In this new Systematic Review and Network Meta-Analysis, Melatonin appears to outperform Donanemab, Lecanemab, Aducanumab and aerobic Exercise in AD patients as discussed here :
' The analysis included 10 randomized placebo-controlled trials with 4,599 patients. Although melatonin and aerobic exercise for a short time were significantly more effective than donanemab, lecanemab, aducanumab and placebo in the primary analysis, there was significant heterogeneity. In the sensitivity analysis excluding exercise, melatonin was significantly more effective than donanemab, lecanemab, aducanumab and placebo, with no significant heterogeneity. Aerobic exercise for a short time was significantly less acceptable than donanemab, aducanumab and placebo. Donanemab, lecanemab, and aducanumab were significantly less tolerable than placebo and donanemab and lecanemab were significantly less acceptable than placebo. '
This seems like a testimony to the lack of effective drug treatments for AD. Other studies have also shown benefit from melatonin for AD and PD.
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The full study is behind a paywall and they did not mention any dosing in the abstract, but in a meta analysis, they often don't go into dosing. In order to see dosing, you would have to use the study references in the full study and then go to individual studies to see the dosing used in individual studies. I can search through other means to see if I can find a melatonin study dosage used for AD.
For the 50 mg study, didn’t they use “pharmaceutical gel“ melatonin or something like that? Just trying to find out the form of melatonin they used… Also was it instant or sustained release? I’m thinking about doing this but I’m a little confused about what the best brand would be…
You might be better starting off at a low dose and working your way up to your desired dose as some people do not tolerate melatonin well or are sensitive to it. I take 132 mg melatonin per day, but worked up to that level from lower dose levels.
I have not tried or seen an intranasal version. I have seen a vape version, but have not tried it. I have tried topical application and based on studies feel it is a good method.
The dose in the PwP/melatonin study that returned oxidative stress levels and mitochondrial function to healthy control levels used 50 mg/day in two divided doses of 25 mg each.
I agree, there doesn't seem to be much good about the available drugs for AD. I think a wealthy person with AD would be better off visiting a country that will give FMT for AD and get much much better benefits.
' Numerous studies have shown that FMT can improve AD, which may be related to reducing the abundance of pathogenic bacteria, exerting the anti-inflammatory effects, decreasing the deposition of Aβ, regulating synaptic plasticity, increasing short chain fatty acids, and curbing histone acetylation. '
Melatonin in a low dose plays an essential role for me in reducing my PD symptoms. The improvement in my sleep by 1 to 2 hours per night with 1 mg of melatonin before bedtime will certainly contribute indirect to this. Maybe also directly, who will say it. Unfortainly an increase in this dosage leads to side effects, particularly headaches. For the skeptics, it is definitely not a placebo. Every time I had the familiar, too-short Parkinson's night, it turned out that I had forgotten to take my melatonin. It is indispensable, Art!
The study that WhyRBD linked to, suggests that some people are slow metabolizers of melatonin. You perhaps? 😊
It also suggests that taking the melatonin on a rigid schedule is preferable, as that has the best effect on stabilizing circadian rhythms. I linked the full study in my post below
Indeed I may have a slower metabolism of melatonin! This means that the effects of melatonin can last longer in the body. Even with a low dose it can have a longer-lasting impact on sleep / wakefulness and therefore on the PD.
I take 20 mg each night. That, combined with half a teaspoonful of mannitol, a bit of coconut oil and occasional Lithium orotate and B1 have kept some early symptoms at bay for about 7 years now.
“Patients were divided into two groups using random generator software: the melatonin-placebo group and the placebo-melatonin group. The melatonin-placebo group received 25 mg melatonin at noon and 30 minutes before bedtime for three months, followed for four days without treatment (washout period), and then received 25 mg of placebo at noon and 30 min before bed for three months. The placebo-melatonin group received initial placebo during 3 months followed by a washout period and then received melatonin. This melatonin administration dosage and schedule were used in a previous clinical trial of our research group in which the expression of two clock genes (PER1 and BMAL1) were assessed and in which no adverse effects were observed except daytime sleepiness and nighttime problems [11]. Additionally, a control group of thirty clinically healthy individuals was also included to compare the baseline values of the oxidative stress markers and enzymatic activity analyzed in this study”
In the 50 mg study, they took 25 mg at noon and 25 mg 30 minutes before bed. Personally, I would rather take the first dose at 4:00 or 5:00 pm to give some continuity to the two doses, but I don't know their reasoning behind that dosing schedule that they used.
Not me, but others have reported as much. I apparently have low sensitivity to melatonin. I think forum members Jimcaster and Marc are similar in this respect as both take higher dose melatonin. Obtaining melatonin from natural means appears to eliminate this problem. I wrote about multiple ways to get melatonin naturally because that seems to resolve most if not all oral melatonin issues. Here is a link to that article :
Antibody therapy either provides antibodies that help white blood cells attack something in the body, or bind to cell sites to prevent the body from attacking as in autoimmune diseases. With PD I believe the antibody therapies are aimed at stopping the production of the proteins that clump and kill the dopaminergic neurons. Though I believe the newest one that shows promise preserves the liquid protein that is used in immune response while clearing out the clumped ones.
Drugs ending in "mab" are monoclonal antibodies. Ones ending in "nib" are inhibitors. 20 years ago antibody therapy was going to cure everything. Pharma bet big on it and then that crashed when it didn't pan out right away. But researchers like Jim Allison (discovered the T cell receptor back in the early 70s) kept up the work and eventually invented one of the first successful drugs Ipelimumab (Yervoy) for cancer.
These tiny fragments are a breakthrough for autoimmune diseases and will only get better as they are able to tweak them for individuals.
Maybe I asked it wrong, I am extremely familiar with antibodies and interference of catalysts. What I meant was much more specific...what is the posited mechanism with each specific antibody or Ig inhibitor on which experiment's target species/organism and how has that specie been modified for the study? So was it viruses, bugs, mice, or people? Which immunoglobulin inhibitor or antibody? Where the targets modified in any way such as knockout, artificially created disease, disease created by overdose of toxin, etc. and what is the investigated substance supposed to do specifically?
"The tingling or "creepy-crawly" feeling in the legs that often keeps people awake could be worsened by melatonin. The supplement can intensify RLS symptoms because it lowers the amount of dopamine in the brain, according to the Restless Legs Syndrome Foundation."
The quote I posted is for people who have primary RLS. My husband's Is likely another symptom of his parkinsons. We did test melatonin because it has so many good benefits but it did exacerbate his RLS.
I wonder if the exercise with the melatonin is what stops the rls. If I take too much melatonin I go to sleep ok but wake up at about 2am feeling wired.
“The fact that melatonin is available anywhere at low cost provides the perspective of immediate clinical application in patients at risk for clinical synucleinopathy” grrrr not in NZ it’s not without becoming an illegal substance importer.
For me the question would be how would you determine that you had actually altered the rate of disease progression? In PD it seems like some people go through long periods of no to minimal progression and others can go through periods of relatively fast progression. I guess you could do the MDS-UPDRS testing once a month as a potential indicator.
I mean stopping progression entirely would be the main thing. If MDS-UPDRS was staying the same Year over Year for a couple of years and part of your regime was Melatonin it would probably be a good thing to take regularly.
I only know of two forum members who are taking higher dose melatonin, but I don't think either one has been taking it long enough where they would be able to tell if they had halted disease progression.
One of the two 50 mg melatonin studies in people with PD showed that melatonin returned elevated oxidative stress levels in PwP to healthy control levels in 3 months while significantly improving mitochondrial function. Imo, those two things should slow disease progression at a minimum, but that remains unproven.
' Overall, melatonin supplementation for 12 weeks to patients with PD had favorable effects on the UPDRS part I score, PSQI, BDI, BAI, hs-CRP, TAC, GSH, insulin levels, HOMA-IR, total-, LDL-cholesterol, and gene expression of TNF-α, PPAR-γ and LDLR, but did not affect other metabolic profiles. '
I was asking bcuz I've been taking 50mg for 6 months but as you say, can't measure benefit when taking so any other supplements. Hopefully, progression slows but I have progressed. On year 10 of PD diagnosis and just recently added 1mg a day rasagiline to my 25-100 2each/3xday C/L. (of course I exercise and take a slew of supplements)
In the 50 mg melatonin/PD study they used the melatonin in two divided doses of 25 mg each, which is likely to be more effective because melatonin is active for up to about 5 hours after taking it orally. They took the first dose at 12:00 pm and the second dose at 30 minutes before bedtime. This potentially made the melatonin available for up to 10 hours as opposed to just 5 hours. Is this what you are doing?
Quite a while back you had a HU post where you spread out the melatonin over the hours before bed, versus not taking all at once. That’s what I been doing. I have not done 1/2 at 12 pm and 1/2 30 min before bed.
The purpose for that spreading of the dose was to try and mimic pineal gland release of melatonin for the purpose of trying to improve sleep. It does spread the total time that melatonin is available in the system, but not quite all the way to 10 hours as the study dose likely does. Two different dosing schedules for two different purposes.
I've mentioned about that study many times. The 10 mg melatonin/PD study and the two 50 mg melatonin PD studies, but I can see how they would be easy to miss since postings add up quickly on this forum.
This study is about melatonin in relation to PD: sci-hub.se/10.1016/j.clineu.... Conclusions: Overall, melatonin supplementation for 12 weeks to patients with PD had favorable effects on the UPDRS part I score, PSQI, BDI, BAI, hs-CRP, TAC, GSH, insulin levels, HOMA-IR, total-, LDL-cholesterol , and gene expression of TNF-α, PPAR-γ and LDLR, but did not affect other metabolic profiles. I think it's worth a try. The dose used was: 10 mg melatonin (two melatonin capsules, 5 mg each) once a day, 1 h before bedtime for 12 weeks.
I have worked up to 132 mg per day and take that in berry flavored tablets that dissolve in the mouth to try and improve upon the very poor bioavailability of oral melatonin which has been shown to be only 3% in one study.
I've written so much about melatonin on this forum and you can see my profile if you want to read about any of that. Aside from the neuroprotective and mitochondrial protective effects of melatonin, it also protects against cardiovascular disease which people with PD are at increased risk for. It can also help to prevent atherosclerosis and help with recovery from stroke and heart attack.
Melatonin, imo helps the body to maintain homeostasis through multiple methods of action. I'm pretty sure it is the most potent antioxidant that is naturally occurring in the body because its metabolites also have similar antioxidant effects to the main molecule and indirectly, it also activates many of the bodies own potent antioxidants.
It also has potent anti inflammatory effects and for the past year and a half I have been testing topical melatonin and have found that it is very useful for multiple types of pain in joints, muscles and spine. Based on studies, topical melatonin also may have some spinal reparative effects. I worked with a friend who was taking oral melatonin at 360 mg/day that got zero pain relief from that oral dose of melatonin, but when I made him topical melatonin, he got very good pain relief. Based on a study that I read, topical melatonin may be a better delivery method than oral melatonin which only has 3% bioavailability. Topical melatonin, according to the study, starts accumulating in the layers of the stratum corneum and then is slowly dispersed into the blood over a 24 hour period, whereas, oral melatonin is essentially done in about 5 hours or less after you swallow it. I have had about 15 friends try the topical melatonin for pain in various areas of the body and all of them found it useful for the purpose. Overall, I am impressed with topical melatonin and clearly it can reach local tissue levels that even high dose oral melatonin can not. One friend even told me that it got rid of her migraine headache by applying it to areas of her head. She said migraines last her for a week and hers was gone the same day, which she told me never happens for her.
Recently, I have also found that foods that have melatonin in just nanogram levels actually do have positive health effects. Previously I thought that ng levels of melatonin can't possibly offer any health benefits, but I was wrong on that point and apparently melatonin gotten from food sources has good bioavailability and no side effects. To give this statement a little perspective, one milligram equals one million nanograms.
Jas, I could go on and on about melatonin, but like anything else, it will take trial and error testing in order to see what, if anything it can do for you, but even if melatonin could affect PD progression, you very likely would notice no difference.
would you mind sharing a link to the melatonin cream you have had good results with? there's so many on amazon to pick from. some are mixed with magnesium which seems good too
I make the melatonin lotion myself because I make it stronger than most commercial products. I will be writing about it within a week on this forum and explain how to make it easily and relatively inexpensively.
Just to add my pennies worth - I've been taking 24 mg melatonin daily since being diagnosed with PD 2 years ago. Actually , for the first year I took around 60 mg daily. Trouble is I'm taking up to 20 or so other supplements as well, as I expect many others do too! So it's impossible to say with certainty what is doing any good. But I haven't got enough years left to try one at a time 😜. Interestingly I have suffered with RLS in the past but it has now cleared up. Some of the other dozen or so symptoms are getting better and others worse. Too much to list. I can't be sure but I suspect it is the regular Magnesium, both L threonate and glycinate, which has helped the RLS. But it could also be finally balancing the B vitamins, or a combination of everything. Including sinemet 75/300 mg per day. Plus mucuna 350mg x 4. I exercise a lot, running, cycling, yoga, HIT, walks. At least 10 hrs a week, up to 20 hrs. When I had RLS it did not appear to be related to the amount of time spent working out. Luckily (or not) my condition hasn't progressed rapidly over the 2 years since diagnosed. In hindsight the symptoms were there 3 to 4 years before.Oh yes, I've had FMT, use my red light hat daily, on very low carb diet, no rice, potato or pasta, just a few Organic oats and a little fruit. Definitely no added sugar. I have a cue 1, though don't use much anymore, only put it down a sock if I get a touch of RLS. Seems to be a good distraction.
Oh, probably very significant is that I've stopped doing the very stressful job, running out own business.
Interestingly, several people on this forum have reported that melatonin exacerbates their RLS. I guess this varies by individual since it doesn't seem to have worsened your RLS?
would you mind sharing a link to the cream you have had good results with? there's so many on amazon to pick from. some are mixed with magnesium which seems good too
My husband, who passed on with PD at the age of 80, was sun downing. He left in the middle of the night on one occasion and I found him face down in the dirt with hypothermia. He had to be taken to the emergency room by ambulance.
I started giving him 10 mg of melatonin in tablet form at 4 pm and another 10 mg melatonin at 9 pm. He never sun downed again except for one time when my son forgot to give him his first dose until 6pm.
The study linked by WhyRBD on melatonin/RBD is really interesting. I think something very important that it suggests, is that melatonin (in prodromal PD, at least) seems to "work" by virtue of it's chronobiological effects, not it's activity as an antioxidant. As the writer points out, this makes timing of the delivery crucial, and may also mean that very large doses could be counterproductive.
"Because melatonin influences its own receptor (Gerdin et al., 2004), it is important to have a melatonin-free period over the day. Supraphysiologic melatonin doses, especially in low metabolizers, prevent the absence of melatonin during the day and could induce insensitivity in melatonin receptors the next evening (Braam et al., 2010)." medrxiv.org/content/10.1101...
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