Update – Mannitol and Parkinson’s disease


Over the two weeks we have had a lot of interest in our post regarding the sweetener, Mannitol and preclinical studies suggesting that it prevents the clustering/aggregation of the Parkinson’s disease associated protein, alpha synuclein (Click here to read that post).

Such high levels of traffic had us scratching our heads as to why the sudden interest.

Yesterday the reason became very clear.

Today we are following up the Mannitol post with an update about some of the interesting developments.


On the Thursday December 15th, Channel 1 (MABAT) in Israel ran the following news article:

This presentation was in association with a new start-up called ‘CliniCrowd‘ which is a “crowd sourcing platform exploring disease treatments that Pharma companies have no interest to investigate or promote”.


CliniCrowd is a social impact company that has built an online platform, which provides a registry for people to sign up to and share personal experiences of researched nutriments.

Sounds interesting – how does it work?

The community at CliniCrowd “searches for nutriments that are safe for human consumption, recognized by FDA as GRAS (Generally Recognized as Safe), and have scientific evidence (in research papers) to be used to hopefully enhance wellbeing and possibly impact symptoms of diseases” (Source: CliniCrowd).

People with Parkinson’s disease are able to voluntarily sign up on the registry and start reporting back about their use of a particular ‘nutriment’, particularly what benefits or side effect that they may be experiencing. In turn, CliniCrowd will present its findings as is to the crowd.

The sweetener Mannitol is the first nutriment being proposed by the company.

After signing up on the website, “patients voluntarily register for the registry and enter their health information, purchase and administer the products themselves, and enter treatment outcome data on the website” (Source: CliniCrowd).

Cool idea. Where can I find more information?

In addition to the TV news article above and the company’s website (CliniCrowd.info), numerous videos have also been posted online, including this one introducing the scientist behind the original Mannitol research, Prof Danny Segal (who also sits on the Advisory board for ClinicCrowd):

There are also testimonials from people already taking part in the Mannitol-Parkinson’s disease assessment:

What happens to my personal information?

The information you provide will be used for the analysis conducted by the company. Some of your unidentifiable information may be shared with third parties, but the company’s privacy policy insures that your ‘identifiable’ information is kept strictly confidential.

And remind me again what is Mannitol?

Mannitol is a colourless sweet-tasting, poorly metabolized crystalline alcohol sugar that is Food and Drug Administration (FDA)-approved as an osmotic diuretic agent.

In plain English: it is a sweetener. Stick it on your tongue and it tastes like sugar.

Usually made from fructose and hydrogen, Mannitol increases blood glucose to a lesser extent than sucrose, and so it is commonly used as a sweetener for people with diabetes or sugar intolerance. The fact that Mannitol can be produced artificially is the only reason that it is often referred to as an ‘artificial sweetener’, but it does not fall into the same class as proper artificial sweetener, such as aspartame.

The Parkinson’s disease foundation in the US have a useful information sheet on Mannitol (Click here to read it – PDF files requires Adobe Acrobat to read).

Is Mannitol safe?

The short answer is yes. FDA approved and it is widely used in many processed foods.

The longer answer (specific to Parkinson’s disease) is more complicated.

A critic of the CliniCrowd concept may point out that the research supporting the beneficial effects of Mannitol in Parkinson’s disease is limited to just one peer-reviewed journal paper. And this is currently true. Supporters, however, would counter that Mannitol is widely available and already being privately tested by many individuals with Parkinson’s disease, so why not offer a forum where they can provide their personal feedback.

In addition, Mannitol is added to a wide variety of processed products (simply check the packaging of your shopping for ‘mannitol’ or food additive number e421 – Food Standards Agency, 2014). On top of this, Mannitol is naturally occurring. Cauliflower, for example, contains 3 grams of Mannitol per every 100 grams of weight. We are all consuming it on a daily basis.

A health warning here – Mannitol should not be taken in excess or abused as it can have an osmotic effect (in particular, attracting water from the intestinal wall). Consumed in excess, it will cause diarrhea, abdominal pain, and excessive gas. In addition to intestinal problems, Mannitol has also been associated with worsening heart failure, electrolyte abnormalities, or low blood volume. Importantly, we also do not know what effect it may have on absorption of L-dopa and other Parkinson’s disease medications. Thus, please discuss any change in your treatment regime that you may be considering with your doctor before doing so.

What does it all mean?

As the company suggests on their website, CliniCrowd is in essence a protest against big pharmaceutical companies who have and still are ignoring possibly effective therapeutic agents simply because they are un-patentable (and thus providing no protection from competition). Such treatments do not justify the cost of clinical trials for those companies, as the profits would be minimal.

Some of these un-patentable medications are currently being tested in clinical trials set up, funded and run by Parkinson’s disease charity groups, such as Parkinson’s UK, the Cure Parkinson’s Trust, and the Michael J Fox Foundation. The cost of those trials, however, is great. In addition, they are long and heavily regulated processes – it can take years to determine if a medication is effective. On top of this, there is always the possibility that a treatment which works for one individual won’t work for another. Across a large clinical trial population this effect can result in any positive result being cancelled out, and the trial failing to show any positive outcome at all.

CliniCrowd is not proposing an alternative system to the clinical trial process. It is simply providing a rapid method of filtering and identifying the agents that exhibit some level of benefit in humans with Parkinson’s disease. It is critical to understand that what CliniCrowd is proposing can not constitute or replace a clinical trial. Since the participants on the CliniCrowd registry would not be randomly allocated to a treatment or control group (nor would they be assessed by blinded clinical assessors), this process could not be described as scientifically valid. Any treatments that exhibit beneficial effects on the CliniCrowd website would still need to go through the clinical trial process to be considered thoroughly tested and ready for regular clinical use.

There is obviously the potential for the placebo effect to jump in here. Given that participants know that they are taking a particular treatment and are largely self assessing themselves, there is the possibility for people to start experiencing miraculous benefits that may have no pharmaceutical explanation. And the placebo effect is particularly strong in Parkinson’s disease when compared to other conditions. So this must always be kept in mind when considering the results of any treatment being taken by people on the registry.

Here at the SoPD, we are always looking for new treatments and innovative ways of speeding up the process of getting therapies to the clinic. In addition, we are keen to see more research on Mannitol and (if validated) have it tested in clinical trials. A platform like CliniCrowd could provide a Parkinson’s charity with some initial human validation data that would justify a clinical trial, saving precious time and money and allowing them to focus on treatments that have exhibited some kind of effect in humans with Parkinson’s disease.

Thus, we are very curious to see how the CliniCrowd registry system will work out, and we look forward to the discussion that will result from this innovative step forward.

EDITOR’S NOTE: Full disclosure – The TV news article and CliniCrowd website was brought to our attention by the people running the platform. Given that they are not selling a particular product and simply trying to do some good for the Parkinson’s community, SoPD is presenting an unbiased and balanced review of their efforts here. SoPD is in no way benefitting (financially or otherwise) from this presentation, and is providing it here to the Parkinson’s community for educational purposes.

In addition, under absolutely no circumstances should anyone reading this material consider it medical advice. Before considering or attempting any change in your treatment regime, PLEASE consult with your doctor or neurologist. SoPD can not be held responsible for actions taken based on the information provided here.

The banner for today’s post was sourced from Qualifirst

24 thoughts on “Update – Mannitol and Parkinson’s disease

  1. The problem is getting the mannitol to the brain. When ingested, very little gets in the blood and therefore little gets to the brain. So, what about vaping mannitol? Get the stuff right in to the blood in the lungs. Can mannitol be vaped?


      1. I’ve tried the coffee thing. The problem is not the BBB. Mannitol can do the BBB. The problem is getting enough Mannitol into the bloodstream to get to the BBB. Very little Mannitol is absorbed via ingestion. For that reason, when Mannitol is administered as a drug for inner cranial pressure issues and whatever, it is injected, not ingested.


      1. I’m relying on literature I’ve read about mannitol. It is understood that mannitol is not well absorbed in the digestive tract. So, it’s not getting in the bloodstream when ingested orally. That’s why when mannitol is administered for medical purposes, it is injected directly into the blood stream. Once in the bloodstream, it reaches the brain and is known to easily penetrate the “Blood-Brain-Barrier” (BBB). So, the challenge for treatment of Parkinson’s is to get the mannitol into the bloodstream. As warned here by Simon and it’s just plain good sense, consult your physician about trying anything experimental with mannitol. My thought is that it seems vaping is worth some research. How does one determine how much mannitol reaches the brain? I don’t know.


      2. Hi Mark,
        Further to Bill’s comments: Measuring Mannitol absorption levels is done via urine levels, as everything that passes through the intestinal wall into the blood is eventually filtered out in the kidneys and excreted. The amount of Mannitol absorbed will vary from person to person, but urine excretion studies suggest that on average only 1-2% of the ingested mannitol is being excreted per hour via urine up to 6 hours post ingestion (for example http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0099256 ). This suggests that only small amounts are being actually absorbed through the intestinal walls (and this is why Mannitol is a useful tool/test in medicine for determining intestinal absorption).
        The good news is that Mannitol is being absorbed through the intestines, the bad news is that it does it the hard way. In the small intestine, about 1/3 of mannitol permeability was mediated by general passive diffusion, while the other 2/3 is mediated by ‘solvent drag’ (the process of passing through the intercellular space between the cells in the intestinal wall, rather than through cells via ions pumps/channels etc). In the colon, this ratios climbs to about 90% solvent drag. Solvent drag is the hard way through the intestinal wall (here is the research on this:
        https://www.ncbi.nlm.nih.gov/pubmed/8149845 ).
        The important thing to remember though is that you don’t need large amounts of Mannitol to be absorbed in order for it to be active, which leads to additional issues at the ‘excretion’ end of things. Mannitol is freely filtered through the kidneys, but it is not reabsorbed. And it can hang around in the renal system, where it continues to be osmotically active, which accounts for its action as an osmotic diuretic (in plain English: causing one to need to pee more).
        How much Mannitol one should take must be carefully controlled and this should ONLY be done through consultation with a medical physician. As we have suggested in the post, we are in uncharted waters here in that we do not know what impact a substance like Mannitol will have on other PD medications, so we need to be very careful when considering any changes to an established treatment regime.
        Kind regards,


    1. It seems like it would make more sense to snort it, by your logic. No idea how safe that would be. It increases permeability of the BBB, I would had to see it do the same in the lungs and flood your chest w pulmonary edema.


  2. Hi Bill,
    Thanks for your comment. And yes, this is one of the key issues with Mannitol – it is poorly absorbed from the gut (see this excellent open-access review for a good background on this: http://ceaccp.oxfordjournals.org/content/early/2012/01/12/bjaceaccp.mkr063.full).
    Inhalation of Mannitol (using a nebuliser) is a reality. There are products (such as Aridol, with a half life of 4.5 hours and a peak blood level at 1.5 hours post inhalation), but before attempting this approach understand that it can cause bronchoconstriction (tightening of the airways in the lungs). As always: PLEASE consult your doctor before considering any change in any treatment regime.
    Kind regards,


    1. Simon,

      Thanks for the reply and the link. The bronchoconstriction sounds dangerous. Are there precautions to avoid this, at least at any serious level? Would vaping be the same as nebulizing?


  3. Hi Bill,
    Sorry, just getting to this now – I’ve been chasing my “three-nager” around all day.
    I have to be careful how I word things here. Aridol itself is not approved for therapeutic purposes. It is a lung function test designed to help doctors diagnose and manage asthma by detecting active airway inflammation through measuring airway hyper-responsiveness. Patients inhale increasing doses of Aridol via a simple hand-held device. Thus, to say that people are using Aridol for therapeutic purposes would be wrong.
    But the Australian company behind Aridol, Pharmaxis ( http://www.pharmaxis.com.au/ ), has a similar product they call “Bronchitol ®”, which is dry powder mannitol which is inhaled twice daily using a small handheld device. It is approved for the treatment of certain patients with cystic fibrosis to help them clear mucus from their lungs. It is approved for sale in Australia and major European countries. It is certainly NOT approved for use in Parkinson’s disease.
    The bronchoconstriction can occur, but the reasons why inhaled mannitol could be causing it are unknown. And yes, bronchoconstriction would be pretty serious if that occurs. It may also be one of the reasons why the FDA has thus far refused to approve the Bronchitol product for use in the US (see – http://www.fiercebiotech.com/regulatory/fda-raises-red-flag-for-pharmaxis-bronchitol). And this leads to our ever present warning to consult your medically certified physician before attempting any change in treatment regime.
    Regarding the difference between vaping and nebulizing:
    Now have to get the three-nager to bed – wish me luck.
    Kind regards,


    1. Simon,

      Thanks, again for your thoughtful and considered reply. Your warning to consult my physician about treatment is well heeded. I’m very interested in Mannitol and Parkinson’s. I have Parkinson’s and would like to learn of a safe way to try vaping Mannitol. It just seems to me to have some potential as a treatment. But I will proceed with all due caution.

      Thank you

      Bill Jenkins


  4. Thats quite an eye opener. People have been using mannitol via the gut route and maybe not getting enough into the brain where it would have done what it was supposed to do. I am sure more needs to be investigated about the amount of mannitol needed which may vary from individual to individual.


  5. Hi Rocksteady,
    Thanks for your comment. Yes, more research is definitely needed. I should mention that the integrity of the intestinal wall does seem to be affected in PD, leaving it more permeable than normal ( http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0028032 ). It may well be that this would allow more mannitol through, but this needs to be investigated further.
    Kind regards,
    PS I like your website!

    Liked by 1 person

    1. Hi Bill,
      Thanks for your question. I haven’t heard anything recently about Mannitol (either research-wise or from the folks at Clinicrowd). I was supposed to be going out to Israel later this year, and I was hoping to visit the clinicrowd folks. Unfortunately that trip has recently been cancelled so I will have to reach out to my contacts in clinicrowd the old fashioned way and ask if there are any updates. I’ll let you know if I hear anything interesting.
      Kind regards,


      1. Hi Simon, I am a 62 years young woman in uk with Parkinson’s for 36 years! Since I was 26. I have taken a variety of drugs to control my symptoms. Started to get rapid deterioration of balance in the last few years and was told to decrease my dose of ropinirole to 6 mg per day. I also take amantadine, sinemet, artane, paroxetine,and imaldipril for high blood pressure. I recently read an article on mannitol and decided to give it a go. My balance returned to near normal in three days! This was the most dramatic result but other symptoms also responded… My energy levels improved, tremor was reduced and lethargy disappeared.
        I take three to four teaspoons through the day in a hot drink of coffee. I have kept my PD drugs going but try to keep them two or more hours apart from the mannitol. I am anxious to know if I shoul be taking any supplement with it or any precautions that I need to heed!
        To me it is a major miracle. I have taken off fifteen years of struggle in a single week!


  6. Simon,

    Could wide variability in capability to absorb Mannitol in the gut explain results such as Ms. Corkett’s?

    Bill Jenkins


  7. D mannose is too cheap and big pharmaceutical companies won’t make money off of it. I have two family members with bipolar disorder. Big pharma has lithium carbonate in which the lithium is not bioavailable and has caused serious toxicity…so they put patients on their drugs…however lithium orotate is bioavailable and safer but they use old data that was researched incorrectly to say it was unsafe…. It is available as a supplement and my family gets excellent results….if this was made available by prescription so many people would benefit…. But would cost pharmaceutical companies because it is cheap and most people would not need their expensive alternatives…


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