The other day I was having a conversation with forum member Millbrook about the potential use of melatonin (one of my favorite supplements) for PD and I was discussing how well PD deficits align with what melatonin seems to offer based on other studies, but I was dismayed by the lack of meaningful human studies of the two together and my hesitancy to even mention melatonin for PD on this forum due to the lack of a useful human study of melatonin in PWP.
Here is a link to that brief exchange in which I mentioned that from other studies, it appears that melatonin ticks many of the boxes that would be desirable in a PD supplement or drug :
Today I decided to see if there were any new studies on this subject, and I found this new (May 2020) randomized, double blind, placebo controlled study at just 10 mg/day! It is not the dose I would like to have seen, but this is a real step in the right direction!
Melatonin is a highly potent antioxidant among many other things and the study shows that melatonin increases glutathione significantly and PwP seem to be more focused on glutathione, but directly and indirectly, melatonin is a much more potent antioxidant and antiinflammatory than glutathione because melatonin upregulates the gene expression of glutathione peroxidase, catalase and superoxide dismutase.
Melatonin itself is a very potent scavenger of reactive oxygen species/hydroxyl radicals, H2O2, reactive nitrogen species and peroxynitrite! Melatonin also has potent antiinflammatory effects and lowers multiple inflammatory cytokines and mediators that are known to be elevated in PWP.
Melatonin promotes the Nrf2/KEAP1 pathway and this results in increased total antioxidant capacity (TAC) and this is important because TAC is decreased in PwP.
Melatonin Lowers IL-1b, IL-6, Tnf-alpha, NF kappa-B, IL-17, MMP-2, MMP-9 and IL-8 among others. You may remember the chemokine IL-8 from a post I wrote about it where I described that IL-8 level is low in the blood of PwP, but maliciously elevated in the cerebrospinal fluid (CSF).
Well melatonin enters the CSF and melatonin and its metabolites not only easily cross the blood brain barrier (BBB), but also repair damage to the BBB! In PWP, brain inflammation and brain oxidative stress are elevated and feed off of each other in a vicious cycle that can destroy neurons and cells of all types as well as mitochondria and melatonin works against this cycle by reducing inflammation and excess oxidative stress.
IL-8 is higher up in the inflammatory cascade and reducing it is important because a reduction of IL-8 means a reduction of proinflammatory mediators that are downstream from IL-8 in the inflammatory cascade and that is important. Here is a link to that post that helps explain the usefulness of lowering IL-8 in PD.
As you can see from that post, lowering the IL-8 level in the brain and CSF should clearly be beneficial for PWP and people with MS. Many diseases present with elevated IL-8 levels in the blood, but MS and PD show elevation in the CSF, not in the blood and this can be very damaging and nothing that PwP or MSP want!
Another important point about the antioxidant power of melatonin itself and not even counting the melatonin induced upregulation of the bodies own potent antioxidants is the fact that melatonin can neutralize as many as 10 oxygen radicals because once it neutralizes a radical it becomes a metabolite that can also reduce oxygen radicals and this process just keeps repeating with different melatonin metabolites, whereas other antioxidants like vitamin C and vitamin E which are only able to neutralize one oxygen radical each and this starts to give you a clue of what melatonin can do in the body, including the brain because melatonin easily enters all tissues of the body. Add in the potent antiinflammatory effects which melatonin can express in the brain and body in general and you start to get an idea of the potential value of melatonin in PwP.
There are many other positive health effects that melatonin is known for such as its ability to act as a potent anticarcinogenic at high dose or greatly increase your chances of surviving Covid-19 and recovering faster.
Finally, a study I have waited years for, has arrived and hopefully it will be one of many human studies that attempts to show the value of melatonin for PWP! Now it looks like melatonin could potentially be useful for Covid-19 and PD at the same time! Future studies could consider pharmacologic dosing of melatonin in PD patients.
You should not just jump in and start using melatonin without your doctor's consent and supervision because some people can not tolerate melatonin and it may not be compatible with the medications you are currently taking, so your doctor's or professional health care provider's approval and supervision is definitely needed to stay as safe as possible!
Art
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Thanks, Art! I have been taking melatonin for approximately one month, primarily as a sleep aid. I'm very pleased to learn about all of these additional benefits.
Sounds promising. Any knowledge about long term use side effects, such as decreased natural output, problems upon withdrawal, or any effects at higher dosages out there?
I'll have to find it, but I'm pretty sure I have seen a longer term study in women and I have seen other studies at higher dosage, such as the children's study I linked to in the melatonin Covid-19 post where they used 70 mg/day for 9 months in children. The highest dosage I have seen is over 300 mg/day for cancer treatment used by Dr. Shallenberger on his cancer patients.
Years ago I used to see articles saying that melatonin supplementation may cause pineal gland production of melatonin to decline, but I have not seen such articles lately and I have never seen a study that confirmed such thinking. My personal experience after my 9 month / 70 mg / day, did not seem to confirm such an idea as when I stopped the experiment, I had no trouble sleeping as might be expected after 90 day of higher dose melatonin if pineal production had actually diminished, but melatonin production by the pineal gland does definitely diminish with age as outlined on the Melatonin For Covid-19 page.
Sorry about that bass! Yes, very vivid dreams and nightmares are a known effect of melatonin in some people. I have read where some are able to stick it out and get the nightmares down to vivid dreams, but getting from point A to point B seems like it could be a very rough road!
We are thankful to you and Dr. Mischley who recommended Malatonin. I have witnessed its benefits as my husband's trips to the bathroom have decreased considerably after starting Melatonin. He can only take 2 mg though as any higher dose makes him very drowsy the next morning, and he doesn't want to take any higher dose, as Dr. Mischley recommended.
I started my husband on 4 mg and upped it to 8 mg last few days and he’s sleeping better and night visits are about 3 x as opposed to 6-8 times. Hopefully I can report better results as I slowly increase his dose
Hello Millbrook! Always so glad to read about good results. Husband started 3mg last night, but he took it right before bed and it wasn't as effective. Tonight, he took it about 1 1/2 hours before bed and hopefully he will get good results again.
Thank you! I will try it. But Art posted a Japanese clinical trial further down that showed 2 mg was enough to get an improvement. I will try 10 mg since my husband has no side effects from melatonin
My husband can't take more than 2mg. Any higher dose makes him drowsy the next morning. In Europe, more than 1mg requires a doctor's prescription! Go figure.
I also found this study regarding melatonin and olfaction (sense of smell). My sense of smell has improved during the past month. I attributed it to an increase in the duration of my exercise regimen, but it just occurred to me that it also coincides with my use of melatonin.
Thank you for putting up this post. I started my husband on 4 mg and upped it to 8 mg because I read from another post that it helps nocturia from 10 mg and above. I also ordered melatonin in 20 mg and 60 mg. A small percentage of people do suffer from active dreams when on high dosage which is unfortunate . I also do recall that too much vitamin B1 also causes this effect as well.
Will keep you posted on his progress.
Thanks so much for your dedication to sharing discoveries with us here.
I was thinking about our discussion the other night and when I saw that study today, I thought, is this a coincidence? Whatever it was, I know that you showing Dr. Shallenberger's video definitely inspired me to look! Thank you for the video, Millbrook!
I took 9-12mg melatonin for a year or so for REM sleep disorder. It worked fabulously for that and I slept very well. Then a few months ago I started feeling a bit depressed and sluggish. It never ocurred to me that it could be the melatonin until I forgot to take it one evening. I woke up feeling better the next day, and decided to suspend for a while. Depression and sluggishness got better. I've gone back to 3mg and don't seem to have problems with that dose. I'm going to ease up slowly to find what dose I can tolerate. Maybe I just need periodic breaks.
Could be the breaks are needed every so often. I've currently boosted my 80 mg dose to 100 mg which is the highest dose that Dr. Neel has mentioned for his Covid-19 patients. I've got another melatonin test running concurrently and this is a dosing level higher than I have ever experimented with, but significantly lower than used for cancer or cancer prevention.
Art, I started at1 mg , the local health food store had 1 & 2 mg... those lasted a month and then we went to COSTCO and they had a larger volume @ 10mg. reason for increasing dose was 1 mg did nothing for me . Now at 10 mg I have a chance to fall asleep shortly after lights-out, sleep to between 3 and 5 , wake and have my usual trip to the toilet and have my middle of the night C/L 75/300 CR dose and usually back to sleep till the sun hits the eyeballs as this time of the year @ ~ 51* N. so far I have had zero vivid dreams. I seldom recall any dreams at night since Dx. Will continue this dosage until I can't get to sleep or have other negative effects...
thanks for posting the COVID 19 dosage too. We still have no patients locally.
Yes, I do not have the vivid dreams either or if I do, I do not remember them. I seem to tolerate melatonin well myself and as of tonight will be up to 170 mg. I want to get to the 180 mg level on this current test and so far have not noticed any problems.
You said, ' We still have no patients locally ', that's good to hear!!!
Please keep us posted on how you do with melatonin. The study at the top of this thread saw benefit after 12 weeks of 10 mg / night of melatonin.
Art, I have a question about sub-lingual vs the swallow right away variety, which version do you use?
I ran out of my Costco brand, Natures Bounty. regular pill and went to the local pharmacy and they had sub-lingual 10 mg dosage. I noticed over the 10 days we were at the lake that I was not getting drowsy with these Sub-L so I upped the dose to 30 mg , and then got a good sleep of 7 hrs that night but the efficacy appears to be spotty...? I am thinking that I should revert to the original 10 mg. brand Natures Bounty...
I don't use the sublingual type so I can't comment on those and have never seen any studies that used that type. I think melatonin in capsule form releases quickly anyway, so I don't see much advantage to a sublingual form.
I use the standard release type and the timed release type and to me they have subtle differences. Even in studies though, the immediate release type is typically what is used. I can't remember if it was Dr. Shallenberger or Dr. Reiter or both who said that the time released type doesn't work. They may have meant that it does not work in terms of high dose, but I think in terms of insomnia, they both work, but slightly differently from each other.
Your experience might suggest that sublingual is not better delivered and absorbed, so the Costco ones sound fine.
thanks Art, my only experience with Sub-L delivery is Vit B-12 1200 mg Sub-L. Appeared to me to be very fast absorption.... the blood test 1 week after starting showed a commensurate rise in B-12 levels, noticeable up tic in energy etc
looked around with Google: got these...
Is sublingual faster than oral?
Compared to commonly used tablets, capsules and other oral dosage forms, sublingual absorption is generally much faster and more efficient. ... Peak blood levels of most products administered sublingually are achieved within 10‐15 minutes, which is generally much faster than when those same drugs are ingested orally.Dec 8, 2010
and from NIH
"Pharmacokinetics of oral and intravenous melatonin in healthy volunteers"
This cohort crossover study estimated pharmacokinetics of oral and iv melatonin, respectively in healthy volunteers. Bioavailability of oral melatonin was only 3 %
Hmmm only 3% , then 10mg would be 0.3mg +-
there are some good graphs of the depletion of both delivered doses... I am a little unsure of what all the data is telling us...
In the bioavailability study, they don't say, but it was probably given during the daytime, which would likely yield a different reading than a night time dose reading. During the day, the body may attempt to limit melatonin in the blood. Unfortunately they rarely do night time studies for practical reasons.
As you can see in the graph, melatonin is absorbed quickly and released quickly. Perhaps sublingual is just too fast to be practical for sleep usage. I find that for sleep, the timed release can sometimes be slightly more effective when I use melatonin 123 as my prefered method for melatonin as a sleep aid.
The low bioavailability highlighted in that study, could also explain why Dr. Shallenberger and Dr. Reiter both are able to use such high dosing as they do.
Perhaps you can show your doctor the studies attached to the melatonin/Covid-19 post or even the study at the top of this post or both to get a prescription. The study at the top of this page might be the most useful as 20 mg is a relatively low dose that would need a constant refill if it is tolerated well.
This company says they ship to New Zealand, but I don't know if your customs department will let it through. Maybe you can contact the company and see what they say.
Thanks Art. I placed an order and it seemed to go through! It was only $21 NZ so worth a shot! Usually I get to the paying stage and other companies say I can’t ship to your country. Will take a while to get here but will try it when it arrives!
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He had about 1/3 of a 5mg last night. Didn’t make any difference at that level. He slept well for the first part of the night but as he takes a tiny bit of mirtazapine which knocks him out that isn’t unusual.
He has become very anxious again after a long good period the whole lock down thing has really set him back. His symptoms have suddenly got a lot worse after no decline for ages. We had run out of mannitol as the order didn’t arrive so not sure if that made it worse, but now he is back on it he hasn’t improved again.
In the study at the top of this thread, after 12 weeks at 10 mg per evening, they saw improvement in depression test scores and anxiety test scores, as well as a reduction in the UPDRS Part 1 test score, so hopefully your husband will see that benefit.
I’m taking part in a similar trial run by the University of QUeensland. I’m only two weeks in to a three month trial so far. It’s purpose is to see in melatonin improves sleep. I
No idea! I presume I’ll find out at the end of the study. I have a different pack for six two week periods. Some are Placebo. I hope I’m on that at the moment because I haven’t noticed any difference yet.
Progress report on the Melatonin study. I have six boxes of pills - one box for each two weeks. They consist of 3 boxes of placebo and three of Melatonin - in random order. So far I'm on week 4
It was fairly obvious that the first two weeks were placebo. There was absolutely no change in my sleep - or lack of it - pattern. The last two weeks have been quite different. I've woken once or twice during the night, but quickly fallen asleep again. No vivid dreams. It will be interesting to see what happens next!
I experimented because I didn't ask the doctor about it; i just researched it a little on line. At 4 pm i started him on 6-10 mgs, then at 10 pm i gave him another 6 to 10 mg. It never caused any side effects. He was sundowning badly to the point of crawling out of windows and laying in the dirt 1/4 away ,ending up in the emergency room with hypothermia. Every evening and all night long was horrible.He never had another sun downing incident after starting the melatonin regimen except once, when i was out and my son didn't give it to him on time. It has to be given before dusk. He was already taking melatonin to sleep, it was the 4 pm dose that stopped it.
Sun downing is when the person acts erratic when the sun goes down. He is up all night and wants to wander all around. My husband would get up during the night and ended up in the dirt 1/4 mile away with hypothermia. He acted like he had dementia during sun downing. At other times he was fairly normal. We started having to lock him in his room. One time we couldn't figure out how he escaped, and it turned out that our cat had learned to open levered doors. Melatonin stopped the sun downing.
Hi Arte, although I have no problems to sleeping, I still wanted to try melatonin, 5/10 mg. before going to bed. Sleep was different. I got up less rested. I tried to take melatonin in the morning, but this caused me tiredness. What do you think about this? Thanks
I would say for some people, there is an adjustment period where your body has to adjust to increased melatonin. Melatonin production decreases as we age and as we are exposed to extensive night lighting so by the time we are senior citizens, production is very minimal. Some studies show that less than 1 mg can be effective to induce sleep, but I have never experimented in that range, so can't really comment on that. It may be that 5 or 10 mg may be too much initially for you, but can possibly be worked up to. Generally, melatonin is not recommended to be taken during the day except possibly in cancer treatment or other severe disease states. The pineal gland produces and excretes melatonin in response to day light turning to night. So pineal gland production of melatonin occurs mainly in the evening, not in the light of day. So I can see why it would have made you tired during the day.
The main reasons I am discussing melatonin in these posts is for potential usage for Covid-19 and for potential usage in PD, so melatonin as a sleep aid I have already discussed months ago and simply put, it helps some people get to sleep and it does not help others with sleep, so the sleep aspect is sort of done for now.
The available studies for melatonin are considerable and the potential uses outlined in those studies is more where I am focused now. I have always known that melatonin is an effective anticancer treatment, but more recently, the dosing needed to get those anticancer benefits have come forward. The PD study at the top of this post showed that even a low dose of 10 mg has positive effects in PWP.
Dr. Reiter, a very well known melatonin researcher is showing that melatonin at pharmacological dosing (HDM) can do some pretty amazing things, but he is using dosing that is at least 18 times higher than what was used in this PD study above.
Dr. Shallenberger is using dosing that is up to 36 times higher than the PD study above and is having very good results in his cancer patients and other conditions which he mentions in his videos. His minimum dose that he uses in his patients is 180 mg /day, so as you can see, I am not talking about dosing in the 1/3 ~5 mg sleep dosing range.
Both of these doctors feel that the dosing they are describing is safe for the majority of people and Dr. Shallenberger says that in his patient experience, about 5% of his patients can not tolerate melatonin at these high doses and so those patients are not able to use melatonin, but he goes on to describe the extraordinary results he is seeing in his cancer patients and other patients with the addition of HDM.
So my interest at this point is to continue to gather information about these pharmacologic dosing levels and hopefully the studies will start to reflect higher dosing and confirm what these doctors are saying about the very good safety profile of HDM.
Thank you for the information about Melatonin but I disagree with taking Melatonin as a supplement simply because we block all other biochemical pathways in production of Melatonin and give a readymade substance to our brain. If we take enough tryptophan from our diet or {5HTP} and support methylation by taking enough p-5-p (active form of B6) + B9 + B12 we can naturally produce Melatonin as the end product of Seretonin metabolism.
This video shows the synthesis of Melatonin and metabolism of Seretonin in a simple way.
I understand what you are saying about through natural production you can achieve melatonin also. I think in studies where a known dose is needed in order to accurately represent the human or animal response, very specific dosing is needed in order to try and produce a specific reaction. I'm not sure about being able to reach pharmacological melatonin dosing via the natural process though when melatonin used as a cancer treatment, can require over 300 mg of melatonin per day or melatonin treatment for Covid-19 can require up to 100 mg/day. This may not be possible through natural production means.
For normal melatonin production not related to therapy of any type, natural production seems adequate. In terms of the PD study at 10 mg/day that they used with positive effects, we have no clue yet what an optimal dose is. If it turns out to be fairly high, natural production levels may be inadequate without supplementation. Melatonin production declines with age and seniors have marginal production of melatonin which is even lower than newborns. In seniors, because of the method by which we manufacture vitamin D in the skin, seniors can not manufacture enough vitamin D to stay in the reference range year around no matter how much time they spend in the sun. It looks similar with melatonin and seniors where seniors have even lower levels than newborns.
My problem is in using Melatonin supplements for a better sleep not in treatment of COVID-19 or cancer. Of course we cannot reach a pharmaceutical grade with foods.
Yes ,the Melatonin supplements can help for those seniors whose pineal gland might have been calcified or but not for anyone who has simply insomnia.
It is such an involved process trying to put the circadian rhythm back in order if it becomes off. Basically retraining the body to react to light as it should and is much easier said than done with all of the artificial night lighting we are continuously exposed to. A good blast of morning sunshine every morning is a good starting point!
Heya. Just a note that 5-HTP, when taken with carbidopa, can make you rather nauseous. Check the 5-HTP page on Wikipedia if you want a ref. There are other potential downsides, too. Not saying it's all bad, but it's worth researching.
I personally feel more comfortable taking melatonin, and I'm staying away from 5-HTP. But that's just me.
Back In the 80's I would occasionally take a 10 mg melatonin for sleep. I did experience vivid dreams, but that didn't bother me. Presently I do the same, except for a smaller dose, 3 mg. It still helps with sleep, except it now makes me lethargic the next day. I'm trying 1.5 mg next.
You might try your dose earlier in the evening and see if that can help with lethargy in the morning. What I'm finding with moving up my experiment to 100 mg/evening from 80/mg evening, I felt a little sluggish this morning, but I have felt this before at lower dosing and it tends to go away with regular use, at least for me.
Well definitely, I could take a little feeling drunk if it helps me through Covid-19 with no serious issues during or after infection! My experience when first starting at a new higher dose is that I can feel a little lazy, but with regular use, that aspect of supplementing melatonin seems to go away for me.
Hi Art, I did several attempts this year with Melatonin. Every time, dose above 3mg made me feel same as if overdosed with Thiamine.. Same worsening of the symptoms during the day, increased tremor and poor balance. I think it is going to be similar story i.e. very individual response to eventual treatment protocol..
You might consider watching this video that forum member Millbrook posted the other day about Dr. Shallenberger and his use of melatonin in his patients. If you are pressed for time and do not have time to watch the whole thing, try to watch the time range from 43:00 ~ 47:00 on the time count. He also mentions one or two possible ways to possibly work around melatonin issues. At some point during the video another doctor suggests that some melatonin issues are related to detox symptoms, but does not elaborate on what exactly that means.
You're welcome! I have not noticed a difference between brands, but in the video right above your post, Dr. Shallenberger does have a couple of recommendations. Btw, this video was posted by Millbrook and it gives some definite clues about the usefulness of melatonin in multiple health issues when used at high dose (HDM). It is worth the full viewing, but if you are pressed for time, try and at least watch the 43:00 ~ 47:00 minute range. Here is the link to the video:
I did another post awhile back about the fact that the chemokine IL-8 is at very elevated levels in PD and MS in the cerebrospinal fluid (CSF) and melatonin is an IL-8 inhibitor that crosses the blood brain barrier. That post will be quite useful to review alongside this melatonin post because it gives a better idea of what melatonin might be doing in PWP.
It would have been nice if they had used a higher dose of melatonin, but Dr. Shallenberger's video tends to give an idea of what a higher dose study might show.
I think you will be surprised by what Dr. Shallenberger has to say through most of this video. It sure makes you wonder why there are not more high dose studies done with melatonin!
Art, I take Melatonin daily primarily for sleep as you recommended and appreciate as well.
But I would refrain from anything dr shallenberger states. As I read one of his articles which stated he can cure covid19 but hasn’t even tested his theory. That’s a heck of a statement! Additionally I recommending reading this entire short article. Just bringing to your attention in case your unaware of his past.
I've read the article before and that was 17 years ago! Kind of hard not to treat cancer and not have patients die. I have not seen any other articles about him like that. I'm sure any doctor treating cancer patients will have many cases that they can't save and he was not using melatonin yet at that time. Before you condemn him for that one malpractice case, consider this quote :
.................
' A recent study by Jena and colleagues found that nearly 10% of oncologists face a malpractice claim annually, the 10th highest among the specialties surveyed. '
................
So if he has had two malpractice cases in 17 years, that seems much better than average!
As far as his claims of curing Covid-19, I have not seen that claim. He does suggest using a method of inhaling H202 using a nebulizer (not his method or idea), but I am in disagreement with part of that claim. His contention is that the inhalation method can not only kill virus in the lungs, but "possibly the whole body" and imo, that is not possible. H2o2 is a potent oxidant and that is the method of action by which it is able to destroy pathogens of many types, but being an oxidant means that there are natural antioxidants in the body that can neutralize it and that is exactly what catalase will do to it, neutralize it into water and oxygen and I suspect that catalase will do that far before the H2o2 can get to other places in the body. I am in agreement with the idea that inhalation of H2o2 can kill the virus in the lungs, which is great if you have just inhaled the virus and it has not made it past the lungs yet, there is a possibility that you could potentially stop the virus right there, but how useful is that really, if your body has not had time to generate any antibodies? So for the rest of the body I would not feel comfortable using H2o2 alone in the form of a nebulized inhalation.
What Dr. Neel is finding is that melatonin is not allowing the disease to advance from the point that HDM is initiated and symptoms turn around in about 24 hours in all of his patients(20) so far. So if Dr. Shallenberger is including melatonin along with the H2o2 inhalation, then I would say he is getting closer to a cure while the addition of ozone therapy may get a little closer to an actual cure. My personal belief is that HDM and AgNPs could be a relatively safe and effective treatment to destroy the virus in humans while allowing the opportunity for antibodies to be made by the adaptive immune system, but that is just my opinion. The safety profile of AgNPs at dosing and particle size that is known to destroy pathogens of many types while having minimal impact on normal cells is established as is the safety profile of melatonin at these higher doses.
Dr. Shallenberger is using traditional chemo and radiation treatment in conjunction with melatonin, ozone and other anticarcinogenic supplements like curcumin in some cases and seeing very good results in his cancer patients. The alternatives allow him to lower the chemo and radiation amounts delivered to the patient while lessening side effects very significantly and melatonin has been proven many times in studies to not only have anticarcinogenic effects, but it has shown synergy with chemo and radiotherapy as well as the ability to circumvent many of their side effects, so I am in complete agreement with his use of melatonin as part of his cancer protocol. The curcumin he uses also has many studies to support its use as adjunctive treatment of multiple cancer forms, so I am in agreement with that use also. I can not comment on the use of ozone as I have not read enough studies on its use to form an opinion.
The basis for my interest in melatonin is from the hundreds of studies I have read about it. He and Dr. Reiter just happen to be in agreement with the studies and they suggest dosing that is at the top of the range of current studies, so I am not really seeing a problem with what either one of them are saying about melatonin.
Thanks, Art! I've recently had trouble staying asleep, and my MDS recommended I take an extended release form of melatonin, which I wasn't even aware of. I've also had more issues of late with a restless leg (just on my tremor side), and the melatonin seems to help calm that, too. The only downside I've noticed so far is that I seem to have a bit of a headache when I wake up the next morning, but it's definitely bearable to have a good night's sleep!
For anyone interested, the brand I found is Natrol. I found it in 5mg time release formula, and I believe I saw a 10mg extended release option, too.
I'm glad to hear you are getting good rest, that is very important to maintaining health. Try a glass of water first thing in the morning to see if it does anything for the headache.
Just a heads up that slow release melatonin (such as natrol's) often comes with vitamin b6 in the form of pyridoxine. This form of B6 can be problematic if taken at high doses for long periods.
It should be fine if you are taking one or maybe two pills a night. But if anyone is considering high doses of melatonin, you will want to take care that you are not overdosing yourself on pyridoxine.
Just read your first paragraph Art. Apparently the dr didn’t do due diligence.
“At no time from the initial presentation of medical symptoms did he examine the patient, order a test or record in the medical records why those actions weren't taken," Cousineau said.
Horton was later diagnosed by emergency room doctors with stage-four colon cancer and told he had six months to live.
(Shallenberger diagnosed hemorrhoids without a full exam)
I've only seen one other reprimand and that was 11 years ago. If you have more I would like to see them.
Something you have to consider is how litigation works in the US court system. If his attorney tells him the best way to deal with this is to just admit to whatever the prosecuting attorney is saying for the purpose of expediency and to minimize cost, then I think that many doctors may do the same under similar circumstances rather than give their side of the case or litigate it out at extensive costs. I do not know exactly what happened in that case, but I think if it were as bad as was outlined in the complaint, he likely would have lost his license or at a minimum been put on some type of probation. Instead he paid a modest fine and moved on as his attorney probably advised him to do
I currently lean the other way. Often times, people who choose a doctor who also uses "alternatives" alongside standard of care treatments as part of their treatment plan are patients who are late stage or past the point of no return as their previous doctor has told them there is nothing more to be done for them, so patients tend to die at a higher rate while under the care of their last choice, but it doesn't sound like this is the case for him.
For another side to the story here is more information on what other doctors have to say about Dr. Shallenberger as well as his side of the story.
They have not actually done studies on melatonin and tremor and that was not an end point they were looking at in this 10 mg/day study, but if it is even possible, I would think it would take more than 10 mg/day to see such a change. Probably dosing that Dr. Shallenberger uses would be more likely to find out what all melatonin can do in PD. This study showed an improvement in depression, decreased hs-CRP, decreased total cholesterol, increased total antioxidant capacity, increased glutathione, decreased anxiety, decreased serum insulin, decreased TNF-alpha, increased PPAR-y and decreased insulin resistance. It seems for just using a 10 mg dose, the results were very good!
Interestingly, all patients had
rapid eye movement behavior disorder or restless leg syndrome.
I am currently at 130 mg/evening in my self test of melatonin and so far it seems agreeable with no apparent problems.
Art, I see through reading these threads that you have been increasing your melatonin gradually, at one point was 80 mg, then 100, and now 130 mg/evening. My husband decided to try melatonin and started two nights ago with 4 tabs of 5 mg each, total 20 mg at night. What are your thoughts about how long he should remain at that dosage, and how should he procede with increasing dosage if he does not realize benefit?
Unfortunately we only have this study to go by in terms of use for trying to see what it can do for PD and they only used 10 mg/night to good effect in 12 weeks. This is the first randomized, double blind, placebo controlled study for this purpose. Previously there are studies using higher dosing such as the children's muscular dystrophy study that used 70 mg/day for 90 days, but that was an MD study, not PD.
I'm not a doctor so I can't recommend a dose, but the doctors in the videos below mention the dosing they are using for different purposes. A lot has to do with if you can tolerate it or not and it seems as though if you tolerate it, there is no problem at any dose according to Dr. Reiter in the following video link below. Dr. Reiter says there is no LDL50 for melatonin because in animal testing, no test dose has killed animals to date. There is an LDL50 for almost everything you might consume including salt.
Dr. Reiter uses 180 mg /night of melatonin as a preventative and has done so for over 25 years. I am almost there myself and have noticed no problems so far at 160 mg/last night and I will use 170 mg/tonight.
Dr. Neel recommends up to 100 mg/day to treat covid-19.
Dr. Shallenberger is using 300 ~ 360 mg/day of melatonin in his cancer patients to very good effect as outlined in the video link below. He also takes 180 mg / night of melatonin as a preventative for himself and says that if you are his patient, he will put you on 180 mg/night of melatonin as a preventative.
Given the study at the top of this thread, they showed safety of 10 mg/night of melatonin for 12 weeks with clear measurable benefit, so if you are going to try and replicate their results, 12 weeks would be the time frame. Dr. Reiter and Dr. Shallenberger both use 180 mg/night for years.
From what these three doctors have said, the problem lies in whether you are able to tolerate HDM or not. If you clear that obstacle, they seem to feel that HDM is safe.
I think if you had to pick one thing that does significant damage in PD, it might be oxidative stress which feeds much of the cellular and mitochondrial degeneration that occurs in PD. Melatonin is the most potent antioxidant in the body, even more than glutathione, which melatonin also boosts and it upregulates the gene expression of the bodies other potent antioxidants, catalase, glutathione peroxidase and superoxide dismutase. Melatonin is a potent scavenger of ROS, RNS, H2o2 and peroxynitrite and it can scavenge up to 10 oxygen radicals whereas vitamin C or vitamin E can only scavenge 1 oxygen radical each. So these potent radical scavenging and antioxidant activities of melatonin suggest that this may be a major benefit in PWP. Melatonin also is a potent antiinflammatory which is also likely to be beneficial for PWP since both inflammation and oxidative stress are elevated in PD. Melatonin readily crosses the blood brain barrier and can express its beneficial effects in the brain and throughout the rest of the body.
In any case, Ruth, please come back and share what your husband does and how he does on melatonin.
My husband took a 10 mg dose for 3 nights and then got scared that it was too high a dose though he had no side effects. There seems to be a residual effect because though he stopped for a week the effect continued. He could manage 4-5 hours of continued sleep and bladder retention capacity has increased from 120 ml to 300 ml for each pee. Amazing! Wondering what to do next though I started him back on 2 mg last night. I tried melatonin myself but at just 4 mg I was groggy and stoned up to 2 days after I stopped. I am wondering how does one take 180 mg?
Yes, the groggy feeling is a common effect of melatonin and you sound very sensitive to it. You already know that Dr. Shallenberger said that about 5% of his patients can not tolerate melatonin, but he seemed to be talking about the vivid dreams issue.
Your husband sounds more like me where 10 mg is like I have taken nothing. I did make it to 180 mg which was my goal to make sure it is tolerable for me at that dose since both Dr. S and Dr. Reiter describe that as a preventative dose. Now I am down to 60 mg. Glad to hear it helped him improve his nocturia issue!
Wow! Thanks a lot Art. That’s on just 2 mg. what a great alternative compared to taking vesicare. I am just wondering what would be optimum dose to kill many birds with one stone
Art, Thank you so much for your detailed reply! John has taken 20 mg (went down to 10 for a few days) now for over 2 weeks. He feels like it makes him sluggish or sleepy during the day, not necessarily just during the morning. It is almost 5 p.m. and he still feels that way today. I suggested that he take it earlier in the evening so has been doing so about 6:30 or 6 at the earliest the last few days. I believe that you said in a previous post that this feeling went away for you with continued use. How many days do you think it would take to go away? Should he wait for that to go away before increasing the dose? Does that feeling typically go away with usage of higher doses? I don't know how long he is going to be willing to hang in there with this experiment. Thank you for all your help!
I can only speak for myself on how the higher dosages work for me. It has been my experience that the melatonin hangover took one to two weeks to go away when I experimented at 70 mg / day. Now it does not last as long for me even at the 180 mg dose that I tried recently. I got a little hangover for a day or two and then it was fine with no more hangover. For now I am not going to continue the 180 mg dose, I just wanted to go there to make sure I could tolerate it should I ever find a need for that high of a dose. I do not find that there are studies to support using that dose long term. For me, 20 mg /night is the same as if I took nothing, but I had been taking 30 mg every night for quite awhile already and that never bothered me either.
Thanks so much for your helpful reply, Art. Tonight John went up to 30 mg, and has been taking it around 6 or so p.m. lately, but he usually walks in the evening and felt tonight that it was slowing down his walking. We are in the heat of the desert and having over 100 and 110 degrees now so walking any other time is impossible, for the length of time he needs to walk. Blessings to you!
Dr. Neel is now recommending one (1) mg per kilogram of body weight to be used only if sick and tested positive. This is the recommendation he is giving to other doctors. He has not mentioned using vitamin C anymore either, but a study I posted higher up in this thread suggests that vitamin D and melatonin might be synergistic together.
If melatonin is slowing your husbands walk, maybe he should just keep it to no melatonin until needed. The walking is important for PD so slowing down may not be a good thing. From what Dr. Neel has said, if you wait til you test positive, that should be doable as he says the reversal of symptoms is fast at just 24 hours and apparently none of his 50 patients had advancement of Covid-19 disease so far and the 50 patients have recovered already.
The temperature you mention for this time of the year sounds like Arizona, hot hot in the summertime!
Thank you for the helpful info concerning the melatonin and Vitamin C. Today John started the mannitol. Yes, we are in the heat of Arizona! This weekend is moving "day" for us, just to another place in the desert here about an hour away. We've moved in freezing temps in Tennessee years ago, and now this, the opposite end of the spectrum, but so grateful to have some place to move to!
Thanks a ton. Any brand you recommend? What about its safety profile? I am ready to experiment but I will first try with B1 HCL starting Saturday 13 June 2020.
It is better to wait to see what your response to B-1 is first and establish your correct dose. If you start something else before you have made a determination about B-1, you will have no way of knowing what is working for you and what isn't working for you.
The dose used in the study was 10 mg/ per night. For contraindications you should check with your doctor to be safe.
I'm pointing out a study from last year that discusses the relationship of glutathione, melatonin and PD. The reason I am pointing this study out is because the study by itself might give the impression that melatonin is not good for PD, but what this study may actually be showing is that melatonin is elevated in PD because more melatonin is needed as the body tries to compensate by increasing melatonin production as the glutathione level drops well below normal.
They didn't use melatonin in this study, just measured native levels of melatonin and glutathione. Now with the arrival of the new 10 mg study, it appears that the reason that glutathione is low in PD is because it is being used up so fast because of the elevated oxidative stress levels associated with PD and the melatonin production is increasing as the bodies way of trying to compensate for the declining glutathione by increasing production of melatonin within the limitations of the body and this increased melatonin production is insufficient to boost the glutathione high enough to offset the high burn rate of glutathione in PD. The new study shows how supplementing just 10 mg/night of melatonin is able to reverse the negative correlation between melatonin and glutathione shown in the older study. In the 10 mg study, melatonin raises the blood level of melatonin and also shows that this increase in melatonin results in an increase in glutathione or essentially the opposite of what the older study shows. Context is important!
Keep in mind that in the PD/Melatonin 10 mg /day study , the addition of melatonin increased the total glutathione level and the melatonin level as is reflected in many other studies where they actually supplement melatonin as opposed to just comparing native levels. I think the newer study puts the older study into proper perspective and just begins to shed light on the value of melatonin in PD treatment.
The older study is one reason why I never really tried to discuss melatonin as it relates to PD, but now I think I have a better understanding of that study and what it is really showing.
Some important points we don't know from this newer 10 mg study is what would the numbers look like had the study gone for an additional 12 weeks? Would the improvement have continued upward? What would the results have looked like at 50, 100 or 180 mg/day instead of 10 mg/day?
Dr. Reiter and Dr. Shallenberger are both using 180 mg /night and Dr. Reiter has been doing that for over 25 years so clearly he believes in the value of melatonin for humans.
Art, all I can say again is THANKS so much. Sharing your understanding is so helpful to us who are trying to get a grasp of what is going on with PD. Indeed I will come back and share how my husband is doing with Melatonin.
To the best of my knowledge, melatonin is only elevated in PD because the body is trying to compensate for a significant reduction in its own natural antioxidant defenses, catalase, superoxide dismutase and glutathione peroxidase as three important ones. Unfortunately the depletion of these antioxidants is more than the bodies melatonin producing capabilities can manage.
Melatonin upregulates the gene expression of all three and more and the 10 mg melatonin PD study shows that that addition of just 10 mg is enough to get glutathione higher again. What we don't know is what would have happened had they gone 24 weeks instead of 12 weeks and what would have happened had they used 100 mg instead of 10 mg.
Melatonin also helps because it is a very potent scavenger of multiple radicals and it can neutralize up to 10 radicals compared to other antioxidants that can only neutralize one.
Two nights ago I posted about a 2019 study that illustrated a negative correlation between melatonin and glutathione in PWP that made it appear that melatonin may be the reason why or a contributing factor for the dropping glutathione levels in PWP. I used the newer 2020 study at the top[ of this thread to explain that discrepancy.
Yesterday I saw another new melatonin study that showed somewhat similarly to the 2019 study in that PWP show higher plasma levels of melatonin than healthy controls, but this study was not looking at glutathione so much as how the specific melatonin levels relate to cardiovascular disease issues, sleep disorders and gastrointestinal dysfunction. This study like the 2019 study, showed elevated levels of melatonin in PWP, but this study also showed that the higher the melatonin level, "with statistical significance", the less cardiovascular issues were seen, the less sleep disturbance issues were seen and the less gastrointestinal dysfunction were seen!
!!
Those are three very common issues in PWP and again, when you combine the information that this study delivers with the study at the top of this thread, it adds confirmation to the whole idea that melatonin is healthful for PWP. Older studies also add bits of confirmation to the idea of melatonin being good for PWP in terms of helping to alleviate some symptoms of PD, even at low dosing. Here is a link to this new study.
It is pretty well established that PWP are twice as likely to develop heart disease and it is also pretty much established that melatonin is heart protective! Not much good to figure out a way to effectively get good control of your PD symptoms only to run into life threatening heart problems!
It is also pretty well established that gut issues are common in PWP and melatonin has shown itself in studies to be protective of the gut and this topic has been discussed on this forum before, so having a potential way to improve gut function could certainly be quite useful in PWP.
Many on this forum have reported sleep disturbances of varying effects and again having a potential option to improve sleep issues is once again a very useful option for PWP to have.
I will try to keep this thread updated as new studies come out.
This study suggests that prolonged release melatonin (PRM) may be helpful for some PWPs with poor sleep quality to get sleep improvement at just 2 mg / night.
Thank you for the link! Personally I would choose melatonin & AgNPs over Ribavirin due to the side effects of Ribavirin. The side effects sounds like it gives you the flu! Nausea, vomiting, diarrhea, dizziness, headache, tiredness, irritability, stomach pain or upset, anxiety, trouble sleeping, cough, hair loss, blurred vision, flu-like symptoms (e.g., fever, chills, sore throat, muscle aches or pain), loss of appetite, tooth and gum problems, trouble breathing and the list goes on! I've never had any of those effects from AgNPs.
This recent abstract suggests that melatonin can reduce the severity of Covid-19 disease and possibly reduce post disease issues. This sounds very familiar!
Although the study link below is not about melatonin, it is relevant to this thread because it discusses a need for a peroxynitrite scavenger(ONOO) in Parkinson's disease as it is an oxidant promoter that can cause significant cellular damage and it is worth noting, in this context, that melatonin is a potent scavenger of peroxynitrite! Peroxynitrite directly damages dopaminergic neurons in the substantia nigra and melatonin scavenges peroxynitrite and melatonin is also an inhibitor of NADPH oxidase which increases production of peroxynitrite so melatonin is working from two different angles to effectively reduce peroxynitrite! Melatonin easily crosses the blood brain barrier while being an inhibitor of the chemokine IL-8 that was previously discussed in a post I put up late last year on HU that shows that IL-8 is highly elevated in the cerebrospinal fluid (CSF) of PWP and melatonin enters the CSF! Melatonin also inhibits production of IFN~y which is also elevated in PD! IFN~y is a cytokine that causes cellular death and is inflammatory. Here is a link to the recent study :
Although none of this was mentioned in the study at the top of this thread, it just helps to illustrate that melatonin does many things that could be useful in the battle against PD, much of which is already known via previous PD and non-PD related studies and some of which is still being discovered!
This newer study (June 2020) suggests that melatonin acts as an antidepressant by way of reduction of neuroinflammation, reducing proinflammatory cytokine levels and importantly, a reduction of reactive oxygen species. All important issues in PWP.
My personal opinion is that PWP tend to have significantly elevated levels of oxidative stress with reduced total antioxidant capacity and so do most Covid-19 patients which means that the dramatic increase in oxidative stress and inflammation that comes with Covid-19 is highly likely to worsen PD symptoms very significantly for an extended period of time.
Increasing your total antioxidant capacity is likely a very good step in fighting Covid-19 and helping PWP to try and return to their base normal in a shorter period of time. Obviously prevention would be a better way to go, but that may be easier said than done with an economic reopening!
Another interesting perspective with lots of evidence. It's fascinating to read.
I'm wondering what amount of melatonin you would think appropriate for a basically healthy person (me....no PD). I have occasionally taken melatonin to hel sleep but it leaves me feeling slightly woozy.
My husband (pwp) seems to be able to tolerate everything very easily. Be is currently on a low dose of Sinemet 3x/Day and thiamine, D, C, mannitol, and a supplement that may/may not help with preventing kidney stones, and Lipitor. This last, I think, is way over-prescribed. His doctor prescribes it for virtually all men in his practice, along with a daily baby aspirin. From what I read, it lowers the bad cholesterol....which was never really high for my husband.....but there is little proof that it actually reduces the number if strokes and/or heart attacks.
We are going to Dana Farber for treatment. First..ADT (androgen deprivation therapy) IM injection monthly for 2 years. Then LDR for 28 days. The HDR (the surgical component) hopefully just once in early November. It's all this radiation that I'm worried about. I realize you're not a doctor but reading through all of this is overwhelming. So that I don't have to ask you directly for a recommendation, could you highlight 2 or 3 lines in these studies which might give me an indication of optimal melatonin supplementation?
In the melatonin PD study above, they used 10 mg/night to good effect in PWP. This was a randomized, double blind, placebo controlled study and just 10 mg /night for only 12 weeks to get measurable improvement! So that would be an idea to try and replicate the study results.
This old melatonin/cancer very brief abstract showed positive results at just 20 mg / night.
This recent very brief study abstract showed that inhalation of a fungicide by mice caused Parkinson's like symptoms and melatonin helped ameliorate the damage caused by the inhaled fungicide. Melatonin offered neuroprotective effects through multiple mechanisms of action.
Here is another article describing the usefulness of melatonin in PD via one of its well established methods of action, reduction of oxidative stress which is at elevated levels in PWP and is a main factor in why total antioxidant capacity (TAC) is at reduced levels in PWP.
Melatonin is the most potent antioxidant in the human body for multiple reasons. First, melatonin increases gene expression of the bodies own very potent antioxidants Superoxide Dismutase (SOD), Catalase (CAT) and Glutathione Peroxidase (GPx) as well as glutathione (GSH) which results in increased production of all three and recycling of GSH. This combination of events caused by melatonin increases the depleted TAC.
Melatonin is also a very potent antioxidant itself and is a highly potent scavenger of reactive oxygen species (ROS), reactive nitrogen species (RNS), H2O2 and Peroxynitrite (ONOO). The scavenging of ONOO is very important because vitamin C, vitamin E and other conventional antioxidants can not scavenge ONOO. ONOO is active in PD and is a contributing factor to the oxidative destruction that occurs in PD and this is important to scavenge these peroxynitrite radicals to help with the prevention and control of PD and is rarely mentioned or discussed, but very important all the same! The following study link explains how melatonin maintains glutathione homeostasis while vitamins E and C can not.
Melatonin is also able to neutralize oxygen radicals up to 10 radicals per one melatonin molecule by up to 10 times more than vitamin C or vitamin E can do.
Oxidative stress and scavenging of radicals that are active in PD are becoming more of a focus in studies because oxidative stress is proving to be highly active and damaging in PD as well as many other diseases and the effective control of these damaging radicals may help to improve the overall disease state. The following abstract link describes how TAC is lower in PWP compared to controls.
Melatonin also lowers inflammatory parameters. PWP are at increased inflammatory levels and it is the increased oxidative stress and inflammation which does most, if not all of the cellular damage in PD.
My personal experience is that melatonin taken even once increases L/C startup time (by approx 50%) and decreases duration (approx 30%).
i.e: i'm saying that 2mg (special formula with high absorption - 80%) taken before bed interfered with meds morning 1st dose of L/C = 25/6.25mg and 90mg of LD from Mucuna, therefore taken 8/10 hours later.
May be this happened to me because of the very low Carbidopa vs Levodopa (1/20) I was taking.
My understanding is that its potent detox and cleaning properties reduce residual circulating Carbidopa and requiring to increase dosage.
Did anyone experienced a similar effect with melatonine?
I've tried many brands and have never noticed a difference between brands. One of the brands I am currently using is Carlyle and the other was a house brand from Sam's club. I used to use another one by Schiff that had extra ingredients to help you sleep, but they have since discontinued it. I can't remember the others I have tried as I have been taking melatonin for years.
I have tried melatonin for sleep which works but on low dosage 1.5mg n 3mg only. But I don't use it frequently. Someone mentioned getting back lost of smell. Do u know the dosage used by that person? Cos my smell has been acting weird this month.
I must have missed that post that you are describing as I have never heard anyone say that melatonin brought their sense of smell back. I have heard multiple forum members say that they have gotten their sense of smell and taste back with Mannitol and to a lesser extent with HDT/B1. The dosage varies depending on who you talk to, but I remember someone mentioning one tablespoon per day, but I have never heard if that is a heaping tablespoon or a level full US measuring tablespoon.
One member who was just passing through, as he never came back, said that he was symptom free on 80 mg melatonin/night. No corroboration, just that statement and he never came back so that statement has no value. He also never mentioned what his condition was before melatonin.
I remember now, thank you for finding it! It wasn't clear to me if it was the exercise or the melatonin, that's why I didn't remember Jim's reply. On the other hand, I haven't heard anyone report the benefit of improved sense of smell from melatonin or exercise and if I remember correctly Jim is on B-1 which has been reported to improve sense of smell and taste also.
Sun downing is when the person starts acting erratic when the sun goes down. He wanders around all night. He acts like he has dementia. He has no plan for what he is doing or where he is going. My husband eft the house in the middle of the night and I found him about 1/4 mile away in a field, face down in the dirt. He had hypothermia and had to spend the day in an emergency room. After i started giving him melatonin at sun down and again around 10 pm, he didn't sun down again, except once when my son was watching him and didn't give it on time.
I can;t find the place to respond to the person who asked me this.
I saw the question too and was going to answer it regarding sundowning and melatonin which I learned from you, but I thought it better that you answer it, since you have the actual experience. I can't remember who it was because I have been engrossed in reading all day.
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Preventive treatments to slow substantia nigra damage and Parkinson's disease progression: A critical perspective review
Melatonin supplementation and the effects in Parkinson's disease
