98 replies to this topic

[Daniel Cooper]

Hi Daniel,

Glad to see you back! Yeah I went ahead and picked up the torch. However, an issue is that the price I've been quoted for essentially the same product is much higher than the quote they provided you with. Unsure why the significant difference, but I'm going to try to negotiate them down.

At this point I've shipped them 3 lbs of Trehalose for testing purposes. When they receive the shipment, they will check to see if they can even work with the substance. No guarantee that they can successfully encapsulate it yet. We'll see.

 

Who are you dealing with there?

 

I was also going to ship them the trehalose since they said they couldn't procure it from their normal sources and I did not include that in the pricing. 

 

I had some issue pinning them down on what level of trehalose they could encapsulate.  At first it was 100mg/ml then I pressed them to go to 200mg/ml which they said they could do then they backed off. 

 

Also, I was trying to work it so that we could all place our orders to them and have them ship it as long as we hit their minimum buy so that I wouldn't have to reship it.  We seemed to have a communications issue as I never could get a clear committal on that.

 

In any case, sorry I vanished.  I have been working on some major projects at work that have taking a lot of 60~70 hour work weeks.  That now appears to be behind me.  Glad you decided to run with the ball.  If I can do anything to help you please let me know and I would really like to get at least 1L if this comes off.

[Cmdr_Burrito]

I think I got assigned a different rep to work with at Actinovo with than you did, my reps name is Malika Klycheva.

 

Yeah, I haven't factored in the cost of my having to purchase and ship them the Trehalose into the final cost of the product either.

 

In terms of concentration levels, yeah, I initially wanted them to commit to 150mg/mL.  While they were initially receptive, they later explained that they probably could not hit that target after all.  Anything much higher than 100mg/mL was probably not attainable because with their current process, the amount of PC in any sample is effectively capped at 130mg/mL.  So realistically, to ensure that product is entirely covered with phospholipids they need to keep the concentration either at or preferably slightly below the 130mg/mL maximum.  Otherwise you'd end up with unencapsulated product in the solution, and effectively just be wasting money if you attempt to get a higher concentration level.  At least that's the way I understand it. 

 

I'm also planning to try and work it so that they take the orders and ship the product directly, since I am also not really interested in ordering and then reshipping the product.

 

Will keep y'all informed as to their progress and/or success with getting the Trehalose encapsulated.

 

 

 

 

Edited by Cmdr_Burrito, 16 August 2018 - 12:13 AM.

[Rocket]

So before we get too far ahead, how much of an effect will trehalose have on arteriosclerosis? I can't find too much about this...

[Daniel Cooper]

So before we get too far ahead, how much of an effect will trehalose have on arteriosclerosis? I can't find too much about this...

 

Longish thread on it here:

 

https://www.longecit...therosclerosis/

 

 

Also here:

 

https://medicine.wus...therosclerosis/

 

If you google "trehalose atherosclerosis" you'll find more.

 

Also may treat Huntington's, Parkinson's, and Alzheimer's.

[roscotx]

i am in for this group buy for 1L

[Rocket]

All I read is *may* and *possible*... Nothing that says it will reduce athersclerosis, sounds like another boondoggle like the infamous foxo4 peptides fiasco that doesn't translate into humans.

[Daniel Cooper]

All I read is *may* and *possible*... Nothing that says it will reduce athersclerosis, sounds like another boondoggle like the infamous foxo4 peptides fiasco that doesn't translate into humans.

 

There are definitely no guarantees here.  We are certainly years from human clinical trials.  If that's not acceptable then I wouldn't participate. 

 

For me, the MOA seems reasonable enough and the benefit substantial enough and the cost low enough that I'm interested and will purchase.  We're talking something like $150 for a years supply so it's not like the FOX04DRI buy in that respect.

[Cmdr_Burrito]

There are definitely no guarantees here.  We are certainly years from human clinical trials.  If that's not acceptable then I wouldn't participate. 

 

For me, the MOA seems reasonable enough and the benefit substantial enough and the cost low enough that I'm interested and will purchase.  We're talking something like $150 for a years supply so it's not like the FOX04DRI buy in that respect.

 

Daniel,

Regarding product cost, I've mentioned before (and want to reiterate again), that the price Actinovo quoted me for the product was substantially (~58%) higher than the quote they provided to you.  Currently they want ~$662 from me for 5L of product (i.e., ~$133 per liter or ~$33.25 per 250mL bottle).

How long the product will last obviously depends heavily upon the desired target daily dose.  For example, if you plan on taking in 4g of encapsulated Trehalose per day, at a concentration of 100mg/mL, you'd have to consume 40mL (~8.2 tsp) per day.  In which case, 5L of product would only last you a bit over 4 months.

 Starting Product Amount:  5L (5000mL)
 Target Daily Dose / Concentration:  4000mg / 100mg/mL = 40mL (~8.2 tsp)
 Total Days before running out of Product:  5000mL / 40mL/day = 125 days (~4.1 months)

 

As such, at the 4g daily dose rate, a years worth of the stuff (~15L) would end up costing more like $1,986, rather than $150 per year.  As I stated previously, "At these prices, I honestly don't see a lot of takers for a product that is unproven in terms of its actual efficacy."  I still plan on trying to negotiate them down on the price, but no guarantees.

Edited by Cmdr_Burrito, 23 August 2018 - 10:39 PM.

[Cmdr_Burrito]

FYI, the company I ordered the 3 lbs of Trehalose from ran into some kind of problem with my order.  As such, they didn't actually begin shipping the Trehalose out to Actinovo until today.  :(

 

So I figure it's going to be "at least" another week before Actinovo receives the product and I get the results back from their testing.

[Kevinsan]

Lets get his party rolling. Just hit the news stands:

 

https://www.news-med...c-syndrome.aspx

 

New research, in mice, indicates that a natural sugar called trehalose blocks glucose from the liver and activates a gene that boosts insulin sensitivity, reducing the chance of developing diabetes. Activating the gene also triggers an increase in calories burned, reduces fat accumulation and weight gain, and lessens measures of fats and cholesterol in the blood.

The findings, from researchers at Washington University School of Medicine in St. Louis, suggest new possibilities for treating metabolic syndrome, a cluster of related conditions that includes obesity, diabetes and fatty liver disease.

The study is published Aug. 23 in JCI Insight.

 

Or buy lactotrehalose.

 

However, DeBosch said, trehalose may encounter enzymes in the digestive tract that break it apart, releasing its two glucose molecules, which would be counterproductive. The researchers investigated a similar sugar -- lactotrehalose -- they found has the same beneficial effects from triggering Aloxe3 but does not break apart as easily.

[Cmdr_Burrito]

Lets get his party rolling. Just hit the news stands:

 

https://www.news-med...c-syndrome.aspx

 

New research, in mice, indicates that a natural sugar called trehalose blocks glucose from the liver and activates a gene that boosts insulin sensitivity, reducing the chance of developing diabetes. Activating the gene also triggers an increase in calories burned, reduces fat accumulation and weight gain, and lessens measures of fats and cholesterol in the blood.

The findings, from researchers at Washington University School of Medicine in St. Louis, suggest new possibilities for treating metabolic syndrome, a cluster of related conditions that includes obesity, diabetes and fatty liver disease.

The study is published Aug. 23 in JCI Insight.

 

Or buy lactotrehalose.

 

However, DeBosch said, trehalose may encounter enzymes in the digestive tract that break it apart, releasing its two glucose molecules, which would be counterproductive. The researchers investigated a similar sugar -- lactotrehalose -- they found has the same beneficial effects from triggering Aloxe3 but does not break apart as easily.

 

There are most definitely many Trehalose analogues which are resistant to breakdown in the GIT, while still offering benefits similar to unmodified Trehalose.  However, the problem has been (and continues to be) that "large-scale chemical production processes for trehalose analogues are not readily available at the moment due to the lack of efficient synthesis methods".

 

https://www.ncbi.nlm...les/PMC4490520/

 

While I could be wrong, but I don't see this situation changing any time in the near future.

 

The problem with mouse trials, is that mice do not express the Trehalase enzyme in their GIT like people do.  The point of this exercise is to develop a Trehalose-based product that, like the aforementioned (but unavailable) Trehalose analogues, will not be broken down by the Trehalase enzyme in the human GIT before entering the bloodstream.

Edited by Cmdr_Burrito, 24 August 2018 - 08:07 PM.

[Daniel Cooper]

I'm still onboard at that price and may increase my purchase from 1L to 1.5L

 

I'm targeting around 2g of trehalose per day.

 

The only thing I'm confused about is that I've seen concentrations quoted of 100mg/ml and 150mg/ml. When I was talking to Actinovo we were talking about 100mg/ml but I thought that you had talked them up to 150mg/ml.  Do you have a final number out of them?

 

The solubility of trehalose in water is quite high - 68.9 g per 100 g at 20 °C.  I'm surprised they can't go even higher than the 150mg/ml number.  But, even at 100mg/ml I think I can hit an effective dose target.

 

I think that liposomal trehalose will actually be better than BioBlast's IV delivery for treating atherosclerosis in terms of plasma half life and targeted delivery to the vascular endothelium.  So, I feel pretty good about 2g/day.

 

 

 

[Cmdr_Burrito]

Daniel,

 

I think you might have missed my post on the 16th where I tried to address the concentration issue...

 

...

In terms of concentration levels, yeah, I initially wanted them to commit to 150mg/mL.  While they were initially receptive, they later explained that they probably could not hit that target after all.  Anything much higher than 100mg/mL was probably not attainable because with their current process, the amount of PC in any sample is effectively capped at 130mg/mL.  So realistically, to ensure that the product is entirely covered with phospholipids they need to keep the concentration either at or preferably slightly below the 130mg/mL maximum.  Otherwise you'd end up with unencapsulated product in the solution, and effectively just be wasting money if you attempt to get a higher concentration level.  At least that's the way I understand it.

...

 

In summary, the max concentration of the final encapsulated product is apparently limited by the max concentration of the liposomal / phospholipid carrier (in this case phosphatidylcholine (PC)) in solution, not the solubility potential of the substance that's being encapsulated (i.e., Trehalose).  At a concentration of 100mg/mL and a 2g (2000mg) target daily dose, 1.5L of product would last about 2.5 months:
 

Starting Product Amount:  1.5L (1500mL)
Target Daily Dose / Concentration:  2000mg / 100mg/mL = 20mL (~4.1 tsp)
Total Days before running out of Product:  1500mL / 20mL/day = 75 days (~2.5 months)

 

Based on Actinovo's currently quoted price (before factoring in the cost of shipping, or the procurement of the raw Trehalose source material), the cost of 1.5L of encapsulated product would be ~$199.50.  So not exactly cheap.

 

[Daniel Cooper]

Has Actinovo given you a reason one why they've increased the price?  Was it the change from ethanol to potassium sorbate as the preservative?  That really seems unlikely since they both should be relatively cheap and the quantities are minimal.  

 

I'm still interested.  I may either lower my daily consumption or increase the amount.

 

For what it's worth, I don't think you would need to take this stuff on a continual basis.  In fact that might not even be desirable.  But, we have so little testing to fall back on figuring out how long of a course you'd need to make a meaningful plaque reduction is difficult.

 

We could look at other companies doing liposomal products.  I think the trick is to find a small enough of a supplier that they are willing to do it, but not so small they don't have decent experience.  That's how I came up with Actinovo in the first place.

 

 

 

[Daniel Cooper]

BTW - here's my thinking one why liposomal trehalose will be better than IV trehalose.

 

BioBlast is doing IV trehalose as a potential treatment for Huntington's, Parkinson's, and Alzheimers.  Obviously, they are going IV to get past the breakdown of trehalose in the gut by the enzyme trehalase.  However, trehalose is also metabolized by the liver and I think they are only getting significant plasma concentrations for something on the order of a half  to one hour.

 

By liposomal encapsulating trehalose we not only get it past the gut, but we should get a significant shielding effect from metabolism in the liver.  How much?  That I couldn't qualify but we should get a longer useful plasma dwell time.  So, gram for gram our trehalose should be somewhat more effective than IV trehalose, at least for addressing atherosclerosis.  I was someone skeptical of liposomal trehalose getting past the BBB, but apparently there is a study showing that works as well.

 

 

 

[Cmdr_Burrito]

Wow, this is turning into a bit of a cluster truck.

 

FYI, turns out that the German customs authority intercepted the Trehalose sample that I shipped to Actinovo on the 09/05/2018.  They've been "processing" it ever since.  Today (09/12/2018) I just received word that the German customs authority wants to know "the specification of Trehalose" and they want someone (probably going to be me) to pay a fee of 28.50 euros for customs clearing.  Additionally they want both of those things to be completed by tomorrow 09/13/2018, or they're going to ship the sample back!

 

I'm going to try and give them with what they want, but they haven't provided me with any examples of what exactly is needed in terms of "specification", or any idea about what format that data should be supplied in.  Also I've been given no details about how to pay the customs clearing fee.  Ugh.

 

I'll keep y'all updated as the situation develops.

[Daniel Cooper]

Cmdr_Burrito -

 

I'd be willing to split those costs with you.  If you do PayPal PM me a email and I'll go in halves with you.

[Cmdr_Burrito]

Thanks Daniel,

 

No need to split costs at this point.

 

FYI, at the last minute the Actinovo folks actually managed to provide the German customs folks with the "specification" info that they wanted.

 

However, the German Customs Authority now says that the sample still has to be checked by the laboratory (which apparently takes "at least" 2 weeks).  After the approval, the sample will reportedly be passed through customs clearance.  Total it takes 3 weeks.  So its still a ways off.  Ugh.  Unsure if this process will have to be repeated for all future production batches, or if it will be streamlined after this one-time initial delay?  Will find out...

[John250]

So trehalose can increase autophagy even if your not fasting?

[docmaas]

Wow!  When I started reading this thread I was sure I'd missed the boat now it turns out the boat hasn't yet completed construction.  However it looks promising.  I tried it rectally as well and seem to be high in trehalase with pretty strong reactions both orally and via suppository.  This sounds like what I was hoping for.  Count me in.

 

Mike

[roscotx]

Please up my request from 1 liter to 2 liters.

roscotx

[granmasutensil]

I'm curious why wouldn't just making the liposomal trehalose be an option? Seems by far the easiest. Just dissolve in some water, throw the solution in a ultrasonic jewelry cleaner with some liquid lecithin and bam liposomal trehalose, fresh. The daily dose seems low enough that you'd need little solution to lecithin. People normally take 1-2 tablespoons lecithin as a supplement that's 15-30 ml right there that you only need 2 grams of trehalose in if 2 grams is the daily dose. Is the max concentration of trehalose you can get in solution very low which is the issue? Not having absolute fully 100% encapsulation shouldn't be much of a concern it's used as a sweetener and encapsulation should still be extremely high and easy to get at that ratio.

[Daniel Cooper]

I guess my issue with DIY liposomal trehalose is that I have no way to know how much encapsulated trehalose I actually ended up with.  I agree that the unencapsulated trehalose certainly won't harm you, but whether I ended up with 25mg/ml or 100mg/ml of encapsulated product is important if I'm trying to hit a 2g/day dose target.  I just have no confidence that I'd ever know what I was consuming in terms of concentration.

 

 

[granmasutensil]

I guess my issue with DIY liposomal trehalose is that I have no way to know how much encapsulated trehalose I actually ended up with.  I agree that the unencapsulated trehalose certainly won't harm you, but whether I ended up with 25mg/ml or 100mg/ml of encapsulated product is important if I'm trying to hit a 2g/day dose target.  I just have no confidence that I'd ever know what I was consuming in terms of concentration

That's specifically why I commented. Assuming the amount of trehalose you can dissolve isn't absolutely terrible the amount of solution is very small needing to be encapsulated by the amount of lecithin people normally take in a standard daily dose. Which is far more than would normally would be used to liposome that amount of solution. There is a huge excess, so  liposoming that tiny amount is complete overkill, so amount encapsulated shouldn't be a concern. I brought that up more because of the lack of safety concerns than encapsulation. Since it's made fresh a person can just make 1-2 weeks worth at a time and store in the fridge right away so degradation shouldn't be an issue for loss of liposome. A person doesn't need to make a lot (like the whole tub of the jewelry cleaner) at once, just put the lecithin and solution in a glass jar in a water bath in the ultrasonic jewelry cleaner, store the jar in the fridge and take the measured spoonful of lecithin everyday.

 

This is all assuming you want to take lecithin at supplement dosage 1-2 tablespoons instead of going for a standard amount used for liposoming said amount like people do with vitamin C at home, and of course the trehalose dissolves well, otherwise then there would be too many questions for sure. But even assuming standard amount of lecithin to solution ratio is used and amount encapsulated is more variable like you brought up there really isn't any risk since it's a sweetner and that downside may be acceptable to some given it's a longterm approach (dosage seems to vary greatly discussed here anyways). It seems like an awesome candidate for a diy liposomal approach if people so desire because of price, safety and so on which should get a lot of people excited.

 

Just as a side note has it ever been brought up in any diy liposomal topics than you can buy handheld liposome extruders with disposable tips?

https://ttscientific...er-mini-sterile

[Daniel Cooper]

So tell me, how many mg of trehalose do you expect to encapsulate in each ml of phosphatidylcholine (lecithin)?

 

 

[Kevinsan]

Tried many times with many products. The home version never really works. This is why we I came here to see if we could get the lipo trehalose idea some traction. Lets see if we can get the lipo professionally manufactured. It eliminates one variable.

 

It appears the Dutch company can manufacture the product. Lets have them put up a pay link and we all jump in. Maybe set a time limit to deter the undecided. I believe we have shown enough interest.

Edited by Kevinsan, 20 September 2018 - 03:10 AM.

[Daniel Cooper]

Tried many times with many products. The home version never really works. This is why we I came here to see if we could get the lipo trehalose idea some traction. Lets see if we can get the lipo professionally manufactured. It eliminates one variable.

 

Agreed.

 

We've got someone in the business of making liposomal formulations telling us they don't think they can get much past 100mg/ml.  That already puts us consuming more lecithin than we'd like.  Presumably someone that doesn't know what they are doing will achieve less.

[granmasutensil]

So tell me, how many mg of trehalose do you expect to encapsulate in each ml of phosphatidylcholine (lecithin)?

 

Depends on how much can be dissolved first of course. I would expect easily at least 70-90%+ encapsulation if a high concentration can be reached in solution. Liposoming isn't exactly rocket science. The difference in concentration from the manufactures and what I am proposing is due to difference in liposomal process used. They can only make their solution so thick before the pressure is too high in their extrusion device. Ultrasonic encapsulation doesn't have that issue but at the same time you can't choose the exact uniformity of liposome size. But in this case from what I gather that is largely irrelevant all we want is the trehalose to survive digestion in the gut.

 

The only issue is if you want to take lecithin as a supplement or not at those doses. I think generally many people wouldn't mind it's also just a food item with health benefits.

 

That's why I posted I think there is a good case to be made for doing this ones self. Especially given stability issues. Isn't there going to be some serious stability issues buying a years worth of liposomal trehalose anyways both in shelf stability and once the container is opened?

[Daniel Cooper]

Depends on how much can be dissolved first of course. I would expect easily at least 70-90%+ encapsulation if a high concentration can be reached in solution. Liposoming isn't exactly rocket science. The difference in concentration from the manufactures and what I am proposing is due to difference in liposomal process used. They can only make their solution so thick before the pressure is too high in their extrusion device. Ultrasonic encapsulation doesn't have that issue but at the same time you can't choose the exact uniformity of liposome size. But in this case from what I gather that is largely irrelevant all we want is the trehalose to survive digestion in the gut.

 

The only issue is if you want to take lecithin as a supplement or not at those doses. I think generally many people wouldn't mind it's also just a food item with health benefits.

 

That's why I posted I think there is a good case to be made for doing this ones self. Especially given stability issues. Isn't there going to be some serious stability issues buying a years worth of liposomal trehalose anyways both in shelf stability and once the container is opened?

 

If you think you're going to encapsulate something with an ultrasonic jewelry cleaner I think you are mistaken.  You need a high power sonicator to do what you're proposing.

 

And you'll have zero idea if your encapsulation was successful or not without some way to test it.

 

I need something that is a known quantity.  Not some mystery goo.

Edited by Daniel Cooper, 20 September 2018 - 03:53 AM.

[granmasutensil]

If you think you're going to encapsulate something with an ultrasonic jewelry cleaner I think you are mistaken.  You need a high power sonicator to do what you're proposing.

 

And you'll have zero idea if your encapsulation was successful or not without some way to test it.

 

I need something that is a known quantity.  Not some mystery goo.

 

I think the threads on liposomal vitamin C have shown you can do it. You can test for example the ascorbic acid simply with baking soda in the solution to see if it reacts. So we clearly know it works. I call it a ultrasonic "jewelry cleaner" but in reality I'm just talking about a ultra sonic cleaner that is used to clean for example mechanics tools. Those machines are high powered in comparison and not hard to get or very expensive.

 

Like I said it's not rocket science, creating a liposome when there is that much lecithin to solution is going to be very easy by ultrasonic means. The only reason it isn't widely used is largely uniformity of liposome size which as far as I can tell isn't an issue here we just want it to survive digestion we aren't looking for specific liposome size for delivery.

 

Also you and no one else as far as I can tell have brought up or addressed the serious issue of stability. Which isn't a problem when done at home. It's a conversation worth bringing up. Also like I said earlier irregardless of everything else said, dosage discussed seems to vary greatly and these are all food items anyways(that's really good news!).

 

I think there is good reason for people to be excited here, it certainly makes things way more simple diy bypassing the stability issues and wondering how much trehalose is even still liposomed.