IGF-1, IGF binding proteins and how to run it

[dr. Doping]

@SalvatoreCorvus and @Einherjar we have discussed IGF1 and suggested we make a new thread, so here it is. What are the different strategies to bypass IGF binding proteins?

 

[Einherjar]

I want to clarify what was discussed in the previous episodes...

Todd Lee in his video is most likely referring to IGFBPs (Insulin-like Growth Factor Binding Proteins) — these are proteins that bind to IGF1 and regulate its activity in the body. Exogenous IGF1, taken externally (for example, through injections), may not have the same effect as growth hormone (GH), because growth hormone stimulates the production of endogenous IGF1 in the body, and this process depends on various factors, including the level of IGFBPs.

When you introduce exogenous IGF1, it may be metabolized more quickly or limited in its activity because it’s not transported or activated in the body as effectively as endogenous IGF1, which is produced in response to growth hormone. Exogenous IGF1 can also bind to IGFBPs, but if the level of these proteins in the body is insufficient or imbalanced, it can limit the effectiveness of IGF1.

Thus, Todd Lee suggests that IGFBPs are important for the proper transport and activation of IGF1, and it may be necessary to take into account their levels and role to achieve the same effect as high doses of growth hormone, which also stimulates the production of IGF1 through these proteins.

As for bypassing this issue, it could include:

• Using high doses of growth hormone, which stimulates the natural production of IGF1.
• Using supplements or drugs that may regulate or increase the level of IGFBPs to improve the transport and effectiveness of IGF1.

Therefore, the question is how to structure the experiment in such a way as to use exogenous IGF1 with maximum effectiveness, considering the necessity of IGFBPs for its proper functioning.

 

[Einherjar]

You mentioned that you want to use the IGF-1 LR3 version. And apparently, this changes the game a bit. Here’s what our friend GPT chat says about it:

IGF-1 LR3 is a modified form of IGF-1 that has increased activity compared to regular IGF-1. Unlike standard IGF-1, IGF-1 LR3 has an extended amino acid sequence, which makes it more resistant to metabolism and increases its half-life in the body. This allows it to remain active for a longer period, theoretically giving it an advantage in stimulating cell growth and increasing muscle mass.

How this works theoretically with IGF-1 LR3:​

• Increased activity: Due to the structural change, IGF-1 LR3 can activate androgen receptors with greater intensity, which can be beneficial for muscle growth stimulation. This allows it to have a greater effect than regular IGF-1, even at lower doses.
• Less dependence on IGFBP: IGF-1 LR3 has greater resistance to binding with IGFBP (Insulin-like Growth Factor Binding Proteins), which can limit the activity of regular IGF-1. As a result, IGF-1 LR3 may have a higher degree of availability in the body since its binding with IGFBP is minimized.
• Effectiveness without the need for high doses of growth hormone: Since IGF-1 LR3 is more active on its own and has increased stability, it can work effectively even without the need for high doses of growth hormone. This bypasses the issue faced by users of regular exogenous IGF-1, where raising the IGFBP levels is required for optimal functioning.

Although IGF-1 LR3 is less prone to binding with IGFBP, its effectiveness can still depend on the levels of IGFBP in the body, as IGFBPs play a role in regulating the activity of IGF-1 and its transport. This doesn’t mean that IGFBPs are completely unnecessary, but their role is much less significant when using IGF-1 LR3 compared to regular IGF-1.

 

[dr. Doping]

Yeah, I think Todd Lee has a point here, because the anecdotal data we have on IGF1 is so mixed. I'm running 3ius of GH per day until November (check my cycle log to see the progress) and I ordered 4 vials of IGF1-LR3 and 4 vials of MGF from Driada. I will use 2 vials ov each alone and then 2 vials of each together. I have the perfect circumstances for an experiment like this and will post the results (I will probabl include bodyweight, progress pictures, bodypart measurments, strength and other metrics, if someone suggests anyting else)

 

[Einherjar]

Yeah, I think Todd Lee has a point here, because the anecdotal data we have on IGF1 is so mixed. I'm running 3ius of GH per day until November (check my cycle log to see the progress) and I ordered 4 vials of IGF1-LR3 and 4 vials of MGF from Driada. I will use 2 vials ov each alone and then 2 vials of each together. I have the perfect circumstances for an experiment like this and will post the results (I will probabl include bodyweight, progress pictures, bodypart measurments, strength and other metrics, if someone suggests anyting else)

It will be interesting, but it is important of course that your rest stack does not change

 

[dr. Doping]

It will be interesting, but it is important of course that your rest stack does not change

Ofcourse, that's my plan

 

[BellaMasculine]

btw if you want to use IGF, use REAL IGF-1 not IGF-1 LR3... or just do it for a short time.
Even though IGF-1 LR3 sounds amazing on paper — longer half-life, stronger effects — many experienced athletes and coaches prefer “real” IGF-1 or avoid LR3 completely. Here’s why:

Too Long Half-Life = Uncontrolled Cell Growth
IGF-1 LR3 stays active for ~20–30 hours, constantly stimulating cell receptors.
This leads to non-selective cell growth — not just in muscles, but also organs, connective tissues, and potentially cancer cells.
High risk of organ enlargement (like heart or intestines) and tumor growth, especially with long-term use.

Not Targeted for Muscle Growth:
Real IGF-1 or IGF-1 DES works best when used locally and post-workout, stimulating growth in the exact trained muscle.
LR3 acts systemically, not localized — this can reduce anabolic efficiency and even blunt muscle protein synthesis when misused.

Insulin Receptor Cross-Activation:
IGF-1 LR3 can bind not only to IGF-1 receptors but also insulin receptors, due to its altered structure.
This can disrupt glucose metabolism, causing:
Hypoglycemia
Insulin resistance over time
Unstable blood sugar if combined with GH or insulin

No Natural Regulation:
The body normally controls IGF-1 activity via IGF Binding Proteins (IGFBPs).
LR3 is engineered to avoid IGFBPs — which means it bypasses natural safety mechanisms.
This makes it more dangerous: the body has no way to slow it down once it's circulating.

IGF-1 LR3 is like a sledgehammer — powerful, but non-specific.
Real IGF-1 is more like a scalpel — targeted, controlled, and safer.

 

[Einherjar]

btw if you want to use IGF, use REAL IGF-1 not IGF-1 LR3... or just do it for a short time.
Even though IGF-1 LR3 sounds amazing on paper — longer half-life, stronger effects — many experienced athletes and coaches prefer “real” IGF-1 or avoid LR3 completely. Here’s why:

Too Long Half-Life = Uncontrolled Cell Growth
IGF-1 LR3 stays active for ~20–30 hours, constantly stimulating cell receptors.
This leads to non-selective cell growth — not just in muscles, but also organs, connective tissues, and potentially cancer cells.
High risk of organ enlargement (like heart or intestines) and tumor growth, especially with long-term use.

Not Targeted for Muscle Growth:
Real IGF-1 or IGF-1 DES works best when used locally and post-workout, stimulating growth in the exact trained muscle.
LR3 acts systemically, not localized — this can reduce anabolic efficiency and even blunt muscle protein synthesis when misused.

Insulin Receptor Cross-Activation:
IGF-1 LR3 can bind not only to IGF-1 receptors but also insulin receptors, due to its altered structure.
This can disrupt glucose metabolism, causing:
Hypoglycemia
Insulin resistance over time
Unstable blood sugar if combined with GH or insulin

No Natural Regulation:
The body normally controls IGF-1 activity via IGF Binding Proteins (IGFBPs).
LR3 is engineered to avoid IGFBPs — which means it bypasses natural safety mechanisms.
This makes it more dangerous: the body has no way to slow it down once it's circulating.

IGF-1 LR3 is like a sledgehammer — powerful, but non-specific.
Real IGF-1 is more like a scalpel — targeted, controlled, and safer.

The risk of organ growth doesn’t come from the half-life itself, but rather from the total duration of exposure. I once spoke with a professor who synthesized IGF-1 in large-scale lab production. He explained that the most important factor is how long IGF-1 acts on the tissues. That’s why cycles are usually kept under 6 weeks.

As for the idea of localized action — that’s also a controversial topic. What I was told is that it's impossible to guarantee localized effects just from an injection. Endogenous IGF-1 does act intracellularly, and transporting IGF-1 into the cell requires specific carriers. To keep exogenous IGF-1 concentrated in one area, you'd need other methods — for example, using plasmid DNA to make local cells synthesize IGF-1 themselves.

Also, any IGF-1 binds to insulin receptors, just as insulin can bind to IGF-1 receptors — that’s not a problem.

But I fully agree with the statement that IGF-1 LR3 is like a sledgehammer — powerful but crude, while recombinant IGF-1 is like a scalpel — precise, controlled, and safer.