Melatonin
★★★★★
This new meta-analysis (10/10/2023) of randomized controlled trials (RCT's) utilizing melatonin in people with PD suggests that melatonin is useful for PD at 10 mg/day and even more so at 50 mg/day or more, and usage length of a year or more is additive to the beneficial effects of melatonin in PD.
Immediate-release melatonin was shown to be superior to prolonged release melatonin. It is also suggested that earlier application of melatonin in the disease may be even more beneficial than application in advanced disease states.
https://www.frontiersin.org/articles/10.3389/fneur.2023.1265789/full
Some relevant quotes from the meta-analysis of RCTs :
' These findings reinforce the rationale of our study, suggesting that melatonin, when used in specific treatment regimens, may alleviate symptom severity and reduce sleep disturbances in Parkinson's disease.'
' Analysis of UPDRS total scores indicate that after at least 12 weeks of treatment, melatonin significantly impacts Parkinson's disease progression when doses of ≥10 mg/day are used. This trend of enhanced melatonin efficacy with higher doses at longer treatment durations has been consistently reported in trails comparing 50 mg/day melatonin with 0.25 mg (61,62) and 50 mg/day melatonin with 5 mg (63) for various outcomes. Furthermore, trials included in our analysis also reported significant results with 50 mg/day melatonin for 1 year (56) and non-significant results with 10 mg/day or 4 mg/day melatonin for 12 weeks (57,58). These findings, supported further by melatonin's ability to exhibit virtually no acute or chronic toxicity (64,65), strongly advocate its long-term utilization at higher doses as a safe choice. '
' Analysis of UPDRS total scores in groups receiving melatonin ≥10 mg/day revealed significant results with no heterogeneity (I2 = 0%). However, including studies with <10 mg doses increased heterogeneity substantially (I2 = 63%). Potential contributors may include dose-dependent and formulation-dependent pharmacokinetics of melatonin, as low dose studies used prolonged release formulations and high dose studies used immediate release formulations (44). Moreover, variations in treatment duration could also play a role, as longer durations with higher doses consistently demonstrated enhanced efficacy in previous studies (56–58). '
' Apart from dosage and duration, a crucial difference among these trails was the timing of melatonin intervention. In the significant study (56), melatonin was initiated in newly diagnosed patients immediately after observing a satisfactory response to anti-Parkinson's therapy. In contrast, patients in non-significant studies (57,58) had mean disease duration of 5.7 ± 1.9 and 5.0 ± 3.9 years respectively, indicating significant pre-existing damage at the time of melatonin introduction. This selection of patients with longer disease duration and introduction of melatonin at a later stage reveal an inherent flaw, as starting melatonin before neuronal loss is crucial for its free radical scavenging and antioxidant properties (18,19,31,33,42) to effectively prevent degeneration and reduce symptom severity in Parkinson's disease. In addition, a sub-analysis focusing on only immediate-release formulations, also yielded significant results, however, use of prolonged-release formulation in only one study (58) hinders appropriate comparisons. '
' Hence, melatonin can indirectly lead to an improvement in motor symptoms through sleep improvement. This effect appears to be unrelated to its antioxidant properties, indicating a multifaceted potential for melatonin in Parkinson's disease treatment. '
' As far as we know, a systematic categorization of melatonin into dose groups for motor symptoms and sleep disturbances in Parkinson's disease has not been conducted before, and is a defining feature of this meta-analysis. Furthermore, it strongly recommends the use of long-term, high-dose immediate-release melatonin in future investigations and emphasizes the significance of selecting patients with shorter disease duration and initiating melatonin early to fully explore its true therapeutic potential. '
::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::
My favorite quote from this meta-analysis:
' These findings, supported further by melatonin's ability to exhibit virtually no acute or chronic toxicity (64,65), strongly advocate its long-term utilization at higher doses as a safe choice. '
I'm glad to see studies confirming the potential of melatonin in PwP, whereas earlier studies only hinted at such possibilities based on the known healthful methods of action of melatonin in humans.
Art
Melatonin
★★★★★
Now I would like to talk about one of my favorite supplements, melatonin, that a recent randomized, double-blind, placebo-controlled study showed was beneficial for PD patients after just 12 weeks of supplementing only 10 milligrams per night! Yes, finally, a quality human study confirming that melatonin is beneficial for people with PD.
This study showed multiple benefits in patients that include the following. Using standard testing, melatonin showed improvement in anxiety, depression, total antioxidant capacity, increased glutathione, and improved UPDRS Part 1 test results! Melatonin also significantly lowered the inflammatory marker, hs-CRP, or high sensitivity C-Reactive Protein and inflammatory TNF-a while lowering LDL cholesterol and improving insulin resistance! Some of these improvements are suggestive of the idea that a more extensive study and or higher dosing may produce even better results because many of these improvements imply a reduction in total oxidative stress and oxidative stress is one of the most damaging factors in PD that destroys dopaminergic neurons and other cells in the substantia nigra of the brain.
To say I am excited that this study would be an understatement! Studies showing benefits like these in humans with PD from a single supplement are almost non-existent. Hopefully, they will follow through on this study with similar studies using pharmacological dosing of melatonin and more extended length studies.
While this study is very good and confirmed that melatonin can be beneficial in people with PD, it leaves many unanswered questions such as what would have happened if the study had been 24 weeks long instead of 12 as 12 weeks is very short for a study like this? Would the benefits range increase, would the benefits stay the same or increase the level of improvement seen? What would have happened at higher dosing?
Remember that Dr. Shallenberger is using dosing that is as much as 36 times higher than what was used in this study in some of his patients, and he gives all of his patients 180 mg of melatonin per night in the form of three 60 mg capsules in the evening. He considers this a preventative dose.
Overall, I feel this study has opened a door that has been closed for too long, and hopefully, there will be follow up studies to answer these questions! Here is a link to that very recent study abstract :
https://pubmed.ncbi.nlm.nih.gov/32417629/
Art
Probiotics
★★★★★
I wrote the following on another health forum and it was specifically with Parkinson's Disease in mind but the information applies to many health issues and may be useful for general health improvement!
::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::
There are many potential reasons why probiotics, prebiotics and synbiotics may be useful for PWPs. Although the great majority of PD / probiotic studies involve animals, there are many human studies that show benefits that would definitely be useful for PWPs!
This video brilliantly explains why glutathione is important for PWPs:
https://www.youtube.com/watch?v=KWuOezgVHdI
In this first study, it is shown that probiotics increase glutathione production.......something that every PWP can definitely use because glutathione is a highly potent antioxidant and radical scavenger which is often at suboptimal levels in PWPs! In studies, glutathione has shown great benefit for PWPs and one doctor has used glutathione to very good effect in some of his PD patients as has already been shown in other posts here on this forum. The problem with glutathione is that you can not just take a supplement of it because it will not do well as it passes through the gut. There are even lypospheric glutathione products out there to try and overcome the gut issue. There are also injections and infusions, but these are not very practical for long term use, but probiotics are doable for this purpose.
https://www.ncbi.nlm.nih.gov/pubmed/21058502
In these next studies, it is shown that probiotics reduce high sensitivity C reactive protein or hsCRP, which is a common marker used to determine inflammation levels. PWPs can definitely have a use for reduced inflammatory levels which are elevated and neuro damaging in PWPs.There are B-vitamins that can help reduce hsCRP, but one or two are sometimes contraindicated with certain PD meds.
https://www.ncbi.nlm.nih.gov/pubmed/25453395
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4573418/
https://www.ncbi.nlm.nih.gov/pubmed/23899653
Two very common symptoms of PD is depression and anxiety and these two do not get discussed enough considering how prevalent they are in PWPs. The next study shows how probiotics can reduce both!
https://www.ncbi.nlm.nih.gov/pubmed/25470391
Inflammation is a major player in PWPs who generally have elevated levels of inflammation, but other things can add to the total inflammatory load in the body, such as arthritis. In PD, it is well established that exercise is highly beneficial, but arthritis makes exercising difficult if not impossible for PWPs. On that note, the following study suggests that probiotics can lower the inflammatory load and symptoms related to arthritis!
https://www.ncbi.nlm.nih.gov/pubmed/24355439
Along those same lines, any disease that raises inflammation and oxidatative stress levels is going to be counter productive or disease worsening for PWPs and diabetes would be one such common disease. The following study suggests that probiotics can ameliorate many symptoms associated with diabetes including inflammation, insulin resistance, oxidative stress and reduce intestinal permeability, a very common problem in PWPs, as many of you already know! These activities of probiotics also improve insulin sensitivity, which anyone with diabetes can truly appreciate the value of. Improved insulin sensitivity can help to lower the total inflammatory burden of the body!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4078018/
Since it is already established that moderate to heavy aerobic exercise can be quite beneficial for PWPs, something that will help reduce the muscle damage associated with this type of exercise would be very useful for PWPs in order to get the most out of the exercise you do, and probiotics may be just the thing according to this next study.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963221/
Neurodegeneration is a hallmark aspect of PD and probiotics have a broad spectrum of health benefits of which neuroprotection is one along with antioxidant improving, oxidative stress lowering, GABA increasing and increased dopamine levels as outlined in the following abstract!
https://www.ncbi.nlm.nih.gov/pubmed/26450608
The following two studies add to that line of thinking.
https://www.ncbi.nlm.nih.gov/pubmed/29492848
https://www.ncbi.nlm.nih.gov/pubmed/29154736
It is well known that many PWPs have a disturbed gut microbiome and constipation and other gut disturbances are common symptoms of this disease. Probiotics have the ability to help in this area also according to the following.
https://www.ncbi.nlm.nih.gov/pubmed/21587143
https://www.ncbi.nlm.nih.gov/pubmed/19083380
Psychological stress can worsen symptoms of PD and probiotics can help to ameliorate psychological stress according to the following abstract.
https://www.ncbi.nlm.nih.gov/pubmed/25224893
Given the typical age range of PWPs, it can be considered that this group may also have elevated LDL cholesterol, VLDL, and tryglycerides while having reduced HDL cholesterol (the good one). Doctors typically prescribe statin drugs to try and normalize cholesterol levels, but statins are well known for their bad effects on muscle tissue and muscle pain in some people which can be a major setback for PWPs. Probiotics are quite effective at not only lowering LDL, VLDL and tryglycerides, but also elevating HDL cholesterol according to the following study!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984795/
PWPs in general have a disturbed microbiome that can create other health issues which I discussed previously in an earlier post about mannitol at this link:
That post discussed the fact that prebiotics like mannitol can increase the production of thiamine, hydrogen sulfide (H2S) and butyrate of which all three are important in terms of symptom relief in PWPs........hugely important!
There is much more I can say about probiotics, prebiotics, synbiotics, fermented foods and the like in terms of overall health benefits, but I think the above is more than enough to highlight the potential of these health supplements as it applies to PWPs and other disease states!
If your neurologist told you he/she could prescribe one drug that has the potential to lower hsCRP, raise glutathione, lower inflammatory markers, increase insulin sensitivity, reduce or eliminate constipation, restore the gut microbiome to a healthier state, increase dopamine levels, reduce stress, reduce anxiety, reduce depression, reduce tryglycerides, increase HDL cholesterol, act as a neuroprotectant and help with arthritis symptoms and diabetes, would you tell your neurologist that you are not interested?
Something that PWPs have to deal with is the amount of pills they have to take everyday, so finding pills that have multiple benefits in one pill is useful and can potentially make it easier to stick to your regimen while reducing symptoms with minimal side effects, if any!
Art
Vitamin D
★★★★★
Mucuna Pruriens
★★★★★