132 replies to this topic

[Daniel Cooper]

Possibly.  Maybe @aconita will chime in.

 

If it can get the trehalose past the gut wall without it being broken down into glucose, into the bloodstream and then release it's trehalose payload to do the plaque cleanup we'd all like it to do.

 

The really aggravating thing here is that you can't walk into a doctor's clinic, plop down a reasonable quantity of currency, and say "Doc, give me some IV trehalose and keep it coming".  Because governments and their antiquated drug approval processes have inserted themselves between us and the doctor .... purely for our own good you understand .... we are forced to come up with various Rube Goldberg schemes rather than doing it the right way. 

 

Hopefully someone with some sound education on liposomal encapsulation will chime in, but even then without doing various tests to determine how good of a job we did at encapsulation, how much of the encapsulated trehalose is successfully making it past the gut and into the bloodstream and what sort of plasma concentrations we are achieving, we have to take it on faith that what we'd like to have happen is actually happening. 

 

Sorry, just unusually frustrated tonight at the enormous effort we have to go to in order to circumvent the smothering embrace of our munificent protectors.

 

BTW, I don't mean to discourage the idea of liposomal encapsulated trehalose.  Without going to a hell of a lot of trouble to make up your own sterile IV solution and having it administered to yourself as CycloQuest is contemplating, it may be the only viable game in town.

 

 

 

 

Edited by Daniel Cooper, 15 October 2017 - 04:22 AM.

[OP2040]

I've been interested in Trehalose for a long time.  I take about 2 tablespoons orally every day for long periods.  It's probably doing nothing, but it does work great as a sugar substitute so I'm not really losing out.

 

Anyway, just like everyone else here, I'd eventually like to get this stuff circulating in my bloodstream.  Unlike Cyclodextrin, it seems to have almost no downside.

 

Everyone here seems quite educated on these matters, so please excuse me for what a couple questions that stem from complete ignorance.

 

Given that IV administration and liposomal oral both seem like huge pains, why is everyone ignoring IV injection (not continuous) or even SC injection?  I assume there must be something about delivery or purity when it comes to SC as this would be much, much easier to do.  Also, I assume you'd still need the endotoxin-free to avoid a nasty infection.  Thoughts?

[Daniel Cooper]

The quantities we think you need wouldn't be feasible for intramuscular or subcutaneous injection.  And honestly, if can gin up a solution for either of those routes you can put it in a bag and do IV.  The trouble is coming up with a pure sterile solution that is safe to inject. 

 

Liposomal is probably the least trouble if we could find a company that would make it for us.  I was talking to a German company in this business last year about that but let it fall through the cracks.   The only downside is that all of the studies are on IV trehalose, so it's uncharted territory in terms of effectiveness.

 

 

 

 

 

[OP2040]

Thanks Daniel,

I was thinking that we can presume a small quantity would at least have some effect, since 100 grams orally, very little of which probably gets through, seems to have a good effect.  My mom is diabetic, so I've seen SC done hundreds of times, and one-time IV injection I'm sure I could handle.  Something about getting a bag and placing a pick line somehow seems difficult to me. 

 

I agree that the purity/sterility issue is the main concern.  I'm not sure I would bother with liposomal without evidence of delivery.

 

The delivery issue seems like it will end up being the final limiting factor for age prevention/reversal.  It seems like there are already some great, proven concepts for a number of the hallmarks, but no translatable way to deliver.  FOXO4-DRI being the obvious, and pretty awesome, exception.

 

For trehalose, there are two great studies in mice.  One of them shows some reversal of atherosclerotic plaques.  The other shows some reversal of age-related endothelial dysfunction.  Assuming that is translatable, those are THE two big hitters for CVD, not to mention stroke and KD.  This is really quite a huge deal, so I'm hoping we can cook up a good delivery system soon. 

Edited by OP2040, 08 March 2018 - 10:05 PM.

[Daniel Cooper]

Welll, for what it's worth there's an Israeli company that is pursing IV Trehalose for the treatment of degenerative brain diseases (Huntington's, Parkinson's, and Alzheimer's) for which it has also shown some promise.

 

I think they are in phase II trials at the moment.  If they make it out of phase III you'll probably be able to get a doc to prescribe it off label, though the cost is going to be sky high (maybe ~$100k ish).

 

In any case, I think they've made a good case on the safety side of IV Trehalose, which isn't surprising.

 

BTW, don't discount liposomal trehalose.  If IV trehalose works for atherosclerosis, liposomal trehalose also probably works.  In fact, it may work better because it may be better at delivering more compound to the endothelium. 

 

 

[extendcel]

What exactly is a therapeutic dose of trehalose via IV dosage? I see that the solubility of it in water is 68g per 100g of water at 20 degrees Celsius, or 680mg per 1ml of water. Making a subcutaneous injectable would not be difficult. One just needs a powder that is low on endotoxin and other toxic contaminants. For a basic sterile formulation, you can mix the trehalose with deionized water, add 0.9% in weight of benzyl alcohol as a preservative, and then run it through a 0.22/.20 micron filter into a sterile vial. Though the amount of dosage you can get in with subq is an issue, as 1ml is usually the maximum recommended amount. Some solvents may be able to get the concentration up.

Edited by extendcel, 12 March 2018 - 06:42 AM.

[Daniel Cooper]

I would be afraid that putting a bolus of trehalose solution into tissue subcutaneously would probably cause tissue damage.  The concentration would be the issue.  If nothing else you'd probably drive osmotic pressure the wrong way and pull most of the water out of the surrounding tissue.  Sounds like a way to end up with a lot of necrosis at the injection site.  Maybe someone with a better medical background could chime in here.

 

This would not be an issue with a more dilute IV infusion over a longer period of time which obviously isn't going to sit in one localized area for a protracted period.  

 

As for therapeutic dose, I think BioBlast is doing something in the range of 13.5g to 27g IV per infusion weekly over 6 months for neurodegenerative disorders.  I'll bet that you don't need that many treatments to reverse atherosclerosis since the vascular endothelium is highly available to IV infusion.  They did a study in the maximum tolerated dose as well and I want to say it was something like 54g infused, but I can't find those results at the moment.

 

The more I think about it, I really do think liposomal trehalose might be the way to go.  If you could get get several grams into the bloodstream daily, you'd think that might even be more effective that once per week infusions.  And that quantity doesn't sound unrealistic to me.  

 

Another plan that has also been discussed is to take something that would knock out the enzyme trehalase which is responsible for the digestion of trehalose temporarily, then simply consume plain old trehalose.  That's something that should be looked at as it sounds promising as well. 

 

 

 

Edited by Daniel Cooper, 12 March 2018 - 03:35 PM.

[Daniel Cooper]

BTW guys, here's a 2016 study showing some benefit from 100g oral trehalose per day:

 

 

https://www.ncbi.nlm...ing-08-1167.pdf

[aribadabar]

BTW guys, here's a 2016 study showing some benefit from 100g oral trehalose per day:

 

 

https://www.ncbi.nlm...ing-08-1167.pdf

 

Thanks for pointing to this study.

 

I decided to run it at 25g/d for the stated 12 weeks via a homemade liposomal mix prepared by a blender with lecithin and then sonicated with a ultrasonic jewelry cleaner hoping that I am approaching the bioavailability of the 100g oral dose.

 

I have no idea how my plaques are but I guess I have some as I am approaching 40 so I guess it won't hurt.

[Heisok]

The original Nature article was published in Nature volume 553, pages 291–294 (18 January 2018). My only conclusion would be to avoid taking any Trehalose orally if I were to be put into a situation which might expose me to favoritism of C. Dificile of any sort. Maybe antibiotic treatment or hospital or other medical exposure. This could also suppor for me that I personally would ONLY choose IV  treatment. Others might come to different conclusions.

 

 

"On the basis of these (following) observations, we propose that the widespread adoption and use of the
disaccharide trehalose in the human diet has played a significant role
in the emergence of these epidemic and hypervirulent strains

 

Both isolates, in addition to every RT027 strain sequenced so far, contain the L172I
substitution in TreR. RT078 strains were also present in humans before
2001, but epidemic outbreaks were not reported until 2003

 

Second, RT027 and RT078 lineages are phylogenetically distant clades
of C. difficile, yet have convergently evolved distinct mechanisms to
metabolize low levels of trehalose.

 

Third, increased disease severity of a RT027 strain that can metabolize trehalose in our mouse model of
C. difficile infection is consistent with increased virulence of RT027 and
RT078 ribotypes observed in patients.

 

Fourth, the ability to metabolize trehalose at lower concentrations confers a competitive growth advantage
in the presence of a complex intestinal community.

 

Finally, level of trehalose in ileostomy fluid from patients eating a normal diet are
sufficiently high to be detected by RT027 strains.

 

https://www.sciencea...itive-trehalose "A Common Sugar Additive Might Be Driving The Rise of One of The Most Aggressive Superbugs"

"The C. difficile lineages Britton is referring to are RT027 and RT078. When the researchers analysed the genomes of these two strains, they found DNA sequences that enabled them to feed off low doses of trehalose sugar very efficiently.

 

in fact, these particular bacteria need about 1,000 times less trehalose to live off than other varieties of C. difficile, thanks to their genetic make-up.

To test their findings, the scientists experimented with mice given the RT027 strain. In the group given low doses of trehalose, the death rate was much higher – not because of more bacteria, the scientists found, but because the sugar enabled it to produce more poisonous toxins.

Further testing on fluids from three human intestines showed that RT027 was able to grow from small amounts of trehalose, while other bacteria strains weren't.

At this stage it's not certain that trehalose has contributed to the rise of C. difficile, but the study results and the timing of its approval as an additive are pretty compelling. More research will now be needed to confirm the link."

[Daniel Cooper]

That sounds like an excellent plan.

 

The only thing that shies me away from the DIY approach is that I don't have any ability to determine how much trehalose I've actually managed to encapsulate.  But, even if you only get a few grams past the gut wall you'd think that daily use would do some good. In fact, if you could get just 4g per day into the bloodstream, that would be equivalent to BioBlast's 27g weekly infusion.  

 

Still, I'd really like to some some commercial entity with some track record make this as a standard product.

 

 

 

 

[Daniel Cooper]

The original Nature article was published in Nature volume 553, pages 291–294 (18 January 2018). My only conclusion would be to avoid taking any Trehalose orally if I were to be put into a situation which might expose me to favoritism of C. Dificile of any sort. Maybe antibiotic treatment or hospital or other medical exposure. This could also suppor for me that I personally would ONLY choose IV  treatment. Others might come to different conclusions.

 

snip 

 

https://www.sciencea...itive-trehalose "A Common Sugar Additive Might Be Driving The Rise of One of The Most Aggressive Superbugs"

"The C. difficile lineages Britton is referring to are RT027 and RT078. When the researchers analysed the genomes of these two strains, they found DNA sequences that enabled them to feed off low doses of trehalose sugar very efficiently.

 

in fact, these particular bacteria need about 1,000 times less trehalose to live off than other varieties of C. difficile, thanks to their genetic make-up.

To test their findings, the scientists experimented with mice given the RT027 strain. In the group given low doses of trehalose, the death rate was much higher – not because of more bacteria, the scientists found, but because the sugar enabled it to produce more poisonous toxins.

Further testing on fluids from three human intestines showed that RT027 was able to grow from small amounts of trehalose, while other bacteria strains weren't.

At this stage it's not certain that trehalose has contributed to the rise of C. difficile, but the study results and the timing of its approval as an additive are pretty compelling. More research will now be needed to confirm the link."

 

 

I've read that article and commented on it in other threads.

 

That study was in vitro, not in vivo so we have no idea if what happens in a test tube also happens in the human gut. 

 

Secondly, the study author wants to link the availability of commercially available trehalose to the rise of C. difficile.  The old saw about correlation not equaling causation holds here.  While it's true that this superbug shows up about the same time that a means to synthesize trehalose cheaply occurred, trehalose is still very rare in the Western diet.  In fact, go to your grocery store and try to find food products sweetened with trehalose.  I did and couldn't find any.  So, that author makes no case for where these patients are getting trehalose from.  

 

There is however one country were trehalose is somewhat available in the diet - Japan where it is used as a sweetener.  So, if trehalose is feeding C. difficile and that is causing an explosion of C. difficile  infections, then we should see a lot of that going on in Japan compared to Europe and America.  But ... we don't.

 

So, I'm not buying their argument.

 

 

Edited by Daniel Cooper, 13 March 2018 - 07:17 PM.

[Heisok]

Thanks.

Edited by Heisok, 13 March 2018 - 07:32 PM.

[Benko]

 if you could get just 4g per day into the bloodstream, that would be equivalent to BioBlast's 27g weekly infusion.  .

 

The thread on SL NR made me wonder, would sublingual trehalose e.g.  work e.g. if you put 1/2-1 tsp under your tongue would you get enough absorbed?
 

Edited by Benko, 21 March 2018 - 02:34 AM.

[OP2040]

 

 if you could get just 4g per day into the bloodstream, that would be equivalent to BioBlast's 27g weekly infusion.  .

 

The thread on SL NR made me wonder, would sublingual trehalose e.g.  work e.g. if you put 1/2-1 tsp under your tongue would you get enough absorbed?
 

 

 

I was wondering about this too.  My reasoning is that even a very small amount is probably better than none, so until we figure out the more complicated methods, something like this might help improve bioavailability for those of us taking it orally.

 

Back to the liposomal option. 

 

Daniel, if you can find a company to make it for us, that would be great.  I'll be in for the group buy on that one.

[Daniel Cooper]

@OP2040

 

I'm found a German company that says they will make it for us.  Their minimum order is 4L.  I'll follow up with them and maybe start a new thread to see what sort of interest there is in liposomal trehalose.

 

I'll really just like to get enough people interested that would place their orders directly with the company rather than I take delivery of it and re-ship it.  Less hassle and since it is a relatively heavy liquid that would be the cheapest route due to shipping costs.

 

My interest would be contingent on their price and their ability to analyze the end product to give us a measurement of how much encapsulated trehalose per ml they obtained.

 

It will probably take a several days to follow up on this as I'm covered up at work at the moment.  Meanwhile, if anyone is interested respond in this thread or send a PM so I can gauge interest.

 

 

 

 

[Daniel Cooper]

 

 if you could get just 4g per day into the bloodstream, that would be equivalent to BioBlast's 27g weekly infusion.  .

 

The thread on SL NR made me wonder, would sublingual trehalose e.g.  work e.g. if you put 1/2-1 tsp under your tongue would you get enough absorbed?
 

 

 

That's a thought.  My initial impression is that multiple grams of material is a lot to take in via the sublingual route.  But, at least you might improve on how much normally makes it through the gut without being digested by trehalase enzyme. 

[OP2040]

@OP2040

I'm found a German company that says they will make it for us. Their minimum order is 4L. I'll follow up with them and maybe start a new thread to see what sort of interest there is in liposomal trehalose.

I'll really just like to get enough people interested that would place their orders directly with the company rather than I take delivery of it and re-ship it. Less hassle and since it is a relatively heavy liquid that would be the cheapest route due to shipping costs.

My interest would be contingent on their price and their ability to analyze the end product to give us a measurement of how much encapsulated trehalose per ml they obtained.

It will probably take a several days to follow up on this as I'm covered up at work at the moment. Meanwhile, if anyone is interested respond in this thread or send a PM so I can gauge interest.

Sounds good to me. Thanks for taking the lead on this!

[Benko]

I talked to a compounding pharmacy today.  They said none of their suppliers carry trehalose and unless I can find them a supplier who has pharmaceutical grade trehalose they can't help us.  A quick search means that it must be 99% or better pure (and obviously pyrogen free).  not sure what other requirements there are.

[OP2040]

@OP2040

 

I'm found a German company that says they will make it for us.  Their minimum order is 4L.  I'll follow up with them and maybe start a new thread to see what sort of interest there is in liposomal trehalose.

 

I'll really just like to get enough people interested that would place their orders directly with the company rather than I take delivery of it and re-ship it.  Less hassle and since it is a relatively heavy liquid that would be the cheapest route due to shipping costs.

 

My interest would be contingent on their price and their ability to analyze the end product to give us a measurement of how much encapsulated trehalose per ml they obtained.

 

It will probably take a several days to follow up on this as I'm covered up at work at the moment.  Meanwhile, if anyone is interested respond in this thread or send a PM so I can gauge interest.

 

Daniel,

Have you had any luck with this?  Any quotes?  No pressure.  I'm sure my hardening arteries (like everyone's) are going to take another 20-30 years to kill me, given my age.   That said, a lot of people, including myself, are really excited about trehalose so I just don't want the thread to die.  Let me know if there's anything I can do to help.

 

 

[Rocket]

What is the enzyme in the gut that breaks it down? Maybe that has a known way to circumvent it.

[Daniel Cooper]

The enzyme is trehalase.  It is also present in the liver and is responsible for breaking down circulating trehalose as well.  There are research groups currently engaged in finding a way to knock out trehalase temporarily so that you could consume therapeutic trehalose and get it past the gut and also have it remain in circulation longer.

 

 

 

Daniel,

Have you had any luck with this?  Any quotes?  No pressure.  I'm sure my hardening arteries (like everyone's) are going to take another 20-30 years to kill me, given my age.   That said, a lot of people, including myself, are really excited about trehalose so I just don't want the thread to die.  Let me know if there's anything I can do to help.

 

 

Not yet.  I've been out of town for the last couple of weeks.  I'll fire off an email to the vendor tonight.

[OP2040]

Not yet.  I've been out of town for the last couple of weeks.  I'll fire off an email to the vendor tonight.

 

Thanks!

[OP2040]

The enzyme is trehalase.  It is also present in the liver and is responsible for breaking down circulating trehalose as well.  There are research groups currently engaged in finding a way to knock out trehalase temporarily so that you could consume therapeutic trehalose and get it past the gut and also have it remain in circulation longer.

 

 

 

 

 

Not yet.  I've been out of town for the last couple of weeks.  I'll fire off an email to the vendor tonight.

 

Did you end up getting any responses?

[Daniel Cooper]

Yep, I have someone that says they can make it, just waiting on a price quote.

 

Minimum buy is 4L.  The only downside to this material is that it is perishable.  I think we'll want them to make it with ETOH added to extend shelf life but even then, I suspect you won't want to buy more than an half liter due to shelf life issues.

 

So we'd like to have at least 8 interested parties.  As soon as I get a quote I'll create a group buy thread and post a link to it in this thread.

 

The way I'd really like this group buy to go is to get 8 people to place a half liter order with the vendor, instead of me talking delivery on all 4L and re-shipping it.

 

 

 

[OP2040]

Good news!

 

Any idea how much actual trehalose is in 1/2 liter, since it is a mixed product? 

 

Assuming it is a reasonable price, which is a big assumption, I'd like to keep stocking the stuff for a period of time, especially if I see some benefit. 

 

I don't blame you at all for not wanting to get involved in reshipping.  I hope they will allow us to do that without asking too many questions.

 

I'm definitely in for the group buy, so assuming you are too, that makes two of us.

 

Anyone else interested?  We need 6 more people.  Just a motivational reminder.  I read a lot of studies and Trehalose has more widespread beneficial effects than almost any other substance I've studied.  Off the top of my head, atherosclerosis, endothelial function, copd, brain health....  It has been studied a lot and has an excellent safety profile.  If could be delivered to the bloodstream affordably and conveniently, I'd supplement it long term.

Edited by OP2040, 16 April 2018 - 09:45 PM.

[Daniel Cooper]

That is also one of the questions they have outstanding to me - how many mg of encapsulated trehalose per ml.  We'll need to know that number.  I think you'd probably want to consume about 3g of encapsulated trehalose per day.

 

 

 

 

 

 

[OP2040]

That is also one of the questions they have outstanding to me - how many mg of encapsulated trehalose per ml.  We'll need to know that number.  I think you'd probably want to consume about 3g of encapsulated trehalose per day.

 

It sounds like you are asking all the right questions. 

 

Anyone else out there interested?  We still need 6 more people for a group buy.

[Daniel Cooper]

So the price quote I'm getting is 17 euro ($21) per 250ml bottle (272 euro/$337 for the whole 4L buy not including shipping).  With ethanol preservative shelf life would be 1 year, which is longer than I expected.

 

I still need to get answered how much encapsulated trehalose per ml and how they determine that number.   

 

At that price and shelf life I'd be in for at least half a liter to a whole liter.

 

I'll update as soon as I have information.  When I've gotten everything settled, I'll post a group buy thread.

 

The way I'd like this to work is that people place their orders directly with the vendor and we're good as long as we make the 4L minimum.

 

 

 

[OP2040]

 

 

 

That's fantastic!  At that price, I'd definitely be in for the 1L, even though we have no idea on price/mg/g yet. And that means we would not need 6 people.  Even if it came down to just the two of us, I'd purchase whatever the remainder is just to make sure we can do it.  The shelf life is great too.

 

Looks like all we need is that last bit of information and we're good to go.

 

I assume the storage would just be normal refrigeration? 

 

I still don't know much about liposomal delivery, so I'm going to do some research.  You seem confident that it should enhance delivery which is really the whole point of this venture.  Be nice if there was an inexpensive way to test blood levels of trehalose.

 

Also, I think I've read that trehalose doesn't spike blood sugar even when it's in the bloodstream, but I'm still 100% on that.  Either way, I usually stay pretty low carb, so it shouldn't matter much.