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Metformin + Peri-Workout Protocol?

I am and have been using Peri-Workout Nutrition Protocol from Thib’s forum. I think we all know what it is, so, my question is… Could I somehow incorporate Metformin into the mix to intensify the effects? I have access to 300 1000mg tablets.

I have used them while dieting down before, but was curious if it could be a valuable addition to my peri workout nutrition, and if so, how it would be used? BTW, I am not dieting and my calories are above 3500 a day. Thought it might help drive the carbs into the muscles similarly to Receptormax. Thanks, I hope I dont get flamed for asking a stupid question.

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I guess I won’t… Thanks for letting me know. BBB, I know you are pretty knowledgeable in regards to insulin and supplementation, would you mind if I pick your brain and ask you to explain why Receptormax if beneficial before a workout using the Para-workout protocol? The whole thing is a bit confusing to me. I thought Metformin was suppose to make you insulin sensitive? Now I read that it blunts insulin effect, but does indeed help transport carbs and nutrients to the muscle. It was my understanding that some people take it in place of insulin? I guess thats why I assumed that it would be good to take before the workout.

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[quote]bushidobadboy wrote:
I didn’t say that metformin blunted the effects of insulin, I said that it lowers the insulinogenic effects of carbohydrates.

And yes, chronic use of metformin does make you more insulin sensitive. In the long term it may be a useful drug for body composition, just not pre-workout.

If Receptormax increases insulin receptor density (I have not looked into Receptormax, since I don’t plan on using it, so I don’t know if this is what it actually does), then that would be a good thing. More receptors = more effect from a given amount of insulin release.

BBB

[/quote]

I am not sure that more receptors mean more effect for the same amount of hormone.

For example, say x amount of hormone/drug gives 50% of saturation, then increasing receptors at that point will not increase the amount of hormone-receptor complexes but simply mean that same x amount of hormone now achieves 42% saturation - the same effect but with potential to have a higher effective dose/saturation point.

Does that make sense?

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The biggest problem with metformin is that it causes a massive drop in T levels. On top of that, it increases SHBG. Because of the drop in T production, DHEA levels are increased - and you know some of that is going to end up as estrogen.

[quote]bushidobadboy wrote:
J-J wrote:
bushidobadboy wrote:
I didn’t say that metformin blunted the effects of insulin, I said that it lowers the insulinogenic effects of carbohydrates.

And yes, chronic use of metformin does make you more insulin sensitive. In the long term it may be a useful drug for body composition, just not pre-workout.

If Receptormax increases insulin receptor density (I have not looked into Receptormax, since I don’t plan on using it, so I don’t know if this is what it actually does), then that would be a good thing. More receptors = more effect from a given amount of insulin release.

BBB

I am not sure that more receptors mean more effect for the same amount of hormone.

For example, say x amount of hormone/drug gives 50% of saturation, then increasing receptors at that point will not increase the amount of hormone-receptor complexes but simply mean that same x amount of hormone now achieves 42% saturation - the same effect but with potential to have a higher effective dose/saturation point.

Does that make sense?

I think it depends on whether all the hormone is activating receptors and whether it’s the type of relationship that means the hormone can activate one receptor to signal second messengers to do their thing, whilst the hormone buggers off and activates other receptors.

As I said, I didn’t really look into the receptormax thing, but it would make sense that marketing hype would tout ‘increased receptor density’ as a good thing, even if it were not.

However, since insulin circulates in the blood, I would think that increasing the number of insulin receptors in skeletal muscle would be a good thing for ‘our’ goals.

BBB[/quote]

Would that be different?

[quote]J-J wrote:
bushidobadboy wrote:
I didn’t say that metformin blunted the effects of insulin, I said that it lowers the insulinogenic effects of carbohydrates.

And yes, chronic use of metformin does make you more insulin sensitive. In the long term it may be a useful drug for body composition, just not pre-workout.

If Receptormax increases insulin receptor density (I have not looked into Receptormax, since I don’t plan on using it, so I don’t know if this is what it actually does), then that would be a good thing. More receptors = more effect from a given amount of insulin release.

BBB

I am not sure that more receptors mean more effect for the same amount of hormone.

For example, say x amount of hormone/drug gives 50% of saturation, then increasing receptors at that point will not increase the amount of hormone-receptor complexes but simply mean that same x amount of hormone now achieves 42% saturation - the same effect but with potential to have a higher effective dose/saturation point.

Does that make sense?[/quote]
I understand your logic, but I am afraid it has a little too much math and a little less chemistry. BBB is correct.
The ligand receptor relationship is a chemical equilibrium. So an increase in the “amount” of receptors would positively increase the amount of ligand-receptor complex. This is obviously to only a certain extent, as there will be an asymptote in the curve at some point.

Are you saying that receptors will decrease as the ligand decreases and the receptors will increase as the ligand increases, and if you increase the amount of receptors you will automatically increase the amount of ligand in the blood (for endogenous compounds)?

[quote]J-J wrote:
Are you saying that receptors will decrease as the ligand decreases and the receptors will increase as the ligand increases, and if you increase the amount of receptors you will automatically increase the amount of ligand in the blood (for endogenous compounds)?[/quote]

No. Lets say that there was an x amount of receptors in the body and a y molar concentration of ligand. They two reactants will reach a chemical equilibrium to which they become one complex xy.
So we have the chemical equilibrium x+y <–> xy. This just means that there is a certain amount of x, y and xy in the body, and that they are all present with x and y forming to be xy. And xy disassociating to become x and y separately. By increasing the amount of X or the amount of Y you will allow a greater probability for x to become bound to y. So by increasing EITHER of the reactants you will increase the product formation. So WRT what BBB and you were talking about. If receptor max increases X, it will increase XY for the same amount of Y present.

Hope that made sense to you. Now remember this is only to an extent As eventually increasing either X or Y will no longer be beneficial as the complex depends on both. Hence the presence of the asymptote if you were to graphically look at it.

Thanks but i am afraid i know about the hormone/drug-receptor complex to that degree - or trust me i wouldn’t be having this conversation!

Look at it like this.

With insulin, there are always an abundance of receptors compared to hormone correct? We never could eat enough to secrete the amount (or eat enough to offset hypoglycaemia with that amount injected) that comes even close to saturation point. Agree?

So… say one secretes 10iu of insulin, ALL this is bound. There are plentiful receptors for the hormone to bind.
I understand that an increase in receptors will increase the chance of it binding but that whole amount will be bound anyway - so the speed of binding would increase but the amount of effect from the drug would not.

Remember the point isn’t the probability of binding (unless we are talking about the point where diminishing returns comes about due to saturation) - but getting more effect from the same amount of hormone.
If that hormone is 100% bound, then throwing all the receptors at it will make no difference.

So… more receptors does not increase the effectiveness of that same dose of insulin.

IF however we get to the higher end of the curve, as the receptors are mostly all bound, and they are less frequent for any hormone to bind you see the curve drop off (saturation). Agree?

THEN increasing the amount of receptors will definitely increase the effectiveness of the available secreted or injected insulin.

If this is still wrong, can someone please explain why and actually what happens physiologically instead of just repeating that more receptors mean more hormone-receptor complexes?!

The only other way i can think of where this is true is - if there are more receptors, then there is a higher chance of the hormone being rebound again and again before it is metabolised and excreted, increasing the potency(? is it?).

If that isn’t it and no-one can actually give a real explanation that they thoroughly understand then i give up!

[quote]J-J wrote:
Thanks but i am afraid i know about the hormone/drug-receptor complex to that degree - or trust me i wouldn’t be having this conversation!

Look at it like this.

With insulin, there are always an abundance of receptors compared to hormone correct? We never could eat enough to secrete the amount (or eat enough to offset hypoglycaemia with that amount injected) that comes even close to saturation point. Agree?

So… say one secretes 10iu of insulin, ALL this is bound. There are plentiful receptors for the hormone to bind.
I understand that an increase in receptors will increase the chance of it binding but that whole amount will be bound anyway - so the speed of binding would increase but the amount of effect from the drug would not.
[/quote]
No to say that all of it is bound would be incorrect. While the kd of insulin is quite small, it is very very unlikely that all of insulin is bound at one time. In fact I can confidently say there will always be free insulin in the blood. That is what you seem to be forgetting, it is an equilibrium! BOTH the reactants and products are always present!
Remember the point isn’t the probability of binding (unless we are talking about the point where diminishing returns comes about due to saturation) - but getting more effect from the same amount of hormone.

It is (almost) never the case that 100% of the ligand will be bound. S

Yes after a certain point, their will be an asymptote in the curve. HOWEVER speaking physiologically this is COMPLETELY dependent on the protein we are talking about. For example myoglobin this would be (practically) always true. Hemoglobin, it would be completely dependent on where it is in tissue. For insulin, this is not the case, or at least I do not know of any evidence that says it is. If you have some piece of evidence that shows this, let me know = ).

[quote]
THEN increasing the amount of receptors will definitely increase the effectiveness of the available secreted or injected insulin.

If this is still wrong, can someone please explain why and actually what happens physiologically instead of just repeating that more receptors mean more hormone-receptor complexes?!

The only other way i can think of where this is true is - if there are more receptors, then there is a higher chance of the hormone being rebound again and again before it is metabolised and excreted, increasing the potency(? is it?).

If that isn’t it and no-one can actually give a real explanation that they thoroughly understand then i give up![/quote]

I guess I don’t understand what you don’t get, if this didn’t clear it up for you…

OK… i get it. Thanks! :wink: I really do appreciate you taking the time to try to get me to understand, you didn’t have to so i really do appreciate that.

It is a game of chance as to whether the hormone will bind to a receptor before it gets metabolised or excreted, and this probability is increased or decreased with a higher/lower amount of hormone or higher/lower amount of receptor.
So, a higher the amount of receptors the greater the chance of binding - thus a little more effect for the same dose of hormone.

:wink:

I think the difference in actual hormone/drug effect is negligible when the hormone or drug is in its optimum dosing range - BUT with insulin i think it would only make a difference as muscle sensitivity would increase… improving the storage of glycogen and inhibiting the storage of fat.

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