the pancreas and stomach.

"Recent reports suggest that oxygen-derived free radicals play an important role in the pathogenesis of [acute pancreatitis]," researchers commented. By preventing lipid peroxidation, melatonin may help preserve the integrity of the cell membranes, preventing the "leaks," or increased permeability, that cause tissue edema. It may also cut off free radical-triggered inflammatory mechanisms, such as the leukocyte migration and accumulation in injured tissue that often fuels pancreatitis and its complications.

"...melatonin is highly protective of the gut against a variety of toxic agents," researchers noted. "The implication of these findings is that melatonin may have utility in treating a variety of degenerative gastrointestinal conditions."

These results add to a large body of clinical evidence supporting melatonin's role as a "highly efficient free radical scavenger" that can inactivate potentially destructive agents of oxidative stress, including the highly toxic hydroxyl (OH) and peroxyl (LOO) radicals, investigators point out. "Additionally [melatonin] stimulates several antioxidative enzymes, including SOD [superoxide dismutase], gluthathione peroxidase, and glutathione reductase."

Researchers speculate, in fact, that melatonin may even be more powerful and pervasive than most other antioxidants in the body, since it can be absorbed into both water and fat, allowing it easy access - and thus the ability to protect - virtually all parts of the cell.

NOTE: By evaluating the circadian secretion pattern of this critical antioxidant, the Melatonin Profile reveals deficiencies that may be playing an important contributory role in a variety of degenerative conditions and diseases, especially those associated with aging and free-radical damage.

Source: Qi W, Tan D-X, Reiter RJ, Kim SJ, Manchester LC, Cabrera J, Sainz RM, Mayo JC. Melatonin reduces lipid peroxidation and tissue edema in cerulein-induced acute pancreatitis in rats. Dig Dis Sci 1999;44(11):2257-2262.



The cap letters above are from Great Smokie Lab

Posted by Truthfinder (Member # 8512) on :
(Gee, I had to go back and edit my last post - spelled my own name wrong - "Tract". Good grief.)

Thanks for the tips, Claire and Gigi. The last chlorella I bought is not the "broken cell wall" variety so I've not taken any. I'm not sure I can digest it. I've heard it can be "hard to digest" but I don't really know what that means. Pain? Cramping? Constipation? Slow GI transit? I guess I will just have to bite the bullet and try it.

Good point, Claire, about the possible peppermint in the melatonin! I do use the lozenges, but I checked them and they only have citrus flavoring. Glad you brought it to my attention, though.

As Tree pointed out, she seemed to adjust to the melatonin over time and the hangovoer effects went away. It is possible that I have never taken melatonin consistently enough to see if that is true for me, also.

Thanks for the additional info, Tree. I was surprised to see the one part that warns against melatonin if you have known mercury issues. That one surprised me.

I'm glad some of you have already sorted a lot of this out. [Big Grin]

Tracy (yes, I spelled it right this time)
Posted by treepatrol (Member # 4117) on :
Originally posted by Truthfinder:
Thanks for the additional info, Tree. I was surprised to see the one part that warns against melatonin if you have known mercury issues. That one surprised me.

Where it said >{ mercury induced autoimmune problems}
That got my attention its from a cfs fms webpage I dont believe in autoimmune. I think what is going on is actual recognition of a bacteria or virus that has takin in our dna and when the body attacks because of the to being combined dna from bacteria or virus with our bacteria it causes a cascade of cytokins

{{Definition: Cytokines are a group of proteins and peptides that are used in organisms as signaling compounds. These chemical signals are similar to hormones and neurotransmitters and are used to allow one cell to communicate with another.}}}

The body is attacking the foriegn peptides,that are bound up with ours because of the bacteria's like Bb ability to latch on to our peptides and use them as stealthing, hiding, immune evasion technique.

Well thats what I think anyway [Big Grin]
Posted by treepatrol (Member # 4117) on :
Immunotropic properties of pineal melatonin]

[Article in Russian]

Arushanian EB, Beier EV.

Pharmacology Department, Stavropol State Medical Academy, ul. Mira 310, Stavropol, 355024 Russia.

An analysis of the presently available data shows that the principal pineal hormone melatonin is capable of influencing, both directly and indirectly, the state of the immune system. The immunotropic activity of this hormone can account for the stress-protective, antitumor, and antiviral effects of melatonin.

Publication Types:
English Abstract

PMID: 12596522 [PubMed - indexed for MEDLINE]
Posted by treepatrol (Member # 4117) on :
[Big Grin]

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