435 replies to this topic

[Daniel Cooper]

A good overview of Cyclodextrin and Ototoxicity - Cyclodextrins and Iatrogenic Hearing Loss: New Drugs with Significant Risk.

 

 

[OP2040]

I've juked the ototoxicity issue by taking Alpha-cyclodextrin.  There is some evidence for a similar effect, though the evidence is not as dramatic and promising as with B-cyclodextrin.  For what it's worth, my hearing ability is legendary among friends and family.  More of an annoying curse if you ask me.

[Daniel Cooper]

I've juked the ototoxicity issue by taking Alpha-cyclodextrin.  There is some evidence for a similar effect, though the evidence is not as dramatic and promising as with B-cyclodextrin.  For what it's worth, my hearing ability is legendary among friends and family.  More of an annoying curse if you ask me.

 

If you're taking it orally it isn't an issue at all, because almost none of it will make it through the gut into the blood plasma.  It also isn't going to treat atherosclerosis for the same reason.  You'll have to do it IV, or subQ, or some other route to get it past the digestive tract.  If you do that, you will potentially have an issue with hearing loss.  It's looking like the effect we want, the efflux of cholesterol out of the arterial walls, is also causing the efflux of cholesterol from the cell membranes of the hair cells in your cochlear causing their death.  Therefore it is hard to get the one effect without the other.

 

There's a reason these cyclodextrins are on the FDAs GRAS (Generally Recognized As Safe) list - they just don't make it to the bloodstream when consumed orally. You can eat large quantities of this stuff all day long and see almost none of it end up in the bloodstream.  There are papers in this thread detailing this issue.

[OP2040]

A couple of the studies I base it on, it was taken orally.  That's not to say the effect seen is definitely due to a-CD, we all know even positive results can be placebo or bad study design, etc.  But we've been through all this before.  There is one study that shows the mechanism may be thorough gut flora, similar to how Berberine works while being poorly absorbed.

[Daniel Cooper]

A couple of the studies I base it on, it was taken orally.  That's not to say the effect seen is definitely due to a-CD, we all know even positive results can be placebo or bad study design, etc.  But we've been through all this before.  There is one study that shows the mechanism may be thorough gut flora, similar to how Berberine works while being poorly absorbed.

 

Could you post those studies?  This thread is a clearing house on cyclodextrin as it applies to atherosclerosis and those studies would be a worthy addition.

[OP2040]

Hi Daniel,

They main study is on my computer, below is the title and synopsis.  There are other studies on it that are in vitro which obviously means nothing here.  And yet others in vivo dealing mostly with diabetic or other diseases which are relevant here because they show in vivo effect. This is all assuming mouse-to-human translation which is yet another conversation.  I could swear I've seen a human study or two but don't have them, maybe they were not addressing atherosclerosis either.

 

2017 "Dietary α-cyclodextrin reduces atherosclerosis and modifies gut flora in apolipoprotein E-deficient mice"

 

 

apoE-knockout mice were fed either low-fat diet (LFD; 5.2% fat, w/w), or Western high fat diet (21.2% fat) containing either no additions (WD), 1.5% α-CD (WDA); 1.5% β-CD (WDB); or 1.5% oligofructose-enriched inulin (WDI). Although plasma lipids were similar after 11 weeks on the WD vs. WDA diets, aortic atherosclerotic lesions were 65% less in mice on WDA compared to WD (P < 0.05), and similar to mice fed the LFD. No effect on atherosclerosis was observed for the other WD supplemented diets. By RNA-seq analysis of 16S rRNA, addition of α-CD to the WD resulted in significantly decreased cecal bacterial counts in genera Clostridium and Turicibacterium, and significantly increased Dehalobacteriaceae. At family level, Comamonadaceae significantly increased and Peptostreptococcaceae showed a negative trend. Several of these bacterial count changes correlated negatively with % atherosclerotic lesion and were associated with increased cecum weight and decreased plasma cholesterol levels.

 

 

It would be interesting if all that was needed to reduce lesions was the right form of fiber fed to gut bacteria.  It doesn't sound as outlandish today as it would have a few years ago for sure.  As I was saying, I think either Berberine or Metformin or both work via this mechanism at least partially.

 

 

[OP2040]

An in vitro study is nevertheless quite interesting because it shows that IF cyclodextrins could get to the bloodstream, a-CD would probably be your best choice, title and snippet referencing other studies below.

 

2109 Alpha-cyclodextrin inhibits cholesterol crystal-induced complement-mediated inflammation: A potential new compound for treatment of atherosclerosis

 

 

In vivo, oral administration of ACD has been shown to reduce levels of proatherogenic lipoproteins and improve fatty acid profiles in LDLr-knock out (KO) mice fed a high-fat/high-cholesterol–containing diet25. Furthermore, oral administration of ACD reduced atherosclerotic lesion size, with only minimal change in plasma lipids, but was associated with potential beneficial changes in gut
flora in apoE-KO mice26. In humans, oral intake of ACD has also been shown to have beneficial effects. In obese type II diabetic patients, oral intake of ACD was shown to increase insulin sensitivity and to reduce LDL-cholesterol in the patients that begun the study with hypertriglyceridemia27. In overweight patients, oral intake of ACD reduced body weight and reduced LDL-cholesterol and total serum cholesterol28. In healthy individuals, oral administration

 

[Daniel Cooper]

Hi Daniel,
They main study is on my computer, below is the title and synopsis.  There are other studies on it that are in vitro which obviously means nothing here.  And yet others in vivo dealing mostly with diabetic or other diseases which are relevant here because they show in vivo effect. This is all assuming mouse-to-human translation which is yet another conversation.  I could swear I've seen a human study or two but don't have them, maybe they were not addressing atherosclerosis either.
 
2017 "Dietary α-cyclodextrin reduces atherosclerosis and modifies gut flora in apolipoprotein E-deficient mice"
 
 
 
It would be interesting if all that was needed to reduce lesions was the right form of fiber fed to gut bacteria.  It doesn't sound as outlandish today as it would have a few years ago for sure.  As I was saying, I think either Berberine or Metformin or both work via this mechanism at least partially.

 
Thanks.  Abstract here: Dietary α-Cyclodextrin Reduces Atherosclerosis and Modifies Gut Flora in Apolipoprotein E-deficient Mice.  I'll post the full article this evening if I get around to it.

 

Without reading the article, I'm going to have a slightly different take on what is going on there. Alpha cyclodextrin is used as a weight loss supplement based on it's supposed ability to encapsulate and sequester fats and allow them to pass through the digestive tract without being digested.  And apparently there is some evidence that it does work for this application and in this manner, i.e. you consume it with a fat containing meal and it allows a reasonable amount of the fats to pass through without digestion.  If that's the case, it might be just mitigating the fat they added to the Western diet fed mice.  That's a useful effect, but it's more of an atherosclerosis prevention strategy rather than an atherosclerosis reversal strategy.  

 

Maybe I've got it all wrong, but we can say that that paper only demonstrates prevention rather than reversal.  Again, prevention is very valuable.  

 

On the other hand, where they were administering cyclodextrin IV they saw pretty rapid reversal of atherosclerosis.  More rapid than I would think likely by changing gut flora which I am certain that CD will do.

 

So, maybe there's two effects in play. 

[OP2040]

Ya, we will not in our healthy lifetimes have something definitive which is why I insist on speculation and educated guesses based on the current research.  The biggest problem to my mind is not just that we constantly reference moue studies but that the mouse studies are almost always models.  Good two see two mouse models covered here, APOE-null and LDL, but nevertheless it doesn't instill confidence.

 

Basically, if one has active atherosclerosis (anyone over ~40) and would like to be avoid humanity's biggest killer until we have better solutions, then we MUST choose among a large variety of studies that can be extrapolated from.   For me, access is also important and that's exactly what a-CD provides.  A good balance of studies, easy access, ok cost, risk-free, and off-target benefits to boot.  I've seen threads focused on cutting edge, inaccessible, potentially harmful, patented therapies go down in flames too many times to wait for them to manifest.  Don't get me wrong, I'm in no way risk averse, it's more about easy access and lack of conclusive trials, which somehow never, ever get done.

[Daniel Cooper]

Well, we're almost never going to get good studies on a compound with no patent potential, which is a shame because there are undoubtedly a plethora of unpatentable compounds with many useful and life changing effects.  

 

It's a pity. That sort of basic not for profit research used to be done by Universities which of course receive significant amounts of public funds.  But, 30 years ago they all realized that they could be out there searching for the next patentable block buster drug just like private industry so they have to a large extent abandoned that kind of research.  In my mind, if they are no longer going to preform that sort of public service, I think the public would be within it's right to reevaluate the funding they receive.  Using pubic funds to capture patents who's proceeds go back to the Universities and the researchers seems ..... inequitable.  It's saying "I'm going to do research on your dime, but if I discover anything useful it belongs to me".

 

We're left with many inexpensive and widely available compounds where we have hints that they have useful effects, but will never have anything definitive.

 

 

 

 

 

 

[OP2040]

Amen to that. 

[Rocket]

Looking for some advice...
I have been supplementing with 1g cyclodextrin 6x a day under my tongue to avoid the digestive system. I have noticed a very slight ringing in my ears.... Is this ototoxicity perhaps?

[Daniel Cooper]

6 grams per day sublingual?  Yeah, I'd halt that right now if you're getting ringing in the ears.  Once those hair cells are gone, they ain't coming back.

 

I always thought if I worked up the nerve to do cyclodextrin I'd get some good wired ear buds and one of the many hearing test apps out there, establish a baseline, and then test my hearing every single day.

 

How long have you been doing this regimen?

 

 

[OP2040]

You didn't tell us the most important part, are you supplementing with Alpha- or Beta-   Beta is most probably ototoxic.  Alpha is not known to be and has actually been tested for it.  I think all the cyclo versions were tested for ototoxicity in one study. 

 

Nevertheless, Daniel is probably right.  If you value your hearing and your atherosclerosis is not terminal, then you should probably stop or reduce the dose. 

 

Interestingly, I do think if a b-cyclodextrin was seen to functionally cure atherosclerosis and yet cause some possibly serious amount of hearing loss, that's a trade-off a lot of people would still take.  After all, we can wait as long as we want for science to regenerate hearing, we don't have that luxury with atherosclerosis which will definitely kill you sooner or later.

[Rocket]

6 grams per day sublingual? Yeah, I'd halt that right now if you're getting ringing in the ears. Once those hair cells are gone, they ain't coming back.

I always thought if I worked up the nerve to do cyclodextrin I'd get some good wired ear buds and one of the many hearing test apps out there, establish a baseline, and then test my hearing every single day.

How long have you been doing this regimen?

3 or 4 days counting today. I also mix a few grams in with homemade pomegranate protein smoothies.

This ringing is so fine that I don't know if I had it before and wrote it off as that's life. Its periodic and not constant. Very faint.

I am getting to the age where I have seen guys in the gym occasionally get taken away on a stretcher, i.e the later 40s. So I started a stack of red rice yeast, pomegranate, mk7, and cyclo.

Edited by Rocket, 17 June 2020 - 12:05 AM.

[Rocket]

You didn't tell us the most important part, are you supplementing with Alpha- or Beta- Beta is most probably ototoxic. Alpha is not known to be and has actually been tested for it. I think all the cyclo versions were tested for ototoxicity in one study.

Nevertheless, Daniel is probably right. If you value your hearing and your atherosclerosis is not terminal, then you should probably stop or reduce the dose.

Interestingly, I do think if a b-cyclodextrin was seen to functionally cure atherosclerosis and yet cause some possibly serious amount of hearing loss, that's a trade-off a lot of people would still take. After all, we can wait as long as we want for science to regenerate hearing, we don't have that luxury with atherosclerosis which will definitely kill you sooner or later.

b-cyclodextrin

Ive read that squalamine has the same ptb (as I recall without looking) effects as trodusquamie so I plan on buying that.

Edited by Rocket, 17 June 2020 - 12:11 AM.

[Daniel Cooper]

b-cyclodextrin

Ive read that squalamine has the same ptb (as I recall without looking) effects as trodusquamie so I plan on buying that.

 

 

If you find a good source for squalamine or need other parties to reach a minimum order please let us know.  I'm interested in squalamine as well.

[adamh]

Why not use serrapeptase? It has no known toxicity if used responsibly and has been proven to dissolve fibrin which holds the blockage together in our arteries. Its also an anti inflammatory, reduces pain after surgery and has other benefits direct and indirect. 

 

https://draxe.com/nu...n/serrapeptase/

 

There are studies out there if you don't like dr axe

 

Edited by adamh, 17 June 2020 - 11:41 PM.

[Rocket]

Why not use serrapeptase? It has no known toxicity if used responsibly and has been proven to dissolve fibrin which holds the blockage together in our arteries. Its also an anti inflammatory, reduces pain after surgery and has other benefits direct and indirect.

https://draxe.com/nu...n/serrapeptase/

There are studies out there if you don't like dr axe

Good info from everyone! There's really too much info for one person to know everything.

I found a source for squalamine and I am planning on buying and megadosing. I will post up when I have more time as I am moving to a new house and swamped with all the busy work changing addresses and packing.

From what I read on trodusquamie, squalamine *may* be a winning ticket for us. Maybe someone else can read up... I am just buried in moving.

Its threads like this and you guys that make longevity a great resource!

I am getting blood work tomorrow as a pre stack as I stopped everything until the blood work as I wasnt on anything long enough to have a lasting effect on blood work.

Then I am going back on my heart stack along with an anti aging stack of hgh peptides, dhea for insulin sensitivity, lipsomal resveratrol, dutasteride EOD (to keep bph in check as I age), and epithalon with periodic dasatanib.

[Daniel Cooper]

We actually have a multi-page thread on trodusquamie. You'll find it if you search.
 
Edit to add links:
 
Trodusquemine reverses atherosclerosis
 
Trodusquemine Reverse Plaque - Group Buy Share Data

Edited by Daniel Cooper, 18 June 2020 - 12:58 AM.

[Rocket]

We actually have a multi-page thread on trodusquamie. You'll find it if you search.

Edit to add links:

Trodusquemine reverses atherosclerosis

Trodusquemine Reverse Plaque - Group Buy Share Data

Well it seems squalamine alsominhibits ptp-1b. Soooooo is that the mechanism by which trodusquemine clears arteries? That's the question.

[Daniel Cooper]

Well it seems squalamine alsominhibits ptp-1b. Soooooo is that the mechanism by which trodusquemine clears arteries? That's the question.

 

Honestly, I don't think we know exactly why it clears arteries.  I'm skeptical of that proposed ptp-1b mechanism since there are other compounds with a similar effect and no one has ever noticed that they miraculously clear clogged arteries.

 

But, the research looks promising and squalamine is structurally so similar I'd take the chance it would have a similar effect.  It has been shown to have similar in vivo effects in other areas except it doesn't cross the BBB.  The Parkinson's patients are looking at trodusquemine specifically because it does.

[Rocket]

A lot of nature has chemicals with similar properties. Creatine is a myostatin inhibitor, but it's very weak compared to the injectable myostatin inhibitors, as an example, and creatine won't cause muscle growth.

Green tea also affects ptp1b as another example and isn't there anecdotal reports of green tea and heart disease?

Well I'll have it b in hand in about 10 days to add to my stack. I literally know of no one online talking sqalamine so I'll be a lab rat.

Edited by Rocket, 19 June 2020 - 05:04 PM.

[Daniel Cooper]

The question for you is how to dose it.  You ought to read the relevant papers carefully.  If I recall, the mice that got a single dose of trodusquemine showed arterial plaque regression.  Those that got trodusquemine continuously for a period of time did not.  If I remember that correctly, I don't know what the hell to make of that.

 

 

 

 

[Rocket]

The question for you is how to dose it. You ought to read the relevant papers carefully. If I recall, the mice that got a single dose of trodusquemine showed arterial plaque regression. Those that got trodusquemine continuously for a period of time did not. If I remember that correctly, I don't know what the hell to make of that.

Yes, those test results are counter to intuition.

[Wookie]

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.

 

I think this is saying adding a phospholipid like PS or PC to make the treatment more effective. 

 

https://patents.goog...2002043742A1/en

 

 

 In a preferred embodiment the treatment comprises administering a composition containing the low affinity cyclodextrin to the individual, such as by intravenous administration. The composition may also contain phospholipid vesicles. Alternatively, it is possible that the individual may have sufficient levels of phospholipid vesicles in their bloodstream to not require further administration of phospholipid vesicles. In a further aspect, the present invention provides a method for treating atherosclerosis in an individual by treating said individual with a cyclodextrin having a high affinity for cholesterol, said cyclodextrin being present with phospholipid vesicles and in a concentration below that at which said cyclodextrin can remove free cholesterol from cells in the absence of phospholipid vesicles

[Wookie]

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.

 

 

Did you ever end taking HPBCD orally? If so did you get any benefits or have any tests done? I just started taking it orally along with phosphatidylserine.  

[Wookie]

Good info from everyone! There's really too much info for one person to know everything.

I found a source for squalamine and I am planning on buying and megadosing. I will post up when I have more time as I am moving to a new house and swamped with all the busy work changing addresses and packing.

From what I read on trodusquamie, squalamine *may* be a winning ticket for us. Maybe someone else can read up... I am just buried in moving.

Its threads like this and you guys that make longevity a great resource!

I am getting blood work tomorrow as a pre stack as I stopped everything until the blood work as I wasnt on anything long enough to have a lasting effect on blood work.

Then I am going back on my heart stack along with an anti aging stack of hgh peptides, dhea for insulin sensitivity, lipsomal resveratrol, dutasteride EOD (to keep bph in check as I age), and epithalon with periodic dasatanib.

 

 

Did you ever do this?? I am trying to do the same. What dose, did it work? Thank you in advance.

[Rocket]

Did you ever do this?? I am trying to do the same. What dose, did it work? Thank you in advance.

I am still in process. I bought a new house and moved and at the same time started taking college classes in mathematics for fun and my gym reopened soooo I am back to lifting seriously . I also started a website all at the same time.

Sqalamine and avodart in process of being shipped. My most recent psa test shower a 0.2 increase a month ago over a years time. I am at that age where I believe all men should take something for bph especially when messing around with Hgh as Hgh can cause the prostate to grow. Hgh peptides didn't pan out per blood work.... That's the problem with peptides is they are hit end miss with quality. Last time from this supplier they were flawless in blood work. This time..... Lets say they were probably damaged molecules I received. Dasatanib isn't time yet. My liposomal resveratrol supplier is out of business and I need to find a new source.

In short I've been swamped with activities and I am just now getting back on track.

I am looking forward to getting the Sqalamine.

When my doctor saw the psa increase 0.2 he immediately started talking biopsy biopsy biopsy. Come on dude 1.2 and middle age is normal and could be affected by the rowing machines at the gym!

[Wookie]

6 grams per day sublingual?  Yeah, I'd halt that right now if you're getting ringing in the ears.  Once those hair cells are gone, they ain't coming back.

 

I always thought if I worked up the nerve to do cyclodextrin I'd get some good wired ear buds and one of the many hearing test apps out there, establish a baseline, and then test my hearing every single day.

 

How long have you been doing this regimen?

 

 

Looking for some advice...
I have been supplementing with 1g cyclodextrin 6x a day under my tongue to avoid the digestive system. I have noticed a very slight ringing in my ears.... Is this ototoxicity perhaps?

CDP or Cyclodextrin polymer

 

Clears plaque more effectively with no hearing loss

 

 

https://www.x-mol.com/paper/6011517

 

https://www.scienced...168365919307400

 

Group buy? I miss cheeseburgers....