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a,a-D-Trehalose dihydrate for the treatment of ATHEROSCLEROSIS

atherosclerosis peripheral arterial disease trehalose carotid artery disease coronary artery disease

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#91 Daniel Cooper

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Posted 14 May 2018 - 02:02 PM

I doubt it.  The activity of trehalose is to promote autophagy, which is a disrupted process in arterial plaques.  The calcification present in atherosclerosis is a secondary process.  Trehalose is working upstream of calcification.  

 

Now, if calcification in scalp follicles actually contributes to baldness (I have no idea), I would think that topical EDTA would be much more interesting.

 

 

 



#92 OP2040

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Posted 14 May 2018 - 02:30 PM

I agree with Daniel on this.  Trehalose is unlikely to be the proper intervention.  Just going on memory here, but I think the latest on MPB is that it is caused by stem cell depletion combined with a type of autoimmunity.  I think hyalauron, which is easily and cheaply attained is an intriguing possibility, but you would need low molecular weight I think for it to actually absorb into the layers needed, and I haven't seen any being sold commercially that designates molecular weight.  Also, keep that bald head of yours out of the sun if you are going to start attempting some regeneration.  As far as I'm concerned, the more people experimenting rationally, the better, so good luck and let us know how it goes!


Edited by OP2040, 14 May 2018 - 02:32 PM.


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#93 bladedmind

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Posted 07 July 2018 - 04:28 PM

I’ve been interested in using trehalose by one means or another.  I just discovered though that low amounts of trehalose can feed a dangerously virulent strain of clostridium difficile

 

The consequences of clostridium difficile infection range from ongoing daily diarrhea to death.  Those who must take a PPI to suppress stomach acid, such as myself (I have explored all of the alternatives and none is feasible) are prone to c.d. population growth.  In my case I came down with weeks-long diarrhea.  My integrated M.D. offered several simple remedies and all failed.  The stool sample sent for culture came back and showed incredibly high population of c.d.  We knocked it down with antibiotics and then probiotics plus saccharomyces boulardii.  That was the only remedy that worked to end two months of the runs.  I speculate that anyone who must take acid suppressors may have a high c.d. population and that oral or rectal administration of trehalose could be a risk.

 

I emphasize that this is speculation and that I do not presume to tell anyone to take trehalose or not.  Just alerting to a possibility that deserves further inquiry. 

 

 

There are 450,000 c.d. infections per annum in the U.S. and 29,000 deaths.

 

https://en.wikipedia...icile_infection

 

 

Journalistic account:  https://jamanetwork....bstract/2675907

The strains belong to 2 C difficile ribotypes, RT027 and RT078. Infections from C difficile had always caused diarrhea and colitis, sometimes leading to surgery and even death. But starting around 2000, as the previously rare ribotype RT027 spread, the infections became more common, more severe, more resistant to treatment, more likely to relapse, and more deadly.

 

Between 2001 and 2010, the US rate of C difficile hospitalizations per 1000 adult discharges roughly doubled from 5.6 to 11.5. In 2011, C difficile caused almost half a million infections and approximately 15 000 deaths. That year, RT027 was associated with around a third of health care–associated C difficile infections.

 

Antibiotic resistance alone doesn’t fully explain the trends. Although RT027 strains are resistant to fluoroquinolone antibiotics, so are other nonepidemic ribotypes. So what was giving this particular brand of C difficile its edge?

 

In 2014, Britton demonstrated that epidemic RT027 strains outcompete other nonepidemic C difficile strains in human fecal bioreactors and mouse models. But the mechanism behind their advantage was still unknown.

 

In their recent Nature study, funded by the National Institutes of Health, Britton and collaborators looked at how an epidemic strain of RT027 responds to around 200 food sources—sugars and sugar alcohols, amino acids, and proteins—found in the large intestine, where C difficile causes disease. One food source in particular—trehalose—stood out as increasing growth 5-fold compared with a non-RT027 strain.

 

The researchers then supplemented 21 strains from 9 C difficile ribotypes commonly found in the clinical setting with either glucose or trehalose alone. Most of the strains grew on low amounts of glucose, but only epidemic strains of RT027 and another outbreak-associated ribotype, RT078, grew on low amounts of trehalose.

 

“That was a smoking gun for us,” Britton said.

 

Microbial genetics and physiology experiments further revealed that the 2 epidemic ribotypes have different mutations that allow them to metabolize low levels of trehalose.

 

In RT027-infected mice fed trehalose, amounts sufficient to promote growth of the epidemic strains survived the trip to the cecum, the pouch that connects the small and large intestines. The researchers also exposed RT027 strains to fluid samples from the small intestines of people eating their normal diets. Two out of 3 fluid samples strongly induced expression of the treA gene, which is required to metabolize trehalose, in RT027 strains. The findings suggest there may be enough trehalose in our diets for RT027 to live on.

 

 

 

https://www.nature.c...les/nature25178

 

Dietary trehalose enhances virulence of epidemic Clostridium difficile

Nature volume 553, pages 291–294 (18 January 2018) |

Abstract

Clostridium difficile disease has recently increased to become a dominant nosocomial pathogen in North America and Europe, although little is known about what has driven this emergence. Here we show that two epidemic ribotypes (RT027 and RT078) have acquired unique mechanisms to metabolize low concentrations of the disaccharide trehalose. RT027 strains contain a single point mutation in the trehalose repressor that increases the sensitivity of this ribotype to trehalose by more than 500-fold. Furthermore, dietary trehalose increases the virulence of a RT027 strain in a mouse model of infection. RT078 strains acquired a cluster of four genes involved in trehalose metabolism, including a PTS permease that is both necessary and sufficient for growth on low concentrations of trehalose. We propose that the implementation of trehalose as a food additive into the human diet, shortly before the emergence of these two epidemic lineages, helped select for their emergence and contributed to hypervirulence.

 



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#94 Daniel Cooper

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Posted 07 July 2018 - 06:06 PM

Yes, we've discussed that study several times, at least once previously in this very thread.

 

What they established is two things:

 

1.) Trehalose causes clostridium difficile to grow more rapidly in vitro.

 

2.) Clostridium difficile infection rates increased in North America and Europe at about the same time that a commercial process was developed to produce trehalose much more cheaply than was possible previously.

 

 

They took those two pieces of information and leapt to a conclusion:  Trehalose fueled the increase in clostridium difficile North America and Europe.  In other words they argue that correlation establishes causation.

 

A few problems with their theory:

 

1.) While a low cost commercial process to produce trehalose more cheaply hit the market about the same time that clostridium difficile infection rates increased, they neglected to notice that trehalose is still very uncommon in the North American and European food supply.  You see, while the cost to produce trehalose decreased significantly, it is still many times more expensive than sugar or high fructose corn syrup which is used as a sweetener in the food supply.  Here's a challenge - go to your grocery store and see how many food products you can find that contain trehalose.  When I did this exercise a year ago, I couldn't find any.  So while it did become commercially available, it is still very rare in the NA and European food supply.

 

2.) Go look at the places where trehalose isn't nearly so rare in the food supply - namely Japan.  The commercial process to produce trehalose was developed in Japan and it is used there in some food products as a sugar substitute.  You can for instance find soft drinks in Japan which are sweetened with trehalose.  I've looked in North America and never seen such a thing.  Now, go look as clostridium difficile infection rates in Japan over the same time period.  They haven't increased.  So if trehalose consumption causes clostridium difficile infection, how come clostridium difficile infection isn't blowing up in Japan?

 

That whole study smacks of sensational bad science in my opinion.

 

 

 


Edited by Daniel Cooper, 07 July 2018 - 06:07 PM.

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#95 bladedmind

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Posted 07 July 2018 - 07:24 PM

Yes, we've discussed that study several times, at least once previously in this very thread.

 

 

Thanks, I appreciate your remarks. and apologies for duplication.   The one new piece I added that some may not know is that continuous PPI use ups the risk of CDI.   Nonvirulent CD was gruesome for me, and even a small risk of virulent CD deters me.  Not telling others what to do.

 

https://www.ncbi.nlm...pubmed/25730198

 

Continuous Proton Pump Inhibitor Therapy and the Associated Risk of Recurrent Clostridium difficile Infection.
....
CONCLUSIONS AND RELEVANCE:

After adjustment for other independent predictors of recurrence, patients with continuous PPI use remained at elevated risk of CDI recurrence. We suggest that the cessation of unnecessary PPI use should be considered at the time of CDI diagnosis.

 

 

 

 

https://www.ncbi.nlm...les/PMC5643276/

 

Proton pump inhibitors therapy and risk of Clostridium difficile infection: Systematic review and meta-analysis
...
CONCLUSION

This meta-analysis provides further evidence that PPI use is associated with an increased risk for development of CDI. Further high-quality, prospective studies are needed to assess whether this association is causal.

 

 

 


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#96 Daniel Cooper

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Posted 07 July 2018 - 08:18 PM

Oh yes, use of PPIs increases the risk across the board for all sorts of GI infections.  There's a reason that the stomach is an acidic environment, and digestion in the main isn't it.

 

 

 

 


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#97 Cmdr_Burrito

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Posted 02 August 2018 - 12:04 AM

FYI, I just found the following article regarding liposomal delivery across the BBB which is very encouraging...
 
"Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier":
 
This meta-analysis of numerous published medical studies, definitively shows in vivo crossing of the BBB using phosphatidylcholine (PC) liposome encapsulated drugs administered either intranasally or via subcutaenous injection.  In addition, many other liposomal formulations were shown to cross the BBB when administered via IV injection.  While all of the in vivo studies in this meta-analysis examined were performed on rats or mice, this is still quite interesting as it seems plausible that it may also work in a similar way in humans.
 
Basically my thinking goes that if liposome encapsulated drugs which are directly introduced into the blood stream (either via IV or subcutaneous injection) can make it across the BBB, why couldn't orally administered liposome encapsulated trehalose (which can make it through the gut unmodified) also get into the blood stream, and then cross the BBB as well?
 
If this actually works, it would be fantastic!
 

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#98 masterlock

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Posted 29 August 2018 - 08:40 PM

Hello everyone,

 

I have been following this thread, and was unable to reply until today due to a technical issue which was resolve today.

 

I wanted to point out that the dosage used in the mouse atherosclerosis study in which plaque volume was decreased by approximately 30 percent was 3 grams per kilo. This works out to approximately 270 grams for a 200 lb person. I've seen some commeters suggesting various other dosages which are far below this, and am curious to know what these are based on. Any links would be appreciated.

 

Secondly, I believe it is known that liposomes are not great at passing through the upper digestive tract, including the stomach and small intestine due to acids, bile salts and enzymes (lipase). That said, the large intestine does not contain enzymes, so as gross as it might sound to some, this could be a viable route of administration which would allow maximal passage from large intestine into blood stream. Another route of administration could, of course, be IV, however, in that case, I'm not sure of the benefit of liposomal encapsulation.

 

I have read that polymerized liposomes, or even liposomes with attached ligands, are better able to absorb through the intestine, for what it's worth.

 

Anyway, I'm curious to know how far along a possible group buy has progressed, as well as any other particulars those 'in the know' care to share.


Edited by masterlock, 29 August 2018 - 08:41 PM.


#99 Daniel Cooper

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Posted 29 August 2018 - 08:56 PM

Welcome aboard.

 

There is a conversion factor to get from an animal model to a Human Equivalent Dose (HED).  To go from a mouse to a human the normal standard is to divide by 12.3.  So for your 200lbs (90.7 kg) human that would be 270/12.3 = 21.95g. And that would be a once per week IV dose.  This is pretty much what BioBlast (a pharmaceutical company investigating IV trehalose for Huntginton's, Parkinson's, and Alzheimer's) is doing on a weekly basis.  Their IV doses have been around 21 - 27 grams a week. 

 

So, liposomal trehalose consumed at around 3 - 4 grams a day 7 days a week will be in the same range.  And there are reasons to believe that liposomal trehalose may be more effective gram for gram than IV which is metabolized in the liver very quickly.  IV trehalose only dwells in the blood plasma for around 30 minutes to an hour.

 

As far as liposomal encapsulations making it intact through the gut, that is a very common application for liposomes and there is a long history of using this technology to get drugs through the gut intact.  I do not believe this is an issue but would welcome anyone with contrary data.

 

 

 

 

 


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#100 Fafner55

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Posted 29 August 2018 - 10:18 PM

...

I wanted to point out that the dosage used in the mouse atherosclerosis study in which plaque volume was decreased by approximately 30 percent was 3 grams per kilo. This works out to approximately 270 grams for a 200 lb person. I've seen some commeters suggesting various other dosages which are far below this, and am curious to know what these are based on. Any links would be appreciated.

 

Figure 9(h) showing lesion regression refers to (f), which indicates that the mice were injected i.p. (2 g kg−1, three times per week), not 3gm/kg. 
“Exploiting macrophage autophagy-lysosomal biogenesis as a therapy for atherosclerosis” (2017) https://www.ncbi.nlm...les/PMC5467270/
 
Converting to a human equivalent dose (HED),
HED (mg/kg) = Animal Dose (mg/kg) x [Animal Km / Human Km]
HED (mg/kg) = (2000 mg/kg)(3/37)
HED (mg/kg) = 1622 mg/kg
 
For a 70 kg individual (me), that dose comes to 11.34 gm
For a 90.2 kg individual, it comes to 14.71 gm.
 
Roughly, assuming liposomal formulations encapsulate at a 50% rate (my guess) for 40% phosphatidylcholine content, and 175 gm trehalose/1000 gm solution, then the target equivalent liposomal dose for 11.34 gm trehalose would need a 324 gm liposomal solution. That is too much to consume.


#101 Fafner55

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Posted 29 August 2018 - 11:34 PM

In contrast to the 2 gm/kg needed to regress atherosclerosis, a 2% solution in the drinking water of mice is a therapeutic dose for many conditions.
  1. “Trehalose ameliorates oxidative stress-mediated mitochondrial dysfunction and ER stress via selective autophagy stimulation and autophagic flux restoration in osteoarthritis development” (2017) https://www.nature.c...es/cddis2017453
  2. “Translational evidence that impaired autophagy contributes to arterial ageing” (2012) https://physoc.onlin...iol.2012.229690
  3. “Trehalose intake induces chaperone molecules along with autophagy in a mouse model of Lewy body disease” (2015) https://www.ncbi.nlm...ubmed/26299928 
  4. “Therapeutic effects of trehalose liposomes against lymphoblastic leukemia leading to apoptosis in vitro and in vivo” (2016) https://www.scienced...960894X15303383
  5. “Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease” (2004) https://drive.google...qjn1Rs78ZX/view
  6. “Mitochondrial Quality Control and Age-Associated Arterial Stiffening” (2014) https://www.ncbi.nlm...es/PMC4252265/ 
 
An average 25 g mouse drinks 4 ml water daily.
A 2% concentration in the water of a mouse is then
= (4 gm)(0.02) / 25 gm
= 80 mg / 0.025 kg
= 3200 mg/kg
 
Converting to a human equivalent dose (HED),
HED (mg/kg) = Animal Dose (mg/kg) x [Animal Km / Human Km]
HED (mg/kg) = (3200 mg/kg)(3/37)
HED (mg/kg) = 260 mg/kg
 
For a 70 kg individual, this dose is 18.2 gm
 
If 0.5% of oral consumption trehalose is bioavailable, then the target liposomal dose of trehalose delivers 
= 18.2 gm(0.005)
= 0.091 gm
 
Assuming liposomal formulations encapsulate at a 50% rate (my guess) for 40% phosphatidylcholine content, and 175 gm trehalose/1000 gm solution, then the target equivalent liposomal dose of trehalose is 
= (0.091 gm) (1000/175) / (0.5 * 0.4) 
= 2.6 gm
 
1 tsp should then deliver the following bioavailable amount of trehalose (assuming 5 gm / tsp):
= (5/2.6)(0.091 gm)
= 0.175 gm
This is a good starting point for self-experimentation.
 

Edited by Fafner55, 29 August 2018 - 11:46 PM.

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#102 Fafner55

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Posted 30 August 2018 - 12:54 AM

 

Do any of you guys have any preferences on preservative?  I'm thinking alcohol unless there is a compelling reason for potassium sorbate.

 

Alcohol improves the creation and stability of liposomes.
“On the Stability of Liposomes and Catansomes in Aqueous Alcohol Solutions” (2008) https://www.ncbi.nlm...pubmed/18225922
It is noteworthy that vesicles could not be formed in pure water from PL-90 and the IPA studied in this work by the semi-spontaneous process. This is apparently due to the extremely low solubilities of PL-90 and the IPA in water
..., significant enhancement of physical stability was found for liposomes formed from soybean phosphatidylcholine (PL-90) in water with the aid of cosolvent addition. In general, liposome stability at first increased with increasing the cosolvent concentration, reached a maximum at a specific cosolvent concentration, and thereafter decreased with further increasing the co-solvent concentration.
 
 
The addition of surfactants like potassium sorbate to liposomal solutions lowers encapsulation rates.
“Modifying the Release Properties of Liposomes Toward Personalized Medicine” (2014) https://www.scienced...02235491530558X

Edited by Fafner55, 30 August 2018 - 12:55 AM.

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#103 masterlock

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Posted 30 August 2018 - 10:23 PM

Welcome aboard.

 

There is a conversion factor to get from an animal model to a Human Equivalent Dose (HED).  To go from a mouse to a human the normal standard is to divide by 12.3.  So for your 200lbs (90.7 kg) human that would be 270/12.3 = 21.95g. And that would be a once per week IV dose.  This is pretty much what BioBlast (a pharmaceutical company investigating IV trehalose for Huntginton's, Parkinson's, and Alzheimer's) is doing on a weekly basis.  Their IV doses have been around 21 - 27 grams a week. 

 

So, liposomal trehalose consumed at around 3 - 4 grams a day 7 days a week will be in the same range.  And there are reasons to believe that liposomal trehalose may be more effective gram for gram than IV which is metabolized in the liver very quickly.  IV trehalose only dwells in the blood plasma for around 30 minutes to an hour.

 

As far as liposomal encapsulations making it intact through the gut, that is a very common application for liposomes and there is a long history of using this technology to get drugs through the gut intact.  I do not believe this is an issue but would welcome anyone with contrary data.

 

Thanks for providing that info!. However, most of what I have read about liposomes, which has not been of a commercial nature, has suggested that liposomes face challenges in the stomach and small intestine. This article, for example, talks about bile salts and lipases. In general, there are plentiful articles on the web that discuss the challenges of getting liposomes through the upper digestive tract undegraded (particularly from lipases). This has been offered as a reason for polymerizing liposomes, as well as adding ligands. 

 

If you have research that suggests to the contrary I would very much be interested in reading it. Thanks again!


Edited by masterlock, 30 August 2018 - 10:26 PM.


#104 masterlock

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Posted 30 August 2018 - 10:26 PM

 

Figure 9(h) showing lesion regression refers to (f), which indicates that the mice were injected i.p. (2 g kg−1, three times per week), not 3gm/kg. 
“Exploiting macrophage autophagy-lysosomal biogenesis as a therapy for atherosclerosis” (2017) https://www.ncbi.nlm...les/PMC5467270/
 
Converting to a human equivalent dose (HED),
HED (mg/kg) = Animal Dose (mg/kg) x [Animal Km / Human Km]
HED (mg/kg) = (2000 mg/kg)(3/37)
HED (mg/kg) = 1622 mg/kg
 
For a 70 kg individual (me), that dose comes to 11.34 gm
For a 90.2 kg individual, it comes to 14.71 gm.
 
Roughly, assuming liposomal formulations encapsulate at a 50% rate (my guess) for 40% phosphatidylcholine content, and 175 gm trehalose/1000 gm solution, then the target equivalent liposomal dose for 11.34 gm trehalose would need a 324 gm liposomal solution. That is too much to consume.

 

 

Thanks for posting this very helpful information! I wasn't aware of this. 



#105 Daniel Cooper

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Posted 12 September 2018 - 12:50 AM

Let's talk about suppositories.  No, seriously.

 

Someone in this or one of the other trehalose threads suggested bypassing trehalose being enzymatically converted to sucrose via trehalase by putting it in a suppository.

 

The enzyme trehalase converts trehalose from a disaccharide to a monosaccharide "in the intestinal wall".  That's what all the textbooks will tell you.  So the question is "where exactly in the intestines".  If there is no trehalase in the lower colon then a trehalose suppository might work.  I would prefer a liposomal formulation but I like to have Plan B at hand as well.

 

So does any one know if trehalase is present in the lower intestine?  If not, how would we go about figuring that out?

 

 

 



#106 Benko

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Posted 12 September 2018 - 01:43 AM

DC,

 

Trehalase is found in brush border of small intestine (not colon).  However from examine:

 

"Unfortunately, not only is trehalose initially poorly absorbed from the intestines but within the intestinal wall there is an enzyme (trehalase) which can rapidly degrade trehalose into glucose. For the trehalose that bypasses this enzyme and gets absorbed, the threhalase present in the liver and the blood appears to finalize the digestion leaving little to no trehalose able to reach a cell and exert its therapeutic effects."

 

So trehalose which bypasses the intestinal wall still goes through the portal circulation i.e. the liver where there is trehalase. 

 

Rectal administration has 2/3 systemic venous drainage and 1/3 portal.

 

Sublingual administration has 100% systemic administration. I.e. bypasses liver entirely.

 

So sublingual administration (which I confess I have been doing) is mildly superior to rectal.  Or am I missing something?

 

 

 



#107 Daniel Cooper

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Posted 12 September 2018 - 02:36 AM

Yes, I was aware that trehalase in the liver would break it down, but if 2/3rds of it goes systemic that's not so bad.  At least that fraction is no worse off than if we went IV.

 

Sublingual is fine, it's just that I feel we'd be somewhat limited on the shear quantity that is movable through that route.  Generally more ends up being washed down the throat than you realize.  But, perhaps I'm being pessimistic about that.

 

 

 



#108 OP2040

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Posted 12 September 2018 - 03:32 PM

Great stuff guys,

As you know I was experimenting with rectal admin, and the 2/3 figure sounds good enough to me.  Anything is better than oral.  As for sublingual, I have tried this too, but I find it impossible because salivation eventually forces you to swallow, especially if it's a larger amount.  Maybe I'm doing sublingual wrong....

 

Unfortunately, a lot of this stuff will be a guessing game unless someone actually finds a way to test the efficacy of various delivery mechanisms.  I am fine with educated guesses and will act upon them without reservation, but it would be so nice to actually see with your own eyes that a substance is being delivered to the bloodstream. 

 

Since these things are often a waiting game, I would encourage people to just replace any sugar they use with Trehalose.  There is still the 10g/day oral study in humans that showed a significant benefit for several metabolic parameters.  I can eat that much a day just in my coffee, but it is a bit more expensive than sugar.  I guess what I'm trying to say is, don't wait for the perfect delivery since there is already evidence for oral delivery doing something.  Perhaps not the reversal of atherosclerosis we are all drooling over, but certainly something.  Also, something that is rarely studied in humans is long time periods because it's just implausible.  It seems reasonable to me that if oral dosing has those effects, then it is working and over a longer time frame of 5-10 years would probably reverse atherosclerosis as well.



#109 Daniel Cooper

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Posted 12 September 2018 - 06:38 PM

Benko - 

 

Where does that 2/3rds going systemic number come from?  Rule of thumb or something specific to trehalose?

 

 



#110 Benko

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Posted 12 September 2018 - 10:05 PM

Benko - 

 

Where does that 2/3rds going systemic number come from?  Rule of thumb or something specific to trehalose?

 

 

Neither.  It comes from anatomic venous drainage of the rectum which is 1/3 to portal system and 2/3 systemic venous drainage. There is a post in one of these trehalose threads listing specific veins.  

 

On a related note, liposomal form which is absorbed, still goes through "liver" i.e. through gut wall, into portal vein to liver, metabolized via hepatic trehalase and then into systemic circulation. VS IV form (not that I'm suggesting it) which totally bypasses the portal vein and the hepatic trehalase.  

 

Sorry to rain on everyone's parade, but sounds like most systemic trehalose by:

 

IV (100%)

Sublingual is close (though as you said, some is swallowed.  Could be a lot).  

Rectal 2/3 systemic

 

and liposomes which I guess bypass the small intestine (brush border) wall trehalose, but they are still absorbed into portal vein and therefore still subject to liver trehalase.

 

Edit: according to Examine.com there is also trehalasse in systemic blood circulation  which would effect all forms (to the extent they make it into systemic circulation).


Edited by Benko, 12 September 2018 - 10:09 PM.


#111 Daniel Cooper

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Posted 12 September 2018 - 10:21 PM

But it is my understanding that the liposomal encapsulation will shield the contents of the liposomes as it makes the first pass through the liver.

 

Is this incorrect?

 

 

 



#112 Benko

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Posted 12 September 2018 - 10:41 PM

Apologies--I  don't know.  IF that is true it would be as good as the other forms, perhaps better if it also shielded against blood trehalose.



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#113 masterlock

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Posted 30 October 2018 - 10:16 PM

I think you've got that right. The conversion factor I use is Mouse Dose(mg/kg)/12.33 = Human Dose (mg/kg) which I believe yields the same results.

 

For my dosing guidelines I'm looking at the BioBlast human clinical trials.  These are for Parkinson's disease and not atherosclerosis, but I think they get us in the ballpark.  They were doing up to 27g IV once per week.

And then there's this:

https://globenewswir...ical-Study.html



#114 masterlock

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Posted 30 October 2018 - 10:20 PM

But it is my understanding that the liposomal encapsulation will shield the contents of the liposomes as it makes the first pass through the liver.

 

Is this incorrect?

You can't directly shield trehalose from trehalase in the various organs (liver, kidneys) or blood. However, you can functionally bypass the metabolism with sufficient dosing. That's why it's so important to know the correct dose. 

 

Based on the Bioblast study, it appears the MTD was determined to be 54 grams (g) administered IV over 60 minutes:

https://globenewswir...ical-Study.html



#115 Fafner55

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Posted 31 October 2018 - 02:37 AM

My self experiments with liposomal trehalose are published here.



#116 AceNZ

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Posted 19 February 2019 - 02:53 AM

Since trehalose is converted to sucrose by trehalase (and sucrose is of course converted to glucose + fructose), it seems likely that for a given dose of trehalose, the more your blood glucose increases, the more trehalose activity is happening.

 

Based on that assumption, it would be interesting to measure blood glucose for several different ways of trehalose administration: straight oral, oral liposomal, rectal infusion, rectal liposomal, and sublingual.

 

Keep the dose and the time delay after administration and before measurement the same for each approach, and repeat a couple of times to increase confidence. Should be straightforward.

 



#117 masterlock

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Posted 09 May 2019 - 08:33 PM

I've seen a lot of discussion in this and other threads about how to best get trehalose into the bloostream, but I don't think I've seen anyone suggest subcutaneous infusion. Given that trehalose is soluble at roughly 50mg/1ml water, this seems to be the most practical means of administering trehalose for the average person, since it doesn't require IV skills, and doesn't depend on more expensive and questionable methods like liposomal encapsulation.

 

This article talks about sub-Q administering of water and nutrients as a viable and effective alternative to IV for the elderly, for example.

https://onlinelibrar...148607116676593

 

It seems to me that a simple sub-Q infusion kit and the right trehalose solution, would suffice. I'm curious to know your thoughts.



#118 Daniel Cooper

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Posted 09 May 2019 - 08:40 PM

Yeah, we've talked about sub-q.

 

The problem with injecting a fairly concentrated sugar solution is that you'll reverse the osmotic pressure in the surrounding tissue and cause water to flow out of the cells, causing them to die.  You'll end up with a nice patch of necrotic tissue wherever you attempt such a sub-q injection.  In fact, concentrated sugar solutions are sometimes injected with the intention of causing inflammation/necrosis (this is the basis of prolotherapy for instance).

 

The ideal way would be IV.  But, making up a sterile solution and getting help in administering it (I'm not up to giving myself an IV) are hurdles.  

 

 


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#119 Rocket

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Posted 10 May 2019 - 05:22 PM

Yeah, we've talked about sub-q.

 

The problem with injecting a fairly concentrated sugar solution is that you'll reverse the osmotic pressure in the surrounding tissue and cause water to flow out of the cells, causing them to die.  You'll end up with a nice patch of necrotic tissue wherever you attempt such a sub-q injection.  In fact, concentrated sugar solutions are sometimes injected with the intention of causing inflammation/necrosis (this is the basis of prolotherapy for instance).

 

The ideal way would be IV.  But, making up a sterile solution and getting help in administering it (I'm not up to giving myself an IV) are hurdles.  

 

Wasn't talk a while ago about a liposomal formulation? 

 

IV is RISKY business. Anyone giving themselves IV injections of stuff bought online and prepared in home is asking for trouble.



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#120 Fafner55

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Posted 10 May 2019 - 07:20 PM

Wasn't talk a while ago about a liposomal formulation? 

 

Here is the discussion -

Autophagy Induction with Liposomal Trehalose

 





Also tagged with one or more of these keywords: atherosclerosis, peripheral arterial disease, trehalose, carotid artery disease, coronary artery disease

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