My husband started 1 tblsp of mannitol per day a month ago.
He responded immediately with a lot more energy, mobility, cognitive clarity, balance....many improvements.
He’s had Parkinson’s for 14 years, and at this point any spike in his dopamine levels causes hallucinations. If he gets too much he goes into a psychotic state. We normally manage it very closely, and lower his dose of Rytary or stop his High dose Thiamine supplements and these resolve in a day or two, then he goes back to his normal meds.
1 week after starting mannitol, the hallucinations started, implying that his dopamine levels had gone too high. We reduced his Rytary. This worked for 2 weeks and then hallucinations returned, so we also reduced his Neupro patch. Last week, even with all of these reductions, the hallucinations are back, so we stopped Mannitol.
This week he is almost on no Parkinson’s meds, (2 mg of Neupro only) still moving pretty well, and still having mild hallucinations, though I think these are resolving.
It could always be other things going on, but it seems like mannitol is significantly increasing his blood dopamine levels. Has anyone had any experience like this?
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LeharLover62
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Which brand of mannitol does he take? I've tried BioFinest (good results from first bag purchased, not as good from second) and Mannitol Balance (horrible digestive upset).
" it seems like mannitol is significantly increasing his blood dopamine levels."
No.
Mannitol is a polyol simple sugar which has no direct impact on increasing or decreasing dopamine levels. It does impact (disrupt) the transport of blood borne substances across the BBB in terms of changing the permeability of the BBB.
However, given mannitol's short half life, oral ingestion (versus infusion) probably leads to minimal impact on transport across the BBB.
Mannitol's best and most valuable function is as an a-synuclein (a-syn) aggregation inhibitor.
It isn't that simple. Multiple variables influence dopamine levels.
Post et al (2018) discusses this complexity by examining calcium ions, dopamine, and a-syn.
Or is mannitol in some complex way impacting a-syn aggregation (either way) with the result that the brain has fewer Lewy bodies meaning slower development of Lewy Body Dementia (with all of its side effects)? If so, is the dysfunction of dopamine a independent variable in the progression of PD?
I would expect that hallucinations, vivid dreams are indicating an increase of dopamine levels in the brain. This can occur if BBB permeability is increased, letting more levodopa enter. If this is true, doesn't look like a good thing in general terms because levodopa will not probably be the only substance increased in brain
While for those who have seen an improvement of their condition and lucidity, may it be that mannitol drain capability helps to detox/clean up neurons' metabolites?
Mannitol is a BBB "disrupter" which means it allows molecules of larger size to pass through the the BBB (which ordinarily they could not), which is both good and bad.
Much more importantly, Mannitol acts as A POTENT ALPHA-SYNUCLEIN AGGREGATION INHIBITOR (in the PD theory of a-syn).
Specific drugs like cocaine, opioids, and DRIs induce increases in extracellular dopamine without the use of l-dopa.
SCZ = schizophrenia (the state of being out of touch with reality to an extreme)
"then use of Mannitol is not suggested if taking L/C and also DA (= Dopamine Agonistics), for its potential interaction with other drugs?"
I never implied or stated that.
I have never read any medical literature or talked to a neuro that states that Mannitol is contraindicated with any DA or C/L drug or contraindicated in general for PD. It is basically and chemically a simple sugar....in SMALL AMOUNTS ( I wrote small in caps for a reason) it may assist l-dopa in passing across or through the BBB.
However, it is not a blanket endorsement of using mannitol anytime, anywhere....
Some people don't like taking mannitol with magnesium...
In general, Avoid with salicylates/NSAIDS/Celecoxib/corticosteriods especially when experiencing renal insufficiency or with any opioids or with diuretics.
More specifically....
1) If you take mannitol by IV at a "very" rapid rate it can cause hypOtension and/or congestive heart failure (but who takes mannitol by IV on their own?)
2) If you have acute renal failure, mannitol should be taken under professional medical observation and delivery only....obviously.
3) If you are on blood pressure medications, or have severe CVD, plus PD, or ICP/IC bleeding problems it is always best to avoid mannitol.
Thank you. I didn’t mean to say that “you implied or stated that”. Hope you understand the need of keeping the sentences short with the difficulties of writing in my not native language
It’s so hard to know what’s happening here without further research. We stopped mannitol for 11 days while he was on an antibiotic, and he needed to increase his C/L dosage again by day 9 or so due to worsening Parkinson’s symptoms (stiffness, poor movement, poor speech.) We’re going to start mannitol again now and see how it goes....but monitoring very carefully. I did ask his doctor who prescribed the antibiotic and she didn’t think mannitol could harm him but it’s obviously having some kind of an effect.
Another good source of drug interactions if you do not have a close MSD is your Pharmacist. Mine searched for an issue I had with Magnesium and had the info in minutes.
PD patients as they progress have very low and lower dopamine levels for a variety of reasons. In my support groups, Those on Sinemet exclusively have never expressed concerns about hallucinations.
Those PD patients who have extreme DA, anti-psychotic, anti-anxiety drug protocols sometimes express hallucination, extreme dreams, visions, etc. which is understandable given those drugs or their combinations.
Therefore I believe this condition is drug induced, not from extreme levels of dopamine.
This is also very interesting. I had heard that DAs were higher risk for hallucinations and have hoped to try to get him off Neupro. Now he’s down to a low dose so maybe we should go all the way.
14 years into PD, visual hallucinations and delusions are common. I doubt it has much to do with any drug(s) he is taking although certain drugs like anti-psychotics and anti-cholinergics (Benadryl is associated with a significant increase in dementia in the elderly leading to hallucinations), can easily cause them (more likely increase them).
Keep a journal where you track any hallucinations, frequency after mediation, duration, etc. You may find an answer with eliminating Neupro. Maybe.... then maybe not.
A clinical study (N = 199) was conducted to establish the efficacy of pimavanserin (Nuplazid). It did NOT change UPDRS part 2 and 3 scores, but it did reduce # of hallucinations.
PLEASE NOTE --- Pimavanserin (NUPLAZID) contains a boxed warning for increased mortality in elderly patients (65 years of age or older) with dementia-related psychosis. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death for a variety of reasons.
Doesn't even that kind of supposition, that in a very short time an established dementia (lewy body) suddenly (a week, or two) noticeably diminishes dementia and side effects, out of development process already long established? Sounds like a magical trip to the past, undoing an entire development process (and brain-wide no less?) would have to happen. That's a lot of change to ascribe to a sugar, and in such a short time. And such interesting different results from a single manufacturer, in one case, and three entirely distinct manufacturers, in another part of the discussion.
So I suspect you are being politely told: a lot of mind bending has to occur to attribute all these effects of a PD mechanism inside a small part of the brain, so probably something else has to be going on, which sounds about right to me.
So let's go back to your intro.
1. How do you know, at any time at all, that there is a "spike in his dopamine levels"? And from what level, and is that a stable level, and is there anything else that seems to be going on some time before these episodes that hasn't been noticed but might be consistently present or absent, anything at all?
2, Have you ever seen such changes when the only thing different is the presence of mannitol, i.e., no change in any other medication or substance entering or leaving his body? The more differences that simultaneously occur, the very much more complex the situation for determining whether any of them have participated in effecting a change, including all the possible combinations that could simultaneously vary.
3. What other patterns in his life occur and what do they "do" before, during, and after these times, how do they change during these episodes and then the return to whatever you would call his baseline? And for that matter, what is his "baseline" in detail in the first place?
4. What all other diagnoses and conditions does he have, when did they start, what has been their course, over what time period for each, what treatments has he had and by whom, and with what course of response to those treatments?
5. What's his entire physical and medical history, and what's his age? Actually, this should be step 1, at least it should be first in order.
As you can see, there are quite a lot of blanks to fill in before any sort of responsible exploring, and that word, as mild as I can make it, should be taken extremely advisably, never a good idea in the case of someone who can become abruptly unstable in the extreme you mentioned in so short a time, because much is at risk and very good, close capable care must be immediately close at hand, for very close and proficient, effective care has to be present to keep the risk to the patient and people nearby safe. I would get thee to as good a professional team as I could if where you started was really your starting point, I would sure as heck not start here. Unless I am really missing a lot, it seems like the task would have to be really like untangling a pound of angel hair pasta somewhat overcooked. Best of luck really.
Is your husband sleeping well? It's possible that his serotonin imbalance may be contributing to his hallucinations. I'm posting a link to my past response why this may be
Also, be sure he is not deficient in B6, which is common in advanced PWP. You might want to try sublingual p5p (active b6) to see if it helps along with tryptophan rich foods.
"15 reported Hallucinations: 80% reported improvement and 20% worsening situation."
The above result is from Clinicrowd which is a very unreliable survey. Specifically, "only 78 (out of more than 1,000 ) of them self-administered mannitol for more than 6 months." No attempt was made to "differentiate" the responders by other relevant variables such as the amount per day or frequency of dosing or previous constipation or hallucinations or other drugs that cause hallucinations.
IOW, as an example did the "smell" respondents (presumably 33 out of 37 who regained their smell) also make up some of those who hallucinated (n-11) and therefore believed they regained the ability to smell, but actually never did?
His movement disorder specialist says we should try it when the hallucinations get worse. Hoping to keep them in check with the right balance of meds and supplements for awhile longer. Do you know anyone whose tried it?
Pimavanserin (NUPLAZID) contains a boxed warning for increased mortality in elderly patients (65 years of age or older) with dementia-related psychosis. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death for a variety of reasons.
Thanks for this counsel. One certainly has to be careful using these drugs. Having a thorough and knowledgeable physician who knows and understands the side effects of and has experience with the drug she prescribes is critical. I took the drug for two years. It has been over nine months since my last dose. I am 67. For me, the drug worked well.
I stopped because I developed deep vein thrombosis (clots) in my legs and the swelling in my legs, ankles and feet became unbearable. The swelling is a side effect of Nuplazid. Whether the clots also developed from the drug is unknown but with Nuplazid anything is possible. The clots have required two vein ablations, many ultrasounds, and damaged my veins severely. I enjoy now having post thrombotic syndrome. The fun never seems to end. But every moment I wake up in the morning and am still breathing is a good day. Thankfully I can manage without Nuplazid. Thanks for your interest
Well, that’s just what’s been exciting and kind of scary. His Neupro dose has been cut in half, his Rytary dose is down to about a third, with the same mobility as prior, and mannitol was the only major addition. This has been for about a month and a half now.
Time will tell if there is any improvement in mobility, or if it’s really the same as it was on the higher doses without the Mannitol. Also, I don’t think it can be placebo effect with him, because he’s not aware of what meds he’s taking anymore.
This is very interesting. There is not much we can do that leads to reduction in meds, so I think you are onto something here.Personally I felt that mannitol helped with mental clarity, specially speech, and sense of smell. I couldn’t imagine a spoonful of sugar Being too bad for me.
Unfortunately for me the gas was too much of a problem so I’ve given up for a a while. Can’t smell a thing now!!
Did you try adding Alpha-D- Galactosidase(Beano's active component) as the Syncolein product does for the purpose of gas control with mannitol supplementation?
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