7 ms·

NMN: A Stable, Reliable NAD+Activator and Anti-Aging Molecule (2020)

LinuxBender 4y ago
This is an interesting topic. I've followed Dr. Sinclairs work for some time. For me specifically I personally did not experience any notable gains but I only used NMN for about 6 months and it was one of the more expensive supplements of the 50 or so that I take. I've since switch back to just taking NAM daily since excess NMN is converted back to NAM for storage. I would like to learn how to improve the process of converting NAM -> NR -> NMN -> NAD+ but I have not found much literature on this process. Just flow diagrams. The literature explains that the bi-directional cycle of conversion slows with age but I can't find anything explaining what the specific mechanisms are that degrade with age and how to modify the root cause of the degradation.
- ziddoap 4y ago
  >of the 50 or so that I take I'm no doctor and have absolutely no idea what I'm talking about with respect to supplements, but my god that seems like just an absurd amount of supplements (especially if some of them are doing multiple things like a multivitamin or whatever). Do you take all 50 of these daily? Do you like... Blend them up so your not popping pills for 15 minutes straight every morning?
  - LinuxBender 4y ago
    I cycle some molecules up and down. Some molecules I take at different times of the day or week. Some can only be taken a couple times a week as they can be toxic if not used correctly. Some are safe to take daily. I have researched all of them extensively. Some of them I take at levels that would make people cringe as the known literature around some of them is incomplete. I am not a fan of multivitamins though I do keep one around and rarely touch it. Most of them contain very low quality components, most notably the vitamin E which is nearly almost always alpha-tocopherol and since I am male that is a major risk for prostate cancer if not taken with the right balance of gamma-tocopherol and selenium. Rather I prefer to take the tocotrienols. Multivitamins also contain a low quality form of vitamin C in the form of ascorbic acid and that is a topic in and of itself. I prefer to get the majority of my vitamin C from green leafy vegetables using a high powered blender that acts as a juicer. I do at times carry with me a small metal canister that can hold about 10-15 pills when I know I will be eating food someone else made, but most of that is for different formulas of garlic extracts, digestive enzymes, TUDCA, oregano oil and other things that assist with digestion and neutralization of pathogens in food. If you are interested in these topics a good starting point is nih.gov, just be highly skeptical of any studies you find. Their search is awful so I would use google and put in "site:nih.gov some topic"
    - jrimbault 4y ago
      I think the underlying question was "Why not eat food ?" or "Why do you use so much complements if you can eat normally ?"
      - LinuxBender 4y ago
        That is a good question. I personally am compensating for the lack of nutrients in food and also over-compensating for damage that I have done to my organs from a lifetime of eating a "standard american diet" or what I prefer to call a "first world diet". A healthy food diet just wasn't cutting it for me, especially given that stomach acid and other aspects of digestion decrease with age. I can compensate with digestive enzymes, tudca, benfotiamine and chelated zinc but that has rapidly diminishing effects. My goals go far beyond what a good diet and moderate exercise and decent sleep alone can accomplish but I would never even try to convince anyone to do what I am doing nor would I even suggest it unless one researches all of the molecules and their downstream effects ad-nauseam.
        simonebrunozzi 4y ago
        Move to Italy. I grew up here, lived abroad for ~13 years, 9 of which in San Francisco (before: Luxembourg and Singapore), working for AWS and other tech firms. I can assure you that the quality of produce I can find in Italy cannot be beaten. Comparable in some parts of the Mediterranean. Whole Foods? Give me a break, not even close. I'm not too serious (I know it's not easy to "move to Italy", just like that), but I find it really interesting that the US is so rich, and yet the quality of food is so poor. The tomatoes are a great example. Visit Italy, buy some tomatoes, eat them raw. You will not believe your senses.
        LinuxBender 4y ago
        I think there is something to be said for this, especially foods that are home grown and home prepared. In the town I grew up in there was an Italian family that owned a restaurant and would get most of their ingredients from Italy. My friends mom made everything from scratch. No highly processed foods. My friend her son was built like a tank. We used to arm wrestle all the time if for no other reason than his insane strength and my laughably futile attempts to win. I should add that since then I have not once in my life enjoyed a calzone like his mom made. It was worth the 45+ minute wait.
- ck2 4y ago
  NAM NR and NMN all use different absorption pathways and have different pitfalls. There's good reason people stopped using NAM once there were alternatives available, topic well outside the scope of HN but not hard to google. You cannot change the conversion process/rate, at least not with current knowledge, it is rate limited by multiple biological processes. I strongly caution to use google scholar and not blogs/youtube for information. Also everyone should be aware because of the high cost there is A LOT of counterfeit NMN out there, never buy unknown brands/sources.
  - LinuxBender 4y ago
    You cannot change the conversion process/rate, at least not with current knowledge That is precisely the wall I have hit but I am a stubborn old bastard and will not give up.
    - ck2 4y ago
      There are PhDs with multi-million dollar grants who cannot do it. I mean let's say they did somehow figure out an enzyme to speed it up, it would likely cost more than just supplementing more of the desired precursors. There might be some obscure food or supplement that does what you want but it will cost more because it will be rare and then you've got the problem of huge consistency between batches because all manufacturing in China/India is the wild-west. Easier to just take the precursors which are mass produced so prices slowly coming down, though covid/inflation/supply-chain threw it a curve.
  - balfirevic 4y ago
    > never buy unknown brands/sources All NMN brands are unknown to me - how do I judge?
- joshu 4y ago
  Do you have a list published somewhere?
  - LinuxBender 4y ago
    I do not. I used to list my methods on a website but I prefer to have people research this topic themselves and fully understand it as their physiology and pre-existing conditions will differ from mine. What works for me may have negative side effects on others and I would prefer they take responsibility for the trial-and-error process they will have to go through. I've even stopped using the scientific method as it is just too slow given the complexity of all the systems in a mammal and how they interact with one another and I could not in good conscience promote that for others.
    - wallfacer77 4y ago
      Do you have a blog? If not, would you be interested in making one? You could post it on HN and as the replies surely are telling you already, people will enjoy reading it. You may get some useful comments too with suggestions for different supplements and stuff.
    - joshu 4y ago
      yeah, i have just thought about making the Big List Of Supplements with what they are supposed to do, just adding papers for/against any to each
evo_9 4y ago
Been taking this for nearly 5 years. Shits the real deal. No pretending when you’re competing still against 20-something that barely washed out of their pro nhl career… but yeah not like being 55 and playing high level hockey is any sort of ‘proof’ around here (or my multiple sets of 20-25 pull-ups I do regularly and I could barely do 10 when I was 30).
- bilsbie 4y ago
  What’s your dose and brand? Why NMN vs NR?
  - mmh0000 4y ago
    These are great questions, I'd also like to know dose frequency.
  - polotics 4y ago
    Also, what about NMN versus Niagen (Tru)? Also as I understand these molecule may be fragile, do you keep them in the fridge?
    - MacsHeadroom 4y ago
      Niagen is a trade name for NR. So you're asking the same question.
    - evo_9 4y ago
      I do put all the more advanced stuff in the fridge including NMN, NR, rapamycin, heavy molecular weight Hyaluronic Acid
  - agrothberg 4y ago
    I take 250mg / day of NMN from NOVOS Labs (https://novoslabs.com/product/novos-boost/ https://novoslabs.com/product/novos-boost/). I can't definitively say I feel the effects. The site offers a nice write up on NMN: https://novoslabs.com/nicotinamide-mononucleotide-nmn-and-longevity/ https://novoslabs.com/nicotinamide-mononucleotide-nmn-and-lo....
joshfraser 4y ago
You can also take NAD+ intravenously. IV clinics in most major cities will be able to offer it and it's nothing short of incredible. The difference to energy levels and mental clarity after taking it are both immediate and undeniable.
- mmh0000 4y ago
  In your experience, how long does the effect last for? At around $600/treatment (at least according to a quick Google), it better last awhile.
  - joshfraser 4y ago
    I do them once every two months. The benefits are most noticeable for the first couple weeks.
- gavinray 4y ago
  Why pay a bunch of money for that? Anyone can buy bacteriostatic water from medical supply websites, along with syringes, themselves. I can personally recommend Hospira brand. Just give yourself the IV.
  - GordonS 4y ago
    Can you IM it too? IM usually has a slight drop in bioavailability vs IV, but it's much easier.
    - cjbgkagh 4y ago
      NAD+ IM will hurt a fair bit at the injection site.
  - amelius 4y ago
    What if the substance comes as a powder? How do you know if it dissolves completely? It just sounds too risky.
tguvot 4y ago
been taking not exactly NMN, but NR (tru niagen) for a few months. my liver enzymes (alt/ast) first time in a very long time are back in proper range.
- samstave 4y ago
  Do you drink a lot? Were you drinking a lot before you started taking them, and reduced drinking - or did you change anything other that adding NR/NMN to your intake?
  - tguvot 4y ago
    Drinking same as before (1.5l-3l at any given day). Also got some different multivitamins, but I doubt that they changed anything. There are some mouse studies that nmn/nr improve alt/ast level, but it not really clear is it just enzyme level normalization or does it actually repair anything. So i am not sure at this point of time is it improvement or "improvement" Edit. in case by drinking it was implied alcohol and not water, no. just some wine here and there. no big changes
    - GordonS 4y ago
      Not the GP, but I'm pretty sure they were asking if you drank a lot of alcohol, not water :)
      - tguvot 4y ago
        ooopsie...(there are also a lot of discussions about how much water you drink, etc...) in this case not more than usual. some wine here and there. nothing major and no alcoholism, if this is what was implied
      - pyrophane 4y ago
        Heh, saw 1.5/3L/day and I just thought, well, that's a lot of alcohol.
joshu 4y ago
i am a bit wary of any doctor with a podcast
evo_9 4y ago
Since a lot of people are asking me different questions in this thread I figured I’d let people know if you wanna just email me look at my profile and reach out. Happy to share my entire stack with anybody that wants to see it… Or if you happen to be a high-level hockey player in Denver we’re starting to look for a few guys to fill out our winter roster =)
nootropicat 4y ago
I tried both NMN and NR. NMN did absolutely nothing for me. NR is noticeable - can sustain heavy exertion for much longer. Much faster recovery.
anoplus 4y ago
Taken NMN 500g pill in morning for the first time last week, for 4 days. I felt physically and mentally very energized. My sleep length reduced to only couple of hours at night, so I stopped completely. First night after stopping was completely sleepless. Second night was solid and back to normal sleep pattern and energy.
sinenomine 4y ago
The problem with NMN and NAD+ activators in general is that these don't[1] seem to increase (even) the mouse lifespan in ITP trials[2], which is more or less a benchmark for preclinical testing of longevity-modulating substances. On the other hand, there is a handful of substances that passed this trial with evidence of some positive influence over lifespan, at least in mice, and as such are interesting candidates for human trials: [3][4][5][6]. There is also a very interesting class of substances that seem not only to extend lifespan in mice but even to rejuvenate some aspects of their physiology upon a short course of treatment: senolytics[7][8]. 1. https://www.fightaging.org/archives/2021/04/the-latest-data-from-the-interventions-testing-program-nicotinamide-riboside-has-no-effect-on-mouse-life-span/ https://www.fightaging.org/archives/2021/04/the-latest-data-... 2. https://www.nia.nih.gov/research/dab/interventions-testing-program-itp https://www.nia.nih.gov/research/dab/interventions-testing-p... 3. https://www.nature.com/articles/s41573-020-0067-7 https://www.nature.com/articles/s41573-020-0067-7 4. https://pubmed.ncbi.nlm.nih.gov/24245565/ https://pubmed.ncbi.nlm.nih.gov/24245565/ 5. https://www.nature.com/articles/nature08221 https://www.nature.com/articles/nature08221 6. https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fasebj.2018.32.1_supplement.533.112 https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/faseb... 7. https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(18)30373-6/fulltext https://www.thelancet.com/journals/ebiom/article/PIIS2352-39... 8. https://www.nature.com/articles/s41591-022-01923-y https://www.nature.com/articles/s41591-022-01923-y

This is an interesting topic. I've followed Dr. Sinclairs work for some time. For me specifically I personally did not experience any notable gains but I only used NMN for about 6 months and it was one of the more expensive supplements of the 50 or so that I take. I've since switch back to just taking NAM daily since excess NMN is converted back to NAM for storage. I would like to learn how to improve the process of converting NAM -> NR -> NMN -> NAD+ but I have not found much literature on this process. Just flow diagrams. The literature explains that the bi-directional cycle of conversion slows with age but I can't find anything explaining what the specific mechanisms are that degrade with age and how to modify the root cause of the degradation.

ziddoap 4y ago
>of the 50 or so that I take I'm no doctor and have absolutely no idea what I'm talking about with respect to supplements, but my god that seems like just an absurd amount of supplements (especially if some of them are doing multiple things like a multivitamin or whatever). Do you take all 50 of these daily? Do you like... Blend them up so your not popping pills for 15 minutes straight every morning?
- LinuxBender 4y ago
  I cycle some molecules up and down. Some molecules I take at different times of the day or week. Some can only be taken a couple times a week as they can be toxic if not used correctly. Some are safe to take daily. I have researched all of them extensively. Some of them I take at levels that would make people cringe as the known literature around some of them is incomplete. I am not a fan of multivitamins though I do keep one around and rarely touch it. Most of them contain very low quality components, most notably the vitamin E which is nearly almost always alpha-tocopherol and since I am male that is a major risk for prostate cancer if not taken with the right balance of gamma-tocopherol and selenium. Rather I prefer to take the tocotrienols. Multivitamins also contain a low quality form of vitamin C in the form of ascorbic acid and that is a topic in and of itself. I prefer to get the majority of my vitamin C from green leafy vegetables using a high powered blender that acts as a juicer. I do at times carry with me a small metal canister that can hold about 10-15 pills when I know I will be eating food someone else made, but most of that is for different formulas of garlic extracts, digestive enzymes, TUDCA, oregano oil and other things that assist with digestion and neutralization of pathogens in food. If you are interested in these topics a good starting point is nih.gov, just be highly skeptical of any studies you find. Their search is awful so I would use google and put in "site:nih.gov some topic"
  - jrimbault 4y ago
    I think the underlying question was "Why not eat food ?" or "Why do you use so much complements if you can eat normally ?"
    - LinuxBender 4y ago
      That is a good question. I personally am compensating for the lack of nutrients in food and also over-compensating for damage that I have done to my organs from a lifetime of eating a "standard american diet" or what I prefer to call a "first world diet". A healthy food diet just wasn't cutting it for me, especially given that stomach acid and other aspects of digestion decrease with age. I can compensate with digestive enzymes, tudca, benfotiamine and chelated zinc but that has rapidly diminishing effects. My goals go far beyond what a good diet and moderate exercise and decent sleep alone can accomplish but I would never even try to convince anyone to do what I am doing nor would I even suggest it unless one researches all of the molecules and their downstream effects ad-nauseam.
      - simonebrunozzi 4y ago
        Move to Italy. I grew up here, lived abroad for ~13 years, 9 of which in San Francisco (before: Luxembourg and Singapore), working for AWS and other tech firms. I can assure you that the quality of produce I can find in Italy cannot be beaten. Comparable in some parts of the Mediterranean. Whole Foods? Give me a break, not even close. I'm not too serious (I know it's not easy to "move to Italy", just like that), but I find it really interesting that the US is so rich, and yet the quality of food is so poor. The tomatoes are a great example. Visit Italy, buy some tomatoes, eat them raw. You will not believe your senses.
        LinuxBender 4y ago
        I think there is something to be said for this, especially foods that are home grown and home prepared. In the town I grew up in there was an Italian family that owned a restaurant and would get most of their ingredients from Italy. My friends mom made everything from scratch. No highly processed foods. My friend her son was built like a tank. We used to arm wrestle all the time if for no other reason than his insane strength and my laughably futile attempts to win. I should add that since then I have not once in my life enjoyed a calzone like his mom made. It was worth the 45+ minute wait.
ck2 4y ago
NAM NR and NMN all use different absorption pathways and have different pitfalls. There's good reason people stopped using NAM once there were alternatives available, topic well outside the scope of HN but not hard to google. You cannot change the conversion process/rate, at least not with current knowledge, it is rate limited by multiple biological processes. I strongly caution to use google scholar and not blogs/youtube for information. Also everyone should be aware because of the high cost there is A LOT of counterfeit NMN out there, never buy unknown brands/sources.
- LinuxBender 4y ago
  You cannot change the conversion process/rate, at least not with current knowledge That is precisely the wall I have hit but I am a stubborn old bastard and will not give up.
  - ck2 4y ago
    There are PhDs with multi-million dollar grants who cannot do it. I mean let's say they did somehow figure out an enzyme to speed it up, it would likely cost more than just supplementing more of the desired precursors. There might be some obscure food or supplement that does what you want but it will cost more because it will be rare and then you've got the problem of huge consistency between batches because all manufacturing in China/India is the wild-west. Easier to just take the precursors which are mass produced so prices slowly coming down, though covid/inflation/supply-chain threw it a curve.
- balfirevic 4y ago
  > never buy unknown brands/sources All NMN brands are unknown to me - how do I judge?
joshu 4y ago
Do you have a list published somewhere?
- LinuxBender 4y ago
  I do not. I used to list my methods on a website but I prefer to have people research this topic themselves and fully understand it as their physiology and pre-existing conditions will differ from mine. What works for me may have negative side effects on others and I would prefer they take responsibility for the trial-and-error process they will have to go through. I've even stopped using the scientific method as it is just too slow given the complexity of all the systems in a mammal and how they interact with one another and I could not in good conscience promote that for others.
  - wallfacer77 4y ago
    Do you have a blog? If not, would you be interested in making one? You could post it on HN and as the replies surely are telling you already, people will enjoy reading it. You may get some useful comments too with suggestions for different supplements and stuff.
  - joshu 4y ago
    yeah, i have just thought about making the Big List Of Supplements with what they are supposed to do, just adding papers for/against any to each

evo_9 4y ago

Been taking this for nearly 5 years. Shits the real deal. No pretending when you’re competing still against 20-something that barely washed out of their pro nhl career… but yeah not like being 55 and playing high level hockey is any sort of ‘proof’ around here (or my multiple sets of 20-25 pull-ups I do regularly and I could barely do 10 when I was 30).

bilsbie 4y ago
What’s your dose and brand? Why NMN vs NR?
- mmh0000 4y ago
  These are great questions, I'd also like to know dose frequency.
- polotics 4y ago
  Also, what about NMN versus Niagen (Tru)? Also as I understand these molecule may be fragile, do you keep them in the fridge?
  - MacsHeadroom 4y ago
    Niagen is a trade name for NR. So you're asking the same question.
  - evo_9 4y ago
    I do put all the more advanced stuff in the fridge including NMN, NR, rapamycin, heavy molecular weight Hyaluronic Acid
- agrothberg 4y ago
  I take 250mg / day of NMN from NOVOS Labs (https://novoslabs.com/product/novos-boost/ https://novoslabs.com/product/novos-boost/). I can't definitively say I feel the effects. The site offers a nice write up on NMN: https://novoslabs.com/nicotinamide-mononucleotide-nmn-and-longevity/ https://novoslabs.com/nicotinamide-mononucleotide-nmn-and-lo....

joshfraser 4y ago

You can also take NAD+ intravenously. IV clinics in most major cities will be able to offer it and it's nothing short of incredible. The difference to energy levels and mental clarity after taking it are both immediate and undeniable.

mmh0000 4y ago
In your experience, how long does the effect last for? At around $600/treatment (at least according to a quick Google), it better last awhile.
- joshfraser 4y ago
  I do them once every two months. The benefits are most noticeable for the first couple weeks.
gavinray 4y ago
Why pay a bunch of money for that? Anyone can buy bacteriostatic water from medical supply websites, along with syringes, themselves. I can personally recommend Hospira brand. Just give yourself the IV.
- GordonS 4y ago
  Can you IM it too? IM usually has a slight drop in bioavailability vs IV, but it's much easier.
  - cjbgkagh 4y ago
    NAD+ IM will hurt a fair bit at the injection site.
- amelius 4y ago
  What if the substance comes as a powder? How do you know if it dissolves completely? It just sounds too risky.

tguvot 4y ago

been taking not exactly NMN, but NR (tru niagen) for a few months. my liver enzymes (alt/ast) first time in a very long time are back in proper range.

samstave 4y ago
Do you drink a lot? Were you drinking a lot before you started taking them, and reduced drinking - or did you change anything other that adding NR/NMN to your intake?
- tguvot 4y ago
  Drinking same as before (1.5l-3l at any given day). Also got some different multivitamins, but I doubt that they changed anything. There are some mouse studies that nmn/nr improve alt/ast level, but it not really clear is it just enzyme level normalization or does it actually repair anything. So i am not sure at this point of time is it improvement or "improvement" Edit. in case by drinking it was implied alcohol and not water, no. just some wine here and there. no big changes
  - GordonS 4y ago
    Not the GP, but I'm pretty sure they were asking if you drank a lot of alcohol, not water :)
    - tguvot 4y ago
      ooopsie...(there are also a lot of discussions about how much water you drink, etc...) in this case not more than usual. some wine here and there. nothing major and no alcoholism, if this is what was implied
    - pyrophane 4y ago
      Heh, saw 1.5/3L/day and I just thought, well, that's a lot of alcohol.

joshu 4y ago

i am a bit wary of any doctor with a podcast

evo_9 4y ago

Since a lot of people are asking me different questions in this thread I figured I’d let people know if you wanna just email me look at my profile and reach out. Happy to share my entire stack with anybody that wants to see it… Or if you happen to be a high-level hockey player in Denver we’re starting to look for a few guys to fill out our winter roster =)

nootropicat 4y ago

I tried both NMN and NR. NMN did absolutely nothing for me. NR is noticeable - can sustain heavy exertion for much longer. Much faster recovery.

anoplus 4y ago

Taken NMN 500g pill in morning for the first time last week, for 4 days. I felt physically and mentally very energized. My sleep length reduced to only couple of hours at night, so I stopped completely. First night after stopping was completely sleepless. Second night was solid and back to normal sleep pattern and energy.

sinenomine 4y ago

The problem with NMN and NAD+ activators in general is that these don't[1] seem to increase (even) the mouse lifespan in ITP trials[2], which is more or less a benchmark for preclinical testing of longevity-modulating substances. On the other hand, there is a handful of substances that passed this trial with evidence of some positive influence over lifespan, at least in mice, and as such are interesting candidates for human trials: [3][4][5][6]. There is also a very interesting class of substances that seem not only to extend lifespan in mice but even to rejuvenate some aspects of their physiology upon a short course of treatment: senolytics[7][8]. 1. https://www.fightaging.org/archives/2021/04/the-latest-data-from-the-interventions-testing-program-nicotinamide-riboside-has-no-effect-on-mouse-life-span/ https://www.fightaging.org/archives/2021/04/the-latest-data-... 2. https://www.nia.nih.gov/research/dab/interventions-testing-program-itp https://www.nia.nih.gov/research/dab/interventions-testing-p... 3. https://www.nature.com/articles/s41573-020-0067-7 https://www.nature.com/articles/s41573-020-0067-7 4. https://pubmed.ncbi.nlm.nih.gov/24245565/ https://pubmed.ncbi.nlm.nih.gov/24245565/ 5. https://www.nature.com/articles/nature08221 https://www.nature.com/articles/nature08221 6. https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fasebj.2018.32.1_supplement.533.112 https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/faseb... 7. https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(18)30373-6/fulltext https://www.thelancet.com/journals/ebiom/article/PIIS2352-39... 8. https://www.nature.com/articles/s41591-022-01923-y https://www.nature.com/articles/s41591-022-01923-y