Inflammatory reaction to TB500

[Annie Sewell]

Hi,

I have a 33yo active male client who has not been able to fully heal from past shoulder, ankle, thumb and back injuries.

His baseline labs (CBC, CMP, TSH, Prolactin, IGF-1, C-peptide, fasting insulin) WNL except for HgA1c 5.7. Except for injuries his medical history is insignificant.

We started him with BPC-157, 250mcg/day for 30 days. After one week he started GHK-cu 5mg/day for ten days (and stopped). After this we stacked in TB500 2mg/twice a week. This is when he started having problems.

At first he developed a flat affect-became withdrawn which resolved as soon as he halved the dose of TB500. He also noted that his appetite increased significantly and that he was very tired. In addition to this his thumb injury has become more inflamed, though his shoulder and ankle injuries have responded favorably.

We halved the TB500 to 1.5mg and his mood improved but not his thumb. He had noted an improvement in shoulder and ankle injury. Becuase he was overall feeling good-(shoulder and ankle pain resolved and ROM increased), we did add CJC/Ipa, 100mcg/200mcg, (5on/2off) for one week.

He has been off of everything for four days now and states that he now seems to be retaining water-is “puffy”, his appetite is still elevated and that his thumb is still inflamed. He is adamant that it was the TB500. We cannot be to sure so have decided to stop all peptides b/c of the unusual response.

I did read about the TB500 pathways and found several of these issues can be related to actin sequestration and a sudden activation of immune response. I believe that we have driven a pathway too hard and that he is reacting.

According to what I understand, Im thinking that my client is in a bit of a metabolic or immune crisis and having a paradoxical response.

I wonder if any of you have seen this and can help me understand what may be underlying cause and what support he may need.

Thank you,

Annie

[Annie Sewell]

I looked into TB500 on and based on what I have read, I believe that I may have found some partial answers to my own questions. I would appreciate any feedback or insight on our understanding of TB500 and clinical judgement and decision making.  I do feel like these cascades of events are what may have been causing the results with my client. I have presented my plan moving forward with this client also for your feedback, insight or critique.

TB500 has an interesting interaction with a protein called actin. I want to address the actin modulation in regard to mood changes, joint and old injury flare-up (think/back) and improved soft tissue healing (shoulder/ankle):

1. Mood: TB500 increase the pool of unbound G-actins. This at the epicenter of what sets off the anti inflammatory cascade (up-regulation of Akt, and the binding of G-actin keeping it from forming F-actin filaments results in macrophage polarization from M1-M2, alters cellular metabolism to increase nutrient uptake-specifically glucose transport, down regulation of of NF-kb and up-regulation of  mTOR, P21 and P27 etc) setting off a significant cascade of tissue repair (via proliferative cell signaling), impacting many tissues in the body. This mechanism of action is also what can impact neurons and may cause flat affect or withdraw.  There is actin present in neurons, and actin activity-specifically binding to G-actins. When F-actin is not produces at the synapse, this can result in long term depression or depressive states. In addition to this the “dramatic” suppression of IL-6 can have the same effect on mood. TB500 increase actin turnover which can temporarily reduce synaptic responsiveness causing flat affect, low emotions and the like. In essence the decrease in actin turnover interfere with excitatory signaling flattening mood. Can potentiate GABA too much. Also, of note, the same inflammatory cytokines that TB500 suppress happen to interact with dopamine, serotonin and cortisol. You likely had a rapid drop in IL-6 which can cause above issues.

2. Inflamed old injuries/joints vs perceived healing of new injuries shoulder/ankle: New injuries are still in an active acute healing phase and TB500 will amplify these processor with generally good outcomes. However, old injuries, have “stiff” collagen, scarring, reduced blood supply and unresolved tears. TB500 will reactivate these “tired” incomplete pathways by resting blood flow, re-stimulating fibroblast remodeling, reopening micro injuries and causing immune re-entry into the tissue. Joints respond differently than soft tissue. Unlike soft tissue, joints have low blood supply, slow collagen turnover, fewer repair cells and high mechanical load. This is a possible mechanism by which TB500 triggers “deeper, slower” remodeling that may produce more initial inflammation. The literature states that this is not harmful but it is “noticeable”.

3. Increased appetite, tiredness with CJC/Ipa: this peptide combo increases GH which increases hunger b/c it is further stimulating your body to go into repair, rebuild, growth mode via different and overlapping mechanisms which requires a ton of energy-on top of the energy required from TB500 and BPC. Increased metabolic demand can equals an energy drain. So-we’ve already activated repair pathways which requires more energy and then added CJC/IPA which accelerated these processes.

Your body went from 25 to 100 in terms of immune response, tissue repair/remodeling and your response was to feel kind of good (shoulder and ankle resolution and “muscles tightening”) but also joints flaring and being tired and ravenous.

Now what? I believe that this is a phase of healing that won’t last. However, I also think that you could use some time away from the heavy hitters (TB500/CJC) while you work on repletion-giving your body the nutrients and calories it needs to keep up with the demand.

The upshot: I don’t want you to lose your gains, but I don’t think continuing to drive this hard is good for you either. I’ve put together a suggested 4 week “reset/conditioning” protocol. I’ll text it to you. Look it over and let me know if you want to do this.

I hope this makes sense to you. Let me know if you have questions.

Refrences: There are really SO many. I posted the resources I found to be most helpful and interesting.

https://journals.biologists.com/jcs/article/120/2/205/29742/Transmitting-on-actin-synaptic-control-of

https://pmc.ncbi.nlm.nih.gov/articles/PMC7139933/#:~:text=Major%20depressive%20disorder%20(MDD)%2C,optimal%20treatment%20for%20MDD%20patients.

https://www.cellsignal.com/pathways/nfkb-signaling-pathway

https://www.cellsignal.com/pathways/pathways-akt-signaling

BPC-157 and TB-500: Background, Indications, Efficacy, and Safety

https://www.sciencedirect.com/science/article/pii/S1570023224000412#:~:text=TB%2D500%20(Ac%2DLKKTETQ,however%2C%20have%20not%20been%20documented.

https://pmc.ncbi.nlm.nih.gov/articles/PMC11426299/#:~:text=In%20one%20of%20the%20many,of%20entry%20besides%20localized%20injections.

[Farhan Tahir]

I believe my patient has encourageuntered the same issues and thanks for explaining it. I askedntoneait a week snenretry, if it happens I am going to stop the combo BPC and TB 500 and may try BPC as single peptide. Thank you.

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