Metformin users.

[RamboStallone]

As is clear from my other posts, I am a proponent of metformin. I think it is safe and benefits almost all people - especially bodybuilders eating a lot and using drugs that reduce insulin sensitivity (like GH). However, one lingering question remains for me...

We know the bulk of the life extension / anti-cancer benefits of Metformin come from its systematic reduction in IGF-1. Where you see lower IGF-1, you see lower rates of cancer and slower cancer progress in general. Calorie restriction and lowered IGF-1 are reoccurring themes in the "life extension" puzzle. When we introduce exo GH, it is converted in the liver (in varying rates depending on the person and also liver health) to IGF-1. The main benefits from GH come from a prolonged increase in circulated IGF-1 levels. If your IGF-1 levels are not up, you will not see the results from GH you are looking for. So if we are diminishing our IGF-1 conversion with metformin, are we losing a lot of the benefit of exo GH use? It would be a fair assumption to say that 1g of metformin use a day will reducing IGF-1 levels, but to what degree? Enough that it would render 4iu of exo GH a waste of money, or would the slight reduction in IGF-1 be negligible in athletes using GH? All of the studies showing IGF-1 reduction from Metformin are from normal, non-enhanced people NOT taking no AAS or GH. Im curious what the implications are for IGF-1 levels when co-administering exo GH, AAS and Metformin. My guess is you still come out ahead but that your IGF-1 may take a slight dip.

Thoughts?

Does metformin only reduce the IGF in the liver? What about IGF local to the skeletal muscles? That's more important for BBing from what I understand. I'm not too concerned with systematic circulating igf if it's reduced some. This assumes I am understanding this all correctly.

 

[G.I.Bro]

Does metformin only reduce the IGF in the liver? What about IGF local to the skeletal muscles? That's more important for BBing from what I understand. I'm not too concerned with systematic circulating igf if it's reduced some. This assumes I am understanding this all correctly.

There are IGF receptors all over the body including intestines (where they are abundant). The actual production of IGF occurs in the liver. Metformin will reduce your IGF levels systematically. The degree and real world impact when taking Exo GH is my question.

 

[Kevinhy]

There are IGF receptors all over the body including intestines (where they are abundant). The actual production of IGF occurs in the liver. Metformin will reduce your IGF levels systematically. The degree and real world impact when taking Exo GH is my question.

https://www.ncbi.nlm.nih.gov/pubmed/14983408

That study seems to suggest it doesnt really impair increased IGF from exogenous GH much, if at all. Unfortunately theres no GH only group in the study for comparison, but its clear Met isnt completely abolishing the effect of GH on IGF-1 production. Dosage was 0.20 IU/kg BW/week.

 

[Stewie]

Nor GH independently.

http://www.tandfonline.com/doi/abs/10.1185/03007998409109558

I'm sure there will be a rebuttal indicating otherwise.

 

[b_cornelius]

If Metformin was so powerful that it just shut-down IGF, then I don't think that a lot of people would be taking it. From what I've seen, Metformin does significantly and systemically blunt the actions of IGF, when you first start taking it, then the body adapts rather quickly and IGF activities increase.

You see the same thing with exercise and AMPK. After the body adapts to exercise, AMPK is not as strongly affected.

After the adaption, Metformin's mechanisms of action become a little more complex.

It's, more or less, all about more-or-less.....and adaption to the same.

 

[RamboStallone]

There are IGF receptors all over the body including intestines (where they are abundant). The actual production of IGF occurs in the liver. Metformin will reduce your IGF levels systematically. The degree and real world impact when taking Exo GH is my question.

I understand that. I also understand there is igf produced locally, not just what is produced/converted in the liver. I was question which it reduced, I guess it depends on what mechanism is being affected.

 

[Thebigone]

I'm always on 3iu GH and had igf levels tested before Metformin and a few months after using it at 1g per day and nothing changed. However I also use peptides so I'm not sure if they were effected since they work off natural igf.

 

[Stewie]

Another hot off the press potential positive response associated with Metformin.

**broken link removed**

New uses for AMPK activators



Inflammatory cytokines stimulate the JAK-STAT pathway and promote cell survival and migration in hematopoietic cells. Chronic or excessive inflammation also contributes to diseases. Drugs that activate the kinase AMPK, such as salicylate and the diabetes drug metformin, have anti-inflammatory effects. Rutherford et al. found that AMPK phosphorylates JAK, inhibiting JAK-mediated STAT activation in vascular endothelial cells exposed to IL-6. Pharmacological activation of AMPK suppressed JAK-STAT signaling in cells expressing a JAK1 mutant associated with acute lymphoblastic leukemia (ALL). JAK inhibitors have had limited success in patients. Thus, the findings not only identify JAK1 as a substrate for AMPK in its anti-inflammatory function but also suggest that metformin might be repurposed to inhibit JAK-STAT signaling in patients with ALL and, perhaps, other inflammatory diseases.