326 replies to this topic

[bluemoon]

ryukenden

 

Sorry, I can't make any recommendations. But, I can share with you my personal experience.  I weigh 205 pounds and am currently taking 750 mg twice per day. Several others in our group are taking 500 mg twice per day and are very pleased with their results. Dr. Sinclair is taking 500 mg once per day.

 

Can you link to where Sinclair says he is taking 500 mg per day? He said in a Washington Post interview in August 2015 that he was taking 1,000 mg of resveratrol a day but nothing then about NMN. 2016 was when i first recall he said he was taking an NAD precursor but not which one, then later said he and his father were taking NMN but not how much. 

 

He also said in 2014 that he expects there will be a pill like one that contains Metformin or Rapmycin in addition to NR. That is when he spoke about NR and NMN as if they were interchangeable.   

[bluemoon]

 

I've never tried NMN, and I'm hesitant because six months of NR at 500mg per day did nothing for me. Coffee seems superior to NR (unless it's actually repairing damages, and who knows about that...)

 

 

Well, we do know that for healthy 60 to 79 year olds 500 mg of NR a day improves walking distance and balance by about 8% for each. I don't think coffee does that. Maybe espresso...

[LawrenceW]

 

ryukenden

 

Sorry, I can't make any recommendations. But, I can share with you my personal experience.  I weigh 205 pounds and am currently taking 750 mg twice per day. Several others in our group are taking 500 mg twice per day and are very pleased with their results. Dr. Sinclair is taking 500 mg once per day.

 

Can you link to where Sinclair says he is taking 500 mg per day? He said in a Washington Post interview in August 2015 that he was taking 1,000 mg of resveratrol a day but nothing then about NMN. 2016 was when i first recall he said he was taking an NAD precursor but not which one, then later said he and his father were taking NMN but not how much. 

 

He also said in 2014 that he expects there will be a pill like one that contains Metformin or Rapmycin in addition to NR. That is when he spoke about NR and NMN as if they were interchangeable.   

 

 

 

Hello Bluemoon.

 

Dr. sinclair states that he takes 500 mg every morning in this interview:

 

http://www.dailymail...ixir-youth.html

 

And he also states that he takes 500 mg in this video:

 

 

It looks like he has learned a lot since 2014.

[ryukenden]

ryukenden

Sorry, I can't make any recommendations. But, I can share with you my personal experience. I weigh 205 pounds and am currently taking 750 mg twice per day. Several others in our group are taking 500 mg twice per day and are very pleased with their results. Dr. Sinclair is taking 500 mg once per day.

Okay,may be 500 mg Per day to start with. Twice a day is better than once daily. Does it matter if taken with food?

[LawrenceW]

ryukenden

 

One thing we did find out early is not to have caffeine in the 3 hours prior to your NMN dose. But, you can have your morning coffee 15 minutes after your NMN dose. My morning routine is to put my NMN dose in a big glass of water, add the betaine and the hydrogen peroxide and drink it on an empty stomach and then do a bit of exercise to get the blood moving.  The evening dose is the same but 12 hours later.   I try to stay on a 6 am and 6 pm schedule. I have taken my evening dose before dinner, during dinner or after dinner and not noticed any difference. 

[ryukenden]

ryukenden

One thing we did find out early is not to have caffeine in the 3 hours prior to your NMN dose. But, you can have your morning coffee 15 minutes after your NMN dose. My morning routine is to put my NMN dose in a big glass of water, add the betaine and the hydrogen peroxide and drink it on an empty stomach and then do a bit of exercise to get the blood moving. The evening dose is the same but 12 hours later. I try to stay on a 6 am and 6 pm schedule. I have taken my evening dose before dinner, during dinner or after dinner and not noticed any difference.

Thank you for sharing your experience.

[MikeDC]

First human NMN clinical trial planned at 250mg dose.

https://clinicaltria...term=NMN&rank=1

I believe this dose is too small and can only raise NAD+ by 3%.

Edited by MikeDC, 01 March 2018 - 05:51 PM.

[Michael]

As Lawrence correctly notes, this whole discussion of RevGen NR is off-topic in an NMN thread; unless anyone objects, I'm going to create a new dedicated thread on that subject and move the relevant posts there.

 

Mike: thank you for saving me the trouble of removing Anthony's personal contact information from your post. I understand that you wanted a way to prove that you were not making up your discussion when challenged, but that was not an appropriate way to do it.

[LawrenceW]

Thanks Michael.  No objections from me.

[ryukenden]

As Lawrence correctly notes, this whole discussion of RevGen NR is off-topic in an NMN thread; unless anyone objects, I'm going to create a new dedicated thread on that subject and move the relevant posts there.

Mike: thank you for saving me the trouble of removing Anthony's personal contact information from your post. I understand that you wanted a way to prove that you were not making up your discussion when challenged, but that was not an appropriate way to do it.

Do you mean NMN subforum? I will welcome that.

[Invicta Immortalem]

Michael, please create this NMN sub-forum. It will be a step forward in clarifying topics and discussions about different types of NAD+ precursors; NMN has no stock market, shareholders or exclusive patents owners. Therefore, we will feel free to share any opinions and experiences about it, without offense Chromadex & co business interests.

Edited by Invicta Immortalem, 01 March 2018 - 07:23 PM.

[sthira]

Thanks Michael. No objections from me.

Yeah, well, I wouldn't get too stoked just yet about opening up your own chamber, Lawrence, because we remember:

...while I have no direct knowledge of him or his motivations, it bears bearing in mind that LawrenceW came out of nowhere, with no prior contact with our community, to announce that he and his fellow participants were getting miraculous results with a product that was only potentially affordably available through his organization — an organization with some extremely sketchy scientific information, laughable parodies of patent applications, and that solicits "“accredited” investors (that have the appropriate health to participate) looking to assess [their proprietary supplement and company] for possible investment into [their] Reg D 506c SEC registered offering" to participate in their "trial," which in turn requires participants to pay for both their supply of the test agent and for diagnostic testing to include some of the more expensive analytes...

[able]

Yes, please move this to its own thread.

 

I apologize for making the post that led us astray.  When I first posted it, I found the email from Anthony interesting on his thoughts on NMN availability vs NR, but realized it had NR news also and didn't know if I should make a new thread just for that.

 

Agree with those who vote for separate NMN sub-forum.

[Michael]

To be clear, I meant a new thread (which I have done, taking weighings-in for a subforum as also supportive of cleaving off the NR material in this thread). I have no power to create a new subforum: I'm a moderator, not a site engineer. IAC, I don't think an NMN subforum makes sense, for reasons given: if the engineers were up to making further changes, I would again advocate for this subforum to be renamed "NAD+ Precursors."

[LawrenceW]

Michael.

 

In that case, please advocate for changing this sub forum name to NAD+ Precursors.

[LawrenceW]

sthira

 

 

"Yeah, well, I wouldn't get too stoked just yet about opening up your own chamber, Lawrence, because we remember:"

 

Just to clarify. I have no ownership, financial, shareholder or employee relationship with Egaceutical. Secondly, if I did then why would I post?:

LawrenceW

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Posted 20 February 2018 - 06:07 PM

ryukenden, on 20 Feb 2018 - 4:19 PM, said:

Which NMN brand is the most reliable right now? I live in the Uk and wonder any reliable sellers who will post it to the uk.

When I bought NR from US a few weeks ago for £600 or so, it costed me extra £200+ as tax.

I am planning to buy NMN for my family and may spend £1,000 or more initially. I appreciate any discounts from the vendors.

 

This seems to be the best deal in the market right now.

 

http://alivebynature...ucleotide-copy/ 

 

Three years ago Egaceutical was the only place where we could get U.S. lab tested and certified NMN here in the U.S.  Now, there are a lot  more economical suppliers that we are buying from for our group.

Edited by LawrenceW, 02 March 2018 - 01:49 AM.

[midas]

Size Exclusion Chromatography Method for Purification of Nicotinamide Mononucleotide (NMN) from Bacterial Cells

 

"Over 12% of the world’s health resources are spent on treating diabetes, as high blood glucose is the third cause of mortality worldwide. Insulin resistance is the basis of the most common form of diabetes: type 2 diabetes. Recent animal studies report successful attempts at reversing type 2 diabetes by the administering of the NAD⁺ precursor nicotinamide mononucleotide (NMN). However, the current high price of this molecule urges for more efficient and cost-effective production methods. This work proposes a method for purifying NMN by Size Exclusion Chromatography (SEC) on silica with a covalently attached coating of poly(2-hydroxyethyl aspartamide) (PolyHEA) stationary phase using an isocratic elution with a denaturing mobile phase (50 mM formic acid) from a complex molecular mixture such as a fermentation broth. The eluted peaks were identified by UV-Vis analysis and confirmed with ESI+ mass spectrometry and a HPLC reversed-phase method. The proposed SEC method is simple, patent-free, directly applicable for industrial production with a minimum scale up effort. The need for multiple chromatographic steps is eliminated and the lysate filtration and clarification steps are simplified. Substantial reduction in NMN production costs and increased purity of NMN to the level suitable for usage in humans are expected."

 

https://www.nature.c...598-018-22806-8

[Nate-2004]

This is such a long thread at this point (I wish you could display all posts on one page for a browser search on a specific thread), that I don't know if this question has been asked or not but here it is again if so.

 

Some of the initial arguments about NMN a while back were that it has to convert to NR anyway just to enter the cell. However, in recent published studies on NR, some interpretations of the data would indicate that NR is mostly broken down into NAM and Ribose anyway and a lot of it is taken up by the liver. Very little intact NR makes it to other cells in the body. So here's the question then, *if* all of that is true, wouldn't it be better to use NMN? If that makes it intact to non-liver cells, then converting to NR first isn't such a bad thing. Right? That's how NR would be delivered intact more effectively, via NM. Do I have this right?

[LawrenceW]

Quote from this very recently released study:

 

https://www.scienced...550413118301220

 

"Whether or not NMN is taken up by a transporter is currently the subject of debate (Mills et al., 2016; Ratajczak et al., 2016). Brenner, Canto´ and colleagues argue that NMN is not taken up quickly enough to invoke the presence of a transporter and that both NAD+ and NMN undergo extracellular degradation to generate permeable precursors that can be taken up by cells (Ratajczak et al., 2016). On the other hand, Imai argues that this is likely a cell-type-specific phenomenon and that some cell types can rapidly take up NMN (Mills et al., 2016). If so, the identification of the putative transporter will help resolve the debate and help identify which cell types and tissues are able to transport NMN across the plasma membrane. Additional studies with isotopically labeled NAD+ precursors to trace the uptake and metabolism of these molecules should help answer these questions."

[able]

This is such a long thread at this point (I wish you could display all posts on one page for a browser search on a specific thread), that I don't know if this question has been asked or not but here it is again if so.

 

Some of the initial arguments about NMN a while back were that it has to convert to NR anyway just to enter the cell. However, in recent published studies on NR, some interpretations of the data would indicate that NR is mostly broken down into NAM and Ribose anyway and a lot of it is taken up by the liver. Very little intact NR makes it to other cells in the body. So here's the question then, *if* all of that is true, wouldn't it be better to use NMN? If that makes it intact to non-liver cells, then converting to NR first isn't such a bad thing. Right? That's how NR would be delivered intact more effectively, via NM. Do I have this right?

 

 

That is the point Nate.  The Trammell thesis made the claim that NR was superior to NMN solely upon their research that NMN must be broken down to NR before entering (some) cells.

 

But there is little if any clue whether in vivo, that conversion is a bottleneck, even if true for all cells.

 

And since the portion of NR that does make it thru digestion is quickly converted to NAD+ in the liver, it is not readily available to tissues throughout the body, it is disadvantaged in that regard since NAD+ would also need to be converted to enter cells.

 

The quote from Dr Sinclair that Lawrence posted above describes the questions well, I think, and is why I trust Sinclair's balanced view a lot more than the biased interpretation from Dr Brenner.

Edited by able, 18 March 2018 - 03:45 PM.

[MikeDC]

Quote from this very recently released study:

https://www.scienced...550413118301220

"Whether or not NMN is taken up by a transporter is currently the subject of debate (Mills et al., 2016; Ratajczak et al., 2016). Brenner, Canto´ and colleagues argue that NMN is not taken up quickly enough to invoke the presence of a transporter and that both NAD+ and NMN undergo extracellular degradation to generate permeable precursors that can be taken up by cells (Ratajczak et al., 2016). On the other hand, Imai argues that this is likely a cell-type-specific phenomenon and that some cell types can rapidly take up NMN (Mills et al., 2016). If so, the identification of the putative transporter will help resolve the debate and help identify which cell types and tissues are able to transport NMN across the plasma membrane. Additional studies with isotopically labeled NAD+ precursors to trace the uptake and metabolism of these molecules should help answer these questions."

Mills et al., 2016 said nothing about some cells can rapidly take up NMN. It is not the speed that is relevant, it is the percentage of NMN that can get into cells before degradation or flushed into urine. A previous study comparing NR and NMN on cells in a dish showed NR and NMN yields similar results. But this study doesn’t translate into a living body because NMN can get flushed out in urine while NMN in a dish has no escape route. The Mills et al., 2016 study demonstrated that only a small percentage of NMN gets into cells since 300mg/kg NMN only raised NAD+ in liver and muscles by 14% for a short period of time. This compares with 185mg/kg NR raising NAD+ in liver and muscles by 100% for a much longer period of time. You can augue forever about how NR gets broken down or not, but NR is effective at raising NAD+ in all tissues tested while NMN is much less effective. A recentl study on NAM showed that NAM does not increase NAD+ in tissues or blood long term. Many people taking Niagen have found NR to be effective for many years without losing effectiveness long term. This is in agreement with the observation that many people who took NAM and Niacin for many years without obvious anti aging results started to see great anti aging results after starting NR. What counts is the end results. It is nice to know exactly how NR achieves the anti aging results, but it is more important to know it works.

[Harkijn]

We simply don't know enough yet to tell. I would not go as far as to call anyone's interpretation biased. However, if NMN were affordable at the moment, I would combine both NMN and NR. (Actually, I did combine them for a while, but NMN costs are just outrageous.)

Even if it will be confirmed that NR only raises NAD+levels in the liver, it is one hell of a supplement to take!

[MikeDC]

This is such a long thread at this point (I wish you could display all posts on one page for a browser search on a specific thread), that I don't know if this question has been asked or not but here it is again if so.

Some of the initial arguments about NMN a while back were that it has to convert to NR anyway just to enter the cell. However, in recent published studies on NR, some interpretations of the data would indicate that NR is mostly broken down into NAM and Ribose anyway and a lot of it is taken up by the liver. Very little intact NR makes it to other cells in the body. So here's the question then, *if* all of that is true, wouldn't it be better to use NMN? If that makes it intact to non-liver cells, then converting to NR first isn't such a bad thing. Right? That's how NR would be delivered intact more effectively, via NM. Do I have this right?

That is the point Nate. The Trammell thesis made the claim that NR was superior to NMN solely upon their research that NMN must be broken down to NR before entering (some) cells.

But there is little if any clue whether in vivo, that conversion is a bottleneck, even if true for all cells.

And since the portion of NR that does make it thru digestion is quickly converted to NAD+ in the liver, it is not readily available to tissues throughout the body, it is disadvantaged in that regard since NAD+ would also need to be converted to enter cells.

The quote from Dr Sinclair that Lawrence posted above describes the questions well, I think, and is why I trust Sinclair's balanced view a lot more than the biased interpretation from Dr Brenner.

Mills et al., 2016 paper showed that there is a bottleneck for NMN to enter cells. Even though NMN was much more bioavailable in the blood stream than NR, NMN only raises NAD+ 14% in the liver and muscles while lower doses of NR raises NAD+ in tissues by 100%. We also know people taking NR gets benefits in the brain and skins.

[MikeDC]

We simply don't know enough yet to tell. I would not go as far as to call anyone's interpretation biased. However, if NMN were affordable at the moment, I would combine both NMN and NR. (Actually, I did combine them for a while, but NMN costs are just outrageous.)
Even if it will be confirmed that NR only raises NAD+levels in the liver, it is one hell of a supplement to take!

It would be a lie to say NR only raises NAD+ in the liver. The NR study showed NAD+ was raised significantly in 3 tissues. People taking NR gets benefits in all organs and skin.
NAM is an effective NAD+ precursor short term. But negative feedback loop makes it unusable as NAD+ precursor. Mills et al., 2016 NMN study clearly showed that NMN can’t get into cells efficiently and most NMN are wasted and flushed out into urine. If we get a large group of people taking 250mg of NMN, I bet that they don’t see the anti aging effects That People taking NR see all the time.

[MikeDC]

After taking NR, my skin is smoother that I was in the 20s. This can only happen if NAD+ in skin cells from taking NR has exceeded my youthful NAD+ levels. I am NOT alone on this. Many friends get this same effects. Even an 80 year old man.
I would like to see a large group of NMN users to report the same effects after taking 250mg NMN.

Edited by MikeDC, 18 March 2018 - 04:36 PM.

[MikeDC]

This picture from the following link shows NAM and NR can readily enter cells while NMN can’t. It also shows NAD+ can readily get out of cells. Maybe one of the reasons NR is effective at raising NAD+ in all the tissues is to convert to NAD+ in liver and plasma cells and the NAD+ will be carried to other tissues and becomes NAD+ precursors for other tissues. Note that NAD+ can break down to both NAM and NMN>NR. So NAD+ is a better precursor than NMN. This is why NR is a much more effective precursor.

https://www.plantsci... metabolism.pdf

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[MikeDC]

The advantage of NR is it uses NRK1 and NRK2 pathways and NAM used NAMPT. So long term NR administration can be effective while longer administration of NAM is not at raising NAD+ in tissues.

Edited by MikeDC, 18 March 2018 - 05:05 PM.

[able]

 

Quote from this very recently released study:

https://www.scienced...550413118301220

"Whether or not NMN is taken up by a transporter is currently the subject of debate (Mills et al., 2016; Ratajczak et al., 2016). Brenner, Canto´ and colleagues argue that NMN is not taken up quickly enough to invoke the presence of a transporter and that both NAD+ and NMN undergo extracellular degradation to generate permeable precursors that can be taken up by cells (Ratajczak et al., 2016). On the other hand, Imai argues that this is likely a cell-type-specific phenomenon and that some cell types can rapidly take up NMN (Mills et al., 2016). If so, the identification of the putative transporter will help resolve the debate and help identify which cell types and tissues are able to transport NMN across the plasma membrane. Additional studies with isotopically labeled NAD+ precursors to trace the uptake and metabolism of these molecules should help answer these questions."

Mills et al., 2016 said nothing about some cells can rapidly take up NMN. It is not the speed that is relevant, it is the percentage of NMN that can get into cells before degradation or flushed into urine. A previous study comparing NR and NMN on cells in a dish showed NR and NMN yields similar results. But this study doesn’t translate into a living body because NMN can get flushed out in urine while NMN in a dish has no escape route. The Mills et al., 2016 study demonstrated that only a small percentage of NMN gets into cells since 300mg/kg NMN only raised NAD+ in liver and muscles by 14% for a short period of time. This compares with 185mg/kg NR raising NAD+ in liver and muscles by 100% for a much longer period of time. You can augue forever about how NR gets broken down or not, but NR is effective at raising NAD+ in all tissues tested while NMN is much less effective. A recentl study on NAM showed that NAM does not increase NAD+ in tissues or blood long term. Many people taking Niagen have found NR to be effective for many years without losing effectiveness long term. This is in agreement with the observation that many people who took NAM and Niacin for many years without obvious anti aging results started to see great anti aging results after starting NR. What counts is the end results. It is nice to know exactly how NR achieves the anti aging results, but it is more important to know it works.

 

Mikedc-"Mills et al., 2016 said nothing about some cells can rapidly take up NMN"

 

wrong...    direct quote from Mills et al, 2016:

 

"NMN was quickly utilized to synthesize NAD+ in tissues"

 

 

 

 

 

 

Mikedc- "the percentage of NMN that can get into cells before degradation or flushed into urine."

 

 

 

You keep making this claim that NMN is "flushed out in urine", which I have never seen any basis for, other than your imagination.

 

In fact, this study shows NMN is retained in the body far longer than NAM:

 

"β-Nicotinamide Mononucleotide, an Anti-Aging Candidate Compound, Is Retained in the Body for Longer than Nicotinamide in Rats"

 

Also you admit NR -> NMN-> NAD+, yes?   But somehow, you imagine that exogenous NMN has no effictient route and gets flushed away, but exogenous NR -> NMN and THAT NMN is somehow different, and doesn't "get flushed away"?  Why do you believe this?

 

 

 

 

 

Mikedc - "The Mills et al., 2016 study demonstrated that only a small percentage of NMN gets into cells since 300mg/kg NMN only raised NAD+ in liver and muscles by 14% for a short period of time"

 

Yes, mice fed NMN for 1 year, HALF THEIR LIFE,  saw increase NAD+ of 14% in the muscle.    

 

I'm sure you know what homeostasis is.  

 

The Elysium study showed NR elevated NAD+ in liver an impressive 90% at one month, which decreased to 40% at three months.  You would have to test for 30 years in humans to have a valid comparison.   As you know, in mice, there is also NO comparable 12 month study with NR.  You keep comparing apples and oranges.

 

 

 

 

 

Edited by able, 18 March 2018 - 05:41 PM.

[able]

We simply don't know enough yet to tell. I would not go as far as to call anyone's interpretation biased. However, if NMN were affordable at the moment, I would combine both NMN and NR. (Actually, I did combine them for a while, but NMN costs are just outrageous.)

Even if it will be confirmed that NR only raises NAD+levels in the liver, it is one hell of a supplement to take!

 

 

I agree, as they likely target different tissues at different rates, it may be effective to take both.  I do.

 

I think your pricing data is wrong though.  NMN is now the same price as NR on Amazon.

[able]

This picture from the following link shows NAM and NR can readily enter cells while NMN can’t. It also shows NAD+ can readily get out of cells. Maybe one of the reasons NR is effective at raising NAD+ in all the tissues is to convert to NAD+ in liver and plasma cells and the NAD+ will be carried to other tissues and becomes NAD+ precursors for other tissues. Note that NAD+ can break down to both NAM and NMN>NR. So NAD+ is a better precursor than NMN. This is why NR is a much more effective precursor.

https://www.plantsci... metabolism.pdf

 

 

That makes no sense.  If you believe NAD+ in the liver is effective at reaching tissues throughout the body, then NAM would be the same as NR.  They have overlapping behavior, but not the same.   There are MANY precursors and other substances that raise NAD+ in the liver.  Reaching all the other cells is where NMN and NR have some advantage.