Hey there! I’m a subscriber to the newsletter. I have been a user of peptides for some time now, specifically BPC-157, TB-500, Selank. As such, I’ve been exposed to Cerebrolysin. Most of my fellow peptide travelers look at it with a healthy degree of suspicion. It sounds more like a witches brew. The science is indeed sketch.
However, I wanted to make some (referenced :) ) corrections to your analysis. I think the general thrust of my argument is this—there seems to be emerging science about small-chain active peptides. These exhibit different stability and transport characteristics than larger proteins. There might be mechanism of action here that you’re not considering.
Glucose Oxidase wouldn’t occur in mammals anyways, it’s produced only by insects and fungi: https://en.wikipedia.org/wiki/Glucose_oxidase I’m not sure what this does to your analysis, but there you have it 🙂
(ok, I am going to leave this, but. I just saw the footnote #4 - I’m still not sure I buy it, but I get the criticism) I challenge the validity of this sentence—“In general, proteins do not retain their signaling potential after so much of their structure has been removed, although some have suggested this is the case with Cerebrolysin.” There is a rapidly growing peptide medical industry with short-chain peptides that retain the signaling section. In fact, this is the whole thrust of this industry::
TB-500: TB-500, also known as TB-4, is a synthetic peptide that is said to have several properties that may help with repair and regeneration. It is presented as a synthetic version of the active region of thymosin-beta 4 (Tβ4).
BPC-157 - a 15 AA section of a protein isolated from gastric juices, helps with repair and regeneration
Tirzepatide is a synthetic, linear peptide molecule that is 39 amino acids long and has a C20 fatty diacid moiety attached. (This applies the the whole ludicrously successful GLPs-1)
Ipamorelin: A pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2) and a ghrelin mimetic with growth hormone (GH) releasing activity. Ipamorelin mimics ghrelin and binds to the ghrelin receptor (or GH secretagogue receptor, GHSR) in the brain, thereby selectively stimulating the release of GH from the pituitary gland.
(there’s lots more)
“This discussion about the likely distribution of peptide sizes in Cerebrolysin is obviously significant, since if most peptide fragments are way smaller than 10 kDa, then the claim about it having neurotrophic properties is very unlikely.”
So, there’s a Soviet peptide—Selank, the structure of which includes a short fragment (Thr-Lys-Pro-Arg) of the human immunoglobulin G heavy chain, which was elongated at the C terminus via the addition of three natural L-amino acids (Pro-Gly-Pro) to enhance its metabolic stability and the length of action of the drug
Selank, Peptide Analogue of Tuftsin, Protects Against Ethanol-Induced Memory Impairment by Regulating of BDNF Content in the Hippocampus and Prefrontal Cortex in Rats https://pubmed.ncbi.nlm.nih.gov/31625062/
The storage instructions for Cerebrolysin are unrealistic for a product that is alleged to actually contain neurotrophic peptides. We are instructed to store Cerebrolysin at “room temperature not exceeding 25°C.”
Greg has worked with brain lysates and dissolved preparations of neurotrophic factors in a lab. Until shown otherwise, the background assumption for peptides in aqueous solution is that they will degrade in a few days. Refrigeration can extend this to a few weeks at most. Moreover, carrier proteins are often required to prevent peptides from sticking to the glass or plastic container in which it’s been stored. There is no indication that any such carrier proteins are added to Cerebrolysin.
So, this is a personal observation, and that is that the lower molecular weight peptides seem to be substantially more stable. Ipamorelin works on the Ghrelin pathway—but since it is way smaller, it’s much more inherently stable. I can’t reference all this, but this is my impression. I mean, it makes sense—I just can’t prove it. :)
Here’s a paper discussing how a small molecule which mimics BDNF is potentially a useful as a Traumatic Brain Injury treatment because it can get across the Blood Brain Barrier (BBB). So, yeah, you shouldn’t expect very much BDNF to get across the BBB. But broken pieces of BDNF could potentially have still functional fragments, and because they are smaller, more easily cross the BBB. But yeah, overall the Cerebrolysin situation seems super sketchy to me.
I do however think that there is potential for figuring out drugs that could potentially have useful BDNF effects in the brain. Of course, too much of a good thing is also bad. Too much BDNF can cause issues in the brain, potentially causing neurons to grow in harmful not-easily-reversible ways, or to attempt to grow but actually stress themselves out and die, etc.
If I were going to look into Cerebrolysin and the anecdotal reports of its effects, I’d start by asking what things have been proven NOT to be in it. Some signalling molecules, particularly hormones, are very physically robust and good at spreading all throughout the body. Much more so than BDNF. Testosterone for instance. And that’s something you’d expect to cause someone to feel energetic and confident… which would lead to positive anecdotal reports of general efficacy.
If pig testosterone is what you want though, it’d be a lot safer to just cook and eat some pig testicles...
Hey there! I’m a subscriber to the newsletter. I have been a user of peptides for some time now, specifically BPC-157, TB-500, Selank. As such, I’ve been exposed to Cerebrolysin. Most of my fellow peptide travelers look at it with a healthy degree of suspicion. It sounds more like a witches brew. The science is indeed sketch.
However, I wanted to make some (referenced :) ) corrections to your analysis. I think the general thrust of my argument is this—there seems to be emerging science about small-chain active peptides. These exhibit different stability and transport characteristics than larger proteins. There might be mechanism of action here that you’re not considering.
BDNF does cross the BBB, CDNF doesn’t, but there seems to be some evidence that BDNF has some sort of transport mechanism : https://pubmed.ncbi.nlm.nih.gov/9886678/
Glucose Oxidase wouldn’t occur in mammals anyways, it’s produced only by insects and fungi: https://en.wikipedia.org/wiki/Glucose_oxidase I’m not sure what this does to your analysis, but there you have it 🙂
(ok, I am going to leave this, but. I just saw the footnote #4 - I’m still not sure I buy it, but I get the criticism) I challenge the validity of this sentence—“In general, proteins do not retain their signaling potential after so much of their structure has been removed, although some have suggested this is the case with Cerebrolysin.” There is a rapidly growing peptide medical industry with short-chain peptides that retain the signaling section. In fact, this is the whole thrust of this industry::
TB-500: TB-500, also known as TB-4, is a synthetic peptide that is said to have several properties that may help with repair and regeneration. It is presented as a synthetic version of the active region of thymosin-beta 4 (Tβ4).
BPC-157 - a 15 AA section of a protein isolated from gastric juices, helps with repair and regeneration
Tirzepatide is a synthetic, linear peptide molecule that is 39 amino acids long and has a C20 fatty diacid moiety attached. (This applies the the whole ludicrously successful GLPs-1)
Ipamorelin: A pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2) and a ghrelin mimetic with growth hormone (GH) releasing activity. Ipamorelin mimics ghrelin and binds to the ghrelin receptor (or GH secretagogue receptor, GHSR) in the brain, thereby selectively stimulating the release of GH from the pituitary gland.
(there’s lots more)
“This discussion about the likely distribution of peptide sizes in Cerebrolysin is obviously significant, since if most peptide fragments are way smaller than 10 kDa, then the claim about it having neurotrophic properties is very unlikely.”
So, there’s a Soviet peptide—Selank, the structure of which includes a short fragment (Thr-Lys-Pro-Arg) of the human immunoglobulin G heavy chain, which was elongated at the C terminus via the addition of three natural L-amino acids (Pro-Gly-Pro) to enhance its metabolic stability and the length of action of the drug
Selank, Peptide Analogue of Tuftsin, Protects Against Ethanol-Induced Memory Impairment by Regulating of BDNF Content in the Hippocampus and Prefrontal Cortex in Rats https://pubmed.ncbi.nlm.nih.gov/31625062/
The storage instructions for Cerebrolysin are unrealistic for a product that is alleged to actually contain neurotrophic peptides. We are instructed to store Cerebrolysin at “room temperature not exceeding 25°C.”
Greg has worked with brain lysates and dissolved preparations of neurotrophic factors in a lab. Until shown otherwise, the background assumption for peptides in aqueous solution is that they will degrade in a few days. Refrigeration can extend this to a few weeks at most. Moreover, carrier proteins are often required to prevent peptides from sticking to the glass or plastic container in which it’s been stored. There is no indication that any such carrier proteins are added to Cerebrolysin.
So, this is a personal observation, and that is that the lower molecular weight peptides seem to be substantially more stable. Ipamorelin works on the Ghrelin pathway—but since it is way smaller, it’s much more inherently stable. I can’t reference all this, but this is my impression. I mean, it makes sense—I just can’t prove it. :)
https://journals.lww.com/nrronline/fulltext/2017/12010/Therapeutic_potential_of_brain_derived.2.aspx
Here’s a paper discussing how a small molecule which mimics BDNF is potentially a useful as a Traumatic Brain Injury treatment because it can get across the Blood Brain Barrier (BBB). So, yeah, you shouldn’t expect very much BDNF to get across the BBB. But broken pieces of BDNF could potentially have still functional fragments, and because they are smaller, more easily cross the BBB. But yeah, overall the Cerebrolysin situation seems super sketchy to me.
I do however think that there is potential for figuring out drugs that could potentially have useful BDNF effects in the brain. Of course, too much of a good thing is also bad. Too much BDNF can cause issues in the brain, potentially causing neurons to grow in harmful not-easily-reversible ways, or to attempt to grow but actually stress themselves out and die, etc.
If I were going to look into Cerebrolysin and the anecdotal reports of its effects, I’d start by asking what things have been proven NOT to be in it. Some signalling molecules, particularly hormones, are very physically robust and good at spreading all throughout the body. Much more so than BDNF. Testosterone for instance. And that’s something you’d expect to cause someone to feel energetic and confident… which would lead to positive anecdotal reports of general efficacy.
If pig testosterone is what you want though, it’d be a lot safer to just cook and eat some pig testicles...