The replies in Michel0220's contribution regarding Jonathan Sackner Bernstein's theory on dopamine restriction naturally pertain to the video. However, I am missing the scientific basis for this. It can be found in JSB’s recent article in the Journal of Neurology. While it is somewhat understandable, it is challenging for me as a layperson to critically assess the supporting evidence for his theory. As I mentioned in my reply to the video, I have become more positive about his claims based on my own experience of gradually reducing my high dosage of L/C to zero over the course of a year and a half. This was not my goal as a fan of Sinemet, but rather because I found that I needed less of it over time. There seemed to be some sort of interaction between the use of C/L and my approach to managing PD symptoms. In doing so, I encountered the phenomenon that JSB mentioned, which seems to contradict the existing understanding among medical professionals who have been taught that PD always involves an increase in L/C dosage, at most maintaining a status quo for a certain period. My neurologist somewhat coerced me into taking higher doses of L/C again, as he believed I would eventually need it in the near future. Naturally, I refused.
On the other hand, I also read here on HU about many PWPers who have been functioning well on Sinemet for as long as 20 years or even more. The studies on C/L usage may only cover a maximum of 40 weeks, but JSB’s discussion of the well-known long-term application of this drug remains underemphasized. Nevertheless, there are many issues associated with prolonged C/L usage, perhaps even the base of existence of this forum...
Among you, there are undoubtedly those who can take a more scientific perspective on the article and consider the possible implications of his Dopamine Reduction Therapy and the use of the drug metyrosine (RB-190).
Abstract
Following reports of low striatal dopamine content in Parkinson’s disease, levodopa was shown to rapidly reverse hypokinesis, establishing the model of disease as one of dopamine deficiency. Dopaminergic therapy became standard of care, yet it failed to reverse the disease, suggesting the understanding of disease was incomplete. The literature suggests the potential for toxicity of dopamine and its metabolites, perhaps more relevant given the recent evidence for elevated cytosolic dopamine levels in the dopaminergic neurons of people with Parkinson’s. To understand the relevance of these data, multiple investigations are reviewed that tested dopamine reduction therapy as an alternative to dopaminergic agents. The data from use of an inhibitor of dopamine synthesis in experimental models suggest that such an approach could reverse disease pathology, which suggests that cytosolic dopamine excess is a primary driver of disease. These data support clinical investigation of dopamine reduction therapy for Parkinson’s disease. Doing so will determine whether these experimental models are predictive and this treatment strategy is worth pursuing further. If clinical data are positive, it could warrant reconsideration of our disease model and treatment strategies, including a shift from dopaminergic to dopamine reduction treatment of the disease.
That is the prevailing mythology of the anti-establishment. But it assumes that the problems result from the use of the drug, and not the progress of the disease. And the scientific evidence suggests the progress of the disease causes the problem. Esperanto notes he lacks the knowledge to critically evaluate the paper and the theory proposed. There is no shortage of scientists out there with those skills. They would include Eric Ahlskog google.com/url?sa=t&source=....
I think it is worth remembering that extraordinary claims require extraordinary evidence (en.wikipedia.org/wiki/Extra... ).
Out of 43 papers listed on Pubmed, JSB has published only 2 papers on PD, both speculative reviews. Compare that, for instance, with the 55 computational and experimental papers penned by Peter Tass on coordinated reset, as another example cited here for a fringe approach.
This is not to say that a reduction of C/L may not be helpful under certain circumstances (particularly when it may cause dyskinesia), but that's a long way from seeing it as the root cause of PD.
I wonder how long JSB has had to come up with more evidence versus how many decades the establishment has had to convince itself and many of us that theirs is the only correct thinking.
>"My neurologist somewhat coerced me into taking higher doses of L/C again, as he believed I would eventually need it in the near future. Naturally, I refused."
This is just nuts. It seems this sort of thing is commonplace. I do not understand what it is with neurologists that has them unnecessarily pushing dopaminergic medication. If you "might need it in the future", then fine, keep some on hand, but not a reason to take it unnecessarily.
I do not need a lot of levodopa but I sure do need what I do take. Can you point to a single most important thing that got you off of L/ C?
It is not only "nuts," but also disappointing that he chooses not to acknowledge that he either made a wrong diagnosis at the time or lacks the professional curiosity to investigate what is going on here and whether he can learn from it.
The main cause was the severe vitamin B6 deficiency that I discovered after experiencing peripheral neuropathy at the same time with PD. According to the same neurologist, it was just a "coincidence." In my opinion, that was unbelievable. The link turned out to be B6 and probably B2 as well, but that was never tested.
However, it cannot end with just one point. There is another factor that can undo everything in a very short time: stress. To prevent that, destressing and avoiding stress are essential in my approach. (Retirement, outdoor living, hikes, slow walking, exercise, avoiding conflicts with your partner, Qi gong, gardening, sun and warmth, enough sleep, etc.)
This is like my worst fear. Always feared a "cure" would be found ... but only for people not taking C/L. I take 2.5 pills total in a full day. My doctor is urging me to take more, but my therapist wants me to take less. It's so confusing.
No stocktiki, that is not what I understood from one of his videos. For the research that needs to take place first, he prefers to work with PWP who have not yet received L-dopa medication to prevent "contamination," but he does not rule out the possibility that the therapy can also be applicable in a later stage. Just like how I unknowingly tapered off my C/L medication from 1000 mg to zero in almost 2 years, it will not happen overnight with his RB-190 either.
But let's not celebrate too early. It is still a theory...
my husband has fast beta dopamine hydroxylase so he also doesn’t do well as I believe he burns through the dopamine very fast and creates harmful biproducts that make him feel anxious . This is just a theory of mine.
I sent Jonathan this message on linked in
“
I just watched your interview with Jim Mc Cann on too much dopamine in the brain. My husband has PD and has found “normal” doses of L/C make him very ill/suicidal.
Genetic testing has come up with his dopamine beta hydroxylase is running very fast so I assume any dopamine reaching his neurons is burned through fast creating toxic biproducts. Could this also be a second part to the problem, and have you considered this? I wonder how many PD patients have this issue.
I can’t find a drug or natural compound that could be repurposed to slow this down. (I was thinking along the same lines as you with the repurposing since his neurologist is uninterested and just wants him to take more and more madopar which he resists because he feels so sick on it.). GPTchatbsuggests flavonoids which is a wide field!”
PS I just asked Chat GPT again as it is a later and better version than last time i asked it. Here is the reply now
'Dopamine beta-hydroxylase (DBH) is an enzyme that converts dopamine to norepinephrine. There are natural products known to inhibit this enzyme, and one of the most well-documented natural inhibitors is cocaine. However, cocaine's psychoactive properties and legal status make it unsuitable for use as a therapeutic agent.
More suitable natural compounds that can inhibit DBH include:
Reserpine: This alkaloid is derived from the Rauwolfia serpentina plant. It has been traditionally used for its antihypertensive and antipsychotic properties and works by depleting norepinephrine from nerve endings.
Quercetin: This is a flavonoid found in many fruits, vegetables, and grains. Some studies suggest that quercetin can inhibit DBH activity.
Epigallocatechin gallate (EGCG): This compound is found in green tea and has been shown to have various biological activities, including potential inhibition of DBH.
Fisetin: This is another flavonoid found in fruits and vegetables, particularly strawberries, and has been noted for its neuroprotective properties.
Salsolinol: This is an alkaloid formed endogenously from dopamine and is present in certain foods like bananas and cocoa. It has been suggested to act as an inhibitor of DBH.
These natural products offer a potential therapeutic approach for conditions associated with dysregulated catecholamine levels by modulating the activity of dopamine beta-hydroxylase. However, the efficacy and safety of these compounds need to be thoroughly evaluated in clinical settings before they can be recommended for widespread use.
Here are some additional foods that contain natural compounds with potential DBH inhibitory effects:
Apples: Apples contain quercetin, a flavonoid that has been associated with DBH inhibition.
Onions: Like apples, onions are rich in quercetin.
Citrus fruits: These fruits, particularly grapefruit, are good sources of flavonoids, including naringenin, which has been studied for its various biological activities.
Green tea: Rich in epigallocatechin gallate (EGCG), green tea is widely available and has various health benefits, including potential DBH inhibition.
Broccoli: This vegetable is high in flavonoids, which may contribute to DBH inhibition.
Capers: These are one of the highest known sources of quercetin.
Red grapes: These contain quercetin and other beneficial polyphenols.
Kale: This leafy green is high in various flavonoids, including quercetin.
Blueberries: These berries are rich in flavonoids and other antioxidants.
Incorporating a variety of these foods into your diet could provide a broad spectrum of natural compounds that may help modulate dopamine beta-hydroxylase activity. However, the levels of these compounds in foods can vary, and the exact effect on DBH inhibition may differ from person to person. It's always best to consult with a healthcare provider before making significant changes to your diet, especially if you have any health conditions or are taking medications."
I think there might be 2 types of sufferers. Maybe both would be helped by less dopamine but some with this fast dopamine beta hydoxylase might benefit by slowing down the breakdown of dopamine.
(Reserpine used to be used as a drug but causes complete depletion of seratonin so isn’t used much now)
I was kind of thinking along the same lines. I tend to always ask whether there could be a both and answer. So I find myself wondering whether some people have too much while others have too little, or maybe it's simply that dopamine levels are not the answer so much as HOW our bodies/brains are using it. Maybe it's a case of dopamine dysregulation (sp?), rather than a lack? And maybe that means everyone can have a very different set of symptoms as we see with PD?
LAJ, you might be so very much right! Did you know that if you exercise a lot to the point your muscles build up sodium lactate because you can't blow it all off as quickly as it's created by the musculature effort, and your muscles start to stiffen up and lock up so you can't keep up your best effort past that point, it's something for instance that speed skaters have to deal with...sodium lactate is a chemical that one might correctly describe as "liquid anxiety. "
He is a strong advocate of low doses of medication combined with movement, rehabilitation, and an interdisciplinary approach (physical therapy, speech therapy, etc.).
He has many patients who are doing very well even after 20 years or more with the disease. He hasn't used DA (dopamine agonists) on his patients since 2012 and abhors methods such as Duodopa and DBS, especially.
quote" Good morning, everyone!!
Many people ask me what will happen when their "honeymoon" with levodopa ends. I think it is appropriate to explain that the end of the so-called honeymoon is marked by the onset of levodopa's side effects due to an excess of the drug. In fact, it is the beginning of drug dependence. This is the moment when the high doses of levodopa have altered the neurotransmitter system, creating the need for ever-increasing doses of the drug to calm the psychiatric disturbances (anxiety and fear) caused by the high demand for dopamine in the frontal region of the brain, which has been created iatrogenically. A true addiction!
In order to control this dependence, which generates severe anxiety and fear, the patient is willing to accept any motor side effects, which are much worse than those caused by the disease. Is it impossible to avoid the end of the honeymoon? Absolutely not. It is enough to avoid using drug doses higher than 300-400 mg of dopamine equivalents, which are more than sufficient to control rigidity and slowness, the only symptoms that respond to levodopa. For all other disturbances, the only effective therapy is exercise!
So stay calm and do the necessary exercises, relying on trained professionals. In this case, the honeymoon will last 30 years!!
For those of you who are interested, this is his Facebook group, where you can find many interesting articles, especially written by an expert professional, not anecdotal accounts or sensations from a single patient.
Will need translation in english for the most of you, but in the modern world with ChatGPT and Google Translate, that won’t be a problem. I hope it will be as useful for you as it is for me. I am undergoing a detoxification process with him and I hope to manage to stay in monotherapy and, above all, to feel better, live better with PD. This doctor is a rare gem in the world of "pill-pushing doctors." You can also find several of his studies on PubMed. Xauxatz debmorris1
Yes and no. And Winnie has a good comment. Also Parkbear. Also Ethin. And Esperanto and LAJ.
All dopamine related therapy is not simple, it is multifaceted and multi-staged. This is because the chore involves not only getting the right amount of dopamine, but also the right location, for the right amount of time. Not every dose of every sort of dopamine product or agonist or blocker goes where you might want it to, because of the blood-brain barrier and because dopamine is produced in multiple locations and functions in multiple locations both inside and outside the central nervous system and peripheral nervous system. And there is the need to adjust for or provide for various enzymes and cofactors and competing factors as they occur, as I think LAJ or Esperanto have talked about, as well as the side effects or adjustment issues in all the realms those enzymes cofactors and competitors also are involved in for other systems.
Dopamine serves many neurological functions and psychiatric functions and has to obtain a large number of different effects, avoid a large number of side effects, and work in the right places in a sort of very elaborate Goldilocks situation in every one of them.
Want to become psychotic and suicidally depressed at the same time that you are bipolar-ly unbalanced? Or on the other hand have too much in a certain spot and gamble away your house and all your retirement savings in an afternoon? Just deprive yourself of dopamine, in the first example of not quite enough dopamine, and bump a little too much in the second, perhaps using a dopamine agonizer or just a little extra dopamine, give yourself an uncontrollable dose of restless legs, or uncontrollable muscle spasm in your neck area which forces your head into a frozen extended position that you can't stop, which is very frightening and could necessitate you landing quickly in an emergency room with all the intervention issues that involves, in the latter example of a tad too much dopamine in a certain location, just the tiniest little deficiency or excess that is sufficiently out of balance can result in such a situation nearly immediately. That's just one of the very many examples of the problem and advantage with dopamine.
Yes with Park bear it seems to be more reasonable to use just enough for as long as you can get away with using just enough. So if your neurologist is saying to up your dose when you were doing just fine, as some sort of anticipation or preventive measure, I would gently challenge the neurologist for some experimental and literature support, because as practitioners, often clinicians simply bypass knowing about research and instead go with the amalgam position of their professional associations, which have lots of exceptions and lots of problems.
.
Alternatively on the prescription I might suggest writing the prescription thus: write the prescription for the higher amount but in smaller incremented pills, so that you can adjust them up or down as you need, with the following instruction added to the specific dose: "up to xx mg. take as directed." Phrasing the prescription this way allows for unwritten flexibility in the prescription by being able to vary the "five rights" so that if you happen to be unable to visit your neurologist for adjustments frequently, you have some flexibility to play around gently and carefully, without running any big risks that you can't reverse.
.
Knowing how to do research and do consume it properly is not a skill they teach in medical school, it is an entire specialty discipline of its own. That is a skill they teach in PhD school because PhD schools train you for the specialty of doing research and interpreting properly research, well by the word "properly" I mean competently...Whereas medical schools train you for the activity of practicing it instead of creating the knowledge into a formal knowledge base. So they have to get it from somebody and that's generally second hand since they are not creating their own experimental research nor are they interpreting their own and the fields ongoing and accumulated experimental research, they're just passing on generalizations in consensus guidelines by various professional, advocacy, producer, science, and political groups which always involve numerous conflict and exceptions which they sort of don't really get into because it is less efficient to become an expert in an area then it is to just go by the broad brushes and broad strokes, which necessarily always, always, including exceptions where the results go the opposite of what the broad stroke generally says. Also broad strokes are generally the starting point, not the end all, of the prospect of doing therapy. What the practitioners do have is the practical knowledge gained by actually practicing in the clinical setting, but that isn't near enough. So anytime you feel like your doctor needs to justify some of the research and what that would say because the doctor may be highlighting one aspect without mentioning other aspects that could go against his thought, you are always entitled to gently ask, is that what the formal research says? Where can I go to verify that for myself? And the second that doctor starts to verbally rely on "research" you are immediately entitled, without causing a fence, to then respond "so you have a PhD then too doctor?" Because some of them do have both MD and PhD. But if the one who is quoting research to you doesn't, you may have an obligation to ask him how does he know that for sure? And get an answer how he/she knows it. Because in all honesty he owes you that. That is not to say that clinical knowledge and experiences not important, it absolutely critically is, because the FDA has succumbed pretty much to corporate pressure and political pressure the way most enterprises have anymore, so that the difference between theory and practice, or experimental literature versus clinical experience, can have a pretty wide gap sometimes; to say nothing of the problem of uncontrolled production and marketing and uncontrolled supplements and all that.
All this talk on this subject is premature, greatly premature. I once said the hypothesis was very intriguing, and in one of my earlier posts I think I was able to describe what the guy was talking about in sufficiently clear terms that I got a couple of compliments from folks. I don't feel like repeating it here but it's in my post somewhere I worked right out of his article. In case Esperanto wonders whether anybody has ever read the guy.
Trouble is many are arrogant (or insecure) and don’t like any questioning of their prescriptions. And patients are too intimidated to question. And when they don’t see people for 6-12 months how can they even manage them? All they can do is prescribe averages.
Content on HealthUnlocked does not replace the relationship between you and doctors or other healthcare professionals nor the advice you receive from them.
Never delay seeking advice or dialling emergency services because of something that you have read on HealthUnlocked.
Parkinson’s and vagal nerve stimulation, promising human studies.
Methylphenidate for \"Parkinson's\"
