Metformin might increase risk for Alzheimer’s disease

[Frito]

Here is the article that I got it from, be aware they are selling sups, but some of the info is quite interesting:

**broken link removed**

And Stewie pointed me in the direction of the study so here it is:
https://www.ncbi.nlm.nih.gov/pubmed/27509335

But it sounds like we can supplement our way out of this
I´m not saying Metformin is bad at all here, just making aware that it´s not all good and certain supplements should be used.

I personally like Metformin, but not sure it should be used year round either.

 

[asteelz]

The biochemical pathway she describes in cell and animal models may not hold true in humans, and the main risks seen with metformin can be easily supplemented against. If metofrmin upregulates ampk and ampk increases mitochondrial biogenesis then does that balance the loss ? But wasn't measured in the study ? Or occurs under different conditions , possibly only in humans ?

Generally when one or a few studies raise more questions then answers I consider the points made and refer to them in specific cases as n:1.

If you look at the neuromolecular pathways in the cells of the brain with Alzheimer's you see a decrease in ampk and subsequent mitochondrial biogenesis and function. So adversely activation would benefit against ad.

 

[MR. BMJ]

Yea, I got turned off by the "We report that in the C57B6/J mice...."

It can raise questions, but not much else.

 

[Stewie]

Frito sent me this, this morning over a Facebook message. Ironically, I was skimming through the full-text of this article just a few days ago when I received it through an email subscription. Thanks Frito for bringing this topic up

From what I gathered, the author (of said article) goes on to erroneously compared statins to metformin.

I agree and have said many times before; cell-line (in-vitro/ex-vivo) cultures and animal models do not necessarily emulate to humans. In some cases, animal models show a close biological/pathological resemblance.

And it's a given to mitigate the potential drawbacks of Metformin. This has been discussed, many of times.

One thing the author of said article fails to elaborate upon is the dose dependent manner Metformin plays on decreasing mitochondrial respiration complex I (MRC-I). As well, diabetes is a possible precursor for AD.

For the sake of comparison of animal models, Bart Wessels et al (2014)., shown that Metformin acts on mitochondrial respiration complex I in a dose dependent manner. What the team of researchers concluded of a human equivalent dose (HED) of approximately 515mg per day (30mg/kg/d used in animal models) there was no impact on MRC-I. In contrast, doses of 100-300mg/kg/d, this did have a significant impact on decreasing MRC-I. (I used the standard equation of rat-to-human of a 90.718kg individual).

Citation: Wessels B, Ciapaite J, van den Broek NMA, Nicolay K, Prompers JJ (2014) Metformin Impairs Mitochondrial Function in Skeletal Muscle of Both Lean and Diabetic Rats in a Dose-Dependent Manner. PLoS ONE 9(6): e100525. doi:10.1371/journal.pone.0100525

Antihistamine (anticholinergic) drugs pose a risk of developing AD. One can mitigate that as well.

Now if one is a carrier of APO-e 4/4 gene trait. I probably would limit my use of Metformin and anticholinergic drugs.

One could consider taking thymoquinone (black cumin) with Metformin for added neuroprotective measure's.

Another footnote: if you use insulin along with Metformin, this has been shown too offset to dreaded chances of developing Alzheimer's, IIRC.

 

[Stewie]

The biochemical pathway she describes in cell and animal models may not hold true in humans, and the main risks seen with metformin can be easily supplemented against. If metofrmin upregulates ampk and ampk increases mitochondrial biogenesis then does that balance the loss ? But wasn't measured in the study ? Or occurs under different conditions , possibly only in humans ?

Generally when one or a few studies raise more questions then answers I consider the points made and refer to them in specific cases as n:1.

If you look at the neuromolecular pathways in the cells of the brain with Alzheimer's you see a decrease in ampk and subsequent mitochondrial biogenesis and function. So adversely activation would benefit against ad.

Here's the full-text in reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5032692/

 

[Frito]

Frito sent me this, this morning over a Facebook message. Ironically, I was skimming through the full-text of this article just a few days ago when I received it through an email subscription. Thanks Frito for bringing this topic up

From what I gathered, the author (of said article) goes on to erroneously compared statins to metformin.

I agree and have said many times before; cell-line (in-vitro/ex-vivo) cultures and animal models do not necessarily emulate to humans. In some cases, animal models show a close biological/pathological resemblance.

And it's a given to mitigate the potential drawbacks of Metformin. This has been discussed, many of times.

One thing the author of said article fails to elaborate upon is the dose dependent manner Metformin plays on decreasing mitochondrial respiration complex I (MRC-I). As well, diabetes is a possible precursor for AD.

For the sake of comparison of animal models, Bart Wessels et al (2014)., shown that Metformin acts on mitochondrial respiration complex I in a dose dependent manner. What the team of researchers concluded of a human equivalent dose (HED) of approximately 515mg per day (30mg/kg/d used in animal models) there was no impact on MRC-I. In contrast, doses of 100-300mg/kg/d, this did have a significant impact on decreasing MRC-I. (I used the standard equation of rat-to-human of a 90.718kg individual).

Citation: Wessels B, Ciapaite J, van den Broek NMA, Nicolay K, Prompers JJ (2014) Metformin Impairs Mitochondrial Function in Skeletal Muscle of Both Lean and Diabetic Rats in a Dose-Dependent Manner. PLoS ONE 9(6): e100525. doi:10.1371/journal.pone.0100525

Antihistamine (anticholinergic) drugs pose a risk of developing AD. One can mitigate that as well.

Now if one is a carrier of APO-e 4/4 gene trait. I probably would limit my use of Metformin and anticholinergic drugs.

One could consider taking thymoquinone (black cumin) with Metformin for added neuroprotective measure's.

Another footnote: if you use insulin along with Metformin, this has been shown too offset to dreaded chances of developing Alzheimer's, IIRC.

Thanks for sharing your thoughts with us Good point about the dosage, seems like 500mg is pretty safe. But from what I read and please correct me if I´m wrong, for a 200lbs male 1000mg is getting up to where damage could happen?

I think many here uses 1000+?

Can we go over the supplements that could help again?

B12
Black Cumin
CoQ10

Any other that should be a staple when using Metformin?

 

[NY Muscle]

Make sure its methyl b12

Sent from my VS990 using Professional Muscle mobile app

 

[Stewie]

Thanks for sharing your thoughts with us Good point about the dosage, seems like 500mg is pretty safe. But from what I read and please correct me if I´m wrong, for a 200lbs male 1000mg is getting up to where damage could happen?

I think many here uses 1000+?

Can we go over the supplements that could help again?

B12
Black Cumin
CoQ10

Any other that should be a staple when using Metformin?

Thinking out loud here, off the top of my head, kinda of in a hurry.

Nicotinamide adenine dinucleotide (NADH).

Maybe a very small doses of DNP, occasionally.

Leucine (may help stimulate mitochondrial biogenesis).

Optimization of thyroid hormones.

L-citrulline.

Creatine.

Magnesium bicarbonate.

Fermented foods.

All of these play a functional role with our mitochondria.

Please keep in mind, even though I'm making suggestions of these supplements/drugs. By no means am I advocating their use. Just mere suggestions.

 

[Js118]

I just saw something on the news saying Benadryl might increase the chance of Alzheimer's too... who the fuck knows

 

[bieberhole69]

I just saw something on the news saying Benadryl might increase the chance of Alzheimer's too... who the fuck knows

Benadryl use is contraindicated in elderly populations as it can increase risk of drug-induced delirium.

In dementia patients (especially with Lewy-bodies) it's almost guaranteed they will get drug-induced delirium from it.

I have not heard down the pipeline anything with it related to Alzheimer's...but if I had to guess--these patients already had Alzheimer's coming, and it just accelerated the appearance of the symptoms.

 

[Mike Arnold]

Here is the article that I got it from, be aware they are selling sups, but some of the info is quite interesting:

**broken link removed**

And Stewie pointed me in the direction of the study so here it is:
https://www.ncbi.nlm.nih.gov/pubmed/27509335

But it sounds like we can supplement our way out of this
I´m not saying Metformin is bad at all here, just making aware that it´s not all good and certain supplements should be used.

I personally like Metformin, but not sure it should be used year round either.

With berberine possessing comparable potency, I would be very interested to know if it comes with the same risks as metformin. At this point I haven't seen any berberine studies demonstrating this same degree of risk, but I haven't looked very hard either. If I had to guess, I would say that berberine is likely to be the safer option, as natural supplements tend to be more well tolerated and less injurious than their chemically altered cousins (drugs). Still, there are always exceptions to the rule.

 

[Stewie]

With berberine possessing comparable potency, I would be very interested to know if it comes with the same risks as metformin. At this point I haven't seen any berberine studies demonstrating this same degree of risk, but I haven't looked very hard either. If I had to guess, I would say that berberine is likely to be the safer option, as natural supplements tend to be more well tolerated and less injurious than their chemically altered cousins (drugs). Still, there are always exceptions to the rule.

Hey Mike. Berberine and Metformin both inhibit mitochondrial complex I. According to this alone, this is one of the purposed actions for the relationship between Metformin and AD in animal models.

Berberine more than likely hasn't been studied to this extent.

 

[Frito]

Thinking out loud here, off the top of my head, kinda of in a hurry.

Nicotinamide adenine dinucleotide (NADH).

Maybe a very small doses of DNP, occasionally.

Leucine (may help stimulate mitochondrial biogenesis).

Optimization of thyroid hormones.

L-citrulline.

Creatine.

Magnesium bicarbonate.

Fermented foods.

All of these play a functional role with our mitochondria.

Please keep in mind, even though I'm making suggestions of these supplements/drugs. By no means am I advocating their use. Just mere suggestions.

Thanks for completing my list, I have forgot a lot I could see.
Citrulline was a stable last time I messed with Metformin.