A theoretical way to make mannitol work better

A theoretical way to make mannitol work better

The underlying problem with using mannitol as a therapy for Parkinson's disease is its poor absorption in the gut. Hence it produces gas and in some cases, diarrhea. If the absorption of mannitol can be increased than it may be taken at a lower dose and also decrease its associated side effects.

Other nutrients and drugs are poorly absorbed and there are strategies to increase their absorption, here are a few examples.

Curcumin is a component of the herb tumeric. Curcumin has been tested for an array of conditions and has great potential but it is poorly absorbed. Researchers found that when curcumin is combined with piperine, a known bio enhancer, its absorption increases to as much as 2,000%

Natural Compound in Black Pepper Increases Curcumin Absorption Up to 2000% dailyhealthpost.com/piperin...

Piperine is being used to enhance the absorption of antibiotics so lower doses can be used and the most notable example is its combination with the #2 TB antibiotic rifampicin. The following is a video stating how piperine has been combined with rifamipicin to make a drug called risorine:

Given the above knowledge I asked the question if mannitol, when combined with another substance, could be absorbed better (and here is what I found):

Oleic acid and docosahexaenoic acid cause an increase in the paracellular absorption of hydrophilic compounds in an experimental model of human absorptive enterocytes

".... we investigated whether fatty acids such as oleic acid and docosahexaenoic acid (DHA), both commonly present in food, negatively affect the integrity of tight junctions (TJ) in the intestinal epithelium and thereby increase the absorption of poorly absorbed hydrophilic substances."

"Absorption of (14)C-mannitol increased and trans-epithelial electrical resistance (TEER) decreased in cell monolayers exposed to oleic acid and DHA, compared to controls."

"Our results indicate that fatty acids may compromise the integrity of the intestinal epithelium and that certain lipids in food may enhance the paracellular absorption of poorly absorbed hydrophilic substances."

researchgate.net/publicatio...

END OF ABSTRACT -The remaining text from the downloadable PDF document.

"Substances with surface

active properties, such as fatty acids, have been used in pharmaceutical research as absorption enhancers of hydrophilic drugs which normally are poorly absorbed through the intestinal epithelium...."

"In the present study the Caco-2 cell model, which is

an experimental model of human absorptive enterocytes, was used to examine the effect of oleic acid and DHA on the paracellular absorption of the hydrophilic substances mannitol and Cd. Mannitol is exclusively absorbed in the gastrointestinal tract through the paracellular pathway...."

"Thus, in the present study we investigated whether

fatty acids such as oleic acid and DHA, both normally present in food, compromise the integrity of the intestinal epithelium and therefore enhance the paracellular absorption of poorly absorbed hydrophilic substances such as mannitol and Cd."

"Absorption of 14C-mannitol through the cell monolayers

increased with an increasing concentration of fatty acid as well as over time at 30, 60 and 90 min of exposure (Fig. 1a). The increase of 14C-mannitol absorption was more pronounced, at comparable concentrations, for DHA than for oleic acid exposed cell monolayers."

"We have demonstrated that fatty acids common in

food and food supplements may increase the paracellular absorption of hydrophilic substances, such as mannitol and cadmium (Cd), through mono-layers of Caco-2

cells."

________________________________________________________________________________________

These results are from testing Caco-2 cells: "Caco-2 cells are derived from colon tumours, but

exhibit characteristics of epithelial cells from the small intestine."

_______________________________________________________________________________________

In so many words anyone who is using omega 3 fish oil should use the highest quality, because if there are chemical impurities in the fish oil, the toxins will be absorbed in the small intestine because of DHA. Molecularily distilled fish oil is best because the toxins are removed.

FYI, the most pure fish oil I know of is produced by Supplement Clinic and it is concentrated, purified and given an attractive lemon flavor. I previously had adrenal therapy and had taken this supplement twice a day for approx...8 months - it is pharmaceutical grade fish oil.

One teaspoon contains a huge dose of EPA and DHA omega 3s:

Omega-3 fatty acids2390 mg

EPA1195 mg‡

DHA795 mg‡

supplementclinic.com/Liquid...

________________________________________________________________________________

The idea of combining DHA and mannitol should be done cautiously for the obvious reason. Lets, for the sake of argument, say that DHA drastically increases the absorption of mannitol over the projected 90 minute period and as a consequence, the active effects of mannitol are increased in the body.

From wikipedia:

"Common side effects from medical use include electrolyte problems and dehydration. Other serious side effects may include worsening heart failure and kidney problems."

en.wikipedia.org/wiki/Mannitol

In the above article, mannitol is injected for medical reasons and perhaps we need a study of PD patients being injected with mannitol to bypass its poor absorb-ability in the intestines.

_________________________________________________________________________________

Many people on this site take one tablespoon a day of mannitol and when if they decide to add DHA, the mannitol dose should be greatly reduced as should be the dose of DHA. Taking 795 mg of DHA with 1 tablespoon of mannitol could be very dangerous, so it is obvious that both the doses should be reduced to say, a quarter or 1/8th a dose to start. If negative side effects occur - stop taking the combination.

It is obvious that people melt mannitol in tea then drink it and fish oil with a lemon flavor would be a good compliment - obviously lesser so in coffee.

__________________________________________________________________________________

Again, this is a untested, experimental protocol and if anyone tries this should be ultra cautious because of possible unpredictable results.

Other concerns: Fish oil is a blood thinning agent and cannot be taken with drugs like warfarin.

Good news: DHA is well known to be neuroprotective agent in Parkinson's disease models.

Impact of omega-3 fatty acids in Parkinson's disease

"We recently demonstrated the efficacy of omega-3 fatty acids to protect against neuronal cell death in an animal model of Parkinson's disease."

sciencedirect.com/science/a...

That's all folks, yea that is from a Bugs Bunny cartoon, and I hope you find this interesting.

15 Replies

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  • Thanks.

    What is DHA? Is it fish oil and would a normal health food store supplement of omega 3 fish oil in capsule form work?

    Many thanks

    Marc

  • Yes it is the same DHA omega 3 found in fish oil and kril oil.

  • Thank you and welcome back. I became lost among the detail. Is the conclusion that mannitol in experimental doses would be better absorbed when taken with fish oil. I wonder if this would also help with the distressing amount of gas it generates.

    Thanks

    Best wishes

  • I think so...if it were better absorbed or a different delivery route like an injection was used, flatulence should theoretically lessen. Poor oral absorbability lessens mannitols potential therapeutic effectiveness.

  • Thank you! Most enlightening. My husband is just starting his 3rd week on Mannitol and is only up to 1/2 tsp. 2X.day. His therapeutic dose according to the Clinicrowd.info website is only 2 tsp./day because of his low weight.

    I have been putting it into his Whey protein shake to which I add a number of other nutrients including 1 Tbsp. Progressive Laboratories flaxseed oil in his AM shake. (His Spoectracell Nutrition test showed him low in Oleic acid and this product is high quality and lists how much is in it.) Based on your research I may try dividing it and also include it in the evening one.

    He has not noticed any improvements yet but then he is only at half the recommended dose so far. (I always start out slow on new protocols to lessen problems with side effects.)

    Some people put their mannitol in coffee or tea. Do you have any theories based on your research whether this has any advantage or disadvantage?

  • Black, green, chamomile, oolong and herba mate tea (s)....... and coffee all have components that are good for PD and my major concern was if hot liquid would degrade omega 3 fatty acids. The following article states that canning and frying largely destroy DHA content in tuna:

    omega3innovations.com/blog/...

    Perhaps after the mannitol is dissolved in hot liquid the drink should sit for a while to lower its temperature and prevent fatty acid degradation.

  • hi Rich i was thimking of trying mannitol, what you think and where can i order it from cheaply

  • Check out Amazon and bulksupplements.com

  • parkie13 is correct. Bulk supplements on amazon.com is the best bargain....better than ebay:

    google.com/search?q=d-manni...

    On ebay I found an inexpensive source for DHA omega 3. It is in powder form and derived from algae. This may make it easier to manipulate the amount of DHA when taking it with mannitol. Like I stated in the above thread, with an untested protocol, you should proceed with caution.

    ebay.com/itm/like/322203337...

  • Silvestrov: would 150 milligrams of DHA be safe with 3/4 tablespoon of mannitol? DHA source from Omega-3 Krill Oil & Fish oil softgels. Thanks, Tom from CALIF.

  • Honestly I have no idea. I posted this with ample warnings because it is untested in any way thus starting with lower doses to see what happens. Perhaps you should use 1/2 a tablespoon of mannitol and go from there. I think you should keep the 150 mg dose of DHA as a constant and raise up (or down) the tea/tablespoon dose of mannitol and see what happens. You will never know at what dose of mannitol or DHA is working if you change both variables. That said, 150 mg could be a starter dose of DHA and that too could be manipulated if the dose of mannitol were constant. Because of the lack of supporting information this combination pretty much has to be experimented with.

    I tried to look up the daily requirement for DHA and the various answers were vague, to say the least. They coupled DHA with EPA so there was no real answer from this info.

  • Thanks. I'm also taking 1/2 teaspoon Mucuna pruriens x 2 daily in a.m. & noon. Plus amino acid supplements now. Continuously experimenting. Anything to avoid meds. Please advise. Thanks, Tom

  • silvestrov I wonder if turmeric and piperine also have a similar effect on Mannitol. My husband has been taking it for a month now but hasn't noticed a great deal of benefit. As he has such a 'delicate' stomach, I give him only 1 teaspoon with tea in the morning and another teaspoon with his coffee later on which he seems to tolerate. However, when I mixed a teaspoon of Mannitol with a teaspoon of coconut oil + a small teasp of turmeric/piperine and made it into a paste - it upset his stomach terribly......strange?

  • Okay I am confused too - Mom is taking sinemet with miraex- then we started mucana ( a few doses a day) . The added NAC, and after that ALC and ALA - she has thyroid issues also //

    Lastly just introduced mannitol - 1/4 teaspoon with tea .. she has a horde of other meds also ..

    Today she wasn't doing good , tired, eyes closed so I asked my dad to take her to ER even if it is just to check her vitals - I am on the other coast and feeling so helpless.,

    My question is could any of these have cause some other stuff - she has gained weight , so now she also has cholesterol issues , while the Thyroid wasn't too bad ( taking meds) - but research says ALA affect T3-T4 conversion - so it will affect thyroid right ? Is this true - just when you think it is good , could it be causing other issues ?

    Are there any other side effects we should know about ?

    Also, I know it doesn't matter for PD - but ALA and ALC also causes hair loss ?

  • Sorry I have not been on this site but I have been working to prevent myself from going bankrupt. I had a bunch of unexpected expenses occur and I either work to pay them off or go deep into debt.

    I am not sure about either one of ALA or ALCAR with hair loss but if you suspect them to be the culprit I would stop taking them. When cutting them out of daily supplementation do not change anything else to see if there is a positive effect. I have been taking both for years with no side effects. Sure this is the neurological condition called Parkinson's disease and everyone reacts differently to various supplements.

    If she has a cholesterol problem she should be on niacin every day. Though 250 mg/day of niacin will not significantly effect the hdl/ldl ratio it will bind with the GPR109a receptor and relieve inflammation:

    Low-dose niacin supplementation modulates GPR109A, niacin index and ameliorates Parkinson's disease symptoms without side effects

    onlinelibrary.wiley.com/doi...

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