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Negative Metformin article

nothuman

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I'm always one of the guys who sings Metformin's praises every time it gets brought up but this is actually a negative article that makes me think, unlike some of the others. This was posted by Dr. John Crisler himself.

Stop the Metformin Madness- Hormones Matter

The vitamin B thing doesn't concern me personally because mine is always high but the rest does. Especially about the reduced insulin benefits from exercise, decreased performance, and mitochondrial disadvantages.
 

little slice

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tl;dr LMAO





:sta;-wars
 

goal245

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I've always been against metformin, did a tons of research a few years ago and it does not make any sense for a bodybuilder to use if you look at its mechanisms of action
 

suppdude

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The insulin sensitivity part of the study included was with already insulin resistant individual. Here we see metformin doesn't attentuate the acute effect on insulin sensitivity in insulin resistant individuals:

https://www.ncbi.nlm.nih.gov/m/pubmed/24682492/?i=2&from=/20071560/related

Second, as noted in one study, the dose used on rats at 30mg/kg/body weight per day equates to 2000mg dose for humans. At this dose, there was no significant effect on muscle oxidative capacity.

Thirdly, most using metformin are supplementing with additional b-12 and CoQ10/ubiquinol.


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nothuman

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The insulin sensitivity part of the study included was with already insulin resistant individual. Here we see metformin doesn't attentuate the acute effect on insulin sensitivity in insulin resistant individuals:

https://www.ncbi.nlm.nih.gov/m/pubmed/24682492/?i=2&from=/20071560/related

Second, as noted in one study, the dose used on rats at 30mg/kg/body weight per day equates to 2000mg dose for humans. At this dose, there was no significant effect on muscle oxidative capacity.

Thirdly, most using metformin are supplementing with additional b-12 and CoQ10/ubiquinol.

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This doesn't seem to address mitochondrial damage though, which I wasn't aware of.

"Metformin and Mitochondrial Damage

Perhaps most troubling amongst the Metformin side effects is its ability to severely impair mitochondrial functioning.

Recall from high school biology, the mitochondria are those bean shaped organelles inside cells that are responsible for cellular respiration or energy production. Through a variety of pathways, the mitochondria provide fuel for cell survival. In addition to cellular energy production, mitochondria control cell apoptosis (death), calcium, copper and iron homeostasis and steroidogenesis. In essence, mitochondria perform the key tasks associated with cell survival, and indeed, human survival. Damage the mitochondria and the cellular dysfunction or death will occur. Damage sufficient numbers of mitochondrion and chronic, multi-symptom illness arises.
As we have come to learn, many pharmaceuticals, environmental toxicants and even dietary deficiencies can impair mitochondrial functioning and induce disease processes that are often difficult to diagnose and treat. Metformin is no different. Metformin impairs mitochondrial functioning quite significantly by several mechanisms and, in doing so, sets off a cascading sequence of ill-effects.

At the center of metformin’s mitochondrial damage is its affect on the most basic of mitochondrial functions – ATP (cellular energy) production. Metformin reduces mitochondrial ATP production in skeletal muscle by as much as 48%. Sit with that one for a moment, a 48% reduction in cell fuel. Imagine functioning at only half capacity. This would make basic activities difficult at best and exercising to lose weight a very unlikely proposition. Imagine similar reductions in ATP production were observed in the brain or the heart or the GI tract (which, when on Metformin are likely), the types of disturbances we might see become quite clear: neurocognitive decline, psychiatric instability, neuropathy, heart rate, rhythm and blood pressure abnormalities, along with gastrointestinal distress to name but a few. Underlying all of these symptoms, and indeed, all mitochondrial dysfunction, is an overwhelming sense of fatigue and malaise.

Metformin Alters Immune Reactivity via the Mitochondria

As I wrote in a previous post:

Some researchers argue that the mitochondria are the danger sensors for host organisms; having evolved over two billion years to identify and communicate signs of danger to the cells within which they reside. The signaling is simple and yet highly refined, involving a series of switches that control cellular energy, and thus, cellular life or death. When danger is present, energy resources are conserved and the immune system fighters are unleashed. When danger is resolved, normal functioning can resume.

If the danger is not resolved and the immune battles must rage on, the mitochondria begin the complicated process of reallocating resources until the battle is won or the decision is made to institute what can only be described as suicide – cell death. Cell death is a normal occurrence in the cell cycle of life. Cells are born and die for all manner of reasons. But when cell death occurs from mitochondrial injury, it is messy, and evokes even broader immune responses, setting a cascade in motion that is difficult to arrest.
Metformin alters this process, first by damaging the mitochondrial ATP factory and reducing energy production capacity and then by inhibiting the signaling cascades that would normally respond to the danger signals. The double hit fundamentally alters immune function and I would suspect predisposes those who take Metformin to more infections and an array of inflammation based disease processes. More details on this in a subsequent post."
 

suppdude

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Actually, I addressed that when I stated the part about muscle oxidative capacity, which deals with ATP and mitochondrial impairment.

Additionally, a dose of 2000mg (30mg/kg in rats) has no significant effect compared to 100mg/kg and 300mg/kg, both of which are very high human doses.


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nothuman

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Actually, I addressed that when I stated the part about muscle oxidative capacity, which deals with ATP and mitochondrial impairment.

Additionally, a dose of 2000mg (30mg/kg in rats) has no significant effect compared to 100mg/kg and 300mg/kg, both of which are very high human doses.


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Ok I didn't know they were connected.
 

Elvia1023

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About 20 guys on promuscle are about to have a nervous breakdown when they read this thread :eek::p
 

liv2pb

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Good post bro. Metformin is one of those drugs that i couldn't pull the trigger on based off what I read. Bittermelon/ala/cinnamon has always kept my a1c perfect.
 

eaglecall

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Most probably in a couple of years the use of metformin will be one more "bro science" in the bucket. I have no experience with GH or insulin but the use of metformin for bodybuilding purposes which is in itself a dangerous drug never made sense to me. If your glucose levels are going out of whack due to GH, reduce the dose or stop using it. Is simple common sense to me.

However, IGF-1 Lr3 is supposed to increase insulin sensitivity. Isn't it better to use that as part of a protocol instead of metformin??
 

devenidas

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About 20 guys on promuscle are about to have a nervous breakdown when they read this thread :eek::p
Not me :) cos I don't use it. Doesn't bother me. Good studies or bad studies.

For the supplement whores who take it how does it feel now bitches , your mitrochondria has been poisoned & its on its way to a slooooow & painful death.


Like really really slooooooooow.

Elvia Yates & Nothuman Coleman I know you both scared shitless but don't worry lovers you won't feel a thing. Trust me.

Oh please make sure you write everything you have ££££ to me in your final will. I will use it to buy gear for the rest of my life & shoot it in both of your names every single time.




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Stewie

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Not me :) cos I don't use it. Doesn't bother me. Good studies or bad studies.

For the supplement whores who take it how does it feel now bitches , your mitrochondria has been poisoned & its on its way to a slooooow & painful death.


Like really really slooooooooow.

Elvia Yates & Nothuman Coleman I know you both scared shitless but don't worry lovers you won't feel a thing. Trust me.

Oh please make sure you write everything you have ££££ to me in your final will. I will use it to buy gear for the rest of my life & shoot it in both of your names every single time.




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No it has not.
 

LEX

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I would assume at the dosages given to the rats bad shit would happen, thats like 11-35 grams daily at my BW.

Suppdude nailed it, at the equivalent of 2000mg daily none of that shit was observed..
 
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Stewie

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Dr.Crisler is against the use of Met for those with T2D. That's not the message he's conveying. His scope is "off label" use for anti-aging. Or so that's my interpretation.


As for Chandler Marrs, PhD. In her views, uncouplers are noxious in a sense that they're the demon-seed.

Well, maybe we shouldn't exercise or hypothyroidism individuals shouldn't take their thyroid hormones. Both are uncouplers.

I disregarded this article a few years ago when someone purposed it's featherweight disputation.
 

G.I.Bro

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Always good to be open minded about what we take. Nothuman is just bringing all evidence to the the table, which is good. However, I'd consider this write up's tone to be an outlier within the the decades long body of studies on Metformin. It's been extensively studied and has a very long track record of safety. In addition, a large majority of recent discussion and studies back it up as a potent longevity drug with anti cancer properties. It's got solid footing as an overall health drug - especially when for bodybuilders who use gh year long (insulin sensitivity) and eat large amounts of carbs. A bonus is that it helps promote better body composition. The longevity community has embraced this drug for reasons beyond anything related to purely building a lean physique. This article doesn't sway me on that in any way. I remain a huge proponent of metformin for overall health.
 
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nothuman

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Always good to be open minded about what we take. Nothuman is just bringing all evidence to the the table, which is good. However, I'd consider this write up's tone to be an outlier within the the decades long body of studies on Metformin. It's been extensively studied and has a very long track record of safety. In addition, a large majority of recent discussion and studies back it up as a potent longevity drug with anti cancer properties. It's got solid footing as an overall health drug - especially when for bodybuilders who use gh year long (insulin sensitivity) and eat large amounts of carbs. A bonus is that it helps promote better body composition. The longevity community has embraced this drug for reasons beyond anything related to purely building a lean physique. This article doesn't sway me on that in any way. I remain a huge proponent of metformin for overall health.
Believe me, I want this article to be wrong more than anyone else. I'm very glad to see some of the intelligent posts in here dispelling it. I won't be stopping my metformin use. Thank god.
 

G.I.Bro

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Dr.Crisler is against the use of Met for those with T2D. That's not the message he's conveying. His scope is "off label" use for anti-aging. Or so that's my interpretation.


As for Chandler Marrs, PhD. In her views, uncouplers are noxious in a sense that they're the demon-seed.

Well, maybe we shouldn't exercise or hypothyroidism individuals shouldn't take their thyroid hormones. Both are uncouplers.

I disregarded this article a few years ago when someone purposed it's featherweight disputation.
As always, much appreciated.
 

Stewie

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Dr.Crisler isn't against the use of Met for those with T2D. That's not the message he's conveying. His scope is "off label" use for anti-aging. Or so that's my interpretation.


As for Chandler Marrs, PhD. In her views, uncouplers are noxious in a sense that they're the demon-seed.

Well, maybe we shouldn't exercise or hypothyroidism individuals shouldn't take their thyroid hormones. Both are uncouplers.

I disregarded this article a few years ago when someone purposed it's featherweight disputation.
Edit:Typo
 

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