Characteristics Of The Subjects
A total of 27 participants signed the IRB-approved informed consent and were randomized to blindly receive oral mannitol or placebo . Three participants withdrew their consent before initiation of therapy. Baseline demographic and clinical characteristics of randomized subjects were similar between the two groups . The adherence of participants to the investigation product was high in both groups .
Figure 1. Trial flow diagram and clinical outcome. First trial visit included both screening for eligibility and randomization. Dosage tolerability among participants who completed the trial in the mannitol and placebo groups.
Table 1. Baseline demographic and clinical characteristics of randomized subjects.
In The Clinical Trial
Although CliniCrowds published results may not be enough to win over skeptics, the project has succeeded in sparking one clinical trial aimed at more rigorously investigating mannitols potential benefit in Parkinsons.
Based on anecdotal evidence from CliniCrowd and other physicians treating Parkinsons cases, David Arkadir, MD, PhD, a physician and neurologist at Hadassah Medical Center in Jerusalem, secured funding for a small Phase 2a trial in 2019.
In 2016, the Israeli government offered grants to physicians studying generic substances that might be medically useful, but had no clear financial benefits. Arkadir and his colleagues submitted a proposal for mannitol and won one of these grants.
His trial consists of about 30 participants, who are assigned randomly to receive either mannitol or dextrose, a similarly sweet sugar that serves as a placebo.
The patients in this trial are followed for 36 weeks, during which the safety and tolerability of mannitol is assessed. As secondary outcomes, they also are collecting data on several clinical features of Parkinsons.
These features include changes in levodopa dosage, the ability to detect scents, and changes in constipation, as well as changes in cognitive and motor symptoms.
Arkadir expects the trial to end in approximately two to three months and hopes to report results sometime in mid-October.
The one risk we run into with a relatively small Phase 2 trial is they often dont replicate in Phase 3, she said.
The Mannitol Pilot Study Results
The findings of a randomised, blinded clinical trial of the sweetener mannitol have been published. The results indicate that the molecule is safe and tolerable, but the study has not replicated the benefits that had previously been reported.
In 2013, researchers from Tel Aviv University in Israel published preclinical data evaluating mannitol in four models of Parkinsons. Mannitol is a low calorie sweetener that is sometimes used to lower increased pressure around the brain. Remarkably, the researchers in Tel Aviv found that mannitol exhibited impressive neuroprotective properties in their models of Parkinsons. These encouraging results compelled members of the Parkinsons community in Israel to set up a crowd funded platform to share their experiences of self-administering mannitol. The platform, Clinicrowd, quickly gained a world-wide following, and is still a community for patients and those at-risk to share experiences, treatments, and insights.
Over time, the Clinicrowd platform collected a lot of data from individuals taking mannitol and this dataset of anecdotal reports provided strong justification for initiating a proper clinical trial. Researchers at the Hebrew University of Jerusalem set up a phase 2a, randomised, double-blind, placebo-controlled, dose-escalating study in 2019. They recruited 22 individuals with Parkinsons who were treated with mannitol or a control treatment for 36 weeks.
Primary Clinical Outcome Measures
Twenty-four participants initiated oral therapy . One participant from each of the groups terminated the study earlier than planned. Early termination of a participant receiving mannitol was due to in situ breast carcinoma discovered 3 weeks after the first visit. This severe adverse event was considered unrelated to mannitol treatment. The participant in the placebo group dropped out of the trial within a week due to nausea. This side effect was considered as related to the investigated product by the investigator.
No mannitol-related severe adverse events occurred during the study. A single severe adverse event , considered unrelated to the investigated product, was documented on the last visit in one patient receiving placebo. Clinically significant gastrointestinal symptoms were reported in 6/14 participants in the mannitol group who completed the study. In 5/14 participants these symptoms required dose reduction . Only a single participant in the placebo group required dose reduction due to abdominal discomfort . Overall, 64% of participants receiving mannitol tolerated well the target dose of 18 g of mannitol per day divided into two doses.
Table 2. Values of whole-blood laboratory parameters at the final visit of participants receiving placebo or mannitol.
Mannitol As A Prebiotic
Mannitol is a type of “diabetic sugar” which has a low glycemic index and is barely absorbed in the body, tending to pass straight through. People with Parkinson’s around the world are finding cumulative benefit with daily use of mannitol as a supplement. Andy Butler of Parkinson’s People, who travels the world talking to PD groups, to seek out and share the best practices of living well with the condition, says “pain and fatigue seem to be helped by mannitol”. No-one really knows why it is working so well for some PwP, but having done the research, but we do know that mannitol is a good prebiotic, as listed in:
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The Latest Research About Mucuna Pruriens As A Treatment For Parkinsons
In 2004, a study was conducted comparing the efficacy of MP with the standard medication used in PD, carbidopa/levodopa . Eight patients were given one dose of a MP preparation or C/L in a blinded fashion and then tested four hours after ingestion. MP acted more quickly and lasted longer than C/L without worsening of dyskinesias. A 2017 study also compared various single dose preparations of MP vs. C/L given blindly and determined that MP had a quicker onset of action, lasted longer and caused fewer dyskinesias.
However, when MP was given for longer periods of time as opposed to in single doses, the results were not as positive. In 2018, a study was conducted in which 14 patients were given MP powder for eight weeks and then carbidopa/levodopa for eight weeks. Seven of the patients discontinued MP, four for gastro-intestinal side effects and three for worsening of motor symptoms.
For the seven who remained on treatment, efficacy of MP was the same as C/L. Nobody discontinued during the C/L phase. Although the study showed that MP can be effective in reducing PD symptoms, it drew attention to the need for additional research into the optimal MP formulation and dose to allow for greater tolerability when taken continually.
H3: The difference between mucuna pruriens and cabidopa levodopa
How Can A Person With Pd Get A Supply Of Mp And What Is A Typical Dose
Interview With Clinical Research Scientist Prof Karen Raphael
Originally published on Tomorrow Edition on May 31, 2018
Phases And Tactics: : Circumvention If You Cant Go Through The Door Go Through The Window
The fusion of a former commandos mentality with that of a technology entrepreneur prompted Vesely to deploy his own resources to address his condition. Dissatisfied with his treatment options, he asked acquaintances for help. A small group of entrepreneurs banded together with him to search the published Parkinsons research. They soon noticed the publishedand forgottenstudy about the possible effect of mannitol on Parkinson’s patients. Vesely and some partners contacted Professor Dan Segal of Tel-Aviv University, who had co-headed the research team, and asked to meet:
It had not yet been tested on humans. So I made an appointment….Prof. Segal told us his story, described the experiment, and said it’s all simply been shelved, theres no incentive for the pharmaceutical companies. We looked at each other and said, So well take it! The professor said, Who exactly are you? You brash Israelis, who are you? But it was clear to us that if you cant go through the door, you go through the window.
The story of the study and the lack of economic feasibility for clinical trials affected the group, comprised of former members of elite military units and high-tech entrepreneurs, coalescing around Vesely. Seeking to apply to himself, as patient, an approach traditionally reserved for researchers , Vesely resolved to test mannitol first on himself. However, his partners dissuaded him. Instead, they agreed to test mannitol on some number of Parkinson’s patients.
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Usual Adult Dose For Oliguria
Renal function test dose prior to initiation of treatment: 0.2 g/kg IV over 3 to 5 min resulting in a urine flow of at least 30 to 50 mL/hr. A second test dose may be administered if the urine flow does not increase. If no response is seen following the second test dose, the patient should be reevaluated.Treatment: 300 to 400 mg/kg or up to 100 g of 15% to 20% solution IV once. Treatment should not be repeated in patients with persistent oliguria.Prevention : 50 to 100 g IV. usually a 5 , 10, or 20% solution is used depending on the fluid requirements of the patient.
The Current Trends And Future Perspectives Of Prebiotics Research: A Review
Due to its low GI/low absorption charaterisics, it seems to work much like the more well known prebiotic “Inulin” as it passes through the system, including that it is an “osmotic diuretic”, drawing water through the gut lining, helping to create stools of good consistency and thus having beneficial impacts on the chronic constipation which many PwP suffer from. Mannitol therefore support sgood gut bacteria and healthy elimination, helping with the chronic digestive problems and the severe microbiome imbalances which are now strongly implicated in PD, e.g.
The evidence that mannitol supplementation is indeed working as a good prebiotic in PwP is that it tends to generate a lot of gas, which is a good sign that gut bacteria are active and reproducingf!
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Treatment Activism: Antecedents And Parallels
Todays digital platforms are re-defining boundaries and connections between patients, their bodies, physicians, and biomedical knowledge . One strand of this revolution manifests as patient activism. Examples include: self-experimentation and crowd-sourcing evidence-based activism self-monitoring treatment-access advocacy and shifts from resistance to cooperation . Each of these appears in the work of CliniCrowd, the Israeli patient-led, crowd-sourced, treatment-research enterprise at the heart of this paper.
For, the pioneering work of AIDS activists three decades ago, who first began attending scientific conferences and were prepared to challenge credentialed biomedical experts on the nature and direction of clinical research, helped usher in a world in which:
ost scientific conferences in the US are now attended by a scattering of ‘amateurs’, and for the professional their level of expertise is astounding, usually exceeding the professional scientist in breadth and depth. Why? Because they care about the subject directly.The amateur cares nothing for papers or grants – she wants to know. Most have educated themselves over the net.
Note that we do not directly address mannitols clinical efficacy. Not only will this likely take some years to become clear, but our purpose is not to investigatemuch less endorsemannitols value in managing Parkinsons. Rather, we explore an interesting form of citizen-science treatment activism from a sociological perspective.
An Entrepreneurial Approach To Turn An Orphan Drug Into A Potential Treatment For Parkinson’s
Mannitol, a natural sweetener, may help treat Parkinson’s disease, yet was not being tested in clinical trials. The story of mannitol is one of many examples of “undone science”: research questions unfunded or ignored for economic, political, or other reasons.
How can public pressure utilizing crowdsourcing, citizen science, and entrepreneurial activism help transform undone into “done science? A new article in the journal BioSocieties, published by Drs. Shlomo Guzmen-Carmeli and David A. Rier, of Bar-Ilan University’s Department of Sociology and Anthropology, chronicles the story of CliniCrowd, an Israeli company established to test the effectiveness of mannitol. A common and fairly inexpensive sweetener used by the food industry, and in hospitals to reduce intracranial pressure, mannitol was demonstrated a few years ago by a group of Tel Aviv University lab researchers as potentially effective in improving the condition of Parkinson’s patients.
CliniCrowd’s efforts involved several stages. Most important was the launch of a crowd-sourced study of Parkinson’s patients who agreed to take mannitol regularly for an extended period and report their results. This research produced preliminary data sufficient to generate public pressure and influence with which to attract scientists to conduct further clinical research — currently ongoing — on mannitol for treating Parkinson’s.
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Effect On Parkinson’s Symptoms
Injected mannitol and mannitol-laced foods were evaluated for their effect on symptoms of Parkinson’s disease in the lab. It is thought that combining mannitol with other PD medications may facilitate the ability of treatments to get more easily to the targeted sites by crossing the blood/brain barrier.1,2
Scientists tested different concentrations of mannitol in a solution of alpha-synuclein. They then evaluated the levels of clumping. They found that low levels of mannitol had the strongest effect in inhibiting the formation of clusters.
Mannitol appears to prevent or reduce the clumping of proteins in the brain, including alpha-synuclein. It has the ability to cross the blood-brain barrier. Clumped proteins are a hallmark characteristic of Parkinson’s disease. Clinical research performed at Tel Aviv University on fruit flies and mice showed promise in destabilizing clumping proteins. By inhibiting the formation of clusters, mannitol destabilizes the proteins.4
Results: An Orphan Drug Start
Meet Dan Vesely, retired Israeli general and high-tech start-up entrepreneur. Here, he describes his response to his own 2013 Parkinson’s disease diagnosis:
This is how I was trained in the service: if theres a problem, deal with it. No crying over spilled milk or grieving about my misfortune, about what I won . Come on, what do we do next? We think of solutions.
This paper examines the solution that Vesely and his associates developed: CliniCrowd, a digital global community adopting an alternative approach to clinical research. The initiative was established after the discovery that a substance called mannitol might improve the condition of Parkinson’s patients. This discovery was, essentially, being ignored for lack of significant profit potential. Below, we describe how CliniCrowd adopted mannitol as a treatment for Parkinsons, and how their efforts evolved over time, employing different tactics to meet their shifting challenges as they sought to turn undone to done science.
Specifically, these key phases have been: identification of and frustration over undone science the decision to circumvent lengthy, inefficient modes of operation framing as resistance and 4) exploitation of ways to avoid direct resistance to established actors, in favour of re-framing themselves as complementing, rather than resisting, the status quo.
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What Are The Side Effects Of Using Mannitol
Greater than 20 grams in one day may cause laxative effect.
What is the scientific background?
In the June 2014 issue of The Journal of Biological Chemistry, a study confirmed two things: Mannitol improved Parkinsons Disease symptoms in genetically modified fruit flies and mice, and it reduced harmful levels of Alpha-Synuclein, protecting the neurons that produce dopamine in the brain. Mannitol crosses the blood brain barrier and prevents the protein Alpha-Synuclein from clumping together, which is a cause of Parkinsons Disease.
In the fruit fly test model, the flies normal movements were restored by Mannitol and their levels of Alpha-Synuclein were reduced by 70%. In the mice test model, the protein levels were also reduced and dopamine-producing neurons protected. The results of these lab experiments encouraged medical professionals to investigate Mannitol as a possible natural supplement and treatment for people suffering from Parkinsons Disease.
What is the required dosage of Mannitol?
Mannitol can be taken at any time of the day. As a sweetener use 5 grams up to 4 times per day. Greater than 20 grams in one day may cause laxative effect.
Can I take Mannitol if I have heart disease, high blood pressure or diabetes?
According to the FDA, Mannitol does not cause a sudden increase in blood glucose and/or insulin. There is no reference in the FDA document that indicates a link between Mannitol and heart disease or high blood pressure.
How does Mannitol work?
When Dan Vesely Was Diagnosed With Parkinson’s He Had To Do His Own Research Which Involved Manipulating The System That Leaves Many Without An Option
Upon discovering he had Parkinsons disease, an Israeli hi-tech entrepreneur decided to take matters into his own hands and find a viable treatment. However, as many natural, less invasive treatments are not pursued primarily for financial reasons Dan Vesely had to do his own research, which involved manipulating the system that leaves many without a better option.
Researchers at Bar-Ilan University published an article about what they called undone science areas of scientific research that remain underexplored because of several potential reasons, such as unprofitability or political ones with the focus of the study being the Parkinsons cure mannitol, a commonly-used sweetener that Tel Aviv University lab researchers determined was potentially effective in improving the condition of Parkinson’s patients.
As a natural substance, mannitol products cannot be patented. Moreover, the global market for existing Parkinsons drugs is already worth billions, thus potentially useful candidates such as mannitol are ignored in favor of more potentially profitable treatments deeming them what the medical community calls orphan drugs.
In classic Israeli fashion, Vesely, a hi-tech start-up entrepreneur and former senior security-services officer, didn’t let this stop him.
When I go to see him, he immediately stands up! Welcome, he says, tell me how you are getting on. There is a sense that we are colleagues, and that I am doing something incredibly important.
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Coconut Oil And Parkinson Disease
In recent years, many people who suffer from PD said that regular consumption of pure coconut oil significantly improved their symptoms. Studies support their claim: it seems that coconut oil contains glucose and other ingredients the brain uses as fuel after PD caused their deterioration.
How to Use Coconut Oil for PD:
Coconut oil can be found in almost every supermarket. It can be cooked or consumed as-is.
A new Parkinsons treatment , while all the natural remedies to Parkinsons Disease mentioned above have their benefits, Mannitol is a whole different level. Mannitol is a sugar alcohol . This natural low-calorie sweetener can be produced from various kinds of fruits, leaves, and other natural substances. You probably know it as the thin powder that covers some chewing gums is mannitol.
What is the connection between this natural sweetener to treating PD symptoms?
In 2013 Parkinsons experts from Tel Aviv University had an amazing discovery: they found that consumption of mannitol significantly improves the symptoms of PD: tremors ceased, the memory came back, thinking became clear, sleep came easier, and more.
How Does Mannitol Powder Work?
PD experts found that all these amazing results could happen because mannitol can dissolve the aggressive proteins which lead to PD. Additional studies from recent years strongly support this finding, as well as a testimonial of people who suffer from PD and felt tremendous improve in their condition.