4 replies to this topic

[Solarclimax]

What are peoples opinions on a Cortexin and IGF LR3 Stack ? Synergistic effects ? Good Idea ? Bad Idea ?

[chrono]

Well, my vote would be for "bad idea," for several reasons. But it depends (somewhat) on what effects you're hoping to synergize.

First, cortexin seems pretty iffy. Much like Cerebrolysin, it's a <10kDa peptide mix, capable of improving certain neurological outcomes. However, unlike CRB, only one or two papers are suggestive of even possible cognitive improvement in the young/healthy. It's based on a kidney hormone rather than brain peptides, and it has other physiological effects—regulation of cardiac activity, and immunomodulating properties, to name two. Nor does it have CRB's long history of use, safety record, and anecdotal reports of nootropic benefit (that I'm aware of). To me, it seems to be somewhere between "not the best option," "long shot," and "unknown risk factor."

As for long R3 IGF-I, this is much, much riskier. It's true that IGF-I can have an impact on cognition; most of the studies show improvement in the elderly, who have impaired IGF-I production. Whether this translates to improvements for the young/health, is anyone's guess. Since insulin can do so, it seems possible. IGF-I is also an important mediator of angiogenesis, and hence neurogenesis. HOWEVER, and this is a big however—it can also accelerate the growth of tumors, even those that would otherwise have been a non-issue (see here). It is also thought to have a negative impact on longevity, possibly through the increase of cell division.

Then there's the problems with LR3 in particular. In the BB world, it's used immediately post-workout, when expression of IGF receptors on muscles is thought to be increased. The best (i.e. only good) way to administer it is through a series of very low-volume injections into the target muscles. This is because injecting a large amount will quickly saturate local receptor sites, and will 'spill over' into other tissues, including the bloodstream. Since the benefit of the LR3 modification is that it won't pair with the IGF binding proteins, it will essentially just float around until it finds more receptors to bind with. Many of these are in the intestine, and prolonged LR3 cycles with systemic spillover will cause growth in the intestines. This is a bad thing.

The next question is: will it cross the BBB? IGF-I does, through a saturable transport system. However, this transport is partly regulated by the binding proteins, which LR3 doesn't bind to. So, I assume this would result in some kind of dysregulation; either an insignificant amount would cross the BBB, or a disproportionately large one. Either option sounds undesirable to me. Its immunity to IGFBP, and increased half-life, might further amplify its effect in the CNS, with unknown consequences. Intranasal administration would likely ensure entry into the CNS, but given the preceding concerns and dubious benefit, it would be an excessively ridiculous thing to do.

So in summary, IGF-I is a target with negative implications for cancer growth and longevity, with a practical impact on healthy cognition that is pretty doubtful. The LR3 peptide in particular has little human data, especially for its entry into and effect on the CNS, and it can't have a simultaneous impact on both muscle growth and the brain without some severely undesirable side effects. In other words, the exact opposite of what a nootropic should be

[Solarclimax]

Cortexin represents liofilizat obtained by acetate extract from the bark of the brain of cattle or pigs

Based on a kidney hormone ?

You don't really give good reasons why you think

cortexin seems pretty iffy

You talk about R3 IGF 1 As though there's a strong chance of it accelerating growth of tumors. The truth is, some studies do suggest there may be a chance but nothing is conclusive. The IGF that accelerates tumor growth usually sits inside the cancel cells, where as IGF R3 sits outside, the significance of that is not fully understood. How come we don't see lots of bodybuilders dropping dead of cancer ? All the pro's take it, in very large amounts all the time.

Its immunity to IGFBP, and increased half-life, might further amplify its effect in the CNS, with unknown consequences.

How do you figure this ?

Prolonged IGF cycles may cause the large belly look, but i was thinking of doing 1 short 50 day cycle of 40mcg a day.

On another note, I'm not sure there's great evidence that IGF LR3 actually does cause gut bloat. If you look at the older bodybuilders with gut bloat that take IGF LR3 most of their bloat came from the earlier versions of HGH. If you look at the up and coming new generation of bodybuilders who also hammer IGF LR3 they have zero gut bloat.

What makes you think IGF LR3 is bad for longevity ? do you have any proof ? I remember reading that IGF has desirable qualities for life extension ?

Do you have links to papers for what you base you claims on ? you seem to make a lot of claims that go against what i have read.

[chrono]

Based on a kidney hormone ?

Purification and mechanism of action of "cortexin," a novel antihypertensive protein hormone from kidney and its role in essential hypertension in men. Though the cortexin-3 gene is expressed in both kidney in brain, so I'm not entirely sure of its origin. But whatever the product description says (I don't think either of us would be comfortable using the word "liofilizat" in conversation ), my point was that it has other physiological functions, and little safety data.

You don't really give good reasons why you think cortexin seems pretty iffy

Yes, I did. If you want me to give positive proof that cortexin will result in negative consequences (which isn't what I suggested at all), then no, I can't. And that's because there's not much information on it either way. Why would you want to use cortexin, instead of any number of better-discussed and better-studied nootropics here? Can you give me any "good reasons" to use it? Or are you implying that an absence of definitive proof of negative consequences is a good reason to inject something?

Its immunity to IGFBP, and increased half-life, might further amplify its effect in the CNS, with unknown consequences.

How do you figure this ?

How do I figure that prolonged half life and immunity to endogenous regulators might decrease the body's ability to regulate it, or that a modified growth factor which is entirely unstudied in a particular application would have unknown consequences? As my wording clearly implies, it's speculation, and a statement of lack of a clear answer in the presence of an unknown; but it seems pretty reasonable.

The truth is, some studies do suggest there may be a chance but nothing is conclusive. The IGF that accelerates tumor growth usually sits inside the cancel cells, where as IGF R3 sits outside, the significance of that is not fully understood.

Here's [url="http://www.ncbi.nlm.nih.gov/pubmed/14710342' post='434758'%5D"%5Done paper%5B/url%5D showing that systemic LR3-IGF can cause growth of tumors. And there are many, many more for regular IGF. Where do you get the idea that IGF "sits inside of cancer cells?" You may want to read more about the influence angiogenesis has on tumor growth, or where the majority of IGF receptors are in a cell.

What makes you think IGF LR3 is bad for longevity ? do you have any proof ? I remember reading that IGF has desirable qualities for life extension ?

Well, I 'remember' reading that low IGF is positively correlated with longer life. This is one of the biomarkers used in CR. I may very well be wrong, and I'm sure it's not "proven" either way. But this has been better-discussed elsewhere.

Do you have links to papers for what you base you claims on ? you seem to make a lot of claims that go against what i have read.

How come we don't see lots of bodybuilders dropping dead of cancer ? All the pro's take it, in very large amounts all the time.

If you look at the older bodybuilders with gut bloat that take IGF LR3 most of their bloat came from the earlier versions of HGH. If you look at the up and coming new generation of bodybuilders who also hammer IGF LR3 they have zero gut bloat.

I appreciate that I didn't provide sources for my assertions, but you asked for opinions, and did so in a way that didn't show any evidence of having looked into the matter for yourself. I did a few hours of research as a courtesy because IGF has some implications for neurogenesis. Unfortunately, I have little enough interest in steroids that I don't feel like making a research project out of this right now.

If I can make an observation, your requirement for evidence seems to be highly skewed in the favor of really wanting to use this. And I hope you see the irony of asking me for papers, when most of your assertions seem to be based on looking at bodybuilders, and broscience forums. Did you ask for proof of LR3's benefits? I doubt it, because unless I missed a flock of papers in my literature searches, there really isn't any. This isn't meant as an insult, but rather offered in hope that you'll take a look at your reasons for wanting to use this, in spite of a lot of unknown quantities and risks.

The fact is that IGF is a growth factor that is critical to many important regulatory functions in the body and brain, has an impact on longevity that isn't perfectly clear, and can influence the growth of tumors. A version that is modified to resist endogenous regulation seems more likely to have these kinds of effects, in addition to increased benefits. If you're willing to take that risk, that's your lookout, but I wouldn't kid yourself that it's based on any solid grounds; a lack of definitive proof of negative consequences does not equal safety. And if you're still intending to use this, I would look for some of the more advanced discussions about systemic vs. local administration.

[Solarclimax]

That's a completely different thing that you're quoting, that just happens to share the same name as the peptide derived from pig and or cattle brain. It's a completely different substance.

Why would i want to use cortexin ? because i used it before and it clearly had positive effects. Cerebrolysin didn't do anything.

How much information do you want ? There was enough for me, it worked. No known sides. No sides for me.
Kicks Cerebrolysins ass. At least for me. (Of course i wouldn't advise people take it, as Chrono rightly says more research needs to be done, But I'm a bit brave sometimes)

From here is where i get "the idea"

A copy for the Sept 07 MD article written by PA:

Well I don’t have any one particular subject to talk about this week so I thought I would go back to my old format of a little short topic stuff, a little question and answer, and a little small talk. Anyway, I am going to the Olympia in a couple of weeks and I am pretty excited about it as I have hardly gotten away from the boring central Illinois area much at all since I got back from prison last February (probation confines me to central Illinois for the most part). Yeah, I got to go to the Arnold in Columbus but they made me go to my room at night because I was on house arrest. Then I also got to go to Orlando for a Vitamin Shoppe expo in July but it was held in some boring Walt Disney World hotel so its not like I got to whoop it up. So Vegas will be my first chance to party a little outside of Champaign Illinois, which is not exactly the party capital of the world. My attorneys actually invited me to go to the playboy mansion in LA on the Saturday of that weekend but I thought that would be too much of a culture shock for me right now. So I will make the most of Vegas, which from what I hear has a lot to offer. I won’t have a booth but I will be walking around the expo and hopefully someone will set me up with some tickets to see the contest (hint). Anyway, if I run into you introduce yourself and say hi.

IGF-1 / LongR3-IGF-1 confusion

I have been reading message boards and articles for quite some time now where people discuss the science and practical usage of LongR3-IGF-1. A lot of misinformation has been propagated about its properties, its utility, and its safety. I am going to try to briefly address some of this. I will discuss myths and realities

Myth: LongR3-IGF-1 was developed for use as an anabolic agent

Truth: LongR3-IGF-1 was originally developed for use in in-vitro research. In other words it was developed to be used in the lab for biochemical experiments with cell cultures. You see, the problem with regular IGF-1 was that it binds to serum proteins, and these can interfere with its direct activity on cells. So they altered the chemical structure of regular IGF-1 in such a way that retained its binding affinity to IGF-1 receptors while losing its ability to bind to the IGF-1 binding proteins (IGF-1BPs). The result was an IGF-1 analog with potent and reproducible activity in the culture systems.

Myth: LongR3-IGF-1 is a long acting form of IGF-1

Truth: Quite the opposite is true in fact. Since LongR3-IGF-1 does not bind to serum IGF1-BPs it is more prone to deactivation by serum proteases. As a result, its half-life in the body is compromised. On the other hand, 80% of normal IGF-1 is bound to IGF-1BP3 and this binding protein protects IGF-1 and greatly extends its half-life in the body. In fact, the overall half-life of IGF-1 in the body is anywhere from 8 to 18 hours. LongR3-IGF-1 according to research degrades approximately 2.5 times faster in plasma than regular IGF-1 (Journal of Endocrinology, Vol 164, Issue 1, 77-86).

On the other hand, LongR3-IGF-1 appears to be a more potent binder and activator of the IGF-1 receptor, so when it comes to actual in-vivo anabolic effects the short half-life may balance out with greater receptor dynamics to put LongR3-IGF-1 and IGF-1 on the same playing field. The downside though is that unlike the protein bound IGF-1, the free LongR3-IGF-1 will exert its hypoglycemic effects unabated, so large dosages can be problematic.

Myth: Your body only produces microgram amounts of IGF-1 per day

Truth: The daily production of IGF-1 in an adult human is actually 10-15 milligrams. Also, clinical research on IGF-1 for anabolic therapy uses doses from 5 to 25 milligrams a day. However don’t go trying to take that much LongR3-IGF-1 per day, as IGF-1 has strong insulinomimetic activity and you may put yourself in a hypoglycemic coma. Like I pointed out, LongR3-IGF-1 does not bind to IGF-1BPs so that dose will be active all at once - unlike standard IGF-1 (the vast majority of which will immediately hook up with IGF-1BPs). Bodybuilders know that you can’t go too much over 200mcg of LongR3-IGF-1 per shot or you will be heading for some troublesome side effects.

Myth: LongR3IGF-1 is a suitable replacement for GH

Truth: LongR3-IGF-1in the short term might have benefits (healing of connective tissue in particular) but for long term use you are really rolling the dice. This is a potent growth factor that can do as much bad as good if things don't go right

It is very important to remember that IGF-1 binding proteins serve important functions. IGF-1BP3 as mentioned protects IGF-1 from degradation and greatly extends its half-life. The bound complex of IGF-1 and IGF-1BP3 circulates throughout the bloodstream, and when it finds the appropriate target tissues it will encounter localized proteases that will free up the IGF-1 for receptor interaction – at that particular tissue. There are also other binding proteins that serve to sequester and permanently deactivate IGF-1 - speeding up its elimination. These apparently serve as protectors and are secreted by certain cells under certain conditions.

Of course tissue growth and regeneration is a vital part of survival and of course growth factors such as IGF-1 are integral to this process. However there can be abnormal cell systems popping up and these do pop up all the time, especially as you age. The body has mechanisms to recognize these anomalies and to suppress them so they do not grow into something like a malignant cancer. The elimination and sequestration functions of IGF-1 binding proteins are essential for proper control of the power of IGF-1. When you use a form of IGF-1 that is engineered to avoid binding to IGF1-BPs (such as longR3) you circumvent these checks and balances and invite all kinds of unforeseen problems

A better alternative to GH would be a GHRP or GHRH analog such as CJC-1295. These GH secretagogues are much farther upstream in the whole GH/IGF-1 cascade from IGF-1, and a good rule of thumb is the farther upstream you provide the exogenous hormonal influence the more naturally balanced the end outcome will be.


Anyway, am I anti LongR3? No, not really. My take on the stuff is that it might be a minimal risk to try for short cycles at times when you are at high catabolic risk. Such use would optimally utilize multiple daily administrations of small doses to overcome the high plasma clearance rate. Alternatively, longR3 could be a useful tool for connective tissue regeneration when used in a localized fashion, perhaps in conjunction with occlusive bands to maximize tissue exposure.
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Questions? My65cuda@aol.com

I appreciate that I didn't provide sources for my assertions, but you asked for opinions, and did so in a way that didn't show any evidence of having looked into the matter for yourself. I did a few hours of research as a courtesy because IGF has some implications for neurogenesis. Unfortunately, I have little enough interest in steroids that I don't feel like making a research project out of this right now.

Thank you for the tip about IGF vs LR3 something i will look into. Just seems you took a quick to fire down (without giving it all a fair look in) stance on the matter. But i may be wrong.

If I can make an observation, your requirement for evidence seems to be highly skewed in the favor of really wanting to use this. And I hope you see the irony of asking me for papers, when most of your assertions seem to be based on looking at bodybuilders, and broscience forums. Did you ask for proof of LR3's benefits? I doubt it, because unless I missed a flock of papers in my literature searches, there really isn't any. This isn't meant as an insult, but rather offered in hope that you'll take a look at your reasons for wanting to use this, in spite of a lot of unknown quantities and risks

By the same token maybe the papers you have seen can be interpreted to mean "really bad" when in actual fact it means "minimal risk with chance of positive benefit" Read the bit above about the fact that children produce large amounts with no apparent link to enhanced chances of developing cancer.

The fact is that IGF is a growth factor that is critical to many important regulatory functions in the body and brain, has an impact on longevity that isn't perfectly clear, and can influence the growth of tumors. A version that is modified to resist endogenous regulation seems more likely to have these kinds of effects, in addition to increased benefits. If you're willing to take that risk, that's your lookout, but I wouldn't kid yourself that it's based on any solid grounds; a lack of definitive proof of negative consequences does not equal safety. And if you're still intending to use this, I would look for some of the more advanced discussions about systemic vs. local administration.

Thanks for your offerings.

For others reading. Don't believe anything i say. I'm a bit daft when it comes to these things. And probably too experimental for my own good.

PS i just got some vitamin B17 :-) "Just thought i would throw another spanner in the works there."

Edited by Solarclimax, 13 October 2010 - 10:19 PM.