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Metformin + Glucosamine = good or bad ? (help needed by biochemist)

metformin glucosamine cell metabolism

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#1 Guest

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Posted 08 February 2019 - 11:20 PM


Dear all,

 

 

as outlined here

 

https://www.longecit...-low-carb-diet/

 

and here

 

https://www.longecit...vention-thread/

 

 

supplementing glucosamine could be benefical for otherwise healthy individuals to increase total life span. Glucosamine so far even has a better track record (albeit based on just a handfull of studies) in promoting longevity than metformin. Metformin of course famously is being tested in the TAME-trial and increasingly used in the LE-community.

 

 

I'm not (yet) supplementing metformin. But I'm taking glucosamine. Both supps act on the cellular energy metabolism. However, I got a hard time understanding their joint actions. 2 well cited papers are of special relevance:

 

 

1. Metformin directly acts on mitochondria to alter cellular bioenergetics

 

Quote: "Thus, cells treated with metformin become energetically inefficient, and display increased aerobic glycolysis and reduced glucose metabolism through the citric acid cycle."

 

 

2. d-Glucosamine supplementation extends life span of nematodes and of ageing mice

 
Quote: "We here find that GlcN inhibits glycolysis to cause an energy deficit that induces mitochondrial biogenesis and alternate fuel use, namely amino-acid oxidation."

 

First to be clear, there doesn't seem to be an acute negative interaction of both supplements. There are dozens of millions of users of both compounds, many of whom are bound to be using both. Also a study in rats using high doses of both did not result in acute toxicity:

http://erepository.c.../view/6729/6614

 

 

But my biochemical knowledge leaves me confused. For example: metformin is potentially anti-carcinogenic, as it shifts cell energy-metabolism - it increases lactate metabolism instead of using pyrovate directly. I.e. as a result cancer cells that aren't supplied with glucose or can't compensatory increase aerobic glycolysis activity are dying (they can't switch to lactate metabolism). Now glucosamine inhibits (but does not block) glycolysis.

 

Does this mean, that healthy cells are driven into fermentation by metformin and on top glucosamin shifts metabolism slightly away from the entire glucose metabolism (so either pyruvate or lactate)? So:

 

metformin = lactate instead of pyruvate = 1 unit of glucose delivers much less energy for the cell (i.e. more glucose is needed for the same energy demand) = glucose metabolism becomes ineffecient

 

glucosamine = production of both (pyruvate and as a result lactate) is inhibited = cell shifts to protein/fat for energy production

 

 

So glucosamine and metformin are additive in their mechanism? They both put the cell into energy stress by different pathways? And energy stress = more mTOR activation etc.

 

 

Also it would be good to know a dose depended interaction, e.g. is a certain amount of glucosamine results in the same mTOR activation as 1000 mg of metformin - does double the dose has the same effect as double the amount of metformin. So you could use glucosamine instead of metformin and vice versa.


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