Mannitol: A Sweetener? A Supplement? A Cure?

You may have heard that mannitol can help with Parkinson’s disease (PD) symptoms. Researchers are looking into whether this is true. So far, the verdict is mixed.1

What is mannitol?

Mannitol is a natural sugar alcohol. Some people may be familiar with it as an ingredient used to sweeten foods for people with diabetes. It tastes sweet, but it does not raise blood sugar levels like table sugar does. It can also be made artificially from fruit sugars.1-3

Mannitol is approved by the US Food and Drug Administration (FDA) for a few different medical uses. But so far, treatment of PD is not one of them.2

What is the link between mannitol and PD?

Over the years, many foods and supplements have been investigated for their benefits in PD. The idea of a beneficial food or vitamin is very attractive. These items are often much better tolerated than medicines. They usually have fewer side effects too.3

About a decade ago, researchers in Israel published data that mannitol may help with PD. They reported that it broke up clumps of alpha-synuclein protein in lab experiments. These protein clumps are a sign of PD. They have also long been a target for new therapies in PD.4

The researchers next studied it in fruit flies that had received PD gene transplants. Again, the results looked promising. Mannitol broke down about 70 percent of the protein clumps in the experimental flies.4

It is common for researchers to move from animal studies to studies in people. But research into mannitol and PD lagged. This may be because mannitol is a natural product, so profits from using it in commercial therapy would be limited.4

How did CliniCrowd help spur more research?

When it was clear that drug companies were not pursuing mannitol research, patient activists stepped in. A group called CliniCrowd created a website that had instructions for people with PD to participate in a long-term experiment on themselves.4

The data collected by CliniCrowd was produced by what is called citizen science. This is where nonexperts collect and analyze data. There was no doctor overseeing people’s use of mannitol. There was no control group to compare the use of mannitol to. But by early 2021, about 2,480 people with PD had registered on the site to take part.4

Ultimately, the group collected enough data that career scientists were forced to take another look at mannitol. By 2018, a large publicly funded clinical trial was underway in Israel to establish the safety and tolerability of mannitol in people.4

Is there news from clinical trials for mannitol and PD?

Results of a phase 2 clinical trial studying mannitol in people with PD were published in 2022. Phase 2 trials generally seek to learn if a therapy is safe and well tolerated in people. They sometimes also report on how well an intervention works, which is called efficacy.1

The study lasted 36 weeks. Twenty-two people with PD participated and completed the study. Participants started at a low dose of mannitol, taken by mouth. The dose was then increased 4 times over the study period. The highest dose was 18 grams each day.1

Six of the participants could not continue the study at higher doses because of pain or discomfort in their belly. But two-thirds of the participants were able to tolerate the highest dose.1

The study was not designed to determine how effective mannitol was in reducing PD symptoms. There has not been any news about if the study will continue to phase 3 trials. This is when researchers determine how effective a therapy is at achieving treatment goals.1,5

How might it reduce PD symptoms?

Researchers do not really know how mannitol might work in people to change the disease course of PD. But they have a few ideas.1

Mannitol may increase the activity of certain proteins that prevent alpha-synuclein protein clumps from forming on the brain. Alternatively, it may help with removing the protein clumps from the body. Or it may also work as an antioxidant that neutralizes unstable oxygen molecules called free radicals. A buildup of free radicals can increase your risks for certain diseases, including cancer.1,6

What have we learned?

The real lessons learned from mannitol have little to do with its possible benefits. Rather, this story shows us a lot about the drug development process.3

Because mannitol cannot be patented, drug makers cannot make a large profit from it. Even if it does have a beneficial effect on PD, having it tested properly for use in people will perhaps be the hardest bar to clear.3

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