Polyethylene glycol: constipation and alpha-synuclein

My version of PD, 8 years post diagnosis, includes an almost continuous problem with constipation. The thing that helps most is Movicol (macrogol 3350, polyethylene glycol).

According to Wikipedia[1] it works by:

"Macrogol is an inert substance that passes through the gut without being absorbed into the body. It relieves constipation because it causes the water it is taken with, to be retained in the bowel instead of being absorbed into the body. This increases the water content and volume of the stools in the bowel, making them softer and easier to pass."

Interestingly, approximately 70% [2] of milk in the UK is sold in HDPE (high density polyethylene).

That's the good news. Now for the bad news.

Uversky et al. write [3]:

"The aggregation and fibrillation of alpha-synuclein has been implicated as a causative factor in [Parkinson's disease], and the process of fibril formation has been intensively studied in vitro with dilute protein solutions. However, the intracellular environment of proteins is crowded with other macromolecules, whose concentration can reach 400 g/l. ... The addition of high concentrations of different polymers (proteins, polysaccharides and polyethylene glycols) dramatically accelerated alpha-synuclein fibrillation in vitro."

Tag: johnt:alpha-synuclein

References

[1] http://en.wikipedia.org/wiki/Movicol

[2] http://plastics.sabic.eu/cases/_en/messageinabottle.htm

[3] "Accelerated alpha-synuclein fibrillation in crowded milieu."
Uversky VN, M Cooper E, Bower KS, Li J, Fink AL
FEBS Letters [2002, 515(1-3):99-103]
http://europepmc.org/abstract/MED/11943202

John

It doesn't sound like a problem since the tests were in vitro and polyethylene isn't absorbed from the gut.

All the info I've read states that polyethylene glycol is inert. Hate to think such a useful product suddenly becomes ert just to mess with our minds . . . .

Jon

Gerry, thanks for your reply. I think in typical cases you are correct, but I'm not so sure whether this will apply to all specific cases.

In our analysis we need to be careful because Polyethylene Glycol (PEG) comes in a range of weights and shapes and any sample may be a mixture of these types. Wikipedia states that [1]:

"The numbers that are often included in the names of PEGs indicate their average molecular weights (e.g. a PEG with n = 9 would have an average molecular weight of approximately 400 daltons, and would be labeled PEG 400. Most PEGs include molecules with a distribution of molecular weights (i.e. they are polydisperse)."

"Since purification and separation of pure oligomers is difficult, the price for this type of quality is often 10-1000 fold that of polydisperse PEG."

We are concerned with PEG 3350 which means that it has an average molecular weight of 3350. I've not been able to find details of the polydispersity. The literature reports that absorption decreases as the molecular weight increases. 3350 is a relatively high figure, which is good news. However, any polydispersity will lead to higher absorption figures than with pure 3350.

Pelham et al [2] report that in healthy subjects 0.19% of the dose was excreted in the urine, and that PEG was quantifiable in plasma for 12-18 hours.

Rxlist states [3]:

"Essentially, complete recovery of MiraLax (polyethylene glycol 3350 - otc) was shown in normal subjects without constipation. Attempts at recovery of MiraLax (polyethylene glycol 3350 - otc) in constipated patients resulted in incomplete and highly variable recovery."

That's good news, provided that you're not constipated. Unfortunately, I am.

It is also worth considering what goes on in the gut. If PEG comes into contact with enteric alpha-synuclein, it may do its damage without ever being absorbed.

My response? You have to put this in perspective, balancing a certain benefit, with an uncertain harm. So, I'll continue to take Movicol, but I'll monitor the situation.

Tag johnt:alpha-synuclein

References

[1] http://en.wikipedia.org/wiki/Polyethylene_glycol

[2] "Clinical trial: single- and multiple-dose pharmacokinetics of polyethylene glycol (PEG-3350) in healthy young and elderly subjects"
AP&T, June 2008
http://onlinelibrary.wiley.com/doi/1...8.03727.x/full

[3] http://www.rxlist.com/miralax-drug/c...armacology.htm

John

An excellent and informative rejoinder. Thanks for looking into this in more detail.