Mammalian cell derived Serostim vs E-Coli cell derived Generics

[bighunanballs]

I wanted to bring this up for debate here since i first heard this theory from a fella much smarter than myself. Would love to here @Type-IIx thoughts on this matter.

Their is a current Generics vs Serostim bioavailability theory I recently heard. The theory as best as i can summarize, describes the method by which Serostim and Generics are derived... Serostim is derived from Mammalian cells whereas Generics are derived from E-coli cells. Even though they are both 191aa and have the same molecular weight, the theory is that the amino acid chain/coil shape differs slightly between the two "seemingly" indistinguishable molecules. The difference may also be in the structure that is not able to be distinguished in typical @janoshik HPLC/MS testing. It has also been theorized that the generics cause fast rHGH Antibody formation compared to Sero's. Thus, it is recommended to cycle off Generics. Adding rHGH Antibody test to lab-work due to this issue is a good idea for generics users. Some may see the need to continually titrate up their generics dosing since there is something about the E-Coli derived 191aa molecule that causes GH antibody production much faster and/or in greater instance than mammalian derived Serostim. Would love to get different thoughts on this topic! this is a little more in-depth conversation than the typical Generics vs Pharma debate.

 

[songsofpyramids]

I wanted to bring this up for debate here since i first heard this theory from a fella much smarter than myself. Would love to here @Type-IIx thoughts on this matter.

Their is a current Generics vs Serostim bioavailability theory I recently heard. The theory as best as i can summarize, describes the method by which Serostim and Generics are derived... Serostim is derived from Mammalian cells whereas Generics are derived from E-coli cells. Even though they are both 191aa and have the same molecular weight, the theory is that the amino acid chain/coil shape differs slightly between the two "seemingly" indistinguishable molecules. The difference may also be in the structure that is not able to be distinguished in typical @janoshik HPLC/MS testing. It has also been theorized that the generics cause fast rHGH Antibody formation compared to Sero's. Thus, it is recommended to cycle off Generics. Adding rHGH Antibody test to lab-work due to this issue is a good idea for generics users. Some may see the need to continually titrate up their generics dosing since there is something about the E-Coli derived 191aa molecule that causes GH antibody production much faster and/or in greater instance than mammalian derived Serostim. Would love to get different thoughts on this topic! this is a little more in-depth conversation than the typical Generics vs Pharma debate.

I might be far far off base here, I am no expert on this crap, but I was under the impression that cell cultures were not even necessary anymore as they are now made via Solid-Phase Peptide Synthesis. Interesting topic though, following to see what smarter people than I say.

 

[Sector]

Very interesting information and theories. Could lead to a good discussion. Unfortunately this a bit out of my realm of expertise but I'll be following if any medical professionals/chemists do chime in

 

[bighunanballs]

Found a quote made by type-IIx in another thread

There may be an association between GH antibodies (i.e., antigenicity) with mammalian cell-derived rhGH versus E. coli (e.g., Iranian Norditropin saw 8.5% antigenicity versus 1.2-2.8% for E. coli-produced Somatropin). Yet, there was no clinical relevance (no decrement in GH response [IGF-I increase] nor height velocity).

There may be some minor influence of excipients used (e.g., some rhGH formulations may use mannitol which is a diuretic) on body composition. Genotropin uses meta cresol primarily. Serono Serostim sucrose & phosphoric acid.

Anyway, with all rhGH formulations there is a "stalling" after some time (due to diminished GH response, likely due predominantly to GHBP/IGFBP dynamics, diminished phosphorylation of downstream elements to the GHR, etc.)

I think the perceived differences by formulation are largely modulated by time * dose and by nutritional and training influences, other drugs.

 

[bighunanballs]

I believe @janoshik has chimed in on this as well. if i recall his view is that they are the same since the are the same molecule and same mol weight.

 

[AlexDavis43]

Found a quote made by type-IIx in another thread

I believe @janoshik has chimed in on this as well. if i recall his view is that they are the same since the are the same molecule and same mol weight.

View attachment 283245

This is my opinion as well. Many additives and all that stuff may differ between pharma and UGL (beyond purity and dimer); I don't doubt that... just don't think it matters that much.

 

[karambit]

Found a quote made by type-IIx in another thread

Thanks for sharing.

 

[bighunanballs]

Bumping this up. I'm trying to compile comments and information from smart folks on the board that may help us better describe and pinpoint differences between UGL and pharma HGH.

There are theories as to why serostim may have slightly different side effects profile than high quality generics. We've seen sero tested at Jano in the 98% and very low if none detected dimer. Also seen similar produced from QSC. All generics use mannitol in the lyophilization process. Serostim does not.... Mannitol acts a a diuretic.

There are also theories that the mammalian derived serostim molecules might be helically shaped differently than the ecoli derived generics. As far as I know, no one has used high power microscopy to check

is that dosage of mannitol high enough to have an effect on dieuresis though? i wouldnt think so but i might be wrong. Its like <30mg mannitol in if i remember correctly

The dose of mannitol as a diuretic is orders of magnitude higher than that used as a filler. Like 100s x more (ref) (many refs).

 

[bighunanballs]

FYI, a lot of assumptions are made by AAS users, understandably, paralleling steroids and peptides.

Peptides, once reconstituted, meaning the proteins at hydrated, do not *fall out of solution.*, ie, "crash".

When a previously clear peptide solution goes cloudy, it means aggregates in the visibile range, larger than >100um, have formed.

Dimer is the smallest form of aggregate (most don't know what dimer is, other than you don't want it in your hgh), while visible particulates represent the largest.

The larger the aggregate, the more of a health risk it represents for various reasons.

Above 20um is considered high risk,

Multiple peptides form unique aggregates, and the immune system response can't be predicted. If the shape just happens to be similar enough to some natural, important peptide, of which there are thousands, the immune system can learn that shape is the "enemy", start attacking them, and cause undetected damage, especially in the brain, where deformed and missing peptides are closely associated with neurodegeneration. IE, a person who's developed severe cognitive dysfunction typically has significant malformed peptides in their body.

Filter your peptides to eliminate the largest aggregates. All peptides can easily pass through a .2um PES filter.

You can filter the entire reconstituted vial at one time into a sterile vial, which will help significantly, However, since aggregates take time to form, once reconstituted, ideally filter as close to administration as possible.

Another compromise would be to use vials with small enough amounts of active ingredient they get used up soon after reconstitution.

And of course, use the same dilution ratio pharma uses, or more. The more
concentrate the solution, the more
aggregation takes place.

Aggregation is almost entirely determined by the conditions of the reconstituted peptide. The PH, the presence or lack thereof of anti aggregation excipients, crap in the vial like silicone etc.

But dimer, and other contaminants produced and not filtered out during peptide manufacturing do act as "seeds" promoting aggregation upon reconstitution. Dimer (two monomers, ie the 'correct' peptide chain, fused together into the smallest aggregate) are formed while the peptide is still liquid, before its freeze dried.

The pharma brands of hgh with the fewest sides reported to the FDA have no significant anti-aggregation excipients, are reconstituted with sterile water not BAC, and used immediately.

I think they have the fewest sides because there's simply no time for aggregates to form.

If you want some real nightmare fuel, while most aggregates are just amorphous shaped trash, wasting good peptide, but otherwise just cause a little inflammation and get destroyed by the immune system, some that slip through the cracks, in just the wrong shape, can act as a "mold", causing other peptides in your body (again, especially the brain), to misform, starting a chain reaction that can last for decades before symptoms are noticeable.

FYI, oligomers are the aggregation stage after dimer.

View attachment 306698

Protein misfolding, aggregation, and conformational strains in neurodegenerative diseases - Nature Neuroscience

A newly recognized process in neurodegenerative disease is accumulation of misfolded protein aggregates that self-replicate to spread damage between cells and tissues. This process has implications in designing strategies for treatment and diagnosis.

www.nature.com

So as you start to drool while the person changing your diaper transforms into looking like a demon from hell, but you forgot how to use words so you can't say a prayer to scare it off, with the last little functioning bit of consciousness you can comfort yourself with the thought "at least I saved myself from having to inject more than once".

-------

If this is all too abstract, here's some GLP-1 intentionally reconstituted at the wrong PH, left in a high heat environment, to quickly grow large aggregates. The fiber shaped aggregates are known as fibrils, and seem to be particularly harmful, vs globules.

View attachment 306700

https://royalsocietypublishing.org/doi/pdf/10.1098/rsfs.2017.0030

 

[bighunanballs]

@janoshik are you able to identify & quantify excipients in HGH? I would be curious to see the testing between Serostim vs popular chinese UGL hgh since the "anabolic bodybuilding" crew and "experts" over there discuss UGL containing "polymers" probably just mannitol...

"its all the additives added to UGL hgh that change the daltons, molecular weight of the hgh, that effect absorption" - Big Paul

"when you then add Biloxone, polymers and all these other fillers it doesnt seem to absorb at the same rate, and youve changed the molecular weight of the whole thing" -Kurt Havens


View: https://youtu.be/K14hh2SPMNE?t=114

We can tell whether something is there or not usually. Other stuff we cannot afford to take on right now.

Mannitol is not a polymer.

If they can name (an existing) polymer, we should be able to detect it.
I had trouble figuring out what Biloxone could be. Didn't manage to find out CAS etc.



1) I strongly don't believe it is so.
2) We have LCMS, we can detect the molecular mass of HGH and we've never seen anything suspicious.


Apologies, cannot listen to the video rn, but I hope my reaction is sufficient.

Quick note: We've ran an aggregate test on a tirzepatide and found no detectable aggregates.

*shrug*

Aggregates take time to form, post reconstitution. "Incubate" is the term I believe. The analysis I've seen of semaglutide had none immediately after reconstitution, detectable amounts after 3 days in the refrigerator and continued to increase in number and size with time.

Density ("viscosity") is another factor that determines the rate of aggregate formation, so how thoroughly the sample is diluted will play a role.

I'm sure Janoshik doesn't intend this to be taken to mean "tirz is aggregate free", case closed, since aggregates are formed dynamically, not "it's present or not" like other contaminants.

Think of very slowly forming crystals as an analogy.

I'm thinking of saving a vial of Tesamorelin from a batch I have for posterity which appears to go from clear to visible particulates forming after a few hours at room temperature. After being filtered again (.2) half a day later more visibile particles appear.

 

[Ghoul]

Probobly important to distinguish (fda approved) generics from UGL. Generics have to demonstrate roughly equivalent bioavailability and in the case of protein based drugs, acceptable immunogenicity levels.

UGL does not, obviously, and therefore no steps to minimize immune responses are taken. They make the product to meet what the market demands, "purity " and lack of dimer, both measured shortly after reconstitution, and nothing else. To UGLs credit, they've made impressive improvements in those two areas.

Not even PH, which is crucial for rHGH stability.

 

[bighunanballs]

Ya we're talking purely ugl vs pharma here. I'm incorrectly calling UGL "generics" which as you indicate is also pharma