Wrangel7
Member
Immunogenicity Intro:
By filtering you're eliminating immune reaction inducing protein aggregates, as well as particulates (glass, stopper rubber, etc) which further increase the immune response.
This vial appears crystal clear to the naked eye:
View attachment 316326
Immunogenicity causes antibodies to develop against the peptide, clearing it from the body more quickly, reducing its effectiveness. Over the long term, you can develop a long lasting, even permanent reduction in effectiveness.
In essence, protein aggregates turn the peptide into a "vaccine" like form, causing you to develop an immunity to it.
There are rare, much worse consequences, like the potential of developing cross immunity to the natural hormones Tirz is replicating, but the loss of effectiveness is the most likely risk.
Here's a FDA produced chart of GLP drugs tested for their immunogenic reactions. The samples on the left of each chart are pharma. The two on the right are compounders (ie, legal UGL). As you can see, the immune response to the non-pharma GLPs is as much as 2000x stronger.
The chart on the right shows the impact of filtering. In one of the two non-pharma samples, filtering reduced immunogenicity by 80%, which would help preserve its effectiveness.
View attachment 316324
HGH Desensitisation Intro:
Could this be causing desensitisation to rHGH more so than very high injection frequency?
Immunogenicity as a Risk Factor:
Yes.
HGH is the only peptide / protein drug routinely monitored for immunogenicity at the clinic level. There's a blood test available for it.
One of the ways it's dealt with is switching brands, to see if antibody levels go down and the HGH starts working again. Since all HGH is somatropin, the only difference between brands are the excipient ingredients in the formulation, which mainly serve to minimize aggregation to prevent immunogenicity.
Here are children who lost response to HGH from immunogenicity and the methods used to try and fix it. "Inhibition" is how much HGH effectiveness was reduced.
View attachment 316328
Here's a measure of the antibodies produced by different pharma formulations, most of which can be attributed to aggregates.
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UGL is certainly worse. No anti-aggregate measures are taken (slightly wrong PH alone can cause aggregation to get 10x worse). No immunogenicity tests are conducted. "I've never noticed immunogenicity". Would you notice a 15-20% drop in effectiveness over a year?
Filtering reduces immunogenicity, ensures sterility, prevents particulates like common glass delamination and stopper rubber from getting into your body and eventually your organs where they accumulate, causing micro embolisms. It's all upside.
"This immunogenicity stuff impacts the sick and weak, not us strong healthy bodybuilders."
Immunogenicity is more pronounced in healthy people with a vigorous immune system.
Read that again and think about it.
A healthy immune system reacts, and develops immunity to neutralize perceived "threats" far more strongly and effectively than those with a weakened immune system.
Don't mix them in the same vial or syringe.
It's a good idea if injecting them at the same time to use sites on opposite sides. Tesa is highly immunogenic, almost everyone experiences site reactions. You don't want another peptide in the same area the immune system is responding to.
Vaccines, proteins engineered to maximize immunogenicity, will sometimes use another compound or particulate that causes a strong immune reaction to induce a stronger response to the vaccine than would ordinarily happen. This is the opposite of what we want to occur with the peptides/proteins we don't want to build an immunity to.
BTW: these "immune stimulators" are called adjuvants. Particulate trash like glass and rubber particles in cheap Chinese vials act as adjuvants, as do aggregated proteins. Filtration removes these, lessening the overall immune response to peptides.
Immunologic adjuvant - Wikipedia
en.m.wikipedia.org
Relatively low serum IGF-1 vs relatively high HGH dose:
Thank you!
Here are my relatively low IGF-1 levels after using about 90iu/day of QSC HGH.
Somatomedin-C (IGF-1) ↑ 977.5 ng/mL 134.0 - 450.0 Serum
Will taking a break help enough if it's this bad, and how long before I can restart with the most effectiveness returned? I'm assuming this can only be figured out after testing.
I've also reduced my frequency, as indicated by the study I sent, before coming off for a little while.
Would you suggest I do RIA for anti-HGH antibody detection? Is ELISA fine? Functional IGF-1 Response Test? Neutralizing Antibody Test? Or is RIA pretty much the only quality go-to?
How long do anti-HGH antibodies persist? I'm assuming my natural production has probably tanked, too.
Would switching brands from QSC temporarily help, or would it have to be a permanent switch? Would it have to be a switch to a pharma brand, or something like SSA would work? Do we know anything about the differences in excipients and aggregation properties between QSC and SSA rHGH?
What about secretagogues for a while?
Do we know anything about the doses taken in this study? Could you please link the study?
Thanks again, Ghoul; so much value each time interacting with you!
HGH protocols, titration, etc...
(embeds work better if you open them; content may be missing otherwise):
HGH section:
To oversimplify it: growth (mostly for muscle, but the acromegalic prognathism also probably countered my slight recession too) and recovery — I simply enjoy training hard, and I like to maximise whatever I'm fixated on at any point in time in a very platonic sense. It's also not as if I started with 90iu straight up. I started with a much lower dose and had sides for a while, which then subsided; then, I increased the dose and continued increasing it as sides weren't really appearing other than a lot of water retention and the HRV & RHR stuff. In fact, the hand numbness was worse at the start at less than a vial a day and was virtually non-existent by the time I got to over 2 vials a day. Only persistent side was the negative impact to HRV & RHR I talked about, which then eventually stopped and reversed (although there was some intervention from me there).
It was only around 90 iu for around a few months. You guys should also remember that my IGF-1 levels are NOT the ones you'd expect from 90 iu:
I'm aware exogenous HGH dosage conversion to IGF-1 is very variable/vague; however, these are IGF-1 levels that are easily representative of sub 20 iu per day dosing, so it's not as if I'm experiencing the IGF-1 elevation usually expected from 90 iu a day. This is the WHOLE POINT of the discussion.
I also had a very high inj frequency, which also causes desensitisation.
I'll add this comment as it's somewhat relevant.
Thank you!
Sides/Experience:
Well, I grew like crazy (including hands, feet and probably nose but not as much — mainly hands from what friends have noticed, although I'm not sure how much was water retention) for a while, and my HRV dropped, and RHR increased as expected. Then HRV & RHR stopped moving negatively and started recovering when it dumped sub 20ms. Then progress kinda slowed. I tested around this time. It's not as if my IGF-1 levels are natty; just not "worthy" of the dosages used.
Regarding injection frequency, I was aiming for every 4-5 hours, excluding sleep/work. More or less even doses other than after training with a slightly increased dose.
The frequency was to maximise lipolysis benefit to gain more aggressively; however, in hindsight, this was not the best decision.
Surprisingly, I'm not insulin resistant. Just over 4 mmol/l blood glucose level about 2 hours postprandial. HbA1c of just over 39 mmol/mol. No exogenous insulin use. No metformin (tried it but stopped it).
Acromegaly doesn't happen that fast, but it has happened. Water retention is the major immediate contributor to foot size in the short term and acromegaly in the long term.
This HGH blast started on the 7th, and the foot issue became pronounced on the 28th of the same month (I'm not saying it's peaked at this point, but this is the day I wrote it down in my log).
Water retention is contributing more in the short term.
Another sign is the very visible edema in the foot unless you don't think that's contributing (it is).
Saturation:
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The effect of four weeks of supraphysiological growth hormone administration on the insulin-like growth factor axis in women and men. GH-2000 Study Group - PubMed
Measurements of serum insulin-like growth factor I (IGF-I) and related markers are routinely used in the diagnosis and treatment of GH deficiency and excess. The validity of these markers for assessment of exogenous GH exposure in healthy adults is, however, unknown. We therefore conducted a...pubmed.ncbi.nlm.nih.gov
Did you measure IGF-1 at each titration point along the way?
0.1 IU/kg/day enough to send many way up into the +4 SD land. See Fig 2 and discussion. Most males saturated at 0.1 IU/kg/day.
Appreciate your data set.
Titration:
Titration was mainly determined (sorry to disappoint) by the rate of PO (progressive overload) + side effects and continuous/non-lab health markers, such as HRV, RHR, BG and the like and also occasional lab blood testing, including HbA1c, organ health, etc… basic/general comprehensive panel to make sure there wasn’t any severe risk to health.
However, IGF-1 testing was rarer due to cost-cutting because I thought my subjective assessment of exogenous HGH effects based on progression, sides and general health markers was sufficient.
Regarding the point where most males saturated around 0.1 iu/kg, and after that point, the change was simply more side effects (which doesn't fit my side effect changes/profile completely), with minimal additional IGF-1 elevation, and the PO I observed after this proposed saturation point, I think we should consider:
1. other growth mechanisms from exogenous HGH dose increases were responsible for additional PO
1.1. non-IGF-1 mediated growth pathways cause significant PO/anabolism
1.2. alternative signalling cascades, direct receptor activation, enhanced satellite cell activation, improved nutrition partitioning, etc..
2. local IGF-1 production (in muscle tissue) was stimulated by increased HGH doses and this may have a saturation point higher than serum IGF-1 / local increases supported growth despite plateaus in systemic IGF-1
3. some other factor which coincided with increased HGH dosing was responsible for increased PO and this is a coincidence / additional HGH was largely wasted (even beyond the expected diminishing returns)
Conclusion: more funding needed (LOL) to repeat (but not to the same extreme extent) up-titration with exogenous HGH with more IGF-1 monitoring, as well as what @Ghoul said about immunogenicity testing.
Liver Function:
Around peak blast data:
Liver Function:
GGT: 22 U/L (Reference range: 8.0 - 61.0 U/L)
ALP: 135 U/L (Reference range: 30 - 130 U/L)
ALT: 52.8 U/L (Reference range: <50 U/L)
Total Bilirubin: 5.7 µmol/L (Reference range: <24 µmol/L)
Investigation, resensitisation, etc:
Investigation:
1: Get a baseline GH Antibody Test.
You can't self order it (too little demand), but if you go to a place like UltaLabTests and ask if they can arrange it for you, I think there's a good chance they'll add it to their "menu" of choices, and at a good discount below the standard ~$200.
2. Start filtering, per dose, just before administration. Aggregates take time to develop, the closer to administration the filtering the less time the trash UGL GH formula will have to recreate more aggregates.
This is the equivalent of changing brands. Given you haven't seen response go to zero, I strongly suspect as soon as the immune stimulating factors are reduced, aggregates and impurities. antibodies will drop, and efficacy will increase.
After a 1-3 months check Antibody levels again. If they're lower, you know you're moving in the right direction and should start lowering the dose to compensate for increased efficacy.
It's rare we see such a clear "loss of efficacy" situation, most of the time it's "feels" reports of members claiming bunk gear, that it worked in the past but this batch isn't working, yet tests show the GH is fine.
That's where the common denominator simian mind on Meso loses interest in trying to establish why (despite the fact this happens with pharma, which is why an anti- immunogenicity protocol and GH antibody tests exist). They take a break, or try another brand or switches to pharma, insists the new brand or pharma is the only way to go, never really digging into why HGH that tests good stopped being effective.
Finally, if you take my advice and get a GH antibody test, which I want to emphasize would be groundbreaking in the UGL community, request the lab provide whatever *raw data* is available. I can't find it at the moment, but I've read a report that said an adult GH non responder (in adults with GH deficiency they look at IGF and not growth like children), didn't show a positive result on the GH antibody test, but in the raw data there were antibodies of another type, not normally considered relevant, that were high. Once those were reduced (with a break and switching brands), HGH treatment efficacy was restored for that patient.
Resens:
If @Ghoul's guidelines on HGH resens work, I would expect similar or maybe even higher serum IGF-1 on 20 iu per day than 90 at the moment when HRV/RHR downtrends were reversing. However, the speed at which IGF-1 levels decrease from the start period of 20 iu per day might be interesting. Sadly, I don't have the budget to compare filtering vs non-filtering and a bunch of other variables, especially on myself. So, I will follow the advice on HGH resens without those controls.
Fyi, I'm currently on zero exogenous HGH supplementation with an IGF-1 test planned for soon.
Natty IGF-1:
"Natty" IGF-1: 341.1 ng/mL
Significant exogenous HGH supplementation (in a way that would significantly affect a blood test) was last done on Feb 2nd.
Pinned small amounts (no more than 12 iu once preceded by a week and followed by a week before the blood test) after this period. However, it's unlikely that this had a significant impact on the result.
I'm young and sleep a lot; no traditionally unhealthy activities outside of the PEDs.
@readalot @Ghoul @bigMoJo
EXTRA:
Filtration:
You can't use the same filters as those for oils .
Use .22um PES 13mm filters, without prefilter.
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Sterile 0.2 μm PES Syringe Filters
Hydrophilic PES syringe filters with single or double-layer membrane. Pore sizes of 0.2μm. Diameter of 13mm/25mm/33mm with Luer lock. Sterile individually packed. Used for sterile filtration of protein solutions, cell culture media, and buffers.shop.cobetter.com
Inject filtered peptide into particle free certified vials like Ultra Spec.
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Ultra Spec Sterile 5ml (20mm neck) Clear Sealed Glass Vials
In order to receive vials in sealed shrink wrap boxes, please order in multiples of 25www.medical-and-lab-supplies.com
Secretagogues (no specific HGH secretagogues used):
Secretagogues boost endogenous productions so you will benefit from several GH isoforms, whilst synthetic HGH is just the 22 kDa isoform (as far as I'm aware). Not sure if there's any meaningful, practical difference, though.
Benefit not that crazy; equivalent to a few or more iu of HGH, from what I recall.