How Metformin Works in the Mitochondria Studied.

[heapsreal]

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?

Immune mod suggestions, im currently on cycloferon and is helping, immunovir i dont think is as good. I have ordered some arbidol to try. Generally trying to rotate these about a month about so they keep working, all are interferon inducers which supposedly increase nk function???

 

[garcia]

Immune mod suggestions, im currently on cycloferon and is helping, immunovir i dont think is as good. I have ordered some arbidol to try. Generally trying to rotate these about a month about so they keep working, all are interferon inducers which supposedly increase nk function???

Thanks for the suggestions @heapsreal. I don't do so well with interferon inducers. Immunovir doesn't do much for me at all nowadays. I'm more looking for drugs which stop pro-inflammatory cytokines (without being overly immune-suppressive). Metformin and Benicar/Olmesartan have been perfect in that regard, but I couldn't tolerate them due to side effects.

 

[taniaaust1]

The doctor and I had a discussion on whether I start Metformin now or not only the other day... so Im very happy to see this thread. Thanks everyone for the comments, I really appreciated them.

Thou she thinks its a good idea for me to be on (as Ive got a blood sugar reading of 11) and does want me to go onto it, she had concerns currently on me starting it right now due to my currently poor diet (missing meals), she said that is very important to have a stable diet before starting it. So we are hoping to have something done about that first.

Ive been worried about it thou due to many of the concerns here eg it affecting DNA and mito. Im sure I have very bad mito issues already so I keep thinking this drug.. I may find to be an issue. (Negative mito affecting drugs, Ive found very bad in the past.. tend to give me major mind fog to the point I can hardly think at all! I cant take statins for that reason). Thing is I need to do something about my worsening sugar levels so Im going to have to do something.

 

[melihtas]

Thanks for the suggestions @heapsreal. I don't do so well with interferon inducers. Immunovir doesn't do much for me at all nowadays. I'm more looking for drugs which stop pro-inflammatory cytokines (without being overly immune-suppressive). Metformin and Benicar/Olmesartan have been perfect in that regard, but I couldn't tolerate them due to side effects.

You should see this thread.

 

[Leopardtail]

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?

The number of things Metformin does is vast - it increases intra-mitochondrial Mg, increases ATP production (thought to be due to Mg by some), reduces absorption of many nutrients including glucose, increases insulin output by pancreatic B-Cells, lowers Glucagon output by pancreatic A-Cells. It's one of those things that has highly fragmented research making it very hard to be certain what chain and effect is going on. Most research for obvious reasons is also on diabetic patients, hence it's effects in ME may be somewhat different or similar.

Given that T2DM and ME both seem to feature poor ATP production my gut hunch is more similar than different.

 

[Leopardtail]

The doctor and I had a discussion on whether I start Metformin now or not only the other day... so Im very happy to see this thread. Thanks everyone for the comments, I really appreciated them.

Thou she thinks its a good idea for me to be on (as Ive got a blood sugar reading of 11) and does want me to go onto it, she had concerns currently on me starting it right now due to my currently poor diet (missing meals), she said that is very important to have a stable diet before starting it. So we are hoping to have something done about that first.

Ive been worried about it thou due to many of the concerns here eg it affecting DNA and mito. Im sure I have very bad mito issues already so I keep thinking this drug.. I may find to be an issue. (Negative mito affecting drugs, Ive found very bad in the past.. tend to give me major mind fog to the point I can hardly think at all! I cant take statins for that reason). Thing is I need to do something about my worsening sugar levels so Im going to have to do something.

Tania,

you might well need it. I suffered some Insulin resistance (20%) despite being Type I diabetics (that's not supposed to happen) and it is a known ME problem. Most diabetic clinics here get free samples of blood meters and give them out free. If you are worried about Metformin there are two things you could try first:

• Ribose at 5g x3 /day for 6 weeks then 10g/day. That a weird one - it can cause a rapid drop in blood sugar and possible hypoglycaemia the first time or two you try it, but thereafter it acts more like sugar, but your body should be able to handle it.
• Magnesium in the form of Mg Aspartate, or Mg Malate. 100mg /day of whichever you choose in at least two doses.

I would like you to have a blood meter available before you do to keep an eye on things. Should you feel increased brain fog, or light headedness, put one teaspoon of sugar under your tongue give it give minutes, repeat as needed. If they give you a blood meter, your BM must be above 4.0 mmol/l. They might want you to keep it a little higher (especially if on Metformin).

Re the Metformin, what is your Adrenal status like Tania?

Leo

 

[Leopardtail]

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?

I agree with all points Ema, and I can offer a hypothesis on that one.

I located research some time ago (University in Tokyo) indicating that Metformin increases ATP production. The inherent operation of ATP synthase means more ATP produces more superoxide. When the mitos are producing enough ATP the superoxide is efficiently dealt with by SOD, or exported via transporters, thus producing high intracellular free radicals, but protecting the Mitos.

The aging process is thought by many to be in large part due to reduced ATP production. Our is rubbish and my local NHS clinic indicated that people with ME often look 'older than their years' hence that all starts to tie in together.

 

[lansbergen]

When the mitos are producing enough ATP the superoxide is efficiently dealt with by SOD, or exported via transporters, thus producing high intracellular free radicals, but protecting the Mitos..

Unless SOD2 is impaired and membranes are affected.

 

[Leopardtail]

Unless SOD2 is impaired and membranes are affected.

Accepted lans, the above text specifcally referred to the content of the article showing higher intra-cellular free radicals and a healthier cell. The ion pumps in the mitos depend on ATP meaning that very lower energy production can makes less free radicals but trap them in the worst place. I was clearing up a quandary over the result of the study relating to this issue. Hopefully when you read the article and the question I responded to my comments will make sense - it was an anlaysis of that specific finding. It's a bit like many anti-inflammatories (e.g. Vit C) being acids only making sense when you know how they work isn't it?

With SOD much depends on the type of impairment, mine for example was impaired due to poor ATP production, when I gave more fuel and more ribose the problem resolve following a healing shock. Genetic SOD impairment would a whole different issue if I have correctly understood those who suffer it.

Everybody is the exclusion to some piece of general good advice though aren't they? Cabbage and related items for example makes me exhausted despite being first class food for most people! However I would never advise others to exclude the crucifiers without compelling grounds.

 

[ukxmrv]

Metformin was really bad for me. I had a terrible stomach ache from this and also felt totally weak in a way that was far worse than normal. Fatigue isn't quite the right word to describe it or malaise. Wish I could find the right word.

Thank you all of this discussion. It's above my brain power right now but areas for me to look at and try and understand when it does come back briefly again. I've often wondered why some drugs hit me in that way (Voltarol/ diclofenac potassium was another).

Leopardtail - there have been discussions on ME and CFS groups before and it appears that many of us look younger than our years as well. There seems to be a subgroup of people who look much younger and in some cases look very young until they suddenly age overnight or in the case of a woman I knew look very young and then suddenly die of cancer or something. I'm one of the young looking ones and it seems to be a trait in my family.

 

[Leopardtail]

Metformin was really bad for me. I had a terrible stomach ache from this and also felt totally weak in a way that was far worse than normal. Fatigue isn't quite the right word to describe it or malaise. Wish I could find the right word.

Thank you all of this discussion. It's above my brain power right now but areas for me to look at and try and understand when it does come back briefly again. I've often wondered why some drugs hit me in that way (Voltarol/ diclofenac potassium was another).

Leopardtail - there have been discussions on ME and CFS groups before and it appears that many of us look younger than our years as well. There seems to be a subgroup of people who look much younger and in some cases look very young until they suddenly age overnight or in the case of a woman I knew look very young and then suddenly die of cancer or something. I'm one of the young looking ones and it seems to be a trait in my family.

That's interesting, when the ME is lighter I look younger than my age too, but seem to be the exception among the people I have met with ME. BTW. I was explaining an article on Metformin. I am not recommending it unless a doctors see clear clinical need and they have tried everything else. Doctor's do not know that much about how it works and it can cause masses of side effects.

 

[taniaaust1]

Tania,

you might well need it. I suffered some Insulin resistance (20%) despite being Type I diabetics (that's not supposed to happen) and it is a known ME problem. Most diabetic clinics here get free samples of blood meters and give them out free. If you are worried about Metformin there are two things you could try first:

• Ribose at 5g x3 /day for 6 weeks then 10g/day. That a weird one - it can cause a rapid drop in blood sugar and possible hypoglycaemia the first time or two you try it, but thereafter it acts more like sugar, but your body should be able to handle it.
• Magnesium in the form of Mg Aspartate, or Mg Malate. 100mg /day of whichever you choose in at least two doses.

I would like you to have a blood meter available before you do to keep an eye on things. Should you feel increased brain fog, or light headedness, put one teaspoon of sugar under your tongue give it give minutes, repeat as needed. If they give you a blood meter, your BM must be above 4.0 mmol/l. They might want you to keep it a little higher (especially if on Metformin).

Re the Metformin, what is your Adrenal status like Tania?

Leo

hi, I do have a glucose monitor.. my specialist got me to get one a few years ago due to the severe hypoglycemia I was getting at that time.

Should you feel increased brain fog, or light headedness, put one teaspoon of sugar under your tongue give it give minutes, repeat as needed.

That's the issue, my symptoms are constantly shifting all the time cause I also have POTS and so many dysautonomia issues going on too. So it would be very hard for me to tell by increased brain fog and light headedness (as those are POTS symptoms which kick every time Im changing posture, or upright too long etc.. or just kick in cause my fluid volume has got to low (which happens all the time, Im ending up in hospital needing drips).

I also have SEVERE reactions if my insulin spikes up suddenly too high (I can smash windows as that then causes me severe mood swings.. I think with my MCS Im severely sensitive to the large insulin spikes I can get) .. Ive been told to stay away from sugar entirely and keep my carbs extremely low due to the severity of my issue with insulin spikes (its even got me into trouble with the police before).

As far as my adrenals go, they arent at all good. 2 out of my three 24hr cortisol tests were out of the normal range (too low). I cant handle stress well at all due to my adrenals. My body does not give out more cortisol when its in extreme pain or if Im trying to exercise (that made not much difference to my test results at all).

 

[taniaaust1]

Unless SOD2 is impaired and membranes are affected.

Thanks as Im SOD2 +- in my gene testing. I wonder how much that would affect things for me ***wondering how much worst then a normal person would my detox there be***

 

[Leopardtail]

hi, I do have a glucose monitor.. my specialist got me to get one a few years ago due to the severe hypoglycemia I was getting at that time.



That's the issue, my symptoms are constantly shifting all the time cause I also have POTS and so many dysautonomia issues going on too. So it would be very hard for me to tell by increased brain fog and light headedness (as those are POTS symptoms which kick every time Im changing posture, or upright too long etc.. or just kick in cause my fluid volume has got to low (which happens all the time, Im ending up in hospital needing drips).

I also have SEVERE reactions if my insulin spikes up suddenly too high (I can smash windows as that then causes me severe mood swings.. I think with my MCS Im severely sensitive to the large insulin spikes I can get) .. Ive been told to stay away from sugar entirely and keep my carbs low due to the severity of my issue with insulin spikes (its even got me into trouble with the police before).

As far as my adrenals go, they arent at all good. 2 out of my three 24hr cortisol tests were out of the normal range (too low). I cant handle stress well at all due to my adrenals. My body does not give out more cortisol when its in extreme pain or if Im trying to exercise (that made not much difference to my test results at all).

Telling whether Dysautomnia vs Low blood volume is causing POTS is hard work and the cause of a lot of debate, most doctors assume it's always one of the other.

Also Aldosterone (anti-urination hormone) is made either from Cortisol or the same precusrors (two methods). Hence low Cortisol can equal low Aldosterone = cause of POTS = cause of further problems.

Which cortisol test (time of day) was not low, and was it high or normal? Has any proper investigation been done into why you are producing so little Cortisol? Has Aldosterone been checked?

The aggression that comes with Hypoclyemia is caused by Adrenalin and/or Cortisol production when the body tries to correct the problem not by the hypo itself. If you are producing far too little Cortisol and Aldosterone, your body may be producing masses of Adrenaline to compensate (mine does) thus causing your rages.

The insulin spikes with sugar are caused in the bowels not the blood stream, if you dissolve it under your tongue, you avoid that problem. Following the teaspoon of sugar with something solid (cereal with bran for example) will help take pressure off your adrenals. The repeat as necessary also matters here, just keep on the sweet stuff until blood sugar settles, then follow up with the stodgy stuff. If you feel like hell with all carbohydrates that could be your SOD function.

Give me as much data as you can about your BP etc etc... and let's see if we can't sort this out.

 

[Leopardtail]

Thanks as Im SOD2 +- in my gene testing. I wonder how much that would affect things for me ***wondering how much worst then a normal person would my detox there be***

SOD function is heavily ATP dependant, irrespective of genetic stuff. That you are heterozygous means it will work normally but break under stress.

You need to get your anti-oxidant status well up -

1. lots of Vitamin C (e.g. 10g / day)
   
2. you may initially also need strong Vitamin E & A tablets.

Also worth trying:

1. high dose CoQ10 200-300mg/day will reduce SOD demand,
2. Carnitine ditto....
3. Alpha Linolenic Acid also worth a try.

Liquorice extract preserves all of:

1. Cortisol,
   
2. Testosterone,
   
3. Aldosterone

meaning your body has to produce less of them

 

[lansbergen]

Thanks as Im SOD2 +- in my gene testing. I wonder how much that would affect things for me ***wondering how much worst then a normal person would my detox there be***

Did you search the net for SOD2 heterozygous?

I know SOD2 impairment is assosiated with the infection I suspect. Superoxide is not neutralized (quick) enough.

Mice lacking the SOD2 gen die soon after birth.

The immune modulator I use is a superoxide scarvenger. I think decreasing the superoxide excess helps. Superoxide is a defense mechanism so be carefull not to got to far.

 

[Leopardtail]

Did you search the net for SOD2 heterozygous?

I know SOD2 impairment is assosiated with the infection I suspect. Superoxide is not neutralized (quick) enough.

Mice lacking the SOD2 gen die soon after birth.

The immune modulator I use is a superoxide scarvenger. I think decreasing the superoxide excess helps. Superoxide is a defense mechanism so be carefull not to got to far.

Which infection are you referring to?

 

[lansbergen]

Which infection are you referring to?

I send you a PM

 

[taniaaust1]

Did you search the net for SOD2 heterozygous?

I know SOD2 impairment is assosiated with the infection I suspect. Superoxide is not neutralized (quick) enough.

Mice lacking the SOD2 gen die soon after birth.

The immune modulator I use is a superoxide scarvenger. I think decreasing the superoxide excess helps. Superoxide is a defense mechanism so be carefull not to got to far.

No I havent researched the heterozygous SOD2 stuff yet, it probably be quite a while till I do that. I need to limit how much I research as I can get sick from doing too much of that. Thanks for the info.

 

[taniaaust1]

SOD function is heavily ATP dependant, irrespective of genetic stuff. That you are heterozygous means it will work normally but break under stress.

You need to get your anti-oxidant status well up -

1. lots of Vitamin C (e.g. 10g / day)
   
2. you may initially also need strong Vitamin E & A tablets.

Also worth trying:

1. high dose CoQ10 200-300mg/day will reduce SOD demand,
2. Carnitine ditto....
3. Alpha Linolenic Acid also worth a try.

Liquorice extract preserves all of:

1. Cortisol,
   
2. Testosterone,
   
3. Aldosterone

meaning your body has to produce less of them

Thanks. I copied that info and printed it for myself. Anti-oxidants in my case do help me a little bit..eg high dose C. So maybe you've just explained to me why. (Vit E thou I havent noticed that helping me). I havent tried the other things you mentioned