392 replies to this topic

[MikeDC]

Ling Liu's dissertation showed circulating NR level in the blood is much higher than NMN. 

This paper shows NRK1 plays major roles in NAD+ production in the liver at baseline without any external supplementation of NR.

Both data point to NR as an important NAD+ precursor our body uses even without NR supplementation.

 

 

 

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

[Harkijn]

Be sure to listen to this great find by @bluemoon: http://www.longecity...d-master-aging/

 

It very lightly touches on some differences between supplements (nicotinic acid or niacin, nicotinamide, and tryptophan) although I don't think Dr. Brenner discusses NMN in the interview. There is a lot of discussion on the various benefits of supplements here on these forums at longecity, unfortunately some of it is entirely uninformed so my advice is go straight to the source. Read the hundreds of studies that are out there on NR, NMN, and the NAD+ cycle and put a far greater weight on the information in the studies more than anything anyone says here. I do feel that this forum needs a library, perhaps pinned to the top of links to studies (even if they are behind paywalls) so that newcomers can quickly get the list, but barring that, google scholar is not too bad.

Yes, a library would be a great idea. The complexity of NAD+ is such that I need to reread the most basic data time and again.

One such a  useful overview of the B3 vitamers is somewhat misleadlingly called Niacin:

http://lpi.oregonsta...thors-reviewers

[able]

University of Washington Study showed 1g NR creates a steady state level of NAD+ that doesn’t change after one additional supplementation. So 1g should be the upper limit on supplementation. This is actually a very good news because current suggested 250mg is affordable and effective. You don’t need to spend a fortune to slow down aging.

 

 

UW study used up to 1,000 mg TWICE per day, so max of 2 grams a day.

 

But it seems to imply these subjects reached max NAD+ increase at the lower dosages tested:

 

 

 

Peak PBMC NAD+ concentrations rose by an average of 4 ± 2 μM at the 100 mg NR dose and reached a plateaued response average of 6.5 ± 3.5 μM at 300 and 1000 mg doses from a baseline average of 12 ± 3.3 μM

 

 

 

 

That sounds like the 300 mg (twice per day) achieved the same NAD+ increase as the 1,000 mg (twice per day).

 

Does the  average response of 6.5, from a baseline average of 12 mean the average was a 50% increase?

 

Of course, these subjects were 21-50 years old, so I wouldn't expect the 90% increase Elysium found at 1 month as they used 60-80 year old subjects.

[MikeDC]

I remember the 8th day was 500mg twice per day. 1000mg in the morning on day 9 failed to increase NAD+ further.

Edited by MikeDC, 23 April 2018 - 03:49 PM.

[able]

From the study:

 

"250 mg NR was orally administered on Days 1 and 2, then uptitrated to peak dose of 1000 mg twice daily on Days 7 and 8. On the morning of Day 9, subjects completed a 24-hour PK study after receiving 1000 mg NR at t = 0"

[LawrenceW]

The old folks in the Elysium study appear to have bumped into homeostasis around day 30 at a 250 to 300 mg dose per day.  It also appears that you can take a higher dose in the beginning, but after you hit homeostasis you are just urinating dollars if you stay on the high dose.

[John250]

What is the go to brand for NR now? Any brand that has the patented Niagen NR?

[MikeDC]

What is the go to brand for NR now? Any brand that has the patented Niagen NR?

Tru Niagen is direct from ChromaDex the patent holder.

[OP2040]

Hi all,

I used to take NR and now take NMN,  Both times I took a relatively small recommended dose.  Here is what I would like to try.  Since it is shown that NMN resets some aging parameters at quite high doses, I want to try those high doses for a while then go back to my usual lower dose.  My reasoning is that the if it truly makes some parameter 15-20 years younger as in a mouse study, then I have literally gone back that far and can try to take a maintenance level dose after that.   I just read the Alzheimer's NMN study, which was what prompted me to get back into this.  The results were truly astounding, but quite high doses were given.

 

What would be the highest dose for the reset period and how long?  I'm seeing up to 2G, but a couple months in mice might be a couple years in humans.  What do you guys take and has anyone else tried this method
?

[MikeDC]

Hi all,
I used to take NR and now take NMN, Both times I took a relatively small recommended dose. Here is what I would like to try. Since it is shown that NMN resets some aging parameters at quite high doses, I want to try those high doses for a while then go back to my usual lower dose. My reasoning is that the if it truly makes some parameter 15-20 years younger as in a mouse study, then I have literally gone back that far and can try to take a maintenance level dose after that. I just read the Alzheimer's NMN study, which was what prompted me to get back into this. The results were truly astounding, but quite high doses were given.

What would be the highest dose for the reset period and how long? I'm seeing up to 2G, but a couple months in mice might be a couple years in humans. What do you guys take and has anyone else tried this method
?

NMN is subjected to the same negative feed back loop as NR. Don’t do massive dose NMN or NR. 1g is probably the highest I would go.

[LawrenceW]

I agree with MikeDC in that 1,000 mg per day of NMN is a good starting point.

[able]

NMN is subjected to the same negative feed back loop as NR. Don’t do massive dose NMN or NR. 1g is probably the highest I would go.

 

Maybe, maybe not.

 

The Sinclair mouse study doesn't appear to show homeostasis at 400 mg/kg  NMN a day after 60 days  (500% increase in NAD).

 

The Mills long term  study shows homeostasis likely  kicked in by 12 months of NMN.

 

I would say its possible NMN has a LOT higher upper limit on effectiveness before homeostasis kicks in.

[MikeDC]

Maybe, maybe not.

The Sinclair mouse study doesn't appear to show homeostasis at 400 mg/kg NMN a day after 60 days (500% increase in NAD).

The Mills long term study shows homeostasis likely kicked in by 12 months of NMN.

I would say its possible NMN has a LOT higher upper limit on effectiveness before homeostasis kicks in.

You can quote me on that the 500% increase was fabricated.

[LawrenceW]

You can quote me on that the 500% increase was fabricated.

 

So now you are accusing Abhirup Das, George X. Huang, Michael S. Bonkowski, Alban Longchamp, Catherine Li, Michael B. Schultz, Lynn-Jee Kim, Brenna Osborne, Sanket Joshi, Yuancheng Lu, Jose Humberto Treviño-Villarreal, Myung-Jin Kang, Tzong-tyng Hung, Brendan Lee, Eric O. Williams, Masaki Igarashi, James R. Mitchell, Lindsay E. Wu, Nigel Turner, Zolt Arany, Leonard Guarente and David A. Sinclair of fabricating data?

 

I think that you had better stop taking NR, as it appears that it is causing you to lose your mind!

Edited by LawrenceW, 23 April 2018 - 09:38 PM.

[MikeDC]

So now you are accusing Abhirup Das, George X. Huang, Michael S. Bonkowski, Alban Longchamp, Catherine Li, Michael B. Schultz, Lynn-Jee Kim, Brenna Osborne, Sanket Joshi, Yuancheng Lu, Jose Humberto Treviño-Villarreal, Myung-Jin Kang, Tzong-tyng Hung, Brendan Lee, Eric O. Williams, Masaki Igarashi, James R. Mitchell, Lindsay E. Wu, Nigel Turner, Zolt Arany, Leonard Guarente and David A. Sinclair of fabricating data?

I think that you had better stop taking NR, as it appears that it is causing you to lose your mind!

Who is losing his mind? You took massive doses of NMN and claim your blood markers were much younger than your real age. A few month later your blood marker says you are much older than your real age. This indicate addiction. You then used low dose NR and said it was not effective and then started massive dose of NMN again and claim NMN is more effective. You don’t have basic thinking skills. Not sure why you keep pumping NMN, but science says NR is a much better NAD+ precursor and our body utilize NR in normal functioning even without supplementation. While NMN in the blood are immediately filtered out by kidney as waste.

[OP2040]

1,0000 mg nmn would be $120 a month. I can’t do that for very long but if I do I’d rather just pay all in one go. Does it store well? Any group buys going on? Which brand of NMN do you guys trust? I’m thinking I can do that for 10 months at most. Sucks that this stuff is so expensive.

[MikeDC]

This new study shows over expression of NRK1 ameliorate liver disease due to aging and high fat diet. This can only happen when there is a supply of NR in our body and it shows our body is designed to consume NR as preferred NAD+ precursor.

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

[LawrenceW]

MikeDC.

 

Yet another example of you misremembering dates, facts and numbers.  My biological age before I began, 70.  I took high dose NMN for 8 months. Biological age 42.  Took nothing for 1 year. Biological age 61. Took 500 mg of NR twice per day for 3 months.  Biological age 76. Stopped the NR and started up my NMN.  After 3 months of NMN my biological age had dropped to 45. My current dose of NMN is 750 mg twice per day.  Science says wonderful things about NMN. It is you and your Chromadex buddies that bad mouth NMN. 

 

The reason why I now take NMN instead of NR is because I have tried both and I look back at my 3 months on NR as lost time while I got 3 months older and those are days I hope that NMN gets back for me.

[MikeDC]

MikeDC.

Yet another example of you misremembering dates, facts and numbers. My biological age before I began, 70. I took high dose NMN for 8 months. Biological age 42. Took nothing for 1 year. Biological age 61. Took 500 mg of NR twice per day for 3 months. Biological age 76. Stopped the NR and started up my NMN. After 3 months of NMN my biological age had dropped to 45. My current dose of NMN is 750 mg twice per day. Science says wonderful things about NMN. It is you and your Chromadex buddies that bad mouth NMN.

The reason why I now take NMN instead of NR is because I have tried both and I look back at my 3 months on NR as lost time while I got 3 months older and those are days I hope that NMN gets back for me.

Enjoy your NMN or fake powder. But science says NR is the real NAD+ precursor our body wants.

[LawrenceW]

1,0000 mg nmn would be $120 a month. I can’t do that for very long but if I do I’d rather just pay all in one go. Does it store well? Any group buys going on? Which brand of NMN do you guys trust? I’m thinking I can do that for 10 months at most. Sucks that this stuff is so expensive.

 

 

Alive by Nature is a good brand. 

 

Whatever you do, do not buy from K2GO.  Those buggers only put 12 mg of NMN into their supposed 150 mg capsule. See attached file.

Attached Files

•  K2go NMN testing-microqualitylabs.png   878.2KB   0 downloads

[OP2040]

Thanks Lawrence, very helpful.

Don’t worry about Mike. I’m new here and even I can tell how transparent he is. He must have his life savings tied up in Chromadex.

[John250]

Anyone experiment with injecting NR. I’m a former competitive bodybuilder so injections don’t bother me at all. It would have to be pure NR powder. Maybe heated in mct oil with a little benzyl alcohol and benzyl benzoate? Or would the heat damage it?

Other method would just be a solution in bacteriostatic water if the NR is pure enough.

Edited by John250, 24 April 2018 - 05:46 PM.

[able]

Anyone experiment with injecting NR. I’m a former competitive bodybuilder so injections don’t bother me at all. It would have to be pure NR powder. Maybe heated in mct oil with a little benzyl alcohol and benzyl benzoate? Or would the heat damage it?

Other method would just be a solution in bacteriostatic water if the NR is pure enough.

 

Sure seems like it would be a lot more effective than capsules, doesn't it?  Heat probably wouldn't be a good idea.  Whats wrong with just dissolving in water?   As long as it didn't sit for long, should be fine.

 

I don't believe there is any source for pure NR powder.  Alivebynature does have a 99% pure NMN powder that I use sublingual.  

[John250]

Sure seems like it would be a lot more effective than capsules, doesn't it? Heat probably wouldn't be a good idea. Whats wrong with just dissolving in water? As long as it didn't sit for long, should be fine.

I don't believe there is any source for pure NR powder. Alivebynature does have a 99% pure NMN powder that I use sublingual.

I’m only familiar with how to make anabolic steroids and reconstituting peptides, HGH, etc. with steroids it’s just a simple heating the powder into a carrier oil with filtering and adding ba and bb for sterility. With peptides,hgh,etc.. it’s simply adding bacteriostatic water to the lyophilized powder. But degradation Is a considering factor. For example most hgh and hcg are stable in bacteriostatic water for at least 4-6 weeks then they can slowly degrade to a minimal factor like maybe losing 5% effectiveness each week. but then more fragile peptides like Igf-Lr3 is good for about 30 days but then can degrade more rapidly so if you plan on using it long term it’s best to add a very small percentage of azelaic acid. So we would have to know the stability of the compound which I don’t think has been studied in injectable form. I would think if one were to do a trial run your best option would be dissolving a single dose at a time in bacteriostatic water as we don’t know how many minutes, hours, days, weeks etc. NR or NMN would be stable. Maybe if one could somehow filter out the cellulose in niagen to the pure powder that would be a good start. Perhaps the nmn powder would be best as it’s 99% pure. Is there a blood test you can get to check your baseline levels and then check again after using it? I’m sure there is I just don’t know what it would be called?

Edited by John250, 24 April 2018 - 07:28 PM.

[able]

I’m only familiar with how to make anabolic steroids and reconstituting peptides, HGH, etc. with steroids it’s just a simple heating the powder into a carrier oil with filtering and adding ba and bb for sterility. With peptides,hgh,etc.. it’s simply adding bacteriostatic water to the lyophilized powder. But degradation Is a considering factor. For example most hgh and hcg are stable in bacteriostatic water for at least 4-6 weeks then they can slowly degrade to a minimal factor like maybe losing 5% effectiveness each week. but then more fragile peptides like Igf-Lr3 is good for about 30 days but then can degrade more rapidly so if you plan on using it long term it’s best to add a very small percentage of azelaic acid. So we would have to know the stability of the compound which I don’t think has been studied in injectable form. I would think if one were to do a trial run your best option would be dissolving a single dose at a time in bacteriostatic water as we don’t know how many minutes, hours, days, weeks etc. NR or NMN would be stable. Maybe if one could somehow filter out the cellulose in niagen to the pure powder that would be a good start. Perhaps the nmn powder would be best as it’s 99% pure. Is there a blood test you can get to check your baseline levels and then check again after using it? I’m sure there is I just don’t know what it would be called?

 

The Mills long term study mixed their NMN in water once a week, and tested to verify it remained at least 95% during that time.   Seems like that would work.

 

I have stirred it in water and find it dissolves completely in seconds.  I don't take it in water myself, but Lawrence mentioned he does take it that way.

[OP2040]

So my NAD+ stack is going to be:

 

1. NMN as much as I can afford, which will always be lower than the study amounts

2. Taurine (1000mg) - On the premise that it increases Hydrogen Sulfide and synergistcally works with NMN

3. Melatonin - Long known as a Sirt1 activator, among it's many other benefits

 

Taurine and melatonin are very cheap too.  I think that's more than enough, and there is such a thing as too much a good thing.  There are so many substances now proven to activate Sirtuins/NAD+.  I think we can say we've got this pathway locked down pretty well, and more focus should be given to other aging pathways that currently don't have good targets (e.g. epigenetics and stem cell loss) .

Edited by OP2040, 25 April 2018 - 02:37 PM.

[LawrenceW]

OP2040

 

As per Slobec, you might want to add some Betaine to your stack.

Slobec

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Posted 08 March 2018 - 04:56 AM

If you are taking higher dose of NAD precursors take some betaine with it   http://www.freewebs....cin_therapy.pdf

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[OP2040]

I'll be getting my yearly blood test soon so I will know of any liver enzyme abnormalities.  These always come up perfect for me, so if it has changed then I know something is up.  There are a lot of people here taking NAD+ precursors and I haven't heard anything or seen any other studies on liver issues.  Sirtuins are so broadly effective for almost any tissue that I can't imagine liver would be an exception.  I don't want to end up with analysis paralysis, so I'm not going to worry about it for now. 

 

I do worry somewhat about cancer.  My family history is almost cancer free.  However, it seems like regeneration and cancer have some pleiotropic relationship in aging tissues, but not in young tissues.  However, these days studies often test for increased cancer rates as a matter of course due to this fear, and I know that at least two of the NMN studies showed no increased incidence.

[MikeDC]

Higher NAD+ levels will increase DNA repair and prevent cancer formation. This mice study showed NR prevents and even cure liver cancer.

https://www.ncbi.nlm...riboside cancer

Felding also found that breast cancer cells has reduced NAD+. Increasing NAD+ reduce growth and migration by 80%.

Cancer has also been recognized as a metabolic disease which means that cancer starts when your metabolic health is impaired. Reduced NAD+ will impair your metabolism.

Just from statistics, we should have seen hundreds of people shouting that they get cancer after taking NR. We have had enough NR users for a long enough time for that to happen if NR has no impact on cancer. Since it is not happening, I would say NR prevents cancer significantly.

[John250]

Is there a specific blood test you can get done to check NAD levels?