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Nad+ and Metformin

nicotinamide riboside; nad+; metformin

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#1 male_1978

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Posted 15 October 2018 - 07:43 AM


Hello,

 

i am not a doctor and i have a very nooby question.

 

I know that David Sinclair takes both NMN and also Metformin. Now i stumbled across this paper

 

https://www.ncbi.nlm...les/PMC5102768/

 

where it says:

 

"We find that complex I supports proliferation by regenerating NAD+, and metformin’s anti-proliferative effect is due to loss of NAD+/NADH homeostasis and inhibition of aspartate biosynthesis. "

 

Does this indicate that the positive effects of Metformin are because less Nad+ is created in the cells? 

 

Could any biochemist give me some advice here? Thanks a lot!

 

 

 

 

 

 



#2 MikeDC

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Posted 28 November 2018 - 08:04 PM

Hello,

i am not a doctor and i have a very nooby question.

I know that David Sinclair takes both NMN and also Metformin. Now i stumbled across this paper

https://www.ncbi.nlm...les/PMC5102768/

where it says:

"We find that complex I supports proliferation by regenerating NAD+, and metformin’s anti-proliferative effect is due to loss of NAD+/NADH homeostasis and inhibition of aspartate biosynthesis. "

Does this indicate that the positive effects of Metformin are because less Nad+ is created in the cells?

Could any biochemist give me some advice here? Thanks a lot!


The positive effect of metformin is to inhibit glucose creation. Decreasing NAD+/NADH ratio is a side effect. It is questionable that metformin will prolong life when it reduces NAD+/NADH ratio.
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#3 male_1978

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Posted 29 November 2018 - 10:16 AM

The positive effect of metformin is to inhibit glucose creation. Decreasing NAD+/NADH ratio is a side effect. It is questionable that metformin will prolong life when it reduces NAD+/NADH ratio.

 

Hmm, but at least we know that metformin lets diabetic patients live longer than nondiaebtic controls :

http://longevityalli...ithout-disease 

 

 

So the hypothesis that it does not prolong life seems to be wrong, even if its effect is small.

 

But even if it decreases the NAD+/NADH-Ratio - couldn't this be because of something beneficial like more Sirtuin activity? In this case lower NAD+ and longer healthspan wouldnt contradict and combining Metformin and NAD+-Boosters would make sense.

 

 

(I am no expert and just speculating). 
 


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#4 MikeDC

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Posted 29 November 2018 - 01:35 PM

I remember reading papers that say the study that shows diabetes taking metformin live onger than non diabetes is flawed. I have seen many diabetes patients taking metformin including my mother and my wife, none of them showed any anti aging effects that we see from NR. I would say metformin’s anti effect is negligible compared to NR.
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#5 male_1978

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Posted 29 November 2018 - 01:57 PM

I remember reading papers that say the study that shows diabetes taking metformin live onger than non diabetes is flawed. I have seen many diabetes patients taking metformin including my mother and my wife, none of them showed any anti aging effects that we see from NR. I would say metformin’s anti effect is negligible compared to NR.

 

 

The information, that the study about diabetes and longer life was flawed, would be new to me. Do you have a reference for this? That would be important for me, because i base my conclusion on the hypothesis, that a (small) life-extending effect of metformin has been proven.

Of course, life extension does not mean rejuvenation. As far as i know, metformin gives some protection against cancer, but that doesnt mean you look or feel younger.

 

On the other hand, NR lets you immediatedly feel younger, but - at least to my knowledge - the long term effects are a little more unpredictable than with metformin. I mean, the underlying damage which leads to loss of NAD+ in the first place, is not being repaired, right? 


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#6 MikeDC

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Posted 29 November 2018 - 02:26 PM

My guess is taking NR does repair loss of NAD+ to some degree. Look at the chart.
The NAD+ increases in the first few weeks. Some of it may be due to less NAD+ consumption from less inflammation?

If A subtance like NR can rejuvenate, it should be very effective at slowing down aging. It just shows that the anti aging force is large enough to turn back the aging clock.

Attached Files


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#7 MikeDC

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Posted 29 November 2018 - 02:32 PM

http://longevityfact...-metformin-use/
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#8 LawrenceW

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Posted 29 November 2018 - 03:36 PM

My guess is taking NR does repair loss of NAD+ to some degree. Look at the chart.
The NAD+ increases in the first few weeks. Some of it may be due to less NAD+ consumption from less inflammation?

If A subtance like NR can rejuvenate, it should be very effective at slowing down aging. It just shows that the anti aging force is large enough to turn back the aging clock.

 

Hello Mike.

 

Could you please provide a link to the study that you sourced your attached chart from.

 

Thanks



#9 MikeDC

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Posted 01 December 2018 - 01:12 AM

Hello Mike.

Could you please provide a link to the study that you sourced your attached chart from.

Thanks


That chart is from ChromaDex presentation. The study has not been published yet. Probably very soon.
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#10 Fredrik

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Posted 06 December 2018 - 08:48 PM

MikeDC: could you post a link to the presentation please? 



#11 MikeDC

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Posted 06 December 2018 - 09:00 PM

MikeDC: could you post a link to the presentation please?


http://phx.corporate...FR5cGU9MQ==&t=1

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#12 stefan_001

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Posted 06 December 2018 - 09:05 PM

 

Thats a great graph!



#13 male_1978

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Posted 07 December 2018 - 07:11 AM

 

I dont find this graph very informative. Page 5 shows that an old person may have only 10% of the NAD+ of a young person. The graph shows ng / mg protein.

 

 

Page 8 shows that NR raises NAD+ by up to 100%. However, its a different scale (mg/ml) and the y-axis is labeled "NAD" (not NAD+). 

 

 

More importantly, the graph does not distinguish by age. If the Nad+-levels of an old and a young person differ so much, i ask first, whether NR rises NAD+ by a fixed amount (which would be a higher percentage for old people), by a percentage in general or any other function.

 

 

Lets just assume you have some old people with an Nad+-Level of averagely 1 ng / mg protein, and their NAD+Level rises to 2 ng / mg protein with Niagen. How would that result translate to a younger person with still 5 ng / mg protein of NAD+? Would it increase to 10 ng/mg, to 6 ng/mg or to something between?

 

 

I also see this presentation as something commercial, made for investors. I would always be sceptical in this case.



#14 Fredrik

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Posted 07 December 2018 - 10:19 AM

Thank you for the link MikeDC.

 

male_1978: Yes, it is from a presentation to current and future investors. A sales pitch. With that in mind I am still interested in seeing how Chromadex view NR now and going forward. It is not to be read as a scientific graph.

#15 MikeDC

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Posted 07 December 2018 - 12:00 PM

The study subjects were from 40-60 year old. The university of Washington study used subjects as young as 20 year old and the results indicate NR can raise NAD+ more in young than old. If you assume young people have higher NAD+ at baseline, then the NAD+ increase appears to be larger for young people than old people. The age range is 21-50.

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Edited by MikeDC, 07 December 2018 - 12:12 PM.

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#16 midas

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Posted 24 December 2018 - 12:10 AM

Dual Inhibition of the Lactate Transporters MCT1 and MCT4 Is Synthetic Lethal with Metformin due to NAD+ Depletion in Cancer Cells

 

https://www.cell.com...1247(18)31806-0


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#17 midas

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Posted 24 December 2018 - 12:15 AM

Unlikely drug pair combine to cut off cancer's energy supply

 

"NAD+ is produced through two cellular pathways, one of which metformin was known to block."

 

https://newatlas.com..._term=Read more







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