413 replies to this topic

[zorba990]

It's a shame that http://www.nu-gen.net/contact/ doesn't respond to emails, as the source material for squalamax seems significantly cheaper (dogfish shark liver) I will try to contact these guys http://www.life-sour...-of-Norway.html

Edited by zorba990, 22 September 2018 - 11:31 PM.

[RWhigham]

Many phytochemicals inhibit PTP1B to some degree. I tried the following stack

Stack (8 capsules)

  Red Sage Root Powder 1 cap 500 mg - Salvia Miltiorrhiza root

  Magnolia Extract 1 cap 200 mg  - 90% "Honokiol & Magnolol"

  AMP-K Stimulator 1 cap 225 mg - Gynostemma Pentaphyllum Extract (leaf)

  Berberine Hcl 1 cap 400 mg

  Bioactive Quercetin (EMIQ) 1 cap 50 mg - 40x bioavailability

  BCM-95 BioCurcumin 1 cap 400 mg - LEF

  Urso-X 1 cap 300 mg, 25% ursolic ac - from Rosemary extract

  Mega Green Tea Ext (leaf) 1 cap 725 mg, 45% EGCG - LEF

 

Experiment (Note: I weigh 130 lbs)

  T0 Took the 8 capsule stack

  T2 Took the 8 capsule stack again   (T2 is 2 hrs later)

  T4 Took the 8 capsule stack again   (4 hrs after the 1st dose)

 

Discussion

I took this stack and 2 hrs later felt nothing so I took it again. Two hours more I still felt nothing and took the stack a 3rd time.  I felt very high energy but that commonly happens to me and may be unrelated. The next day I felt a bit less mentally sharp than normal but was back to normal in another day or so.

 

Tolerance

I did not fee any discomfort after each dose or later.

 

Result

I cannot tell if  my arteries were affected in any way. My normal waking BP of 90/55 did not change. Perhaps I have a bit more stamina but cannot be sure. My arteries may already be pretty clean. My CAC last year showed one small spot of Ca at the bend on my descending coronary artery (CAC = 8).

 

Take Away

I would feel comfortable taking a multiple of this stack (24 caps or more) in a single dose. I had no discomfort. But I would be afraid of multi-day repetition with this stack without monitoring kidney and liver functions daily.

 

Edited by RWhigham, 22 September 2018 - 11:46 PM.

[mikey]

It's a shame that http://www.nu-gen.net/contact/ doesn't respond to emails, as the source material for squalamax seems significantly cheaper (dogfish shark liver) I will try to contact these guys http://www.life-sour...-of-Norway.html

 

Worth noting is that while squalamine does not cross the blood/brain barrier, trodusquemine does.

 

https://scienceofpar.../trodusquemine/

 

It seems that with multiple studies of squalamine occurring that trodusquemine will be studied more, as a superior agent to squalamine. At that time it seems that the price would come down, as happened with FOXO4-DRI.

 

Squalamine does have effects on the vasculature, which is my main concern, blood pressure that has been gradually rising with age.

 

If squalamine was shown to potentially improve the issue for me I would lead a group buy of it. 

I haven't had a spare moment to study the publications on squalamine. If someone else has and knows some things that would provide beneficial effects to reduce my blood pressure/improve cardiovascular health, please chime in and while we can let the troduscquemine group buy go dormant, I would institute a squalamine group buy. 

[mikey]

It's a shame that http://www.nu-gen.net/contact/ doesn't respond to emails, as the source material for squalamax seems significantly cheaper (dogfish shark liver) I will try to contact these guys http://www.life-sour...-of-Norway.html

 

I just ordered two bottles from nu-gen.net for $76. This is a decent price that can only be bettered by wholesale purchases. I found no other sources of pure squalamine, which is more desirable than shark liver oil, as it is the extract that has the most desired effects.

 

If my blood pressure seems to be decreasing after I've been using it regularly I wilt ask nu-gen if my company can buy it wholesale and then vend it. I would sell it on the internet through my company and give LongeCity members a good discount to provide a reasonably priced source so that we have a source to help us contribute anecdotes for our mutual research into longevity. All for one and one for all.

 

Buying it wholesale would allow me to give a "best" price to LongeCity members, while I also vend it to the public for profit.

 

If this works it will be desirable to vend and I know that I can sell anything that I believe in.

 

Thank you for the idea, zorba990. Here's hoping that I can detect a beneficial effect.

Edited by mikey, 23 September 2018 - 03:17 AM.

[mikey]

It's a shame that http://www.nu-gen.net/contact/ doesn't respond to emails, as the source material for squalamax seems significantly cheaper (dogfish shark liver) I will try to contact these guys http://www.life-sour...-of-Norway.html

 

Please consider just ordering the pure squalamine and see how it works. If you settle on shark liver oil, you won't be getting what is possible with the pure extract.

 

This is similar to buying bulk herbs and expecting to get the effects of the important extract that gives the herb its reputation.

 

Why go with something that is cheaper when it most likely won't produce the benefits that one might get from the "essential" extract?

 

Example: Whole ginkgo doesn't perform in studies the same way that the 24% 60:1 extract does.

Just a thought.

[mikey]

I just ordered two bottles from nu-gen.net for $76. This is a decent price that can only be bettered by wholesale purchases. I found no other sources of pure squalamine, which is more desirable than shark liver oil, as it is the extract that has the most desired effects.

 

If my blood pressure seems to be decreasing after I've been using it regularly I wilt ask nu-gen if my company can buy it wholesale and then vend it. I would sell it on the internet through my company and give LongeCity members a good discount to provide a reasonably priced source so that we have a source to help us contribute anecdotes for our mutual research into longevity. All for one and one for all.

 

Buying it wholesale would allow me to give a "best" price to LongeCity members, while I also vend it to the public for profit.

 

If this works it will be desirable to vend and I know that I can sell anything that I believe in.

 

Thank you for the idea, zorba990. Here's hoping that I can detect a beneficial effect.

 

Also, please note if I buy it wholesale then a group buy is not necessary because my pricing for LongeCity members will be lower than a group buy can achieve.

 

Peace!

[zorba990]

The shark liver tissue extract will have some trodusquemine in it while the purified squalamine will not. How much is up for debate until an assay is done. But this is where trodusquemine was found.

Squalamax description:
"There is absolutely no other squalamine dietary supplement on the market that matches the ultra purity and potency of this unique and freshly produced product, the one-and-only Squalamax™ Natural Shark Squalamine Supplement Capsules. Squalamax™ is naturally rich in squalamine, and is derived from the livers of deep-water sharks which inhabit the cold, non-polluted waters off the coast of Newfoundland and other countries.

This superior, all-natural, whole shark liver product is minimally processed to ensure that the squalamine component and all of its natural trace elements are maintained; Harsh processing and heat are avoided which may strip the shark livers of many of its valuable natural constituents. Squalamax is pure and natural, with no artificial coloring, additives or preservatives.

Environmentally Sound: Squalamax™ is a valuable dietary supplement that only uses Dogfish Sharks that were caught as a by-product of deep-sea fishing which would have otherwise gone to waste. Each capsule contains 650mg of Dogfish Shark Liver powder, rendered via an advanced and highly-specialized processing technique, and yields a substantial amount of squalamine.
"

Edited by zorba990, 23 September 2018 - 03:52 AM.

[mikey]

The shark liver tissue extract will have some trodusquemine in it while the purified squalamine will not. How much is up for debate until an assay is done. But this is where trodusquemine was found.

Squalamax description:
"There is absolutely no other squalamine dietary supplement on the market that matches the ultra purity and potency of this unique and freshly produced product, the one-and-only Squalamax™ Natural Shark Squalamine Supplement Capsules. Squalamax™ is naturally rich in squalamine, and is derived from the livers of deep-water sharks which inhabit the cold, non-polluted waters off the coast of Newfoundland and other countries.

This superior, all-natural, whole shark liver product is minimally processed to ensure that the squalamine component and all of its natural trace elements are maintained; Harsh processing and heat are avoided which may strip the shark livers of many of its valuable natural constituents. Squalamax is pure and natural, with no artificial coloring, additives or preservatives.

Environmentally Sound: Squalamax™ is a valuable dietary supplement that only uses Dogfish Sharks that were caught as a by-product of deep-sea fishing which would have otherwise gone to waste. Each capsule contains 650mg of Dogfish Shark Liver powder, rendered via an advanced and highly-specialized processing technique, and yields a substantial amount of squalamine.
"

 

Well, I am in for a penny and a pound. Squalamine seems worth a try and when trodusquemine comes down in price, which could be sooner than expected as happened with FOXO4-DRI, we will continue the group buy. For now I may become a source of squalamine.

Edited by mikey, 23 September 2018 - 04:00 AM.

[docmaas]

I'm pretty leery on squalamax.  I found this:  http://www.experts12...x-product.html " Approximately 150ug per gram."

 

Admittedly it's pretty hard to take this as authoritative but I was unable to find anything else.  It also begs the question of how much trodusquemine  is in that 150 ug of squalamine.  I'm inclined to continue to wait to see if we can get a reliable synthesized product.  

 

Mike

 

 

[The Capybara]

Aside from the moral implications, and the environmental impact of creating a commercial demand for dogfish, there are no studies that I can find that utilized squalamine using sharks as a source.

They all seem to synthesize the stuff, with high yields, in the lab.

I really think you're making this project much more difficult than it needs to be.

 

https://pubs.acs.org...rnalCode=joceah

[zorba990]

I'm pretty leery on squalamax. I found this: http://www.experts12...x-product.html " Approximately 150ug per gram."

Admittedly it's pretty hard to take this as authoritative but I was unable to find anything else. It also begs the question of how much trodusquemine is in that 150 ug of squalamine. I'm inclined to continue to wait to see if we can get a reliable synthesized product.

Mike

According to the product site it's 6.5 mg squalamine per capsule. Not sure what is the effective dose here.

[mikey]

I'm pretty leery on squalamax.  I found this:  http://www.experts12...x-product.html " Approximately 150ug per gram."

 

Admittedly it's pretty hard to take this as authoritative but I was unable to find anything else.  It also begs the question of how much trodusquemine  is in that 150 ug of squalamine.  I'm inclined to continue to wait to see if we can get a reliable synthesized product.  

 

Mike

 

Do you mean a synthesized squalamine or a synthesized trodusquemine?

 

Trodusquemine isn't possible right now at the high costs involved, but  haven't looked for a synthesized squalamine.

 

I'll begin that search and welcome any who want to help search. Or direct me to some potential synthetic chemists, as they may not respond to you unless you have a business that is licensed to buy.

[docmaas]

According to the product site it's 6.5 mg squalamine per capsule. Not sure what is the effective dose here.

 

Where are you finding this number?   The label here:  https://imgur.com/ZDmza6Z says 390 ug in three capsules which works out to 130ug/capsule.  

 

Mike

Edited by docmaas, 23 September 2018 - 08:00 PM.

[mikey]

Aside from the moral implications, and the environmental impact of creating a commercial demand for dogfish, there are no studies that I can find that utilized squalamine using sharks as a source.

They all seem to synthesize the stuff, with high yields, in the lab.

I really think you're making this project much more difficult than it needs to be.

 

https://pubs.acs.org...rnalCode=joceah

 

Good idea.

 

I've requested the full text of "Synthesis of Squalamine Utilizing a Readily Accessible Spermidine Equivalent."

 

Knowing the synthetic process makes it much more likely to find a lab to synthesize squalamine.

Keep ideas coming!

[zorba990]

Where are you finding this number? The label here: https://imgur.com/ZDmza6Z says 390 ug in three capsules which works out to 130ug/capsule.

Mike

This says 650mg/100 capsule bottle
http://www.nu-gen.ne...mg-100-capsules
But honestly I cannot in anyway vouch for this company since their email isn't even working

I haven't seen any other squalamine supplements offered only squaline.

Edited by zorba990, 24 September 2018 - 02:18 AM.

[docmaas]

This says 650mg/100 capsule bottle
http://www.nu-gen.ne...mg-100-capsules
But honestly I cannot in anyway vouch for this company since their email isn't even working

I haven't seen any other squalamine supplements offered only squaline.

 

In the text it says "Each capsule contains 650mg of Dogfish Shark Liver powder, rendered via an advanced and highly-specialized processing technique, and yields a substantial amount of squalamine."  The 650mg is of dogfish shark liver powder.  The actual amt of squalamine is much less as documented on the label I posted earlier.

[docmaas]

Good idea.

 

I've requested the full text of "Synthesis of Squalamine Utilizing a Readily Accessible Spermidine Equivalent."

 

Knowing the synthetic process makes it much more likely to find a lab to synthesize squalamine.

Keep ideas coming!

 

This one: https://www.scienced...001611?via=ihub

might be more useful as while the title talks about squalamine from spermidine the description talks about MSI-1436.  "Aminosterols isolated from the dogfish shark Squalus acanthias are promising therapeutic agents in the treatment of infection and cancer. One of these, MSI-1436, has been shown to possess antimicrobial activity slightly better than squalamine. In this study, a series of analogs of MSI-1436 have been synthesized from stigmasterol. The 7α-hydroxy substituent of MSI-1436 was either omitted or the stereochemistry modified to the 7β position. Also, analogs of MSI-1436 with 24-sulfate, 24-amino, and 24-hydroxy substituents were synthesized in order to assess the importance of the side chain functional group on antimicrobial activity. All of the analogs possess significant antimicrobial activity, suggesting that substitution at C7 and C24 of the aminosterols plays a minor role in their antimicrobial potency."

 

https://www.scienced...001611?via=ihub

[docmaas]

Do you mean a synthesized squalamine or a synthesized trodusquemine?

 

Trodusquemine isn't possible right now at the high costs involved, but  haven't looked for a synthesized squalamine.

 

I'll begin that search and welcome any who want to help search. Or direct me to some potential synthetic chemists, as they may not respond to you unless you have a business that is licensed to buy.

 

I prefer the trodusquemine.

[docmaas]

Zasloff has started a new company targeting Parkinsons disease.  http://enterininc.com/ They are apparently trialing a squalamine derived drug in the gut to alleviate constipation in Parkinson's sufferers.  However there was something about another drug to target the brain.  

 

Mike

[Beetlejuice]

Hi, I’m a total airhead on this unfortunately and can’t chime in cos I don’t even understand the dose calculations. But what I did notice in this were the reference to ‘sub theraputic’ doses still seeming to produce a result? Do correct me as I don’t know 3mg/m2
https://m.marketscre...-1436-13123592/

[tunt01]

Random tidbits from my notes.  Maybe everyone should take a hard look at Ursolic Acid as a PTP1B inhibitor because that is what Johan Auwerx appears to have been working with (in addition to Nicotinamide Riboside   EDIT:  It was urolithin A, not ursolic acid) during his focus on NAD+ enhancing research which was subsequently licensed to Mitobridge.

 

 

PTP1B can inhibit the PI3K pathway

• Over expression deactivates kinase signaling
• Expression Inhibits downstream PI3K activity

 

Acute exercise down regulates PTP1B

 

Leptin receptor in the hypothalamus (ObRb) is inhibited by PTP1B

 

PTP1B inhibits STAT3

 

PTPB1 is an enzyme associated with the endoplasmic reticulum and plays a key role in signaling metabolic pathways that interacts and dephosphorylates insulin receptor and leptin, causing downregulation signaling of both receptors in modulating the mitogenic actions of insulin (He 2014)

 

SIRT1 represses PTP1B, a negative regulator of insulin signaling

 

PTP1B is a therapeutic target for T2D (BJ 2001)

 

Honokiol inhibits PTP1B and reverses T2D in mice (Hu 2015)

 

Ursolic Acid inhibits PTP1B via upregulation of SIRT1 (Bakhtiari 2015)

 

 

BJ, G. (2001). Protein-tyrosine phosphatase 1B (PTP1B): a novel therapeutic target for type 2 diabetes mellitus, obesity and related states of insulin resistance. - PubMed - NCBI . Ncbi.nlm.nih.gov. Retrieved 24 September 2018, from https://www.ncbi.nlm...pubmed/12477292

 

HU, X., Sun, J., Fu, X., Liu, Y., Wang, Y., & Huo, B. et al. (2015). Hypoglycemic effect and mechanism of honokiol on type 2 diabetic mice. Drug Design, Development And Therapy, 6327. doi:10.2147/dddt.s92777

 

Bakhtiari N, e. (2015). Ursolic acid ameliorates aging-metabolic phenotype through promoting of skeletal muscle rejuvenation. - PubMed - NCBI .Ncbi.nlm.nih.gov. Retrieved 9 May 2016, from http://www.ncbi.nlm....pubmed/25976755

 

He, Y., Li, W., Li, Y., Zhang, S., Wang, Y., & Sun, C. (2014). Ursolic Acid Increases Glucose Uptake through the PI3K Signaling Pathway in Adipocytes. Plos ONE, 9(10), e110711. doi:10.1371/journal.pone.0110711

Edited by tunt01, 24 September 2018 - 10:17 PM.

[mikey]

Hi, I’m a total airhead on this unfortunately and can’t chime in cos I don’t even understand the dose calculations. But what I did notice in this were the reference to ‘sub theraputic’ doses still seeming to produce a result? Do correct me as I don’t know 3mg/m2
https://m.marketscre...-1436-13123592/

 

They're going after the diabetes market, so we mustn't give up the ship.

 

If this goes as it should the raw materials price of trodusquemine will drop. We just have to wait a year or so.

[docmaas]

 

https://www.ncbi.nlm...pubmed/25623533

 

Functional properties of Claramine: a novel PTP1B inhibitor and insulin-mimetic compound.

 

 

The in press version of the full article is here:  https://docksci.com/...b7b79cb04a.html

 

Sigma has it listed for sale:

 

https://www.sigmaald...ng=en&region=US

 

Unfortunately while the researchers did do in vivo with mice there is no indication of any tissue or toxicity studies.  Maybe someone with expertise can offer an opinion on the impact of the salt that differs between the two.

Edited by docmaas, 26 September 2018 - 09:45 PM.

[docmaas]

Using the dosing found here:  https://m.marketscre...436-13123592/  

and the conversion tool found here: https://reference.me...tor/bsa-dosing 

 

At 68" tall and 140# I would have to take 5mg of trodusquemine/claramine to see a similar impact.  I haven't been able to find an estimate of the amount of trodusquemine in dogfish liver oil so it's difficult to approximate how much squalamax would be required but for squalamine that comes out to around 38 tablets/capsules.  I could probably handle that over 3 days.  Of course that is squalamine.

 

[docmaas]

This may have already been posted but here it is:  https://www.nature.c...icles/0801599  

 

Title: A spermine-coupled cholesterol metabolite from the shark with potent appetite suppressant and antidiabetic properties

 

 

"MSI-1436 and MSI-1701 were synthesized by coupling spermine to the (5α, 7α, 24R)-3-keto-7-hydroxycholestan-24-ol sulfate steroid intermediate as described.2,6,7 MSI-1814 was prepared by the same procedure as MSI-1436 but by using the opposite chiral catalyst during reduction of C-24 (S-MeCBS from Callery Chemical Co., Pittsburgh, PA). The synthesis of the 7-β isomer, MSI-1673 and other compounds will be described elsewhere (Kinney et al, manuscript in preparation)."

[Daniel Cooper]

Random tidbits from my notes.  Maybe everyone should take a hard look at Ursolic Acid as a PTP1B inhibitor because that is what Johan Auwerx appears to have been working with (in addition to Nicotinamide Riboside   EDIT:  It was urolithin A, not ursolic acid) during his focus on NAD+ enhancing research which was subsequently licensed to Mitobridge.

 
 
I started a thread on Urolithin A some time back here - Anyone Considering Supplementing With Urolithin A?.
 
So far I have been unable to find a commercial source that isn't a very expensive research chemical supplier.  It's a fairly simple molecule that shouldn't be too hard to make. 
 

Of course, the other option is to find a source for gordonibacter urolithinfaciens then consume ellagic acid.  Unfortunately I haven't been able to find an off the shelf source for a gordonibacter urolithinfaciens probiotic either.   Definitely seems to be an unmet market need here.  In any case, if anyone wants to talk about urolithin A I suggest we take it over to the thread referenced above.

 

 

[Rocket]

No group buy,yet?

[mikey]

No group buy,yet?

 

To clearly update everyone who hasn't been able to follow this entire thread, the current cost of TD is extremely high. One dose would cost about $7,700.

 

One dose, if it worked as it did in mice, would completely reverse atherosclerosis and I would pay for it (just because this year I have enough money), but when this was announced no one else on this forum responded, so it's likely a dead issue until the cost comes down. 

 

So, what to do? Well, a diabetes study is now in progress. It will likely be successful and maybe in a year, because of this study, mass production of TD will bring the cost down. We can expect more studies of TD, for obesity, cancer, etc...

 

Hopefully, BIG PHARMA won't find a way to kill TD because it could solve several serious health concerns that could greatly reduce the cost of American medical care.

 

We saw FOXO4-DRI diminish in cost to about 10% of what it was a year ago, so we can hope that this will happen with TD. For now, it's a waiting job.

 

I am looking into squalamine, which does not cross the blood-brain barrier like TD does, but does have some of TD's meritorious metabolic effects.

[docmaas]

I've done a bit more research on Squalamax and I regret to say I don't think it is a viable source. 

 

First I looked at Zasloff's original 1993 research where they first identified both Squalamine and trodusquemine.  The paper is here: https://www.ncbi.nlm...s01102-0225.pdf

In the paper they report that they found squalamine in several organs but that it was most predominant in the liver and gall bladder:  "Liver and gallbladder, the organs in which bile salts are synthesized and stored for secretion into the gastrointestinal tract, are the richest sources identified (4-7 ug/g of tissue)."

 

The next question is how much tissue converts to oil?  In this paper:  

https://www.scienced...001093?via=ihub

it was found that 3 different distillation methods resulted in1g of tissue .68g of oil was recovered.  Using steam the results were .22g of oil for 1 g of tissue. 

 

Using the upper range of 7ug/g of tissue and a 22% recovery of oil/g of tissue gives us maximum potential concentration in the oil .22g of oil yielding 7ug of squalamine.  This assumes that the steam recovered oil contains all the squalamine.  That's a big assumption but it is also the most generous to Nu-gen the company that sells Squalamax.  Using the 68% recovery would make the squalamine concentration in the oil to be only 1/3 of the 22% from the steam method.  

 

Given those numbers and the contents label from the Squalamax bottle we can calculate the most optimistic amount of squalamine/g.  Unfortunately this number turns out to be about 1% of what they claim.  The label says one serving (3 capsules) contains:

 

Shark liver complex 1.95g

    (Dogfish shark liver powder containing natural Shark Liver Oil 117mg, Squalene 1.37mg and Squalamine 390ug)

 

There is a little ambiguity here as we have Dogfish shark liver powder containing Shark Liver oil -- don't know if this oil is pure dogfish or not but my guess would be not which given the small number of sharks that actually have squalamine (only 5 species in my reading) would make the amount of squalamine even more diluted.

 

Back to the numbers:  

 

using 22% conversion via steam

 

1g tissue = .22 g oil (assumes steam extraction gets all the squalamine in its most concentrated form)

 

7ug/.22g oil (assumes the actual concentration is the max measured by Zasloff's team in 1993)

1ug/.03 g oil 

1ug/ 30mg oil

 

distribution assuming above 1ug/30mg oil

117mg on label /30mg/ug 3.9ug per 3 caps vs 390 claimed;  that is 1% of what is claimed.

 

What is the rest of the 1.95g of powder then?  It is probably at least partially the materials used to microencapsulate the oil resulting in the powder.  

 

I tried to get some questions answered in a call to Nu-gen but met with claims of everything I asked about being proprietary information.  I asked if the had had it tested and they said yes but the results of the testing are proprietary.  

 

I certainly will not be buying it unless I see their test results from an outside lab demonstrating the concentration they claim.

 

 

 

 

 

[OP2040]

I wish someone could explain to me the economics of why it costs so much to produce these substances.  Is it something that can be overcome, or is it still inherent in the production process?  It can't be entirely the latter because the Chinese companies have no problem getting the prices down by orders of magnitude. 

 

Not to go off topic, but I'm looking into 2-HOBA for the same reason as this thread was started, targeting atherosclerosis.  It is not a direct comparison because this is just a derivative of Buckwheat, and not a synthesized molecule.  However, once again American companies are selling it at literally 100X the cost of Chinese companies.  That is insane.  China is a fairly wealthy country now, so it can't all be down to labor costs or even quality controls.  Anyone interested in that purchase, feel free to PM me.  Though it is much cheaper, it is still in the range where a group buy could be beneficial.