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Common Natural Sweetener May Treat Parkinsonís Disease

The natural sweetener mannitol, a common component of sugar-free gums and candies, may hold potential for Parkinson’s disease (PD) according to a study, funded in part by the Parkinson's Disease Foundation, in the June 14 issue of The Journal of Biological Chemistry. In this initial study, the compound not only improved PD-like symptoms in fruit flies, but also reduced harmful levels of alpha-synuclein (the hallmark of PD) in the brains of fruit flies and mice.

Researchers took interest in mannitol because, when given as an injection, it has two unique properties. First, it can disrupt the blood brain barrier (meaning the drug can reach the brain). Second, it is able to stop some proteins in the body from clumping together, which is interesting in light of the fact that clumps of the protein alpha-synuclein are a well-known sign of Parkinson’s disease.

Knowing these properties, Daniel Segal, Ph.D., and Ehud Gazit, Ph.D., at Tel Aviv University, in Israel, wondered whether mannitol might be helpful for Parkinson’s disease. So they examined mannitol in the lab and in fruit flies and mice. They studied whether mannitol could improve the motor symptoms of fruit flies with PD-like symptoms, and whether it changed levels of alpha-synuclein in all three experiments.


  • In the test tube, mannitol injections prevented alpha-synuclein protein from clumping into the Lewy bodies that form in the brains of people with PD.
  • In the fruit fly model of PD, mannitol injections restored the flies’ normal movements, for example their ability to climb up test tubes.
  • In the same flies, mannitol reduced alpha-synuclein clumps by 70 percent.
  • In the mice model of PD, mannitol injections reduced alpha-synuclein clumps in several areas of the brain involved with classic PD and protected dopamine-producing neurons, the brain cells affected in PD.

What Does It Mean?

This initial study demonstrates the potential ability of mannitol to prevent alpha-synuclein clumping that takes place in PD. The results indicate that mannitol should be studied for its potential to treat PD.

In the study, mannitol prevented alpha-synuclein from clumping in all three experiments – in the test tube and in the brains of fruit flies and mice with a PD-like condition. Scientists suggest that mannitol appears to function as a chemical chaperone, meaning that the sweetener stabilizes proteins like alpha-synuclein and prevents them from inappropriately clumping together. In support of this idea, feeding mannitol to fruit flies improved their PD-like symptoms, allowing the flies to regain their normal movements.

Yet there is a long stretch from improving the behavior of flies to treating PD symptoms in people. Researchers need to test the ability of mannitol to improve PD symptoms in other animal models of PD, (e.g., in additional mice models). If the results hold up in mice, then mannitol could be tested in clinical trials for the treatment of PD in people.

The US Food and Drug Administration (FDA) has already approved an oral form of mannitol as a diuretic to help flush excess water out of the body, and a mannitol injection to prepare people for chemotherapy.  But much research needs to be done before we understand the impact on people with PD, for example, what doses would be needed to be safe and if the drug would be effective.

People with PD should not attempt to medicate themselves by eating large amounts of sugar-free candy or chewing gum. Even if they were able to consume enough mannitol to reach the level fed to fruit flies, there is currently no evidence that this will help their Parkinson’s.

Reference: Shaltiel-Karyo R, Frenkel-Pinter M, Rockenstein E, Patrick C, Levy-Sakin M, Schiller A, Egoz-Matia N, Masliah E, Segal D, Gazit E (2013) A Blood-Brain Barrier (BBB) Disrupter Is Also a Potent α-Synuclein (α-syn) Aggregation Inhibitor: A Novel Dual Mechanism Of Mannitol For The Treatment Of Parkinson Disease (PD). J Biol Chem 288:17579–17588. DOI: 10.1074/jbc.M112.434787

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Source Date: Jul 10 2013