49 replies to this topic

[OP2040]

I would like to pursue a group buy for Klotho, or one of it's analogs.  I think most of you are aware of how awesome this substance is, so I won't go into that right away.  I will say that the group buy will probably be a slow process, as there are a lot of choices to make, and discussions to be had.  Nevertheless, this is on the top of my list, so I'm here for the long haul and will be the main organizer, unless someone else comes along that has experience in it.

 

The way I see it, here is what we need to discuss and make decisions about:

 

1.  There are 3 possible Klotho purchases that could be made:

      a. rhKlotho - this is actual Klotho, and it is very expensive

      b. PEP-1192 - This corresponds to the 16 amino acids near the center of Klotho.  It would be less expensive,

          and probably close to just as effective.

      c. Compound H (N-(2-chlorophenyl)-1H-indole-3-caboxamide) - This is my personal preference.  It is probably the

          least expensive since I think it is just a fragment, but a couple studies have shown it is very effective.  The drawback

          on this one is that it seems esoteric, although I do see labs selling exactly this compound.

2. Delivery - I assume this would be venous of SubQ injection, but I don't know.

3. Dose - How much is ideal.  I think this is one of those things that I'd like to dose continuously for as long as possible. 

    But due to expense, I'm mostly looking to see if it has any dramatic effects to start.

4. Safety - I don't see any issues here, but maybe others do.

 

Although this may not happen right away, please express your interest now, so that I can base any potential quotes on some kind of realistic number.

 

 

[cassioBJJ]

Hello,

 

I am really interested in this substance. I am in.

Thanks.

[poonja]

Count me in as well.

[OP2040]

I have gathered some prices for our three different options just to get an idea.  These are almost the first options I came across, so they are not set in stone by any means.  And obviously, with a group buy they should be cheaper, but that will be based on how many people we have.

 

1. rhKlotho - $339/50ug

2. Pep-1192 - $89.00/50ug

3. Compound H - $58/100mg  = 100,000ug

 

So, as you can see the third option is exponentially cheaper.  Again, the main issue with that one is the chemistry.  The chemistry makes sense for the first two.  But I know nothing about the last one.  All that I know is that it has been studied twice and increases serum Klotho, and has beneficial effects the same as you would see for Klotho itself.

 

Actually, I just looked them up, and there are three studies on compound H:

 

1. Induction of anti-aging gene Klotho with a small chemical compound that demethylates CpG islands

2.  Compound H Increases Anti-aging Protein Klotho Expression and Attenuates Arterial Stiffening and Hypertension

3. Activation of DNA demethylases attenuates aging‐associated arterial stiffening and hypertension

 

So there we have it.

Edited by OP2040, 08 June 2018 - 03:20 PM.

[orion22]

can you translate those prices into how much will we pay per month for results per kg if you tell me 50ug i don t know what that means do i nedd to take it once a day once a weak once a month

[recon]

I’m interested in this.

However, I can think of some problems that may arise with these substances.

1) Analogues may have a lesser or even no effect as the original substance but yet still takes up the spots at the receptors.
Example: phytoestrogens with estrogens; FOXO4-DRI with some FOXO gene thing

2) Having exogenous intake of a naturally-producing substance may trigger homeostatic negative feedback that reduces the bodily production of that substance.
Example: exogenous antioxidants; melatonin

[OP2040]

I’m interested in this.

However, I can think of some problems that may arise with these substances.

1) Analogues may have a lesser or even no effect as the original substance but yet still takes up the spots at the receptors.
Example: phytoestrogens with estrogens; FOXO4-DRI with some FOXO gene thing

2) Having exogenous intake of a naturally-producing substance may trigger homeostatic negative feedback that reduces the bodily production of that substance.
Example: exogenous antioxidants; melatonin

 

Thanks recon, this is the kind of feedback I'm looking for, however these concerns do show up for almost any intervention.

 

1. All I can say about the analogues is that they do seem to work in the same or similar way in mice as the real deal.   

    That's all I can go on at this point. 

2. Homeostasis and negative feedback comes up as an issue for any long term intervention, so it is just something we

    will have to deal with through cycling if it is an issue.  I don't really understand why this happens with natural

    substances though since presumably some people have more naturally occurring Klotho and therefore better health,

    and yet have no downregulation.  Is it all down to the idea that they also have more receptors for said substance?  If

    that is the case, then even gene therapy is hopeless.  If it's not the case, then I'm lost as to why this happens.

 

Orion,

The ug measurement is just a microgram, which means you need a million of them to make a gram.  This should put in perspective just how small an amount you are getting with those two, and just how costly a usable dose would be. I haven't done the cost calculations, but it seems we probably should just drop those options do to cost.  This is my first group buy, so I have no idea how much we could get the cost down, but I doubt it would be so much as to make those palatable.  Anyone else with more experience, please feel free to weigh in on the measurement and cost of those two options.

[OP2040]

ok, we've only got like 5 people interested, I think we're going to need more than that.  I'm going to query a few companies to get pricing based on like 20-50 people.  This is my first group buy, any suggestions on this process?

[orion22]

so we going for Compound H ?

how much we need to take per month PER KG BODY WEIGHt?

and who is doing the group buy 139 posts here isn t that many 

OP2040

?

will it spoil via mail do to heat to COUNTRY Romania?

can it be sent legally?

why are you not giving more details?

what is minimum amount to buy per person?

 

Edited by orion22, 21 June 2018 - 05:44 PM.

[Bushi84]

Sounds interesting. But i gotta learn more about the substance.

Edited by Bushi84, 21 June 2018 - 09:23 PM.

[OP2040]

Orion22,

 

I am new to group buys, so yes I am either going to need some guidance or it will take some time.  Also, the entire point of the thread is to answer some of the questions you are posing.

 

Why Compound H?  That is my personal choice because it is the cheapest, and still shows much the same beneficial effects as the full Klotho version.  I'm very open to a discussion about why one of the other two options would be better, but so far no one is objecting to that path.

 

How much?  Very good question.   The mouse study that shows great benefits was done for two weeks, daily @ 15 mg/kg IP.  The HED dose for that is something like 1.2 mg/kg, so for a 185 lb man like myself would be 100mg, so very doable.

 

Why me? I really don't care who does the group buy, so if someone else will step in, I'd be more than happy to let them.  As for safeguarding things, I would like to have everyone to purchase and organize their own delivery after the buy is organized.  I have no desire to exchange money, or repackage and ship product.  This is how another group is doing the Trehalose buy, but it may not be feasible for a more esoteric compound like this.

 

I have no idea what the details would be until I place a few requests and then find out what t he companies shipping and payment policies would be.  Before I do that, I wanted to get a decent amount of people involved, and answer some of our questions.

 

For a start, does anyone object to going with compound H?  If so, lets have the discussion.  If not, I will move forward.  I obviously can't look for quotes without getting everyone on board with what we're actually going to purchase.

 

 

 

 

[orion22]

its 100mg per day?

[OP2040]

By my calculation, yes. 

 

Another issue is that I would like to know more about what is called Compound H.  My chemistry is very weak, so I can't look at a compound and make any inferences about it.  Maybe some others can help with that?  Here is the actual molecular structure:

 

N-(2-chlorophenyl)-1H-indole-3-carboxamide

 

It can be purchased based on that structure.  But there is not a lot of information on it other than being listed.  It has not been tested for safety, so that may be a reason for people to say no to it right out of the gate.

 

If we find that the risk/reward on this compound is too much to handle, then we can explore the two other options, for which I think there is some evidence of safety.  The problem of course is all down to money.  The other two are very, very expensive for an individual, and I'm think they will be pretty expensive even with a group buy.  After all, the buys are measured in micrograms, so even that price would be a multiple of a thousand to get near an effective dose.  I highly doubt it's effective at the microgram level, anyway.

 

I'll say it again, I'm not a natural leader and I'm not a biologist.  I'm taking this on out of necessity because I think Klotho is a game changer in a number of ways, and no one else seems to want to move the ball forward.  Even if we can't move the ball today, or even this year, I still think this is worth pursuing and will continue to advocate.  And if someone that IS  natural leader, or a biologist wants to take charge or even tell me where I may be going wrong, I would appreciate it greatly.

Edited by OP2040, 22 June 2018 - 04:31 PM.

[Nate-2004]

I'd rather have a better understanding of what compound H is and why it means klotho.

[tintinet]

Interested so far.

[Ovidus]

intrested...

However "Compound H - $58/100mg  = 100,000ug" and figuring a two week use at 100 mg per day, the cost is prohibitive, no?

if we can get the price down to $50 for 100 mg, we are talking 14*$50 = $700

Quite a bundle.

I am not messing up the calculation, am I?

[OP2040]

intrested...

However "Compound H - $58/100mg  = 100,000ug" and figuring a two week use at 100 mg per day, the cost is prohibitive, no?

if we can get the price down to $50 for 100 mg, we are talking 14*$50 = $700

Quite a bundle.

I am not messing up the calculation, am I?

 

My apologies, that was a hasty quote just to demonstrate how much cheaper Compound H would be in comparison with the others. 

 

I am looking at a quote right now that is $205/g, which would be $20/100mg.  If you were to run a course for a couple weeks that would only be $140.  And all of this is before any group buy discounts.

 

I understand that may still be expensive for some people.  I also think that this is a compound I would want to use more than just the bare minimum of two weeks.  But for me this has been about just conducting an experiment.  I want to know what raising the levels of Klotho will do for me.  Once armed with that knowledge, there is a whole changing world out there in which prices inevitably fall, and new discoveries are made, and raising Klotho cheaply will ultimately be possible.

 

Having said all that, even the minimum 2 week intervention may indeed change the entire course of some aging diseases, particularly arterial aging.  In the studies I've read, the results seemed to imply that the one intervention had a lasting effect.  Klotho in particular has a downstream effect on redox balancing that all the tinkering in the world could not replicate downstream.  This is another reason that I think it's not only worth the risk, but the expense. 

 

As with all these group buy interventions we do here, it may not pan out, and we are taking a calculated risk that nothing good will come of it, maybe even something bad could come of it.  I've made those calculations for myself, but I encourage others to read the literature and make reasoned decisions for themselves too.  The two compound H studies are posted somewhere in this thread, or a similar Klotho thread.

[orion22]

by the way i read somewhere muscle injury increases Klotho would it it be a good idea to do exercise until you break you re muscles at a very high degree?

140$ is much because we buy other supliments also when might the buy happen in 5 moths i will have 1k$ to spend on this can t garante anything before that but if i can spare some i will be in

Edited by orion22, 23 June 2018 - 03:38 PM.

[OP2040]

Exercise increases pretty much everything good in the body, including Klotho expression, you can't go wrong with it.

 

It is expensive, especially if it is to be used as a daily supplement.  That's why I'm using this as an experiment to see what happens first.  Just to put things back in context.  Klotho still holds the record in mice for extending median life span, at least according to my count.  And it is proven to be a longevity booster in humans too.

[Ovidus]

Thanks a lot for the very helpful response OP2040.

 

At those prices it is worth it IMO....

 

[adamh]

I may be interested. One thing about those sky high prices, was that from places like I can't think of all the names but ultra pure chem companies which cater to well funded studies like sigma aldrich? Their prices are always in the clouds, if not bumping into the moon. When I looked for interesting compounds I always saw ridiculous prices like $10 a ug or close to it for tiny amounts. When I find it on alibaba its more like dollars per gram or kilo instead of mcg.

 

Ordering from a chinese or other similar company carries the risk that it may not be the real thing, may be impure, have heavy metals or etc. An analysis by a local lab would clarify that but will cost probably well over $100. Another way to select a vendor would be to look at their feedback and do a search online. If they have been in business for a few years or longer with good reputation that is a good place to start.

 

I took a quick look and did not see klotho on alibaba. But your cheaper compound h might be 100 a kilo if they sell it. Something that indirectly increases kl levels maybe a better approach anyway

[sub7]

Exaclty.... so if buying for more than one or two individuals -as would be the case in a group buy- it makes far more sense to buy from the cheaper supplier and shell out the $100 or so for the test. Net cost per user (assuming that we can come across a product with reasonable quality relatively quickly) will be far lower by taking this route.

 

Ordering from a chinese or other similar company carries the risk that it may not be the real thing, may be impure, have heavy metals or etc. An analysis by a local lab would clarify that but will cost probably well over $100. 

[OP2040]

For me, the extra burden of finding and paying for lab testing is too much.  Not just that, but in the form of Compound H, it is not that expensive to begin with.  Unless people are talking about Klotho itself?  There are hundreds of chemical companies, and I've just chosen a random sample of them to establish a price.  I assume some of the ones I'm looking at are Chinese companies, and I don't see much of a price difference anywhere.

 

I see the Klotho thing in two steps.  This step is basically us testing whether raising Klotho in humans has beneficial effects, objectively and subjectively.  If not, or if there are side effects, game over for now.  In this sense, I don't worry too much about cost just yet.  However, if it works the way I would like, then I would devise a plan so I can keep taking it over time.  In this particular case, cost would then become much more important.  That's just the way I see it, but whatever everyone agrees to, I will go with.

 

Have we found anyone with some chemistry under their belts that can comment on the Compound H, best route of administration and possible safety concerns?  Flying blind with a compound I know almost nothing about outside of two mouse studies is definitely a concern,

[adamh]

OP2040, I can assure you the companies asking $ per ug are not the bulk chinese, indian, etc bulk suppliers. As I said I saw nothing for klotho on alibaba thats why I say perhaps focusing on precursors like h is a better strategy. Klotho itself may never be cheap or not for a few years.

 

As for testing, what would we test for? Heavy metals, purity, other things? The more you test for the more expensive it will be. If it seems like a burden perhaps someone else will come along and want to do it?

 

Then there is the fact that so many compounds did great in testing, people got enthused, and it turned out to be much less than we hoped for. Examples are resveratrol, c60, melatonin and others. They did some good but there was controversy and interest faded somewhat. I doubt this will be the magic bullet. Until we get a number of people to try it and report it will be somewhat doubtful

 

Few will pay hundreds per dose just to try something. Lets find the cheapest precursors and other things that have evidence of the capability to raise klotho levels.

[George2]

OP2040, I can assure you the companies asking $ per ug are not the bulk chinese, indian, etc bulk suppliers. As I said I saw nothing for klotho on alibaba thats why I say perhaps focusing on precursors like h is a better strategy. Klotho itself may never be cheap or not for a few years.

 

As for testing, what would we test for? Heavy metals, purity, other things? The more you test for the more expensive it will be. If it seems like a burden perhaps someone else will come along and want to do it?

 

Then there is the fact that so many compounds did great in testing, people got enthused, and it turned out to be much less than we hoped for. Examples are resveratrol, c60, melatonin and others. They did some good but there was controversy and interest faded somewhat. I doubt this will be the magic bullet. Until we get a number of people to try it and report it will be somewhat doubtful

 

Few will pay hundreds per dose just to try something. Lets find the cheapest precursors and other things that have evidence of the capability to raise klotho levels.

 

I was reading the thread from my casual interest in Klotho. Yes, companies like Sigma charge way way more than the actual price. A good chemistry lab can synthesize these compounds far cheaper. You may need to order a kilo or more to cover the cost of standardizing the synthesis and all the analytical tests that need to performed. Many years ago, I got a small Indian company to synthesize several hundred grams of a super-expensive cancer drug for a relative (at that time it was in Phase III studies with very promising results). The synthesis was very complex (7 steps) and some intermediates were not available and was even more difficult to synthesize. I got a Chinese company to do it although they had to make 3 attempts to get the level of purity that I required. After several months, I had several hundred grams of the drug that met my specs. I think it costed me approx $5000 to make the first batch, but if I went for a second one, it would have been $1000/kg. So you see, if this thing really works, and is not available on Alibaba, there are other ways to get it made that is cost-effective and meeting the specs that you need. Just a suggestion since I am not interested in trying Klotho. I forget the name of the Indian and Chinese labs (they both were very small ones) because it was done more than 10 years ago

[OP2040]

George2,

 

Thanks for sharing with us so we can benefit from your experience.  I don't mind going with a Chinese or Indian lab, I'm just worried that no one will work with me since I don't work at a lab or university myself.  Also, I'm a bit wary of trying to make things perfect for the first buy.  As can be gleaned from your post, these things work better as an evolving process.  That's why I kinda see the first buy as just an opportunity for all of us to experiment with it.  Going with what you said, I suppose I should put Klotho back on the table and see what I can find.  Ideally, I'd prefer the real deal, and it was just expense that had me balking at it.

 

adamh,

 

Obviously, there is the possibility that Klotho will do nothing in humans.  But I don't think it's like melatonin, C60 or Resveratrol, for a number of reasons.  I'm fairly confident it will have beneficial effects.  But that is a debate that cannot be resolved without actually trying.  So we either try.......or we wait around for someone in the medical community to bother with a substance they can't patent, and then spend 10-20 years on clinical trials.  That's a decision we can all make as individuals.

 

Since I tend to use the Hallmarks as my guide, I don't think any one thing we try here is going to be a magic bullet.  It is more about remaining healthy and on the cutting edge, so that when that magic bullet or bullets do come along, we will be ready.  I do think that partial reprogramming of epigenetics will be very close to that magic bullet.  But of all the potential things we could try, that one seems the furthest away from being actionable.

[orion22]

im out of the group buy i got to good results from the protocol from thread '' Stem cell self-renewal with C60 ''

[pinballwizard]

I would like to be in the group buy. Please contact me!

[OP2040]

guys, I'm glad we are getting so much enthusiasm, Klotho definitely deserves to be pursued vigorously.

 

However, I am having a really difficult time finding a chemical company that will work with me.  I do not have a lab I can reference on my inquiries.  This is my first time trying to organize a group buy, and I guess I assumed I could muscle my way through this issue, but apparently not.

 

Can anyone offer any help of advice?

[OP2040]

ok guys,

 

As the spirit of this thread is to find ways of increasing Klotho, and thereby benefiting from it's anti-aging effects, it looks like we have a brand new target t o consider.  This study came out recently:

 

https://www.ncbi.nlm...pubmed/30026406

"Mitochondria‐targeted hydrogen sulfide attenuates endothelial senescence by selective induction of splicing factors HNRNPD and SRSF2"

 

And here's another study which mentions the connection to Klotho:

http://mcb.asm.org/c.../33/6/1104.full

 

At first glance it wouldn't seem to have anything to do with Klotho, except for the fact that the Hydrogen Sulfide target is known to act partially through the Klotho pathway.  Whether it actually increases Klotho or not, it is a pretty promising intervention.

 

If anyone would like to experiment with this, I found one of the three compounds discussed in the article, and it seems it is fairly inexpensive compared to what we have been looking at.  Although if the dose needs to be very high, then it would still be pricey.  Here is the link for that:

 

https://www.caymanch...m/product/17100

 

I haven't done much more digging, other than reading the article and searching for the compound.  I just wanted to see if it generated any interest or discussion first.