Somebody in my REM Sleep Behavior Disorder group mentioned how Magnolia Bark Extract has stopped their episodes. I don't know for how long but I am trying to find out. In the mean time:
Therapeutic effects of honokiol on motor impairment in hemiparkinsonian mice are associated with reversing neurodegeneration and targeting PPARγ regulation 2018 sciencedirect.com/science/a... "The aim of this study was to investigate the therapeutic abilities of honokiol on hemiparkinsonian mouse model by means of motor behavioral testing, animal PET brain imaging, and histopathological staining. We discovered that subchronic honokiol treatment significantly ameliorated motor deficit, progressive loss of nigrostriatal DA neurons, and biochemical variations in a mouse model of PD induced by 6−OHDA. The [18F]FP-(+)-DTBZ PET evaluation further revealed recovery of VMAT2 expression that is reflected by reversal of DA neuron degeneration after honokiol treatment. The revolution of striatal DA neuron degeneration rehabilitated by subchronic honokiol treatment was also accompanied by reduction in oxidation and astrogliosis. However, PPARγ antagonist partly reduced the rehabilitating effects of honokiol on motor dysfunction and a decreased PPARγ expression, suggesting that PPARγ signaling could serve as a viable therapeutic target. Importantly, subchronic honokiol treatment promoted the survival of mice lesioned by 6−OHDA. Therefore, these results extend our previous findings in neuronal protective actions of honokiol and support that PPARγ signaling activated by honokiol might involve in restorative potential for treatment of motor impairments and neurodegeneration in PD."
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Inhibitory effects of magnolol and honokiol on human calcitonin aggregation 2015 nature.com/articles/srep13556 "In summary, our studies indicated Mag and Hon inhibited the oligomerization and fibrillation of hCT, disassembled hCT aggregates at higher molar ratios and more importantly, reduced membrane disruption and cytotoxicity induced by hCT aggregates. Our results suggested a potential anti-amyloidogenic property of Mag and Hon and polyphenols with a biphenyl backbone may further be explored to design effective anti-amyloidosis compounds."
A good animal model for a change. I shall have to investigate further:
"Subchronic honokiol administration for 1–2 weeks, beginning 7 days after 6−OHDA-lesion, dose-dependently ameliorated motor dysfunction in hemiparkinsonian mice"
Therapeutic effects of honokiol on motor impairment in hemiparkinsonian mice are associated with reversing neurodegeneration and targeting PPARγ regulation
"Subchronic honokiol treatment (0.1–5 mg/kg) for 14days significantly and dose-dependently ameliorated the nigrostriatal neuronal loss in 6−OHDA-lesioned hemisphere ...Consistently, the decreased DAT expression in striatum lesioned by 6−OHDA was also dose-dependently rescued by subchronic honokiol treatment for 14 days (Fig. 1E)....
"Conclusions
Taken altogether, the present results demonstrated that subchronic honokiol treatment could extend animal survival in PD mice and exhibit multiple therapeutic activities to restore normal motor function and behavior, rescue DA neuron degeneration, reduce oxidative response and atrocity activation, as well as rehabilitate PPARγ expression. Therefore, honokiol may represent a promising therapeutic agent for management of neurodegeneration and PD, at least in part through PPARγ signaling pathway."
The maximum dosage used in the mouse model was five milligrams per kilogram. Without dosage adjustment this would amount to 250 milligrams for a 50 kilogram human. Normally mouse dosage is divided by 12 to arrive at human dosage. However, 250 milligrams is a reasonable dose and I am inclined to go with that. Most magnolia bark extracts have minuscule amounts of honokiol, however there is one product available at Amazon that is pure honokiol. Not cheap but it is worth it if it works.
" intervention trials employing concentrated MBE for up to 1 y did not report adverse effects. In conclusion, over the recent years different food safety authorities evaluated magnolol and honokiol and considered them safe."
Other benefits:
Many Amazon reviewers saying it helped them to get good sleep. Also studies showing anticancer properties.
I am going to give this a try will post a report if I get benefit.
The person on FB that clued me in uses NutriCology Magnolia Extract, $50 for 120 (4 months worth), but you can't tell what percentage is Honokiol and what is Magnolol. amazon.com/Nutricology-Magn...
This one is similar, amazon.com/dp/B005GCLJ4S/?c... , and the seller says it is 92 mg of Honokiol in the Q and A. $50 for 120. I kind of like the idea of getting both Honokiol and Magnolol. I will do more research on that Honokiol content.
Here is a different study from 2017. I think you will appreciate the methodology: Quantitative analysis of the therapeutic effect of magnolol on MPTP-induced mouse model of Parkinson’s disease using in vivo 18F-9-fluoropropyl-(+)-dihydrotetrabenazine PET imaging journals.plos.org/plosone/a...
"Abstract
18F-9-Fluoropropyl-(+)-dihydrotetrabenazine [18F-FP-(+)-DTBZ] positron emission tomography (PET) has been shown to detect dopaminergic neuron loss associated with Parkinson’s disease (PD) in human and neurotoxin-induced animal models. A polyphenol compound, magnolol, was recently proposed as having a potentially restorative effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- or 6-hydroxydopamine-treated animal models. In this study, 18F-FP-(+)-DTBZ PET was used to determine the therapeutic efficacy of magnolol in an MPTP–PD mouse model that was prepared by giving an intraperitoneally (i.p.) daily dose of 25 mg/kg MPTP to male C57BL/6 mice for 5 consecutive days. Twenty-minute static 18F-FP-(+)-DTBZ PET scans were performed before MPTP treatment and 5 days after the termination of MPTP treatment to set up the baseline control. Half of the MPTP-treated mice then received a daily dose of magnolol (10 mg/kg dissolved in corn oil, i.p.) for 6 days. 18F-FP-(+)-DTBZ PET imaging was performed the day after the final treatment. All 18F-FP-(+)-DTBZ PET images were analysed and the specific uptake ratio (SUr) was calculated. Ex vivo autoradiography (ARG) and corresponding immunohistochemistry (IHC) studies were conducted to confirm the distribution of dopaminergic terminals in the striatum. The striatal SUr ratios of 18F-FP-(+)-DTBZ PET images for the Sham, the MPTP, and the MPTP + Magnolol-treated groups were 1.25 ± 0.05, 0.75 ± 0.06, and 1.00 ± 0.11, respectively (n = 4 for each group). The ex vivo 18F-FP-(+)-DTBZ ARG and IHC results correlated favourably with the PET imaging results. 18F-FP-(+)-DTBZ PET imaging suggested that magnolol post-treatment may reverse the neuronal damage in the MPTP-lesioned PD mice. In vivo imaging of the striatal vesicular monoamine transporter type 2 (VMAT2) distribution using 18F-FP-(+)-DTBZ animal PET is a useful method to evaluate the efficacy of therapeutic drugs i.e., magnolol, for the management of PD."
Recently, we have read about L-Serine, Huperzine-A, L-Theanine, etc. It confuses me more when I read about new nootropics that I haven't heard of before until now. I can't decide which supplement/nootropic is best for PD mental health. However, I trust your judgment, PB, and I will have my husband try it. A little expensive, but it might worth trying it. Depression is one of his symptoms and my aim is to improve his depression.
It's Magnolia Bark vs Melatonin? They both have similar effects.
PS. My neighborhood is flooded with Magnolias and their beautiful flowers!
PS1. I am watching a TV program: "Sweet Magnolias"
Definitely intriguing, very much looking forward to for the developments by PB and anybody else on this. There's a certain ringtone. I wonder how it would compare with clonazepam for RBD, which is what male has been prescribing me for mine. Very small doses do the trip but there is that morning after effect.
I have previously advocated a cautious route for similar reasons.
But..you'll never eliminate the causes. Those of us with PD have, in my own amateur view, a genetic susceptibility to damage from the environment that most humans do not have. Remember, only 2 percent of ppl that make 65 get PD (or show it, anyway. Perhaps there's another 18 percent that have the disease at 65 but aren't showing it yet or die of something else before they do. Even then we are only at 20%). Yet everyone is growing up surrounded by the same pollution, eating more or less the same food, and having similar emotional experiences/trauma, having the same ankle injuries, contracting the same common viruses, being exposed to the same fungi, and having largely the same other experiences that people often attribute their PD too.
Yet most don't develop PD (or the symptoms), even those that live into their 80s. Consequently there is something different about us and it is far too late to correct that difference (it would probably require an intervention before you are born*).
I get why people are willing to roll the dice, and BU/PB are definitely dedicated and well informed.
Can you please elaborate on what you are doing to eliminate causes of progression? I have eliminated or at least greatly reduced a lot myself. No alcohol, no gluten, no grains at all, etc etc
I'm not an enthusiast for the quality of her data, for various reasons I have expressed before (and some I'm sure disagree with me anyway), but in 2017 Mischley wrote:
"Using the food frequency questionnaire, the results of this analysis suggest that a plant- and fish-based diet is associated with the lowest PD severity score (Table 2). Fresh vegetables, fresh fruit, nuts and seeds, fish, olive oil, wine, coconut oil, fresh herbs, and the use of spices were all associated with statistically significant lower rates of disease progression."
I'm sure she has more recently published data but I have difficulty finding it.
Among different ways to be cautious, is the avoidance of products that can hurt us. I use on purpose very generic words. Because we should avoid indeed unsafe food, drinks , behaviours, behaviours of others, medications, supplements.
Even with predisposing genetic factors, to my opinion in many cases additional factors work together to affect us. One should also not forget that safety does not just refer to our brain, to dopaminergic neurons’, but also to the rest of our body. We have a few additional organs to preserve.
I don’t want to frighten anybody have people spend all day waking hours on their health.
I just feel that there is some Street intelligence in first using what has been already tried rather than starting something from scratch due to the unknown safety of new chemical entities. Their origin in nature doesn’t provide any guarantee.
Sorry if I sound like excessively worried. I am not 😀
I'm not sure why you are invoking the fallacy of nature here. I haven't seen anyone in this thread falling victim to it.
"I just feel that there is some Street intelligence in first using what has been already tried"
Would you mind listing these things?
These guys talk about stuff like this here. It's part of the appeal. They aren't advising people on the use of any of it. I would agree that would be an issue, if they started prescribing this stuff. But that isn't likely. Hell, BU mentions his lack of tertiary education in every second thread.
I don't disagree with you cautious perspective, but I understand why some people are willing to take risks. Not sure how much I'm gonna want my other organs functioning when I've got PDD and no mobility whatsoever.
Exactly kevowpd. If I had to bet, I would bet there is no solution. But I am forced to bet that there IS a solution. So if I have to bet there IS a solution, I would bet that it is a solution (or combination of solutions) that have not been tried yet.
And if it is a combination of solutions, I have to think the most common combinations have been tried. So then I have to think about what I can bring in from left field to get myself out of the already tried combinations and into some unique combination that might help.
Indeed I had not seen the note on safety review. Caution is safe though :-)Blame me for advising to be cautious. Surely it is for free and it is not a judgement on people attitude, Caring for each other is nothing wrong. We are not on the border between Russia and Ukraine :-(. My thoughts are with them.
Personally, I still have "tried solutions" I didn't try yet. Such as but not limited to the red light therapy. I also"forgot" to exercise for close to 2 years.
I am giving at least 6-8 weeks of optimal dosing before moving to the next option. Frankly my plan looks better here on the paper than in real life.
Caution is good. I encourage people to stand up for caution.
I like your idea of giving things 6 weeks. 6 weeks might not even be long enough as if the protocol is halting progression (a lofty goal) you may not notice anything.
Now that I pretty much have my list of protocols down, I am hoping I can tweak and gradually remove things.
Agreed. As hard as it is, I think you need to find things that make sense to your understanding of what needs to be fixed and give them some time.
I've gone back to incorporating Zeolite into my stack even though I have never seen a benefit (and it may be acting as a super antigen, which I think would be bad) because I have read a lot about it and what I think it does seems to me like it should be helping. That was a heckofa run on sentence.
Please remind me why you are using zeolite? As an iron chelator? Doesn’t it metaphorically vacuum up everything? Whatever supplements you are taking , nutrients you are eating are being whisked off by the zeolite, I thought ? Please correct me if I’m wrong?
Please note I said 6-8 weeks of optimal dosing.How much time you need to get there is another question. But a few comments on the time needed for disease modification:
- assuming it is anything helping without a change of dopamine levels in the synapse.
- I have experienced symptoms' improvement with mannitol 2 weeks after starting it. On the other hand the improvement continuito evolve for several months.
- After I deteriorated during confinement I made myself a new plan to"bring myself back to baseline".
I wanted to have enough time before I start the next agent, but then I realized that the door could be closed whilst I was waiting. So we need to find a trade-off between both.
There's a big difference between talking about this as a physician or a scientist, and as a patient. This is our brain that is on the table.
Found a perioperative warning on the Natural Medicines Database:
Theoretically, magnolia might cause additive CNS depression and/or excessive bleeding when used perioperatively. Magnolia might have CNS depressant and antiplatelet effects (11946,11952,18273). Tell patients to discontinue magnolia at least 2 weeks before elective surgical procedures
My HWP has magnolia bark combined with PEA for pain in a como pill. No major improvment for nerve pain.
Honokiol is a sirt3 activator, quite unusual, I remember it coming up in a list of sirt3 activators I looked at some time ago. Sirt3 could be an important pathway of PD pathology, even speculated as underlying causative I think, but I'm sure you'll do the research!
Honokiol, a dual SIRT3 activator and PPAR-γ agonist, attenuated the markers of oxidative stress, improved cellular antioxidant defense systems, and altered the AMPK pathway, leading to enhanced mitochondrial functions thereby having a modulatory effect on amyloidogenic pathway and eventually decreasing Aβ levels.
More interesting information: Honokiol and Magnolol Increased Hippocampal Acetylcholine Release in Freely-Moving Rats worldscientific.com/doi/abs...
"Honokiol and magnolol, phenolic compounds isolated from the stem bark of Magnolia officinalis, have been demonstrated to increase choline acetyltransferase activity, inhibit acetylcholinesterase, promote potassium-induced acetylcholine release and exhibit neurotrophic function in in vitro studies."
And then this: Choline acetyltransferase activity and striatal dopamine receptors in Parkinson's disease in relation to cognitive impairment link.springer.com/article/1...
"ChAT activity in PD was reduced in all brain areas examined, being 51% of the control mean in the hippocampus (P<0.001), 57% in the prefrontal cortex (P<0.001) and 64% in the temporal cortex (P<0.001)."
Lot's of good stuff in there, but I want to share the cautions:
"Honokiol is not entirely without risks, although its limited empirical application to humans at therapeutic doses has limited the evaluation of its side effect profile thus far. There are potential risks that can be expected, including increased bleeding and potential neurotoxicity at high doses. Honokiol has been found to be a potent inhibitor of arterial thrombosis, so it may be advisable to avoid honokiol in coagulopathic patients or in those where bleeding or hemorrhage may be of concern (13). These may include patients with hemorrhagic stroke, patients with hemorrhagic changes following ischemic stroke, patients on coumadin or therapeutic lovenox, and patients with clotting disorders such as hemophilia or von Willebrand’s deficiency. And, while honokiol has been found to have neuroprotective effects at low doses, it has also been found to increase neuronal death in vitro at higher doses (100 μM applied directly to fetal cortical neurons) (38). This suggests a need to further study its pharmacokinetic and pharmacodynamic parameters in humans before unintentionally administering a potentially toxic dose of this compound."
This study actually used AICAR (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside) is a substance produced naturally by the body that stimulates AMP activated protein kinase (AMPK), a protein that regulates metabolism in a variety of ways. AMPK acts as an energy regulator and is activated during exercise or other circumstances that use up cellular energy. usada.org/spirit-of-sport/e...
I have not made a decision yet. I am still debating between Honokiol and a combination Honokiol and Magnolol combined. And then I need to find a good one that is not too expensive.
"Our 90% Honokiol Magnolia Extract meets the standards set for scientific research. You'll find the same high standardization in supplements sold through health practitioners but at much higher prices."
Wow, OK just bought some to try on my Mum (MSA). As mentioned above, I looked into this a few months ago from the sirt3 angle, but didnt buy as I thought it was too speculative at the time, and quite expensive. So thanks for the link to cheaper product (also cheap here in the UK), and to you Bolt for all the amazing research, I think time to give it a try. Bolt, what dose are you intending to take? I noticed on the more expensive honopure product that it states a 250mg capsule 1-2 times/day.
I am no expert, but I read somewhere that too much can damage neurons, so I will go with one capsule before bed. I am trying to stop my REM Sleep Behavior Disorder.
Honopure seems to be more effective and based on the research you posted sounded really good. I had a bottle in the cupboard and only started after I read your posts. I had bought it together with the pectasol C from econugenics . My husband was on melatonin for 2 years up to a dose of 60 mg then cut back to 10 mg to completely off this year. But Honopure helped his active dreams so sleep is much better and he wakes up not fatigued. As you know fatigue is the big elephant in the room.
Do you have any links to reports suggesting Tryptophan supplementation for PD? I have been looking. All I have found is that Tryptophan might be a drug "target".
Since c/l induces serotonin deficit over time, it's a good proactive measure for someone as dedicated as you but finding a good balance may be challenging so err on the conservative side.
ncbi.nlm.nih.gov/pmc/articl..
This a reply from Rescuema. I am not getting Tryptophan, instead I am ordering 5-PTH.
Just an FYI he doesn’t know what acetylcholine is or glutamate excitoxicity. I suggested that supplementing with acetylcholine might reduce PWP need for CL and therefore help enable them to try his therapy that reduces dopamine. He didn’t know what it was.
I’m not saying his theory is wrong. I think he had some valid and interesting points but …
He's a cardiologist. I wasn't the least bit surprised that his ability to answer questions outside of his specific PD focus was fairly limited. Not a criticism, to be expected.
There's more excitement (on this forum, anyway) around his work than is warranted, in my view. He has successfully marketed himself as an outsider going up against the 'experts' (where we aren't happy with the experts because they haven't produced a disease modifying treatment) and everyone loves a story like that.
If he's able to undertake some original research (all he has done so far is a literature review) then he will contribute to the body of knowledge but if the question is "are the thousands of people that have contributed to the generally accepted position wrong and am I right" then the answer is probably "no", as it almost always is.
Thanks Rescue, I had looked at that article, but I just make it as far as
"RECAP #1: Tryptophan is an essential amino acid that is involved in the kynurenine pathway. Kynurenine plays a critical role in generating energy in cells.
Intermediates (also called metabolites) in the biological processes of the kynurenine pathway have been found to have positive and negative properties. The balance of these metabolites is shifted in the brain in some cases of Parkinson’s."
and they take a turn towards TDO inhibition. I get that TDO degrades tryptophan but don't see them mentioning supplementing tryptophan (which makes sense to me, but I would expect a mention of it).
Simon went as far as this bit“Next the researchers wanted to test whether the accumulation of tryptophan was involved in regulating proteotoxicity, rather than TDO itself. By supplementing the food of the C. elegans with increasing amounts of tryptophan, the investigators observed a dose-dependent suppression of the alpha synuclein toxicity. This result suggested to them that the inhibition of TDO regulates proteotoxicity by increasing tryptophan levels.”
Wow, they actually did a trial where they depleted tryptophan. Terminated it due to having the opposite effect of goals. clinicaltrials.gov/ct2/show...
No I have not. Just read yr post about ordering it. I will hv to read up on what it does. I am still thinking about how amazing Honopure is to be able to stop my husband thrashing around in bed fighting off abductors. It must be doing something good to the brain.
I had hoped that tryptophan would reduce his fatigue but it did not seem to do anything. It was a 1000 mg horse pill and I was terrified that he would choke on it. Hence it was abandoned.
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