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How Metformin Works in the Mitochondria Studied.

Ema

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In experiments reported in the journal Proceedings of the National Academy of Sciences, the researchers tease out the mechanism behind metformin's age-slowing effects: the drug causes an increase in the number of toxic oxygen molecules released in the cell and this, surprisingly, increases cell robustness and longevity in the long term.

Mitochondria -- the energy factories in cells -- generate tiny electric currents to provide the body's cells with energy. Highly reactive oxygen molecules are produced as a by-product of this process.

While these molecules are harmful because they can damage proteins and DNA and disrupt normal cell functioning, a small dose can actually do the cell good, say the researchers: "As long as the amount of harmful oxygen molecules released in the cell remains small, it has a positive long-term effect on the cell. Cells use the reactive oxygen particles to their advantage before they can do any damage," explains Wouter De Haes. "Metformin causes a slight increase in the number of harmful oxygen molecules. We found that this makes cells stronger and extends their healthy lifespan."

http://www.sciencedaily.com/release...cedaily+(Latest+Science+News+--+ScienceDaily)
 

Ema

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Life Extension magazine I believe has been saying this for many years, if not decades now!

GG
Yes, they have, but it never made sense to me how metformin could be helpful for anti-aging and also toxic to the mitochondria.

This *kind of* clears that up...though I'm still not sure if it would be helpful for the ME/CFS population or not. Isn't it possible that we already have *enough* reactive oxygen molecules in our mitochondria (i.e. more than healthy people), and more might actually be toxic?
 

Ema

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One of my Drs prescribed it to me years ago, still have some in my medicine cabinet. Wonder if I could get my current Dr to prescribe it? Not that I want to live longer in my current state :(

GG
I hear you. I read an article about shortened life expectancy in ME/CFS a while ago and all I could think was thank goodness...

But here is a site where you can buy it pretty cheaply:

http://www.antiaging-systems.com/136-metformin-metforal

It raised my liver enzymes for some reason. Very odd. Something to keep an eye on though.
 

lansbergen

Senior Member
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2,512
Isn't it possible that we already have *enough* reactive oxygen molecules in our mitochondria (i.e. more than healthy people), and more might actually be toxic?

Yes, it is and excess can kill. Balance is the key.
 

alex3619

Senior Member
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Logan, Queensland, Australia
Which raises the question: if ME is associated with more oxidative stress, is metformin actually dangerous to us?

I am currently on metformin. I am also in a slow steady decline.
 

maryb

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@alex3619
Maybe something to think about. I don't take metformin and tests I've had (3) on my oxidative stress levels have been mega high.
 

heapsreal

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not being able to utilize glucose properly one would think would cause oxidative stress. metformin improves glucose metabolism??? It also can improve cholesterol/triglycerides which can reduce cardiac disease risk factors??

Theres a few things that need to be taken into consideration?
 

melihtas

Senior Member
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I tried metformin 2 months ago to lower my triglyceride levels. I felt better for a few days, after then I was in constant PEM because metformin stimulates anaeorobic metabolism in cells and increases lactic acid levels. I stopped taking it after 2 weeks and I got back to my usual health level in a few days. I think people with ME should avoid Metformin.

While these molecules are harmful because they can damage proteins and DNA and disrupt normal cell functioning, a small dose can actually do the cell good, say the researchers: "As long as the amount of harmful oxygen molecules released in the cell remains small, it has a positive long-term effect on the cell.

I think we already have a lot of these molecules in our cells as a part of our health problems. People say I look 10 years younger than my actual age (I am 38 now), so apparently I am having this anti-aging effect which is only bright side of ME.
 

alex3619

Senior Member
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I think our skin might appear younger, for a while, but the underlying biochemistry appears to one of accelerated aging. We get old fast.

Being housebound, or bedbound, might mean we get less sun. Sunlight is a known cause of accelerated skin aging. So the skin is perhaps aging less fast than the rest of us.
 

N.A.Wright

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I think we already have a lot of these molecules in our cells as a part of our health problems. People say I look 10 years younger than my actual age (I am 38 now), so apparently I am having this anti-aging effect which is only bright side of ME.
Not that I now look anything other than my advanced years but the ‘younger than real age’ thing got to be annoying in the past because people generally associate youthful looks with good health, it’s counter intuitive to see signs of youth as being pathological. One needs to be cautious about connecting dots which maybe unrelated, but there is at least one disease that may have some relationship to ME where youthful looks can be a sign of pathology, Ehlers-Danlos Syndrome can cause the skin of some sufferers to remain youthfully flexible. There are also rare genetic conditions which appear to confer delayed aging.

Hypothetically, it would be one more of ME’s perverse jokes if the illness itself were protective of the grosser effects say of reduced activity, so that the illness leaves us unable to do normal levels of activity but also leaves us less prone to the problems of inactivity – at least as far as muscle loss, joint calcification and other ‘youthful attributes’. Another version of sick, but not sick like anyone expects.
 

melihtas

Senior Member
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I think our skin might appear younger, for a while, but the underlying biochemistry appears to one of accelerated aging. We get old fast.

Being housebound, or bedbound, might mean we get less sun. Sunlight is a known cause of accelerated skin aging. So the skin is perhaps aging less fast than the rest of us.

I was just speculating about the current topic. I don't have biochemistry knowledge as much as you do.

My ME progressed slowly over 15 years. At the begining, only heavy anaerobic exercise like weight lifting was causing PEM. My anaerobic threshold lowered continously since then and now sitting upright or standing more than an hour triggers PEM due to orthostatic intolerance. I have been housebound only for the last three years and I have always liked sunbathing and tanning and never used sunscreens. So, I don't think getting less sun is the only explanation for looking younger.
 

melihtas

Senior Member
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Not that I now look anything other than my advanced years but the ‘younger than real age’ thing got to be annoying in the past because people generally associate youthful looks with good health, it’s counter intuitive to see signs of youth as being pathological.

Yes indeed it is really annoying and difficult to explain people how sick I am while I look healthier than most of them :).

Nowadays, I stopped caring about what people think and I don't even try to explain ME. I just tell them I am tired and they should google ME if they want to know more. I don't waste my limited energy trying hopelessly to educate people.
 
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garcia

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I tried metformin for the first time recently (500mg once a day). I was suffering from horrific brain inflammation at the time, and my main reason for trying metformin was as an immune-modulator / anti-inflammatory. It did an amazing job in that regard. I would give it 10/10 for that. It worked very quickly (1 dose) and was very effective.

However, I felt very tired almost immediately after taking even the first dose. Also mood went downhill - just felt "blah" - I think that is mainly from the physical lethargy. I was waking up about 1.5 hours later than normal. Here is a really good page on some of the side-effects people get with metformin:

http://www.peoplespharmacy.com/2000/04/01/metformin/#comments

Fatigue, brain-fog and depression are not uncommon. Remember, these are people who don't have ME/CFS! So we are likely to be more susceptible. Some (all?) of the side effects may be due to lactic acidosis, which can be a side effect, and is obviously a concern for ME/CFS patients.

It's a shame because metformin does seem to have amazing benefits. So the question is does anyone know of any other drugs with a similar immune-modulating profile, but without the side-effects???
 
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Leopardtail

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England
I tried metformin for the first time recently (500mg once a day). I was suffering from horrific brain inflammation at the time, and my main reason for trying metformin was as an immune-modulator / anti-inflammatory. It did an amazing job in that regard. I would give it 10/10 for that. It worked very quickly (1 dose) and was very effective.

However, I felt very tired almost immediately after taking even the first dose. Also mood went downhill - just felt "blah" - I think that is mainly from the physical lethargy. I was waking up about 1.5 hours later than normal. Here is a really good page on some of the side-effects people get with metformin:

http://www.peoplespharmacy.com/2000/04/01/metformin/#comments

Fatigue, brain-fog and depression are not uncommon. Remember, these are people who don't have ME/CFS! So we are likely to be more susceptible. Some (all?) of the side effects may be due to lactic acidosis, which can be a side effect, and is obviously a concern for ME/CFS patients.

It's a shame because metformin does seem to have amazing benefits. So the question is does anyone know of any other drugs with a similar immune-modulating profile, but without the side-effects???
Metformin has the side effect of reducing Methylation, possibly taking Methyl supps may help.
It is a strong medication with endless side effects though.
 

heapsreal

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Metformin has the side effect of reducing Methylation, possibly taking Methyl supps may help.
It is a strong medication with endless side effects though.

I havent read it reduces methylation but have read it 'can' reduce b12 absorption. One of its ways it helps improve insulin sensitivity is it slows the absorption of glucose and i guess other nutrients through the gut, but theres a big difference between slowing and reducing absorption too i guess?? Im not sure on the mechanisms but it generally states for docs to keep an eye on blood levels of b12 when on metformin??
 

garcia

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Metformin has the side effect of reducing Methylation, possibly taking Methyl supps may help.
It is a strong medication with endless side effects though.

Sadly neither methyl-b12 or other methylating supps seem to help alleviate the symptoms. It's my first day off metformin, and I can't remember the last time I felt so weak!

Anyone got any other immunomodulator suggestions?