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Cyclodextrins and atherosclerosis

plaque atherosclerosis cyclodextrin cardiovascular disease

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#31 Daniel Cooper

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Posted 24 August 2017 - 11:06 PM

Has anyone found what they believe to be a safe source of HPβCD?  Anyone dosing themselves?

 

 

 



#32 PWAIN

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Posted 25 August 2017 - 02:42 AM

Has anyone found what they believe to be a safe source of HPβCD? Anyone dosing themselves?


I never found a source for that which is one reason I decided to just go with beta cyclodextrin. I get mine from ebay from a guy in the UK. His price is very reasonable and the product is good.

Since last time I posted here, I have been taking 1 capsule (approx 700mg) every day. I have not got anything to off other than subjective results. I don't generally seem to respond to most stuff I take so any results I do experience I consider most likely valid but that is just my personal opinion.

The main difference I have noticed is when walking fast (usually as part of getting to/from work) I experience a decreased level of discomfort in my chest. It is not completely gone but I do feel that there is a decent improvement. This discomfort is the reason I initially went to the doctor to get checked out along with discomfort sometimes when in bed. I have not experienced the discomfort in bed for a few months so I'm not going to attribute that to cyclodextrin but I suspect it has helped keep that at bay.

I plan to continue using beta cyclodextrin until I have used up the 600mg I brought and then I'll review. I feel this is working for me but it is going to take time to complete it's work.

I hope this info is useful to someone. I would love to see more testing and development of the cyclodextrin family.

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#33 Kevinsan

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Posted 25 August 2017 - 02:50 AM

cyclodex.com/beta-cyclodextrin-food-grade.html They also have pharma grade.



#34 Daniel Cooper

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Posted 25 August 2017 - 03:35 AM

Great source Kevinsan.

 

That company (CTD Holdings) is one of the companies that has won approval from the FDA to conduct CD trials for the treatment of Niemann Pick.  And in fact, most of the Niemann Pick people that are using CD on a compassionate use basis seem to be sourcing their HPBCD from that company, so they should be a reliable source.  I had no idea they would make it so easy to purchase HPBCD online.

 

That is who I intend to purchase from at this point.

 

 

 

 



#35 PWAIN

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Posted 26 August 2017 - 03:49 AM

So would it be best to inject this stuff? Would you use the Hydroxypropyl BCD - Endotoxin Controlled for injection or the Hydroxypropyl BCD - Pharmaceutical Grade? Is sub cutaneous ok or does it have to go in a vein? The food grade seems quite expensive if you are having a gram a doy or something like that. What are your thoughts Daniel? What are you planning to do?



#36 Daniel Cooper

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Posted 26 August 2017 - 04:13 AM

So would it be best to inject this stuff? Would you use the Hydroxypropyl BCD - Endotoxin Controlled for injection or the Hydroxypropyl BCD - Pharmaceutical Grade? Is sub cutaneous ok or does it have to go in a vein? The food grade seems quite expensive if you are having a gram a doy or something like that. What are your thoughts Daniel? What are you planning to do?

 

If you are not worried about ototoxicity and were capable of doing it yourself (no doctor is likely to assist) then yes, clearly you'd rather administer IV.  You could do subQ as well, but somewhere in the "reversing arterial plaque" thread I calculated the volume you'd likely need and it was rather large for a subQ injection.  More likely multiple injections.

 

I am much less worried about ototoxicity than when we started this thread. We now have an attestation of substantial doses IV in human subjects without causing hearing damage.  But, I wouldn't say the risk is zero.  But, the risk never goes to zero.

 

Right now my best guess at a plan is 5g/per day oral for a month.  That's about $150 worth.  If this works I don't think you will need or want to take this 365 days a year.  I might repeat these monthly cycles every other month or so for awhile though.

 

I'm not ready to start yet.  I'm currently navigating around some other unrelated health issues at the moment and I don't want to muddy the water.  Maybe late this year/first of next year.

 

In the meantime I'm going to try to figure out the answers to the following questions:

 

1.) What percent of oral HPβCD ends up in bloodstream?

2.) Can we trade concentration against duration or is there a minimum threshold level needed for the anti-atherosclerotic effect?

 

The most encouraging recent news is that Kevinsan does appear to have found us a decently safe vendor.  I do expect that some of the other cheaper vendors would work as well, but without testing the material how could you be sure?



#37 CycloQuest

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Posted 30 August 2017 - 11:34 AM

Sorry to jump in like this but I saw you disscusing dosage/safety and thought this might be of interest.

2500mg/kg IV hydroxypropyl beta cyclodextrin?

http://addiandcassi....extrin-therapy/

Your thoughts?

Many thanks

Edited by CycloQuest, 30 August 2017 - 12:29 PM.


#38 CycloQuest

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Posted 30 August 2017 - 02:03 PM

Also you guys might be interested in this dutch supplier :

http://www.cyclodext...a-cyclodextrin/

Cheers

Edited by CycloQuest, 30 August 2017 - 02:20 PM.

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#39 Daniel Cooper

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Posted 30 August 2017 - 03:35 PM

There's no doubt that that sort of dose (2,500mg/kg) is not lethal.

 

The question is, at what level is it ototoxic?  If your child has Niemann Pick, whether or not they go deaf isn't your primary concern. But, for the rest of us ...

 

That said, I generally do believe we've probably overblown the issue of ototoxicity.  There are papers here that we've linked to that show that you can do IV infusions of substantial doses of HPβCD without incurring ototoxic effects.  And, where you see the ototoxicity really coming into play is with these animal trials for Neimann Pick where they are infusing intrathecally (into the spinal fluid).  This will make the ototoxic issue much worse since I assume that getting inside the blood brain barrier also gets you inside the blood cochlear barrier.  Those of us interested in this from the point of view of atherosclerosis have no interest in intrathecal infusion.

 

It was interesting that they did mention that they were looking at subcutaneous administration.   That would be very interesting to us.  It would be nice to find out more details about that.  Also, some information on what ototoxic effect these Niemann Pick cases are seeing would be enlightening as well.  I think because of the details of what they are doing they represent a worse case scenario for this issue.

 

We really should try to gleam as much information from the Niemann Pick work as possible.  These doctors, parents, and patients have by far the most experience with HPβCD.  I would like to try to reach out to a clinician treating these patients if possible.  I would however not encourage people to bother the parents.  These are after all parents of children who have life threatening illness and we should be mindful of that.

 

 

 

 



#40 CycloQuest

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Posted 30 August 2017 - 05:31 PM

This is a fairly new one from NPc research:

http://www.raredr.co...nn-pick-type-c1

Edited by CycloQuest, 30 August 2017 - 05:38 PM.

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#41 Daniel Cooper

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Posted 30 August 2017 - 05:38 PM

Also you guys might be interested in this dutch supplier :

http://www.cyclodext...a-cyclodextrin/

Cheers

 

 

Interested.  It's the right compound.  It's all a matter of trusting the supplier and having faith that you're actually getting what you think you're getting.  Would like to know more about this source.

 

 

Clearly it's much cheaper than the HPβCD that CTD Holdings is selling.  On the other hand, people are running FDA trials with CTD's product right now so we have a certain comfort level with the quality of that product.


Edited by Daniel Cooper, 30 August 2017 - 06:16 PM.

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#42 Daniel Cooper

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Posted 30 August 2017 - 09:20 PM

This is a fairly new one from NPc research:

http://www.raredr.co...nn-pick-type-c1

 

 

Very interesting.  It's good that they may be honing in on a MOA and it may not be what was initially thought.



#43 CycloQuest

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Posted 31 August 2017 - 09:19 AM

Also you guys might be interested in this dutch supplier :

http://www.cyclodext...a-cyclodextrin/

Cheers


Interested. It's the right compound. It's all a matter of trusting the supplier and having faith that you're actually getting what you think you're getting. Would like to know more about this source.


Clearly it's much cheaper than the HPβCD that CTD Holdings is selling. On the other hand, people are running FDA trials with CTD's product right now so we have a certain comfort level with the quality of that product.


I can see you point of view but mine is slightly different as follows :

People do run FDA approved trials with CTD's cyclodextrin but FDA did not approve CTD's cyclodextrin but the use of cyclodextrin in a certain medical setting etc and it hapened that CTD's cyclodextrin was used initially by the Hempels so it happened that CTD got involved in all this ( stand to be corrected). What I want to say is that I think the dutch vendor should be "investigated" to see for example if they do sell endotoxin free cyclodextrins and also I would even go over there to just see who they are. It is only around 5-6 hours from where I live in London so...I myself am about to start self administration of IV high dose trehalose infusions in a couple of months my interest in cyclodextrins is to complement the trehalose treatment.

Edited by CycloQuest, 31 August 2017 - 09:29 AM.


#44 Daniel Cooper

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Posted 31 August 2017 - 01:58 PM

I guess my point on CTD's cyclodextrin is that it has been used widely, IV and intrathecally, in high doses, and we're not aware of any issues so far.  So, that does build quite a bit of confidence in that as a source.

 

Your Dutch supplier also looks very legitimate to me as well.  I don't think I'd feel bad about using them either after I got some more information on the endotoxin issue.

 

I'm very interested in your trehalose infusion.  Maybe it would be a good idea to start a separate thread on that?

 

And you going to be able to do anything to measure your progress?  Perhaps a caridoid ultrasound or a CAC score?

 

 



#45 CycloQuest

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Posted 31 August 2017 - 02:15 PM

I guess my point on CTD's cyclodextrin is that it has been used widely, IV and intrathecally, in high doses, and we're not aware of any issues so far. So, that does build quite a bit of confidence in that as a source.

Your Dutch supplier also looks very legitimate to me as well. I don't think I'd feel bad about using them either after I got some more information on the endotoxin issue.

I'm very interested in your trehalose infusion. Maybe it would be a good idea to start a separate thread on that?

And you going to be able to do anything to measure your progress? Perhaps a caridoid ultrasound or a CAC score?

I have emailed the dutch supplier asking for endotoxin controlled (free) and pricing so lets see.
I will start a new thread on trehalose as I think the more we are the better and I am willing to share any info and progress.
Yes I do plan to monitor the situation by ultrasound, CTA etc ( I will cut the costs by flying to eastern Europe and paying around 20% of the costs of private in UK, including flight and hotels).
Are photos allowed on this site as I could post photos of my lab equipment, preparation and protocols so anyone can see ( of course I do not encourage anyone to do what I am about to do).

Edited by CycloQuest, 31 August 2017 - 02:16 PM.


#46 Daniel Cooper

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Posted 31 August 2017 - 03:30 PM

Looks like images are supported.  Go to "more reply options" and find the Image button.  You'll need some picture hosting service that support 3rd party hosting.

 

 

68168-23-0%20(7585-39-9).gif

 

 



#47 CycloQuest

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Posted 02 September 2017 - 07:17 AM

About the Company:
CTD Holdings, Inc. is a biotechnology company developing cyclodextrin-based products for the treatment of disease, including Trappsol® Cyclo™, an orphan drug designated product, for the treatment of Niemann-Pick Type C, a rare and fatal genetic disease in young children. Additional indications for the active ingredient in Trappsol® Cyclo™, including peripheral artery disease, diabetic nephropathy, and acute viral infections, are also in development.

Taken from the link below and we can clearly see that they are looking at this compound to be used for PAD.

http://m.marketwired...tdh-2045983.htm

#48 aribadabar

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Posted 04 September 2017 - 10:24 PM

Fascinating discussion.

 

What about this HPβCD source:

http://www.ebay.com/itm/High-quality-2-Hydroxypropyl-Beta-Cyclodextrin-HPBC-Purified-99-25-g-/291801167110?hash=item43f0b47506:g:e3QAAOSwZd1VVkxM

 

Looks pretty affordable to me though it may or may not be genuine stuff ( one negative buyer feedback).


Edited by aribadabar, 04 September 2017 - 10:34 PM.


#49 CycloQuest

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Posted 05 September 2017 - 08:55 AM

Fascinating discussion.

What about this HPβCD source:
http://www.ebay.com/itm/High-quality-2-Hydroxypropyl-Beta-Cyclodextrin-HPBC-Purified-99-25-g-/291801167110?hash=item43f0b47506:g:e3QAAOSwZd1VVkxM

Looks pretty affordable to me though it may or may not be genuine stuff ( one negative buyer feedback).

Link does not work for me. Anyway the one you should look for must be endotoxin free. As Dan Cooper said, CTD's compound has a track record so even though the price is quite high it is my first choice.I have found one dutch supplier but not impressed because they did not answer my email.

Edited by CycloQuest, 05 September 2017 - 08:56 AM.


#50 aribadabar

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Posted 05 September 2017 - 06:54 PM

 

Fascinating discussion.

What about this HPβCD source:
http://www.ebay.com/itm/High-quality-2-Hydroxypropyl-Beta-Cyclodextrin-HPBC-Purified-99-25-g-/291801167110?hash=item43f0b47506:g:e3QAAOSwZd1VVkxM

Looks pretty affordable to me though it may or may not be genuine stuff ( one negative buyer feedback).

Link does not work for me. Anyway the one you should look for must be endotoxin free. As Dan Cooper said, CTD's compound has a track record so even though the price is quite high it is my first choice.I have found one dutch supplier but not impressed because they did not answer my email.

 

How about this link : http://tinyurl.com/y9qbnkmw

He asks $10 for 25g.

 

Would orally/sublingually work as an administration route and if yes, what % ends up in the bloodstream or IV is a must?



#51 Daniel Cooper

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Posted 05 September 2017 - 07:43 PM

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.

 

 

 


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#52 CycloQuest

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Posted 05 September 2017 - 07:51 PM

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.


Spot on !!!

#53 aconita

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Posted 05 September 2017 - 08:56 PM

Especially so if are planning to go IV



#54 Daniel Cooper

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Posted 05 September 2017 - 09:12 PM

Especially so if are planning to go IV

 

 

I've been reading that some of the NPC people are going subq.  That might actually be more attractive since we can generally do that ourselves and it should spread the dose out over time which should lower any risks.

 

That is assuming that you're injecting HPβCD and not pancake mix you got off ebay.


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#55 aconita

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Posted 05 September 2017 - 09:42 PM

Sublingual, subq, IM, IV, do we have clinical evidence of how those different routes affects outcomes we are concerned with?

 

Subq and IM are likely the same (the dosage dictates which one of the two more than any other consideration) and sublingual not always easy or practical but IV might be kind of another ballgame.



#56 CycloQuest

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Posted 05 September 2017 - 09:53 PM

Sublingual, subq, IM, IV, do we have clinical evidence of how those different routes affects outcomes we are concerned with?

Subq and IM are likely the same (the dosage dictates which one of the two more than any other consideration) and sublingual not always easy or practical but IV might be kind of another ballgame.

No we do not have clinical evidence in humas in regards to atherosclerosis but neither had NPC patients when they started advocating/administering. We only have studies on murine models for the effect of beta cyclodextrin on atherosclerosis. NPC patients had murine and feline studies. In my opinion if it is to work then IV is the way.

Edited by CycloQuest, 05 September 2017 - 09:56 PM.

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#57 Daniel Cooper

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Posted 05 September 2017 - 09:54 PM

Almost all of the studies are on IM.  I agree that subq would be similar, but it would achieve a lower peak plasma level in exchange for a longer duration.

 

There's nothing on sublingual that I've seen.  And the quantity of HPβCD you're looking to move into the bloodstream would somewhat prohibitive for sublingual.  

 

You might be able to achieve something rectally, but all the studies I've seen of rectal CD are as a means to deliver some target drug, not the CD itself.  I think I might worry about dragging unwanted compound along with the CD with rectal delivery.

 

We do have one oral delivery study in mice that shows plaque regression on an oral dose that equates to 5 ~ 6 grams/day in a human using the usual man <-> mouse conversion factors.  Whether this actually works in man?  Who knows.  That study is over on the first page.

 

CycloQuest's trehalos info looks at least as interesting as cyclodextrin btw.  And perhaps the two would be synergistic.  Would be nice if we'd get a few more studies sometime soon.

 

 


Edited by Daniel Cooper, 05 September 2017 - 09:54 PM.


#58 Daniel Cooper

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Posted 05 September 2017 - 09:57 PM

 

Sublingual, subq, IM, IV, do we have clinical evidence of how those different routes affects outcomes we are concerned with?

Subq and IM are likely the same (the dosage dictates which one of the two more than any other consideration) and sublingual not always easy or practical but IV might be kind of another ballgame.


No we do not have clinical evidence in humas in regards to atherosclerosis but neither had NPC patients when they started advocating/administering. We only have studies on murine models for the effect of beta cyclodextrin on atherosclerosis. NPC patients had murine and feline studies. In my opinion if it is to work them IV is the way.

 

 

 

That's true.  The fact that CD seems to be therapeutic in NPC patients is encouraging but not dispositive 



#59 CycloQuest

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Posted 05 September 2017 - 10:13 PM

Sublingual, subq, IM, IV, do we have clinical evidence of how those different routes affects outcomes we are concerned with?

Subq and IM are likely the same (the dosage dictates which one of the two more than any other consideration) and sublingual not always easy or practical but IV might be kind of another ballgame.

No we do not have clinical evidence in humas in regards to atherosclerosis but neither had NPC patients when they started advocating/administering. We only have studies on murine models for the effect of beta cyclodextrin on atherosclerosis. NPC patients had murine and feline studies. In my opinion if it is to work them IV is the way.


That's true. The fact that CD seems to be therapeutic in NPC patients is encouraging but not dispositive

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....

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#60 Daniel Cooper

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Posted 05 September 2017 - 10:25 PM

 

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.







Also tagged with one or more of these keywords: plaque, atherosclerosis, cyclodextrin, cardiovascular disease

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