22 replies to this topic

[Harkijn]

Just when I think I am beginning to understand some of the NAD process,I stumble on this:

http://sci-hub.tw/ht...I3xpFyw0HSyoymS

[Supierce]

If the above link doesn't work, try this one:

 

http://sci-hub.tw/ht.../articles/33246

 

And I agree - this is very interesting.

Edited by Supierce, 16 June 2018 - 02:55 PM.

[LawrenceW]

From the Discussion section on page 13.

 

"Importantly, our findings do not exclude the possibility that NMN import and synthesis via NMNAT3 also contribute to the mitochondrial NAD pool. Indeed, Cambronne et al. recently employed a fluorescent biosensor to demonstrate that mitochondrial NAD levels are sensitive to depletion of either NMNAT3 (mitochondrial) or NMNAT2 (Golgi/cytosolic), implying that both NMN and NAD import contribute to the mitochondrial NAD pool 14 (42). This observation suggests that a mitochondrial transporter for NMN may also await discovery."

[Phoebus]

 

 

Treating cells with nicotinamide riboside that is isotopically labeled on the nicotinamide and ribose moieties results in the appearance of doubly labeled NAD within mitochondria.

 

 

does anyone know what that means exactly? 

[Phoebus]

From the Discussion section on page 13.

 

"Importantly, our findings do not exclude the possibility that NMN import and synthesis via NMNAT3 also contribute to the mitochondrial NAD pool. Indeed, Cambronne et al. recently employed a fluorescent biosensor to demonstrate that mitochondrial NAD levels are sensitive to depletion of either NMNAT3 (mitochondrial) or NMNAT2 (Golgi/cytosolic), implying that both NMN and NAD import contribute to the mitochondrial NAD pool 14 (42). This observation suggests that a mitochondrial transporter for NMN may also await discovery."

 

Huh, that would hint that NMN is superior to NR for supplementing

 

although the whole study would indicate the very best way to approach the whole thing is forgetting about oral supplementing altogether and go with NAD IV 

[Harkijn]

does anyone know what that means exactly? 

I hope someone steps in with an in-depth analysis of this. My impression is that this is evidence that NR is not broken up at some stage in order  to be reconnected in a later phase. In other words inside the mitochondria it is still the same N molecule happily married to the same R molecule.

Edited by Harkijn, 16 June 2018 - 06:40 PM.

[LawrenceW]

Huh, that would hint that NMN is superior to NR for supplementing

 

although the whole study would indicate the very best way to approach the whole thing is forgetting about oral supplementing altogether and go with NAD IV 

 

2 of our guys flew up to the Bay area to try the NAD+ drip for a couple of days.  The only downside is that to get a meaningful amount into their system they had to be hooked up to the IV for 6 hours per day.  That in itself is a non-starter in the real world.

[Phoebus]

2 of our guys flew up to the Bay area to try the NAD+ drip for a couple of days.  The only downside is that to get a meaningful amount into their system they had to be hooked up to the IV for 6 hours per day.  That in itself is a non-starter in the real world.

 

what the hell? why for that long? 

 

I did 100 g Vit IV and it only took maybe 1.5 hours. 

 

is that why NAD IV is so dmn expensive? 

 

did they report benefits from the IV? 

[LawrenceW]

what the hell? why for that long? 

 

I did 100 g Vit IV and it only took maybe 1.5 hours. 

 

is that why NAD IV is so dmn expensive? 

 

did they report benefits from the IV? 

 

Just reporting the news.  They did it under medical supervision and that it was the program that the doctor set up. They also reported that the doctor told them that the NAD+ drips in the rehab centers go for 8 hours per day for 10 consecutive days.

Edited by LawrenceW, 16 June 2018 - 09:39 PM.

[Harkijn]

There is a specific NAD IV thread. Best place relevant posts there.....

[stefan_001]

I think the study opens up an option of a new pathway for NAD. For the rest nice results supporting NR efficacy in my view. The NRK mechanism, with its ability to "call in" support for stressed cells stays unique. Wrt NMN  In any case first need to get the stuff into the cytostol in reall life.

Edited by stefan_001, 17 June 2018 - 08:36 AM.

[Turnbuckle]

 

Treating cells with nicotinamide riboside that is isotopically labeled on the nicotinamide and ribose moieties results in the appearance of doubly labeled NAD within mitochondria.

 

 

 

 

does anyone know what that means exactly? 

 

 

By itself, taken out of context, it means nothing. You'd have to know the percentages, as some proportion will appear as double labeled NAD by chance. 

Edited by Turnbuckle, 17 June 2018 - 10:42 AM.

[Phoebus]

 

 

 

 

 

 

By itself, taken out of context, it means nothing. You'd have to know the percentages, as some proportion will appear as double labeled NAD by chance. 

 

 

 

what does double labeled even mean or indicate? 

[Turnbuckle]

what does double labeled even mean or indicate? 

 

Each part of the two-part precursor molecule has been manufactured with a rare but stable isotope, so that with mass spec you can identify it. If it breaks up before the final product is formed in the cell, there will be a lot of single labeled product. If it doesn't, it will all be double labeled (or not labeled at all).

[Oakman]

From the Discussion section on page 13.

 

"Importantly, our findings do not exclude the possibility that NMN import and synthesis via NMNAT3 also contribute to the mitochondrial NAD pool. Indeed, Cambronne et al. recently employed a fluorescent biosensor to demonstrate that mitochondrial NAD levels are sensitive to depletion of either NMNAT3 (mitochondrial) or NMNAT2 (Golgi/cytosolic), implying that both NMN and NAD import contribute to the mitochondrial NAD pool 14 (42). This observation suggests that a mitochondrial transporter for NMN may also await discovery."

 

What studies like this show is that researches don't know as much about cellular mechanisms as many believe. When you carefully read studies, again and again, researches use words that don't imply they actually know, but only suggest or propose a theory that could show confirmation of results revealed. 

[MikeDC]

You need to know cell physiology to understand what this study means. Mitochandria are inside cells.

This study shows NAD+ within cells can get into Mitochandria and Mitochandria does not make NAD+.

 

This paper does not say anything about NAD+ getting into cells.

 

[MikeDC]

does anyone know what that means exactly? 

 

It means NR can get into cells without breaking up and it contribute to the mitochandria NAD+ pool directly.

[MikeDC]

I think the study opens up an option of a new pathway for NAD. For the rest nice results supporting NR efficacy in my view. The NRK mechanism, with its ability to "call in" support for stressed cells stays unique. Wrt NMN  In any case first need to get the stuff into the cytostol in reall life.

 

It does not. It just says NAD+ formed within cells can migrate to mitochandria inside the same cell.

[able]

You need to know cell physiology to understand what this study means. Mitochandria are inside cells.

This study shows NAD+ within cells can get into Mitochandria and Mitochandria does not make NAD+.

 

This paper does not say anything about NAD+ getting into cells.

 

 

It means NR can get into cells without breaking up and it contribute to the mitochandria NAD+ pool directly.

 

 

It does not. It just says NAD+ formed within cells can migrate to mitochandria inside the same cell.

 

 

 

 

No, once again you are ignoring parts of this study you don’t like and spreading misinformation.  Here are some direct quotes:

 

 

“mitochondria do not synthesize NAD at all, but rather take it up intact from the cytosol, which in turn, can take up NAD from the extracellular space “

 

“leading the authors to propose that intact NAD crosses the plasma membrane and subsequently enters the mitochondria directly”

 

“the finding of Felici et al. that extracellular NAD but not nicotinamide riboside is able to restore mitochondrial NAD in cells overexpressing FKSG76”

Edited by able, 22 June 2018 - 04:11 PM.

[MikeDC]

No, once again you are ignoring parts of this study you don’t like and spreading misinformation. Here are some direct quotes:


“mitochondria do not synthesize NAD at all, but rather take it up intact from the cytosol, which in turn, can take up NAD from the extracellular space “
[color=rgb(0,0,0)][font=Helvetica][size=3]
[size=4]]

“Cytosol is the aqueous component of the cytoplasm of a cell, within which various organelles and particles are suspended.”

Cytosol is also inside cells.

[MikeDC]

No, once again you are ignoring parts of this study you don’t like and spreading misinformation.  Here are some direct quotes:

 

 

“mitochondria do not synthesize NAD at all, but rather take it up intact from the cytosol, which in turn, can take up NAD from the extracellular space “

 

“leading the authors to propose that intact NAD crosses the plasma membrane and subsequently enters the mitochondria directly”

 

“the finding of Felici et al. that extracellular NAD but not nicotinamide riboside is able to restore mitochondrial NAD in cells overexpressing FKSG76”

 

It doesn't matter what one author said sometimes ago. The prevailing knowledge currently is most of the NAD+ inside cells are synthesized from NAD+ precursors like NAM and NR.

There is evidence that some NAD+ are directly imported into cells, but the amount may be small compared to the effects of NAD+ precursors.

 

NR is an important precursor even if you don't take NR supplementation. This study shows over expression of NRK1 is enough to overcome diet and age related NAD+ deficit.

 

https://www.ncbi.nlm...pubmed/29678570

[able]

It doesn't matter what one author said sometimes ago. The prevailing knowledge currently is most of the NAD+ inside cells are synthesized from NAD+ precursors like NAM and NR.

There is evidence that some NAD+ are directly imported into cells, but the amount may be small compared to the effects of NAD+ precursors.

 

NR is an important precursor even if you don't take NR supplementation. This study shows over expression of NRK1 is enough to overcome diet and age related NAD+ deficit.

 

https://www.ncbi.nlm...pubmed/29678570

 

 

What are you talking about?

 

This whole thread is about this study that published June 12, 2018

 

Is that what you refer to as "what one author said sometimes ago"?

 

They are agreeing with an earlier study that shows NAD+ does cross the cell membrane.

 

And it is NOT just ONE author.  I see 11 listed, including Ling Liu, who you love from the study a few months back, Zhang, and Baur and other very respected researchers.

 

 

• Antonio Davila, 
• Ling Liu, 
• Karthikeyani Chellappa, 
• Philip Redpath, 
• Eiko Nakamaru-Ogiso, 
• Lauren M Paolella, 
• Zhigang Zhang, 
• Marie E Migaud, 
• Joshua D Rabinowitz, 
• Joseph A Baur

Edited by able, 23 June 2018 - 03:15 AM.

[MikeDC]

<p>

What are you talking about?

This whole thread is about this study that published June 12, 2018

Is that what you refer to as "what one author said sometimes ago"?

They are agreeing with an earlier study that shows NAD+ does cross the cell membrane.

And it is NOT just ONE author. I see 11 listed, including Ling Liu, who you love from the study a few months back, Zhang, and Baur and other very respected researchers.

• Antonio Davila,
• Ling Liu,
• Karthikeyani Chellappa,
• Philip Redpath,
• Eiko Nakamaru-Ogiso,
• Lauren M Paolella,
• Zhigang Zhang,
• Marie E Migaud,
• Joshua D Rabinowitz,
• Joseph A Baur

No, this study didn’t provide any evidence that NAD+ crosses cell memberane. It just quoted an old study. This is not new to me. I have read before that NAD+ can cross cell membrane to some degree. But someone posted that Brenner mentioned that IV NR is 15 Times better than IV NAD+.