2266 replies to this topic

[ceridwen]

I get prickly feelings around the base of the skull and numbness in my right foot on the top. My second toe is particularly bad but it's mostly where the toes join the foot. Could NR worsen neuropathy also something happens in my left foot that makes me feel like the muscles are collapsing for a few seconds but if it gets worse it could lead to a fall?

[MikeDC]

@thedeparted. If it is ribose that you take, your question has a possible answer. The minute amounts of riboside in NR can have no negative effects but the amounts of ribose I have seen mentioned in the N+R threads may lead to a lot of trouble. Whatever the case may be, I repeat my initial advice: go see a doctor real soon.

Minute? NR is more than half ribose.

Half of 250mg is 125mg. You guys are taking thousands of mg.

[Harkijn]

 

 

Half of 250mg is 125mg. You guys are taking thousands of mg.

 

I did not mean to phrase it like that. I can only say that I have read some saying they would take a few grams daily, just to be sure that it would magically team up with Nicotinamide. My main concern in posting here is that Thedeparted should be helped as best as we can.

So, in case he uses ribose, here are some pros as well as cons:

https://www.google.n...zxfPohMTOmzOPz_

[Thedeparted]

The only supplements I take are multi vitamins, fish oil, allergy medicine,probiotics, and Niagen.

I went to the Dr last night and they ran the following tests :

VITAMIN B-12

GLUCOSE (FOR ASYMPTOMATIC SCREENING)

BASIC METABOLIC PANEL (BMP) (GHC)

TSH (REFLEXIVE)

HEMOGLOBIN A1C

CBC/PLT/DIFF

SELENIUM

The only test not back yet is Selenium, and I had that ran a few weeks ago where it was slightly elevated. Everything else came back perfect. They also did neck x-rays (for the sore neck). I'll update when I find out more.

This is looking less and less Niagen related.

Edited by Thedeparted, 30 December 2017 - 05:41 PM.

[MikeDC]

The only supplements I take are multi vitamins, fish oil, allergy medicine,probiotics, and Niagen.

I went to the Dr last night and they ran the following tests :

VITAMIN B-12

GLUCOSE (FOR ASYMPTOMATIC SCREENING)

BASIC METABOLIC PANEL (BMP) (GHC)

TSH (REFLEXIVE)

HEMOGLOBIN A1C

CBC/PLT/DIFF

SELENIUM

The only test not back yet is Selenium, and I had that ran a few weeks ago where it was slightly elevated. Everything else came back perfect. They also did neck x-rays (for the sore neck). I'll update when I find out more.

This is looking less and less Niagen related.

I would suspect allergy medicine first.

[Thedeparted]

Been on that for years, Niagen was the only new addition.

 

 

The only supplements I take are multi vitamins, fish oil, allergy medicine,probiotics, and Niagen.

I went to the Dr last night and they ran the following tests :

VITAMIN B-12

GLUCOSE (FOR ASYMPTOMATIC SCREENING)

BASIC METABOLIC PANEL (BMP) (GHC)

TSH (REFLEXIVE)

HEMOGLOBIN A1C

CBC/PLT/DIFF

SELENIUM

The only test not back yet is Selenium, and I had that ran a few weeks ago where it was slightly elevated. Everything else came back perfect. They also did neck x-rays (for the sore neck). I'll update when I find out more.

This is looking less and less Niagen related.

I would suspect allergy medicine first.

 

 

[PAMPAGUY]

New clinical trial results of NR.

 

http://journals.plos...&type=printable

[MikeDC]

New clinical trial results of NR.

http://journals.plos...&type=printable

NR in the blood was increased almost 200% after NR was taken. Didn’t someone in the mitochandria dynamics thread say NR was completely digested into N and R before enter liver?

According to the best of my knowledge, most of NR was absorbed in tact and most of them are turned into NAD+ in the liver. A small fraction passed through liver intact. The main source of NAD+ Pre-cursors to other organs is actually NAD+ itself. NAD+ gets converted into NMN and NR and enters the cells. This is why NAD+ IV is very effective.

[able]

 

New clinical trial results of NR.

http://journals.plos...&type=printable

NR in the blood was increased almost 200% after NR was taken. Didn’t someone in the mitochandria dynamics thread say NR was completely digested into N and R before enter liver?

According to the best of my knowledge, most of NR was absorbed in tact and most of them are turned into NAD+ in the liver. A small fraction passed through liver intact. The main source of NAD+ Pre-cursors to other organs is actually NAD+ itself. NAD+ gets converted into NMN and NR and enters the cells. This is why NAD+ IV is very effective.

 

 

 

This seems the wrong thread for discussing this study results, so maybe mods will post a new thread and move these posts there?

 

I don't yet see anything that supports your assertion they show "most of the NR was aborbed intact".  In fact, they say this:

 

 

"NR is expected to exhibit low passive permeability across the human intestinal mucosa. Oral absorption of NR may rely on an active, mediated transport process that varies in active between individuals. It is also possible that NR is degraded to nicotinamide in the gut; nicotinamide is then absorbed and converted to NMN, which can further be converted to NAD+ or dephosphorylated to NR. If true, the degradation of NR to nicotinamide in the gut, which presumably involves purine nucleoside phosphorylase in mammalian and bacterial cells [21] may be a variable step involved in the oral intake of NR "

Edited by able, 31 December 2017 - 12:11 AM.

[MikeDC]

New clinical trial results of NR.

http://journals.plos...&type=printable

NR in the blood was increased almost 200% after NR was taken. Didn’t someone in the mitochandria dynamics thread say NR was completely digested into N and R before enter liver?

According to the best of my knowledge, most of NR was absorbed in tact and most of them are turned into NAD+ in the liver. A small fraction passed through liver intact. The main source of NAD+ Pre-cursors to other organs is actually NAD+ itself. NAD+ gets converted into NMN and NR and enters the cells. This is why NAD+ IV is very effective.

This seems the wrong thread for discussing this study results, so maybe mods will post a new thread and move these posts there?

I don't yet see anything that supports your assertion they show "most of the NR was aborbed intact". In fact, they say this:


"NR is expected to exhibit low passive permeability across the human intestinal mucosa. Oral absorption of NR may rely on an active, mediated transport process that varies in active between individuals. It is also possible that NR is degraded to nicotinamide in the gut; nicotinamide is then absorbed and converted to NMN, which can further be converted to NAD+ or dephosphorylated to NR. If true, the degradation of NR to nicotinamide in the gut, which presumably involves purine nucleoside phosphorylase in mammalian and bacterial cells [21] may be a variable step involved in the oral intake of NR "

Their reasoning does not agree with their data. In order to achieve 200% increase of NR in blood and assume only 5% of NR survives liver, we can assume there is fair amount of NR enters liver.

[MikeDC]

New clinical trial results of NR.

http://journals.plos...&type=printable

NR in the blood was increased almost 200% after NR was taken. Didn’t someone in the mitochandria dynamics thread say NR was completely digested into N and R before enter liver?

According to the best of my knowledge, most of NR was absorbed in tact and most of them are turned into NAD+ in the liver. A small fraction passed through liver intact. The main source of NAD+ Pre-cursors to other organs is actually NAD+ itself. NAD+ gets converted into NMN and NR and enters the cells. This is why NAD+ IV is very effective.

This seems the wrong thread for discussing this study results, so maybe mods will post a new thread and move these posts there?

I don't yet see anything that supports your assertion they show "most of the NR was aborbed intact". In fact, they say this:


"NR is expected to exhibit low passive permeability across the human intestinal mucosa. Oral absorption of NR may rely on an active, mediated transport process that varies in active between individuals. It is also possible that NR is degraded to nicotinamide in the gut; nicotinamide is then absorbed and converted to NMN, which can further be converted to NAD+ or dephosphorylated to NR. If true, the degradation of NR to nicotinamide in the gut, which presumably involves purine nucleoside phosphorylase in mammalian and bacterial cells [21] may be a variable step involved in the oral intake of NR "

Their reasoning does not agree with their data. In order to achieve 200% increase of NR in blood and assume only 5% of NR survives liver, we can assume there is fair amount of NR enters liver.

[Heisok]

I find at least 2 things from tables 1 and 2 which are strange, and they rate insignificant.

 

Glucose mg/dL 93 +- 7 to 97 +- 20       Diff 4        pvalue .51

It did go up, and the standard deviation went up to 20 from 7. Is that move of 4 given the much higher standard deviation in such a small group a concern? significant? Indicate that Ribose might be involved in some way?

 

WBC went from 4.3 to 4 which they show as .2 difference. Maybe they rounded the raw data?

 

 

On topic is that I reported back a ways, that I had a bad virus with subsequent bacterial lung infection illness which lasted a long time which hit me right after taking a very high dose of NR. Extra 750 mg from a baseline of about 250 mg. More sick than I had been at any time for at least 15 years. It turns out that about 1 month later, I had a tooth abscess which required root canal therapy. I will guess that whatever bacteria were sub symptomatically effecting me ran my immunity down around the time which I got the viral/bacterial infection.

 

I doubt NR had any role. (I did not claim a role at the time either.)

Edited by Heisok, 31 December 2017 - 03:11 AM.

[able]

Does it assume 5% of NR survives the liver, or is that a hypothetical you used for discussion?

 

It does seem positive that  they demonstrate increase NAD+ in liver and blood, and also the 200% increase of NR in blood you mention.

 

But I don't understand how the 200% increase gives us much indication of the % of NR that makes it through.  

 

Or for that matter, how do we know if is intact NR, vs NR that has been recycled from NAM?   I personally believe it's likely some NR makes it thru intact, but don't see that an increase in NR levels is proof of that.

 

Also, they find NR in blood at extremely small levels.  Doubling that small quantity might require extremely small % of the 1000mg of NR.

 

What I find most interesting is that Sinclair is editor of the article.  Seem strange.

[MikeDC]

Does it assume 5% of NR survives the liver, or is that a hypothetical you used for discussion?

It does seem positive that they demonstrate increase NAD+ in liver and blood, and also the 200% increase of NR in blood you mention.

But I don't understand how the 200% increase gives us much indication of the % of NR that makes it through.

Or for that matter, how do we know if is intact NR, vs NR that has been recycled from NAM? I personally believe it's likely some NR makes it thru intact, but don't see that an increase in NR levels is proof of that.

Also, they find NR in blood at extremely small levels. Doubling that small quantity might require extremely small % of the 1000mg of NR.

What I find most interesting is that Sinclair is editor of the article. Seem strange.

NAM recycling doesn’t go through NR.
We could argue about this for the rest of our lives. But I will continue taking NR because the evidence from NR users are overwhelming including my family and friends. I have not seen many people mention how NAM made them younger.

Edited by MikeDC, 31 December 2017 - 05:05 AM.

[able]

 

Does it assume 5% of NR survives the liver, or is that a hypothetical you used for discussion?

It does seem positive that they demonstrate increase NAD+ in liver and blood, and also the 200% increase of NR in blood you mention.

But I don't understand how the 200% increase gives us much indication of the % of NR that makes it through.

Or for that matter, how do we know if is intact NR, vs NR that has been recycled from NAM? I personally believe it's likely some NR makes it thru intact, but don't see that an increase in NR levels is proof of that.

Also, they find NR in blood at extremely small levels. Doubling that small quantity might require extremely small % of the 1000mg of NR.

What I find most interesting is that Sinclair is editor of the article. Seem strange.

NAM recycling doesn’t go through NR.
We could argue about this for the rest of our lives. But I will continue taking NR because the evidence from NR users are overwhelming including my family and friends. I have not seen many people mention how NAM made them younger.

 

 

I meant it might be possible NR is assembled in vivo from NAM + ribose as Turnbuckle suggests, and if so, an increase in NR could be from NR supplements broken down to NAM in the gut then reassembled with ribose.  

 

But I would agree there is no proof of that, and probably not a worthwhile explanation.

 

I still don't see any indication in this study of what % of the NR has made it intact thru the gut and into NAD+

[Harkijn]

To all: I am really glad to see a cool headed exchange of opinions here. Specific points about the Washington study, however, can best be raised here:

http://www.longecity...rial-published/

[Turnbuckle]

 

 

Does it assume 5% of NR survives the liver, or is that a hypothetical you used for discussion?

It does seem positive that they demonstrate increase NAD+ in liver and blood, and also the 200% increase of NR in blood you mention.

But I don't understand how the 200% increase gives us much indication of the % of NR that makes it through.

Or for that matter, how do we know if is intact NR, vs NR that has been recycled from NAM? I personally believe it's likely some NR makes it thru intact, but don't see that an increase in NR levels is proof of that.

Also, they find NR in blood at extremely small levels. Doubling that small quantity might require extremely small % of the 1000mg of NR.

What I find most interesting is that Sinclair is editor of the article. Seem strange.

NAM recycling doesn’t go through NR.
We could argue about this for the rest of our lives. But I will continue taking NR because the evidence from NR users are overwhelming including my family and friends. I have not seen many people mention how NAM made them younger.

 

 

I meant it might be possible NR is assembled in vivo from NAM + ribose as Turnbuckle suggests, and if so, an increase in NR could be from NR supplements broken down to NAM in the gut then reassembled with ribose.  

 

But I would agree there is no proof of that, and probably not a worthwhile explanation.

 

I still don't see any indication in this study of what % of the NR has made it intact thru the gut and into NAD+

 

 

 

It's likely that N+R and the bulk of NR go down the same path via NMN. All the studies of NR have studiously avoided comparing NR to N+R, and studies of double labeled NR have been misinterpreted by the authors--a very good reason to question any paper published by researchers who are marketing the product they are researching. 

[MikeDC]

Does it assume 5% of NR survives the liver, or is that a hypothetical you used for discussion?

It does seem positive that they demonstrate increase NAD+ in liver and blood, and also the 200% increase of NR in blood you mention.

But I don't understand how the 200% increase gives us much indication of the % of NR that makes it through.

Or for that matter, how do we know if is intact NR, vs NR that has been recycled from NAM? I personally believe it's likely some NR makes it thru intact, but don't see that an increase in NR levels is proof of that.

Also, they find NR in blood at extremely small levels. Doubling that small quantity might require extremely small % of the 1000mg of NR.

What I find most interesting is that Sinclair is editor of the article. Seem strange.

NAM recycling doesn’t go through NR.
We could argue about this for the rest of our lives. But I will continue taking NR because the evidence from NR users are overwhelming including my family and friends. I have not seen many people mention how NAM made them younger.

I meant it might be possible NR is assembled in vivo from NAM + ribose as Turnbuckle suggests, and if so, an increase in NR could be from NR supplements broken down to NAM in the gut then reassembled with ribose.

But I would agree there is no proof of that, and probably not a worthwhile explanation.

I still don't see any indication in this study of what % of the NR has made it intact thru the gut and into NAD+

It's likely that N+R and the bulk of NR go down the same path via NMN. All the studies of NR have studiously avoided comparing NR to N+R, and studies of double labeled NR have been misinterpreted by the authors--a very good reason to question any paper published by researchers who are marketing the product they are researching.

It is not an easy task to make NR from N+R. Scientists from Cornell University have been working on it for over 10 years. They recently published a paper to synthesize NR. The raw material is not N and R. Nobody has found any evidence that N+R can combine in the body to create NR. Large concentrations of NAM up regulate NAMPT and inflammation. That is one of the reasons NAM does not have the same anti aging effect as NR. NR supplementation down regulate NAMPT and inflammation. I am sorry to say that your followers are not improving their health. https://www.ncbi.nlm...namide riboside

[PAMPAGUY]

Does it assume 5% of NR survives the liver, or is that a hypothetical you used for discussion?

It does seem positive that they demonstrate increase NAD+ in liver and blood, and also the 200% increase of NR in blood you mention.

But I don't understand how the 200% increase gives us much indication of the % of NR that makes it through.

Or for that matter, how do we know if is intact NR, vs NR that has been recycled from NAM? I personally believe it's likely some NR makes it thru intact, but don't see that an increase in NR levels is proof of that.

Also, they find NR in blood at extremely small levels. Doubling that small quantity might require extremely small % of the 1000mg of NR.

What I find most interesting is that Sinclair is editor of the article. Seem strange.

NAM recycling doesn’t go through NR.
We could argue about this for the rest of our lives. But I will continue taking NR because the evidence from NR users are overwhelming including my family and friends. I have not seen many people mention how NAM made them younger.

I meant it might be possible NR is assembled in vivo from NAM + ribose as Turnbuckle suggests, and if so, an increase in NR could be from NR supplements broken down to NAM in the gut then reassembled with ribose.

But I would agree there is no proof of that, and probably not a worthwhile explanation.

I still don't see any indication in this study of what % of the NR has made it intact thru the gut and into NAD+

It's likely that N+R and the bulk of NR go down the same path via NMN. All the studies of NR have studiously avoided comparing NR to N+R, and studies of double labeled NR have been misinterpreted by the authors--a very good reason to question any paper published by researchers who are marketing the product they are researching.

[PAMPAGUY]

Does it assume 5% of NR survives the liver, or is that a hypothetical you used for discussion?

It does seem positive that they demonstrate increase NAD+ in liver and blood, and also the 200% increase of NR in blood you mention.

But I don't understand how the 200% increase gives us much indication of the % of NR that makes it through.

Or for that matter, how do we know if is intact NR, vs NR that has been recycled from NAM? I personally believe it's likely some NR makes it thru intact, but don't see that an increase in NR levels is proof of that.

Also, they find NR in blood at extremely small levels. Doubling that small quantity might require extremely small % of the 1000mg of NR.

What I find most interesting is that Sinclair is editor of the article. Seem strange.

NAM recycling doesn’t go through NR.
We could argue about this for the rest of our lives. But I will continue taking NR because the evidence from NR users are overwhelming including my family and friends. I have not seen many people mention how NAM made them younger.

I meant it might be possible NR is assembled in vivo from NAM + ribose as Turnbuckle suggests, and if so, an increase in NR could be from NR supplements broken down to NAM in the gut then reassembled with ribose.

But I would agree there is no proof of that, and probably not a worthwhile explanation.

I still don't see any indication in this study of what % of the NR has made it intact thru the gut and into NAD+

It's likely that N+R and the bulk of NR go down the same path via NMN. All the studies of NR have studiously avoided comparing NR to N+R, and studies of double labeled NR have been misinterpreted by the authors--a very good reason to question any paper published by researchers who are marketing the product they are researching.

[PAMPAGUY]

Turnbuckle I agree, that you cannot trust any of the studies financed or conducted by any scientist with a commercial interest in the outcome. NAD precussors are ripe for abuse because they are supplements without regulation. CDX, Bremmer,Guarente or Sinclair. They have all had multiple chances to mention all the other precussors, but have declined to do so. As we all have said, we need an unbaised trial comparing NR, N+R, and NMN. Not sure if we will ever get it.

 

They don't care about the elderly patients that are ageing and dying now.  Sinclair said 3-4 years on NMN, but doesn't say a word about NR or N + R which can be cheaply bought now.

Edited by PAMPAGUY, 31 December 2017 - 03:10 PM.

[PAMPAGUY]

Meant NMN, not NAD is last line.

[MikeDC]

You don’t have to wait too long for NR to become a FDA approved drug against premature aging. ChromaDex has filed IND and FDA is expected to approve it within 30 days. The new drug approval can be as soon as less than 2 years. Not sure what other execuses you might have even after NR has been approved by FDA against premature aging.

Edited by MikeDC, 31 December 2017 - 03:24 PM.

[PAMPAGUY]

CDX will never run a trial comparing NR and N+R. They know what the results will be and it would not be pretty for their stock price.

[able]

You don’t have to wait too long for NR to become a FDA approved drug against premature aging. ChromaDex has filed IND and FDA is expected to approve it within 30 days. The new drug approval can be as soon as less than 2 years. Not sure what other execuses you might have even after NR has been approved by FDA against premature aging.

 

Premature Aging - I think not.   Wasn't that for treatment of a specific disease, Cockayne Syndrome?  

[Harkijn]

Turnbuckle I agree, that you cannot trust any of the studies financed or conducted by any scientist with a commercial interest in the outcome. NAD precussors are ripe for abuse because they are supplements without regulation. CDX, Bremmer,Guarente or Sinclair. They have all had multiple chances to mention all the other precussors, but have declined to do so.

It is not as black and white as you think, Brenner, for instance:

 

“Not every cell is capable of converting each NAD+ precursor to NAD+ at all times…the precursors are differentially utilized in the gut, brain, blood, and organs” 

 

https://www.ncbi.nlm...pubmed/18429699

 

As for NAM and Ribose:  as several people have pointed out before, the real reason that no scientist sofar has researched this combination is that no scientist has hypothesized that this would raise NAD+ more than NAM alone.

Edited by Harkijn, 31 December 2017 - 03:38 PM.

[MikeDC]

You don’t have to wait too long for NR to become a FDA approved drug against premature aging. ChromaDex has filed IND and FDA is expected to approve it within 30 days. The new drug approval can be as soon as less than 2 years. Not sure what other execuses you might have even after NR has been approved by FDA against premature aging.

Premature Aging - I think not. Wasn't that for treatment of a specific disease, Cockayne Syndrome?

Cockayne Syndrome is a model human aging. The genetic defects causes the cells to consume too much NAD+. The low NAD+ level resembles an old normal person. It is a perfect model to test the NAD+ aging theory. I have 100% confidence it will be approved by FDA.

[MikeDC]

Turnbuckle I agree, that you cannot trust any of the studies financed or conducted by any scientist with a commercial interest in the outcome. NAD precussors are ripe for abuse because they are supplements without regulation. CDX, Bremmer,Guarente or Sinclair. They have all had multiple chances to mention all the other precussors, but have declined to do so.

It is not as black and white as you think, Brenner, for instance:

“Not every cell is capable of converting each NAD+ precursor to NAD+ at all times…the precursors are differentially utilized in the gut, brain, blood, and organs”

https://www.ncbi.nlm...pubmed/18429699

As for NAM and Ribose: as several people have pointed out before, the real reason that no scientist sofar has researched this combination is that no scientist has hypothesized that this would raise NAD+ more than NAM alone.

“As for NAM and Ribose: as several people have pointed out before, the real reason that no scientist sofar has researched this combination is that no scientist has hypothesized that this would raise NAD+ more than NAM alone.” Exactly.

[able]

 

 

You don’t have to wait too long for NR to become a FDA approved drug against premature aging. ChromaDex has filed IND and FDA is expected to approve it within 30 days. The new drug approval can be as soon as less than 2 years. Not sure what other execuses you might have even after NR has been approved by FDA against premature aging.

Premature Aging - I think not. Wasn't that for treatment of a specific disease, Cockayne Syndrome?

Cockayne Syndrome is a model human aging. The genetic defects causes the cells to consume too much NAD+. The low NAD+ level resembles an old normal person. It is a perfect model to test the NAD+ aging theory. I have 100% confidence it will be approved by FDA.

 

 

Ah, good point.  Obviously I haven't read what Cockayne Syndrome is.  That does seem a great indicator.

[PAMPAGUY]

In my opinion that is not true. Almost all human trials were conducted by vested interest to make a buck. Anything that would jeopardize that will not be pursued.

I took NR for 1 year, and got good results. Most people on this blog are not 65 yo+. I have been getting even more energy at 71 with N+R. When you are cleaning out your cells, you know it. I get exactly the same feelings taking N+R as I did with NR. Im in a unique position because I have takened both and Im over 70. Most people are not going to get great results until they are over 65 when your energy really goes downhill. I was running half marathons into my sixties, until you hit the wall. Before that, I had no need for NAD supplementation. Had plenty of energy.