435 replies to this topic

[CycloQuest]

I was thinking about this today:

Trehalose is a protein stabilizer and autophagy enhancer, has been shown to reduce pathological aggregation of proteins within cells in several diseases associated with abnormal cellular-protein aggregation as well as acting as an autophagy enhancer. We also know it is crossing the BBB and poses almost no risks .What about using it in the treatment of NPC type C? Might be a silly idea but....

The two diseases (atherosclerosis and NPC) have different underlying pathologies. Atherosclerosis very simplified happens when macrophages become engorged with fat and cholesterol and become pathological foam cells that line the interior of arteries.

NPC is a lysosomal storage disease associated with mutations in the NPC1 and NPC2 genes (or at least that's what wikipedia tells me). With NPC you get cholesterol deposits but you don't get the pathological foam cells. I think that for NPC, CD is make the cholesterol soluble so that it can be cleared out. For atherosclerosis it is doing that and causing foam cells to revert back to normal macrophages.

So for NPC, I think you're more interested in increasing the solubility of cholesterol, rather than the autophagy effects you get from trehalose. Whereas for atherosclerosis the improved autophagy is of therapeutic benefit. But, someone that is an NPC expert should be looking at trehalose.

I do think these two compounds would be synergistic at least for atherosclerosis.

You are absolutely correct but I think you missed my point completely.
I was not thinking about trehalose for the treatment of NPC because of its promissing results in the treatment of atherosclerosis but because of the human clinical trials in which trehalose is being used for the treatment of different types of ataxia mostly for the treatment of spinocetebellar ataxia. Keyword : autophagy

[aribadabar]

It's simply not possible to look at an eBay ad and tell you if that is a good source.

 

You pay your money and you get some white powder in a jar.  That's all you know.  Is the white power HPβCD?  Does it have impurities?  It all comes down to trust.  And unfortunately, I don't know how to trust someone that is an anonymous seller on eBay.  So, if I were going to use a source like that I'd have to get it tested, and unless you just happen to know someone that can test it for you, that is going to add appreciably to the cost.

 

You are after all going to put this material in your body.  How much risk do you want to incur to save how much money?  Everyone has to arrive at the answer to that calculation on their own.

 

I agree with your points - I just wanted to share a source I found to see if someone dealt with him in the past so possibly can vouch for /steer us away from him.

I am fine with ingesting powders coming from known/reputable/verified sources on Ebay e.g. Nyles7 used to be on Ebay and I bought ITPP from him for oral use that way.

 

However, there is no way I would use a substance for IV administration unless it is coming from a certified medical supplier/lab source and it seems that echoes this thread participants' sentiment.

Edited by aribadabar, 06 September 2017 - 02:02 AM.

[Daniel Cooper]

 

You are absolutely correct but I think you missed my point completely.
I was not thinking about trehalose for the treatment of NPC because of its promissing results in the treatment of atherosclerosis but because of the human clinical trials in which trehalose is being used for the treatment of different types of ataxia mostly for the treatment of spinocetebellar ataxia. Keyword : autophagy

 

 

Indeed, I misunderstood your point as you suggest.

[Puck66man]

I'm new here and unfortunately have genetics that make early onset atherosclerosis a "surprise" after symptoms and being diagnosed with "anxiety". Of course, since my arteries were all clogged.. 3 stress tests and 3 stress echo's later.. no heart issues and then a CT angiogram showed one blockage 80% not in a main artery. Well, they go in to put the stent in and WHAMO.. CT angiograms are not that accurate. 3 days later I'm on the table 8 hours with 5x bypass.

 

MFTHR gene mutation and genetically high LPA likely the culprits. 3x week in the gym, 2-3x week walking 18 holes.. the most unlikely guy to see this happen to. SO:::

I'm really interested in anything that would help. I know all my important numbers.. LDL/HDL which is not as important as particle size and particle number or LPA. And I know my carotid has an issue.

 

I was looking for a thread on proteolytic enzymes. Any thoughts on those as they "say" in combination some can help? The cyclodextrins sound promising.

Thanks

[Daniel Cooper]

You should check out these threads:

 

 

http://www.longecity...rterial-plaque/

 

http://www.longecity...rterial-plaque/

 

http://www.longecity...therosclerosis/

 

 

 

 

[Richard McGee]

Has anyone located a reputable source of 2-hydroxypropyl-β-cyclodextrin food grade powder (willing to sell to the general public)? I am interested in this for oral use only.

[Daniel Cooper]

Has anyone located a reputable source of 2-hydroxypropyl-β-cyclodextrin food grade powder (willing to sell to the general public)? I am interested in this for oral use only.

 

 

These are the people that are making the HPCB for most of the FDA sanctioned trials:

 

http://cyclodex.com/...food-grade.html

 

 

You can order online with a credit card.  Also, CycloQuest posted a Dutch supplier (page 2 I think) that would be my number 2 choice that is a good bit cheaper that I would feel pretty good about for oral ingestion but maybe not IV or subq.

 

 

You really ought to look at CycloQuest's trehalose thread (linked above in my prior post).  That is very interesting as well but you're gonna need IV administration for that one, but it is very low risk in my opinion.  There isn't quite as much animal testing behind it yet, but if I could pay someone a couple of thousand $$ to give me a series of that IV I'd probably sign up for it tomorrow.

[Jschmoe]

 

Has anyone located a reputable source of 2-hydroxypropyl-β-cyclodextrin food grade powder (willing to sell to the general public)? I am interested in this for oral use only.

 

 

These are the people that are making the HPCB for most of the FDA sanctioned trials:

 

http://cyclodex.com/...food-grade.html

 

 

You can order online with a credit card.  Also, CycloQuest posted a Dutch supplier (page 2 I think) that would be my number 2 choice that is a good bit cheaper that I would feel pretty good about for oral ingestion but maybe not IV or subq.

 

 

You really ought to look at CycloQuest's trehalose thread (linked above in my prior post).  That is very interesting as well but you're gonna need IV administration for that one, but it is very low risk in my opinion.  There isn't quite as much animal testing behind it yet, but if I could pay someone a couple of thousand $$ to give me a series of that IV I'd probably sign up for it tomorrow.

 

 

Have you given up on liposomal delivery?

 

-Ken

[Daniel Cooper]

 

 

Has anyone located a reputable source of 2-hydroxypropyl-β-cyclodextrin food grade powder (willing to sell to the general public)? I am interested in this for oral use only.

 

 

These are the people that are making the HPCB for most of the FDA sanctioned trials:

 

http://cyclodex.com/...food-grade.html

 

 

You can order online with a credit card.  Also, CycloQuest posted a Dutch supplier (page 2 I think) that would be my number 2 choice that is a good bit cheaper that I would feel pretty good about for oral ingestion but maybe not IV or subq.

 

 

You really ought to look at CycloQuest's trehalose thread (linked above in my prior post).  That is very interesting as well but you're gonna need IV administration for that one, but it is very low risk in my opinion.  There isn't quite as much animal testing behind it yet, but if I could pay someone a couple of thousand $$ to give me a series of that IV I'd probably sign up for it tomorrow.

 

 

Have you given up on liposomal delivery?

 

-Ken

 

 

I haven't, but someone that knows more about that than me is going to have to offer some advice.

 

The problem that I see with that is that cyclodextrin is itself used as a method to deliver a payload drug.  It is a cyclic oligosaccharide and it will readily take up compounds inside it's ring structure.   I worry that the cyclodextrin ring will load up with phospholipids.  I am concerned that this may render it ineffective for reversing atherosclerosis if it enters the bloodstream loaded in this manner.  That is a totally uneducated and speculative concern so it may be completely invalid, but I wish that someone with more knowledgeable would address it.

 

Maybe @aconita or @niner?

 

Edited by Daniel Cooper, 29 September 2017 - 06:39 PM.

[aconita]

I can't give a definitive answer but lecithin is itself a plaque remover, I would be very surprised by lecithin-cyclodextrins (liposomal) not working synergically and effectively.

 

A simple overview:

 

http://www.ppt-healt...plaque-removal/

[Daniel Cooper]

I guess one of the routes I've always assumed that cyclodextrin worked by was picking up cholesterol inside it's ring structure and moving it out of the arterial plaques.  I don't believe that is it's only mechanism, but perhaps it is an important one.  

 

It just occurs to me that if the cyclodextrin is "preloaded" with phospholipids then this mechanism might not be available.  I do agree that there is some decent evidence that lecithin is anti-atherosclerotic, but since I'm a pessimist at heart I'm not sure that lecithin loaded cyclodextrin would be synergistic.  Maybe?  Certainly if we thought it was delivering phospholipids to the plaques and then picking up cholesterol that would seem to be a great synergy.  I just don't know that I'd assume that was the case.  If the cyclodextrin retained the phospholipid rather than exchanging it for cholesterol, it might do nothing for you at all.

 

 

Edited by Daniel Cooper, 29 September 2017 - 09:37 PM.

[aconita]

I suspect it would be likely for lecithin to encapsulate cyclodextrins instead of the opposite, possibly the phospholipids softening the plaque and cyclodextrins helping picking it up.

 

I am afraid a sure answer isn't easy just by theoretical speculations, some proper research would be necessary in order to elucidate exact outcomes, nevertheless I am quite confident it should work.

 

The point is easy to do, it is cheap (no real need for IV grade cyclodextrins), it is safe (certainly safer than IV), it is very unlikely to cause undesirable side effects or harm, it has the potential to be very effective (we don't really know for sure but....).

 

Giving it a try might be worth, after all we are quite in experimental territory here anyway, better liposomal than IV at this stage, me think..

[Daniel Cooper]

Yeah, you're right.  If the phospholipid is a much larger molecule than the cyclodextrin, you'll get liposomal encapsulation and nothing more.  I haven't looked so I don't know the answer to that.

 

And, seems low risk.  Idea has merit.

 

 

 

 

[Jschmoe]

Ok but I read, somewhere else on this forum I believe, that ultrasonic encapsulation doesn't actually work as is typically described in Youtube videos (ultrasonic cleaner, etc).

 

I have actually used what I thought was liposomal vitamin C ( I made it myself with lecithin, Vit C powder and an ultrasonic cleaner) to clear up a rather nasty throat infection a couple years ago.  It persisted for 2 weeks so I used my homemade lipo-C and it went away in less than a day.

 

So if that wasn't my lipo-c at work, maybe it was just really really strong placebo.

 

Anyway, how do we make REAL lipo encapsulated vitamins without a ton of expensive equipment?

 

-Ken

[aconita]

With a common blender.

[zorba990]

This is interesting. Complexing with Ursolic acid:

https://www.ncbi.nlm...pubmed/24747649

"The synergistic biologic activity of oleanolic and ursolic acids in complex with hydroxypropyl-γ-cyclodextrin.
Soica C1, Oprean C2, Borcan F3, Danciu C4, Trandafirescu C5, Coricovac D6, Crăiniceanu Z7, Dehelean CA4, Munteanu M8.
Author information
Abstract
Oleanolic and ursolic acids are natural triterpenic compounds with pentacyclic cholesterol-like structures which gives them very low water solubility, a significant disadvantage in terms of bioavailability. We previously reported the synthesis of inclusion complexes between these acids and cyclodextrins, as well as their in vivo evaluation on chemically induced skin cancer experimental models. In this study the synergistic activity of the acid mixture included inside hydroxypropyl-gamma-cyclodextrin (HPGCD) was monitored using in vitro tests and in vivo skin cancer models. The coefficient of drug interaction (CDI) was used to characterize the interactions as synergism, additivity or antagonism. Our results revealed an increased antitumor activity for the mixture of the two triterpenic acids, both single and in complex with cyclodextrin, thus proving their complementary biologic activities."

[Daniel Cooper]

Sounds like they are just using cyclodextrin as a carrier to make those two compounds more bioavailable. That is a fairly well studied use of cyclodextrin.  Ironically, while cyclodextrin can be a very effective delivery vehicle for getting many compounds through the GI tract, it itself don't make it through the GI tract to achieve significant plasma levels, which is what we're looking for as a atherosclerosis treatment.

 

 

 

[Puck66man]

What is the difference between the alpha and beta cyclodextrin's

 

also is HPBCD anything to look at? (the B actually is not a normal B)

 

Just wondering as I am not sure about all I'm reading on other sites.

Thanks

[hav]

Has anyone located a reputable source of 2-hydroxypropyl-β-cyclodextrin food grade powder (willing to sell to the general public)? I am interested in this for oral use only.

 

These are the people that are making the HPCB for most of the FDA sanctioned trials:

 

http://cyclodex.com/...food-grade.html

...

 

Have you given up on liposomal delivery?

 

-Ken

 

 

There is some study in that direction... apparently to package highly volatile but insoluble molecules...

 

https://www.ncbi.nlm...in-in-liposomes

 

But Cyclodextrins are liposomal by nature. They are already a complex-forming inclusion agent of oil-soluble molecules, turning them into a water soluble complex that is much smaller than a liposome formed by multiple rod- or string-shaped polar molecules like lecithin. It's a single molecule that already has a ring structure all by itself with ring-solubility polarity... the center of it's ring is hydrophobic while the outside wall of the ring is hydrophilic causing it to pull any smaller oil-soluble molecule into it's center yielding a water-soluble complex. Personally, I think this nature is largely responsible for the health benefits of cyclodextrin... it probably enhances the bio-availability of any oil soluble nutrient it encounters in the digestive tract. I've been using the HP-beta variety for a couple of years now, not by itself, but compounded with resveratrol, cycloastragenol, or silymarin.  Studies show 1:1 complexes tend to multiply average bio-availability by factors of 2x to 5x.  Here's a good discussion of its inclusion complex formation:

 

https://www.oatext.c...pplications.php

 

And a study contrasting HP cyclodextrin combined with Silymarin in various ways (I use physical mixing with mortar & pestle, myself):

 

https://www.ncbi.nlm...les/PMC3159273/
 

Not sure how this might explain its atherosclerosis health benefit. Perhaps in addition to helping transport nutrients beneficial to cardio health, it also facilitates in cholesterol and calcium removal from the circulatory system :

 

https://www.ncbi.nlm...pubmed/21124786

 

Howard

Edited by hav, 24 October 2017 - 07:09 PM.

[OP2040]

hi folks,

I'm bumping this thread because Cyclodextrin is still very relevant.  Trehalose has largely supplanted it for me when it comes to atherosclerosis or alzheimers prevention.  However, i read the following article (admittedly dated) which shows that it could possibly help for retinal issues, and bam I'm back in the cyclo game.  For me, alzheimers (apoe4/het) and macular degeneration are my biggest genetic susceptibilities.  So you can see why this might seem an attrractive option.

 

https://www.scienced...014483515001372

 

So here we're talking eye drops that could clear drusen and potentially prevent or help with any and all retinal diseases.  It's great to know that it would be bioavailable through such an easy pathway. Apparently, for mice, this route of delivery for cyclodextrin reaches the back of the eye.  But I was surprised that the normal oral route of delivery they claim 40% reaches the retina in mice.  So here are the open questions.

 

1. Translatability - mice do not have a macula apparently, but otherwise the structures and the causes of retinal degeneration are similar.  I'm willing to bet the that it it

     gets to the macula, then it should have the same drusen clearing effect.

2. BBB - I am hoping this would also be a good way to get past the BBB.  The retina is close to the brain after all, but that may also be where a barrier exists.  Can

    someone elucidate this for me?  It would be great if it crossed, then we have another target with really easy administration.  I did not read the article very closely, but

    I do recall something about the cyclodextrin getting to the retina and staying there.

3. Ototoxicity - Similar to the brain question.  I would not be worried so much about ototoxicity with the oral, or even IV route.  But the sheer proximity to the ear cilia

     may or may not matter here. 

4. Combinatons - I would like to combine with trehalose for a couple reasons.  First, trehalose eye drops are already used for dry eyes.  Second, clclodextrin may help

    make the trehalose more bioavailable thus helping it reach more of the eye, and there are trehalose/eye studies showing that it is beneficial like it is for pretty much

    anything else.  So all in all, this would seem a happy combination, or at the very least neutral. 

 

 

[Daniel Cooper]

For what it's worth I believe that I have seen eye drops that actually used cyclodextrin as a carrier vehicle to carry other molecules into the eye.  Sticking a target molecule inside a cyclodextrin ring is a pretty popular application.

 

 

Perhaps one of those might be useful.

 

 

 

 

[OP2040]

I haven't seen any cyclodextrin based drops, at least not for quick and easy purchase.  This is definitely something I want to try.  Since I already have plenty screwed up eyesight, I can report back whether it helps or not.  The main thing for me to know beforehand is that it will be safe and I'm not making things worse.  I know these two substances are generally safe, and I don't know why eye drop delivery would change that.

[OP2040]

Do you think if I were to add cyclodextion powder, bought separately, to trehalose eye drops that would be safe.  Are there precautions I should take?

[OP2040]

I may also add N-Acetyle Cysteine Amide based on this article:

 

https://www.scienced...21009121205.htm

 

After being involved in so many discussions about potential or actual interventions for the last few years, I am convinced of one thing.   There is definitely a risk reward phenomenon, and I tend to have a high risk tolerance because my goals are always reversals ad cures, not "slower rate of decline".  I guess that depends on age, health status and genetics.  I see no point in monitoring a disease process (including aging) and doing marginal interventions to slow a rate of decline.  Not only is it depressing, but the false comfort it brings is counterproductive because people basically rest on their laurels.

[masterlock]

Hate to cross post but here is what we do:

 

Here are some easy ways to clear up that nasty plaque.

 

1. Lipo EDTA - Commercially available. Wake up at night, take your one or two grams, fall back to sleep. Eat breakfast a few hours later and mineral supplements around noon. Half life is 45 minutes. Takes forty treatments. At two treatments a week it takes five months. Total cost: ~$800 USD. Bit of a flush.
2. Lipo Trehalose - Make at home with a sonicator. Take daily. Research says 35% plaque reduction in mice. Cheap
3. Lipo 2 hydroxypropyl Beta cyclodextrin. make at home in a sonicator. Research says 75% plaque reduction. They inject it into the brains of children to reduce plaque so it is perfectly safe. In mice fed obscenely plaque causing diets, the daily dose of HPCD prevented any and all plaque buildup. US made expensive. China made cheap.

Of course all can be injected. But the lipo has added benefits. You can research why. Tried them all. Prefer 1 and 3. Take 3 on a daily basis. For instructions, search DIY Lipo Vitamin C or Glutathione.

I wouldn't call something that can cause permanent hearing loss "perfectly safe".

https://www.ncbi.nlm...les/PMC5676048/

Don't know if this has already mentioned (didn't have to to read ever reply), but Cyclodextrin can cause permanent hearing loss.

https://www.ncbi.nlm...les/PMC5676048/

[Daniel Cooper]

I wouldn't call something that can cause permanent hearing loss "perfectly safe".

https://www.ncbi.nlm...les/PMC5676048/

Don't know if this has already mentioned (didn't have to to read ever reply), but Cyclodextrin can cause permanent hearing loss.

https://www.ncbi.nlm...les/PMC5676048/

 

Yes, we've discussed this extensively in this thread.

 

Cyclodextrin is injected Intrathecally (into the spinal column) in children with Niemann Picks disease.  The problem with this compound is that it can cause the loss of hair cells if it makes its way into the inner ear.  However, it does not cross the blood-brain barrier and probably doesn't cross the blood-cochlear barrier.  The problem for these Niemann Pick kids is they are (of necessity) bypassing these barriers because they have to get it into the brain for it to be effective.

 

I published some human trials where it was injected IV (i.e. not intrathecally) and no loss of hearing was noted.   

 

If one made a liposomal preparation of this compound you'd have to convince yourself that this liposomal delivery wouldn't sneak it past the BBB or the BCB.

 

This is something that I've considered but haven't gotten quite desperate enough to experiment on myself with it.

 

The few human trials that I published seemed to back it being safe to inject IV, but liposomal is another animal and I just don't enough about the pharmacodymanics of liposomal delivery to have any confidence in my opinion.

Edited by Daniel Cooper, 20 February 2019 - 08:35 PM.

[OP2040]

I suppose this thread needs updating, not sure if anyone has posted this 2019 study yet. 

https://www.ncbi.nlm...pubmed/30772772

 

This one involves alpha-cyclodextrin, which we all know is much safer and tested in humans.  There are now a few studies out there showing an in vivo effect in humans.  I am back on this one as I found it helped a lot a couple years ago and then I stopped taking it as it got lost in the mess of so many options.  It is probably npt as effective as b-cyclodextrin.  But if any substance shows any level of chelation activity in humans, then taking it over long periods should help. 

 

I believe there's another study showing atherosclerosis reversal in rabbits with oral doses of this, so all in all probably the best option for now.

 

I've been using Trehalose for a couple years now because I find it's very easy to incorporate into my diet as a sugar.  A welcome break from downing supplements.  But I'm fairly convinced it's not doing much of anything, probably due to bioavailability issues from trehalase.

 

Whether we can get cyclos or trehalose to work, they should help with far more than atherosclerosis. As Daniel has mentioned, they are already being used for one genetic disease.  And there are studies for Alzheimer's as well. 

 

[Rocket]

This very deserving thread has sadly dropped off.

 

I am looking for safety of dosing CD and comparisons of alpha and beta types of CD. 

 

Are there any studies or literature someone can point out? 

[Daniel Cooper]

Rocket - 

 

I agree that it is a shame that interest in this compound and it's ability to potentially reverse atherosclerosis has waned.  I think people couldn't get past the potential ototoxicity. 

 

The different varieties of cyclodextrin are discussed in this thread and there are papers from which you can develop some swag at a dose.  The people that are having trouble with ototoxicity are the Niemann Pick patients (almost exclusively children) that are being administered cyclodextrin intrathecally - i.e. into the spinal column.  Cyclodextrin doesn't cross the blood brain barrier so you have to give it intrathecally to those patients who suffer from cholesterol deposits in the brain tissue.  Presumably it also doesn't cross the  blood labyrinthine barrier either so it should not be as much of an issue if administered IV, but we could never establish that with certainty.

 

I was in the camp that IV or other non-intrathecal routes of administering cyclodextrin were likely to have a much lower risk of ototoxicity, and even I didn't have the guts to try it.  I don't want heart disease but I don't want to go deaf either.

 

It's been three years since this thread started, maybe there are new papers that have been published in the interim.  I'll try to do some searching on PubMed in the coming days if no one else takes a crack.

 

BTW - since we generally don't want to self administer IV and cyclodextrin is mostly destroyed in the digestive tract, I think you'd want to look at making this a suppository if you aren't put off by the ick factor. 

[Daniel Cooper]

Ah, here is one new paper on the subject from this year - Cyclodextrin polymer improves atherosclerosis therapy and reduces ototoxicity.