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Metformin on cycle, androgen receptors, SHBG and IGF

phoenix2

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I've used metformin a couple of years ago, when i was still natty.
I was taking 500 mg/day on very low carbs days and up to 1500 on refeed days.
I'm not diabetic but i'm very carbs sensitive.
I found that with metformin not only i didn't gain too much water/fat and didn't easy spillover with carbs, but it seemed to keep me fuller on low carbs days too.
The pumps after a refeed day or after taking metformin pre workout with some carbs were crazy.
Metformin never gave me any sides effects, not even GI discomfort.
But i quitted taking it when i've read that it can lower free test rising SHBG and it can mess up with androgen receptors.
It seems also that metformin lowers IGF-1 and protein synthesis too.

Now, i would like to try again metformin but on cycle (test e/masteron), in order to help me on recomp/fat loss and manteining more muscle fullness/pump on very low carbs days,
but i'm afraid that it will reduce my cycle efficiency/gains, for the interferences with androgen receptors, shbg and IGF-1.

What do you guys think about?
Has someone ever taken metformin on cycle? If yes, did it impact your gains/cycle efficiency?
 

IronLion2

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Just posted this and before I start may I say this is the worst meme question on the forum;

Met likely not to interfere with IGF for enhanced athletes unless the side effects are delibating for you. AMPk doesnt always mean a negative effect to mtor. Ive yet to see a negative impact to protein synthesis in the MANY met studies. Can impact shbg but not much. Its not a miracle cure for anyone and not a defacto must have for enhance athletes but it has done alot of good for many.
 

phoenix2

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Just posted this and before I start may I say this is the worst meme question on the forum;

Met likely not to interfere with IGF for enhanced athletes unless the side effects are delibating for you. AMPk doesnt always mean a negative effect to mtor. Ive yet to see a negative impact to protein synthesis in the MANY met studies. Can impact shbg but not much. Its not a miracle cure for anyone and not a defacto must have for enhance athletes but it has done alot of good for many.

For me it wasn't a miraculous drug, but it changed a lot the way my body was using carbs. More fullness, less water, less fat. Definitely worth it for me. No sides moreover.
What about androgen receptors interferences instead?
 

IronLion2

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For me it wasn't a miraculous drug, but it changed a lot the way my body was using carbs. More fullness, less water, less fat. Definitely worth it for me. No sides moreover.
What about androgen receptors interferences instead?


I read a write up that's a local effect in the liver IIRC, cant confirm that though. If met made AAS less effective no BB would EVER touch it.
 

Andro308

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Berberine or Metformin is the million dollar question!!!

Going to try Metformin again. Fucked up my stomach something awful last time so starting with 250mgs

Berberine works great so far
 

MyNameIsJeff

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I read a write up that's a local effect in the liver IIRC, cant confirm that though. If met made AAS less effective no BB would EVER touch it.
And how exactly would they be able to tell if their Metformin use decreased androgen receptor (AR) count and signalling pathways by a couple of percent :banghead:

There are plenty of (in vitro) studies that show Metformin
(1) interferes with membrane-initiated AR action (https://www.endocrine-abstracts.org/ea/0029/ea0029p776 and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959597/)
(2) represses AR signalling via downregulation of AR expression (https://www.ncbi.nlm.nih.gov/pubmed/25894097 and https://www.ncbi.nlm.nih.gov/pubmed/25199764)

Again, these are in vitro studies, so it is hard to tell if the plasma levels of Metformin achieved with standard dosages are sufficient to elicit these effects in vivo and how large the effect size is. Is AR density down-regulated by 0% 1%, 5% or 10%? Noone knows. But given the anti-proliferative effects of metformin in prostate cancer observed in human trials, there is good reason to expect these effects to occur to some degree in vivo.

So this is another potential downside to Metformin use in bodybuilders. But guess what's even worse than slightly down-regulated AR signalling? Being fucking insulin-resistant.

It's really very simple guys:

If your priority is to maximize muscle mass, then only take Metformin if you need to, that is, if you fasting blood glucose is above, say, 95 mg/dL. Measure your fucking blood glucose people, it is simple and cheap to do.

If your priority is health, then go ahead and take Metformin despite it's potential negative effects on muscle mass. The negative effects are likely very small, so there is no reason to worry about them unless your goal is to become a fucking freak with as much lean mass as humanly possible. You can have a fucking fantastic physique while using Metformin.
 

IronLion2

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Pure empirical and anecdotal evidence about met making AAS less effective. You admited it, it would be hard to even study its entire effects on muscle growth, fuck they don't even understand the mechanisms after what 30 years of clinical studies?

Weve seen guys with extensive AAS use back met, Meadows is a good example. Hes made progress while on and off met, for a man with his experience you'd imagine he would be able to make a somewhat educated hypothesis about met? Its not like anyones making profits for reccomending met so major bias is out the window. I'll concede though, there could be a mild effect to AR receptors that would hardly be noticed for enhanced athletes, I/you have no way of testing that, besides cutting someones limb off and studying it.

But I 100% agree with the idea if you're not running compounds/diet that negatively affect insulin production, theres little to no reason to use it.
 
Last edited:

phoenix2

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Pure empirical and anecdotal evidence about met making AAS less effective. You admited it, it would be hard to even study its entire effects on muscle growth, fuck they don't even understand the mechanisms after what 30 years of clinical studies?

Weve seen guys with extensive AAS use back met, Meadows is a good example. Hes made progress while on and off met, for a man with his experience you'd imagine he would be able to make a somewhat educated hypothesis about met? Its not like anyones making profits for reccomending met so major bias is out the window. I'll concede though, there could be a mild effect to AR receptors that would hardly be noticed for enhanced athletes, I/you have no way of testing that, besides cutting someones limb off and studying it.

But I 100% agree with the idea if you're not running compounds/diet that negatively affect insulin production, theres little to no reason to use it.

When i first took it i was natty and it gave a great aesthetic enhancement to my physique. I was more hard/dense and vascular, less watery and my body could handle carbs 10 times better than without metformin. No lethargy after carbs meals, rather i felt more energetic.
It didn't seem to impair my muscle growth at all, rather i looked more full/pumped. Adding to these the indiscussed health benefits (on lipid profile also, something to consider while on AAS) and for me personally, i think is worth it even in abscence of compounds that impair insulin sensitivity.
But when i took metformin for the first time i run it for a short time (a couple of months). So i don't know if the negatives effects start after a while you have been on it.
More than the impairment on Gh/IGF axis, i'm more scared of the impairments on androgen receptors signaling and SHBG increase/free test decrease, not only on muscle growth, but in general (sexuality, mood, etc.).
 

liquid_c

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And how exactly would they be able to tell if their Metformin use decreased androgen receptor (AR) count and signalling pathways by a couple of percent :banghead:

There are plenty of (in vitro) studies that show Metformin
(1) interferes with membrane-initiated AR action (https://www.endocrine-abstracts.org/ea/0029/ea0029p776 and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959597/)
(2) represses AR signalling via downregulation of AR expression (https://www.ncbi.nlm.nih.gov/pubmed/25894097 and https://www.ncbi.nlm.nih.gov/pubmed/25199764)

Again, these are in vitro studies, so it is hard to tell if the plasma levels of Metformin achieved with standard dosages are sufficient to elicit these effects in vivo and how large the effect size is. Is AR density down-regulated by 0% 1%, 5% or 10%? Noone knows. But given the anti-proliferative effects of metformin in prostate cancer observed in human trials, there is good reason to expect these effects to occur to some degree in vivo.

So this is another potential downside to Metformin use in bodybuilders. But guess what's even worse than slightly down-regulated AR signalling? Being fucking insulin-resistant.

It's really very simple guys:

If your priority is to maximize muscle mass, then only take Metformin if you need to, that is, if you fasting blood glucose is above, say, 95 mg/dL. Measure your fucking blood glucose people, it is simple and cheap to do.

If your priority is health, then go ahead and take Metformin despite it's potential negative effects on muscle mass. The negative effects are likely very small, so there is no reason to worry about them unless your goal is to become a fucking freak with as much lean mass as humanly possible. You can have a fucking fantastic physique while using Metformin.

Good post. I have looked at both sides as much as I can. We do know and most agree that metformin helps at least in a small degree with fat loss and putting on less fat. There is a lot of debate on whether it effects muscle growth and if so to what degree although most agree that if it does it is likely only a small amount. I think it really depends on what your goals are. At my age, I am willing to take a chance and possibly sacrifice a couple % of gains to give me a few % better lean-ness and health. All about your goals.
 

IronLion2

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When i first took it i was natty and it gave a great aesthetic enhancement to my physique. I was more hard/dense and vascular, less watery and my body could handle carbs 10 times better than without metformin. No lethargy after carbs meals, rather i felt more energetic.
It didn't seem to impair my muscle growth at all, rather i looked more full/pumped. Adding to these the indiscussed health benefits (on lipid profile also, something to consider while on AAS) and for me personally, i think is worth it even in abscence of compounds that impair insulin sensitivity.
But when i took metformin for the first time i run it for a short time (a couple of months). So i don't know if the negatives effects start after a while you have been on it.
More than the impairment on Gh/IGF axis, i'm more scared of the impairments on androgen receptors signaling and SHBG increase/free test decrease, not only on muscle growth, but in general (sexuality, mood, etc.).


Met outside of SHBG wouldnt impair 'aesthetics' or body comp negatively despite what the fuck faces at Enhanced Athlete say. Bostin Lloyd you uneducated twat. The theory of IGF impairment would lead to less growth down the road rather than the short term, but again its purely theory and anyone that says different is pure speculating... As am I

I agree 100% with MyNameIsJeff.

Of course you do, it takes no brain power or time to dick ride
 
Last edited:

Andro308

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My knowledge is very limited in this area, but all the reports i read are showing the effects on the AR in the prostate. I dont see where is specifically mentions the AR in muscle tissue being effected.

I am not able to take large doses of this due to stomach issues but I am going to try again. I have 250mg tablets coming and i plan on splitting them in half and having one with each meal. I have heard working your way up with Met is the best way to go.

found this info (Copy & Paste):
Recent research has demonstrated that Metformin can decrease testosterone production and raise sex hormone binding globulin when dosed consistently for 2 weeks at 1700 mgs a day. When you dose Metformin infrequently as in twice a week, the negative effect on testosterone levels will be miniscule to non- existent. You will benefit from an increased level of AMP-activated protein kinase activity in skeletal muscle, which will increase the translocation of GLUT-4 transporters to skeletal muscle, increasing glucose uptake. AMP-activated protein kinase will also increase fatty acid oxidation by inactivating acetyl-CoA-carboxylase. By regulating acetyl- CoA-carboxylase, carnitine palmitoyltransferase (CPT-1) is not blocked and able to transport fatty acids into the mitochondria for oxidation.

Metformin has selectivity towards muscle cells opposed to fat cells when clearing nutrients from the blood. It has also been demonstrated to serve as an anti-catabolic agent when muscles have been immobilized due to bone or joint complications. A study was conducted to observe the effect Metformin had on maintaining muscle glycogen inside muscle fibers and stabilizing muscle weight during inactivity of muscles in test rats. Researchers discovered that rats not treated with Metformin lost significant muscle glycogen and muscle weight when muscles were immobilized. Inactive muscles also became insulin resistant due to down regulation of insulin receptor substrate-1 (IRS-1) in intra-cellular tissues. Decreased IRS-1 along with GLUT-4 translocation is a recipe for muscular atrophy.


I find it hard to believe that Metformin would cause any muscle loss to a bodybuilder when the study above shows it maintains muscle weight/fiber/glycogen.
 

IronLion2

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I'll hijack as ive been looking for any indicators on this;

Metformin before or after cardio? Ive seen some fear of "met canceling out postive effects of exersize" I don't think that's relative to us, but what about ketoacidosis?
 

mujeriego

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With the IGF thing, do you guys think that Metformin could have any negative effect on IGF conversion from exogenous hgh?

That would be my only worry from it, admittedly I haven't read much into how it affects IGF. Other than that I think Metformins positive effects kinda cancel out any negative effects it could possibly have on muscle growth/body composition.
 

phoenix2

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My knowledge is very limited in this area, but all the reports i read are showing the effects on the AR in the prostate. I dont see where is specifically mentions the AR in muscle tissue being effected.

I am not able to take large doses of this due to stomach issues but I am going to try again. I have 250mg tablets coming and i plan on splitting them in half and having one with each meal. I have heard working your way up with Met is the best way to go.

found this info (Copy & Paste):
Recent research has demonstrated that Metformin can decrease testosterone production and raise sex hormone binding globulin when dosed consistently for 2 weeks at 1700 mgs a day. When you dose Metformin infrequently as in twice a week, the negative effect on testosterone levels will be miniscule to non- existent. You will benefit from an increased level of AMP-activated protein kinase activity in skeletal muscle, which will increase the translocation of GLUT-4 transporters to skeletal muscle, increasing glucose uptake. AMP-activated protein kinase will also increase fatty acid oxidation by inactivating acetyl-CoA-carboxylase. By regulating acetyl- CoA-carboxylase, carnitine palmitoyltransferase (CPT-1) is not blocked and able to transport fatty acids into the mitochondria for oxidation.

Metformin has selectivity towards muscle cells opposed to fat cells when clearing nutrients from the blood. It has also been demonstrated to serve as an anti-catabolic agent when muscles have been immobilized due to bone or joint complications. A study was conducted to observe the effect Metformin had on maintaining muscle glycogen inside muscle fibers and stabilizing muscle weight during inactivity of muscles in test rats. Researchers discovered that rats not treated with Metformin lost significant muscle glycogen and muscle weight when muscles were immobilized. Inactive muscles also became insulin resistant due to down regulation of insulin receptor substrate-1 (IRS-1) in intra-cellular tissues. Decreased IRS-1 along with GLUT-4 translocation is a recipe for muscular atrophy.


I find it hard to believe that Metformin would cause any muscle loss to a bodybuilder when the study above shows it maintains muscle weight/fiber/glycogen.


As i said, i never noticed any muscle loss while taking metformin and i was natty at the time, but i ran it only for a couple of months.
So probably, a better protocol in a cut/bodyrecomp that not includes hgh/peptides/exogenous insulin, could be 1000-1500 mg taken only on carbs refeed days.
In this case the eventual downsides on IGF/test should be minimal to non existant.
But i know that metformin has to be taken in chronic to work at 100%.
I will try and see what will happen.
 

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