7 ms·

Oral administration of NMN is safe and efficiently increases blood NAD levels

70 points by evo_9 4y ago

deleted 4y ago
[deleted]
codevark 4y ago
SemanticStrengh 4y ago
What is the effect of NMN on the lipid/glucose mitochondria consumption ratio?
- metadat 4y ago
  Can you help elucidate us on why this matters?
  - SemanticStrengh 4y ago
    Basically the ratio can be altered and it is very unclear if preferentially consuming lipids vs glucose is healthier than the converse. ALCAR shift said ratio towards pro lipids consumptions, which increase beta-oxidation. Thus it increase a kind of oxidative stress however in most studies it seems to both improve mitochondria bioenergetics and to reduce oxidative stress. ALCAR improve many aspects of health and conditions in a potent way while having no acute nefast side effects. You should see on reddit (e.g. sirsadalot), ALCAR is a very popular supplement and I was hyped like others because of the scientific evidence. Very few people know it but there exist a ~direct opposite to ALCAR: https://en.wikipedia.org/wiki/Meldonium#Physio-pharmacology https://en.wikipedia.org/wiki/Meldonium#Physio-pharmacology This drug decrease beta-oxidation and increase the ratio of glucose consumption. As you can see e.g. on the wikipedia page, the rethoric behind mildronate sounds too very positive except many of the statements pro ALCAR/Mildronate are contradictory, in direct opposition. So either there is an explanatory factor that resolve the contradictions, either one or the other do actually significant harm, despite both having backing scientific evidence of improving health. This topic is major since those are the most potent mechanics toward mitochondria bioenergetics regulation, which is a major way to improve your lifespan/healthspan and even cognition. The issue is that the quality of the dicussion/research needed to elucidate those issues is above the level found on online forums and no paper directly address the question, so I am stuck in uncertainty.
    - chillingeffect 4y ago
      Nmn is generally said w b fast-mimicking. In me it leads to collagen generation, soft skin, much faster than fasting or hyper-green drinks. ...if that helps your question...
    - LinuxBender 4y ago
      I wish I knew someone that had a lot of knowledge of ALCAR. As someone that takes many different supplements, consumes no sugar, does IF, remains mostly keto+, the one supplement I can't seem to take is ALCAR. It makes me feel "ill" for about 24 hours. It's hard to even describe the feeling. Just an overwhelming feeling that something is very wrong and generally just "feel like crap" for a day. I feel relief after a good full nights sleep which suggests to me that my brain is clearing the compound or a byproduct of it but that is just a theory.
      - SemanticStrengh 4y ago
        Hmm that seems like a pretty rare side effects, at least I've never seen it reported on reddit. (Although some people have insomnia/palpitations which can be explained by e.g. TMAO) Maybe ALCAR makes your body consume not enough sugar but that seems unlikely. > that is just a theory well if you try to not sleep or only have a short night duration I think the result would be similar. The half life of ALCAR is ~17h so after 24h you no longer have a pharmacologically relevant dose, assuming you take as low as 500mg. BTW I recently discovered the organelle https://en.wikipedia.org/wiki/Peroxisome https://en.wikipedia.org/wiki/Peroxisome which is actually important in lipid (and therefore glucose) and oxidative metabolism
        LinuxBender 4y ago
        The glucose theory may be a good one to test out. I consume almost no glucose in my diet and I take several supplements that effectively also reduce gluconeogenesis. I also use Berberine. I will try a few different methods to boost either glucose or ketones in the brain prior to experimenting with ALCAR again.
xvector 4y ago
Is an elevation of NAD levels desirable? (Why?)
- TaylorAlexander 4y ago
  It seems it is an anti aging treatment and may help reduce aging related diseases.
- faluzure 4y ago
  Your NAD levels decrease as you age. Returning NAD+ levels to a more youthful state is one of the things researchers are experimenting with to reduce the effects of aging. Quoted from https://www.nmn.com/precursors/what-is-nad https://www.nmn.com/precursors/what-is-nad "NAD+ works as a shuttle bus, transferring electrons from one molecule to another within cells to carry out all sorts of reactions and processes. With its molecular counterpart, NADH, this vital molecule participates in various metabolic reactions that generate our cell’s energy."
faluzure 4y ago
Nice. More NMN studies are a good thing. I've been taking 250mg every morning and I feel like I have more energy, but I'm not convinced it's not a placebo effect.
rhexs 4y ago
I’ve been taking flush niacin, which I believe has the same effect at a much lower cost. Flush is really only annoying the first day.
- Andys 4y ago
  Flush niacin has been the only thing which has reliably improved my "long covid" symptoms.
  - SemanticStrengh 4y ago
    You should consider doing a cycle of magnesium lthreonate for its potent synaptothrophic properties
  - fnordpiglet 4y ago
    Try L Citruline. It easily passes the gut and readily converts to arginine which is a strong vasoprotector. Covid damages the lining of blood vessels. My belief is long covid is a redirection of free arginine to extensive vascular system damage and inflammation. At the minimum, it worked like a miracle for my long covid, YMMV. (Placebo possible of course, but citruline is used for body building as an energy and performance enhancer so the improvement in energy and thought clarity isn’t unexpected and has been shown to be beneficial in sickle cell which causes low free arginine due to the shape of the red cell irritating the lining of the blood vessels https://pubmed.ncbi.nlm.nih.gov/11688916/ https://pubmed.ncbi.nlm.nih.gov/11688916/)
    - dr_kiszonka 4y ago
      Were you taking 0.1 g/kg? How long was your treatment?
      - fnordpiglet 4y ago
        Yes. A few months but I felt results immediately, like within 30 minutes. I checked with my doctor first and she had no anxiety about trying it - she said any excess beyond what my body can manage would be immediately urinated out and citrulline is plentiful in the body.
elihu 4y ago
Interesting. 15 test and 15 control subjects for 3 months seems like a pretty small-scale study to definitively declare something safe, but maybe that's normal procedure for them? I assume the FDA is the final arbiter of what's safe and what isn't, but do they have a position? Or is this in the nebulous world of vitamin and mineral supplements that they don't regulate?
- deleted 4y ago
  [deleted]
- DennisP 4y ago
  If other commenters are correct that NMN accelerates preexisting cancers, then 15 test subjects would only have caught that effect if at least one happened to have cancer at the time.
- mrguyorama 4y ago
  The FDA does not really police supplements.
thelazydogsback 4y ago
Note that this study shows that supplements increase _blood serum_ levels of NAD, not concentrations inside the cell and mitochondria where it counts. So I'd say that without further qualification, this study shows safety more than efficacy. The role (if any) of exogenous NAD precursor supplementation is still a topic of debate, and there's a lot of money in selling these formulations. FWIW, I personally take NAD precursors because they likely do no damage (other than to the wallet), and they possibly do some small amount of good. There are plenty of other supplements I'd spend my money before NAD precursors. (And of course diet and exercise outweigh them all for most...)
- SubiculumCode 4y ago
  Is it generally available to buy?
  - WraithM 4y ago
    You can get NMN at most supplement places. NootropicsDepot sells it for example.
  - thelazydogsback 4y ago
    Sure - you can find many NR and NMN supplements on AMZN for example. NMN has gained popularity over NR, I believe mostly due to longer shelf life. Elysium and TruNiagen are two famous brands, that IIR were sueing each other at some point? I take another/cheaper NMN supplement. Caveat emptor - there's really no way to tell what you're getting from many of these - and even if you're getting pure ingredients, the jury is still out.
    - criddell 4y ago
      For the past couple of years I’ve been taking Nicotinamide Riboside I buy on Amazon and it has basically eliminated inflammation and pain I used to get in my hands, wrists, and sometimes elbows. FWIW, I’m going to be 52 this year.
  - faluzure 4y ago
gauravphoenix 4y ago
Do note conflict of interest: >YU, YF, TaS, and ToS were employees of Mitsubishi Corporation Life Sciences Limited and prepared NMN and the placebo
deleted 4y ago
[deleted]
bearjaws 4y ago
Just a heads up about NAD, its not recommended to take NAD if you or your family has a known history of cancer (primarily at younger ages <50). While it does not itself cause cancer, it accelerates cancer growth and thus can make catching it early less likely. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315198/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315198/
- DennisP 4y ago
  That sounds like a plausible reason for evolution to have given us lower NAD levels when we're older.
  - deleted 4y ago
    [deleted]
  - evo_9 4y ago
    - cpfohl 4y ago
      I have no doubt that you’re making these claims in good faith, but currently the score is 1 citation to 0…
    - thelazydogsback 4y ago
      Most things that increase normal cellular growth by stimulating the mtor pathway and IGF production, etc., will also increase abnormal cellular growth - including things like, well, eating - esp. carbs/sugar and protein. It's certainly possible that a marked increase in NAD _could_ increase the growth of certain types of cancers, but I'd think this effect would be swamped by other factors. As for "medical doctors" -- unless the MD in question is a (sports) nutrition specialist, perhaps oncologist, _and_ has graduated in the last few years or spends many hours a week keeping up with research that is accelerating every week, there's a good chance an intelligent consumer of podcasts/blogs/reddit/books is a better source of info on this topic. (Which is why I had to tell my MD why I wanted to take Metforin.) Not knocking MD's - but most simply don't have the time for this sort of thing the way practices are set up now.

70 points by evo_9 4y ago

deleted 4y ago

[deleted]

codevark 4y ago

SemanticStrengh 4y ago

What is the effect of NMN on the lipid/glucose mitochondria consumption ratio?

metadat 4y ago
Can you help elucidate us on why this matters?
- SemanticStrengh 4y ago
  Basically the ratio can be altered and it is very unclear if preferentially consuming lipids vs glucose is healthier than the converse. ALCAR shift said ratio towards pro lipids consumptions, which increase beta-oxidation. Thus it increase a kind of oxidative stress however in most studies it seems to both improve mitochondria bioenergetics and to reduce oxidative stress. ALCAR improve many aspects of health and conditions in a potent way while having no acute nefast side effects. You should see on reddit (e.g. sirsadalot), ALCAR is a very popular supplement and I was hyped like others because of the scientific evidence. Very few people know it but there exist a ~direct opposite to ALCAR: https://en.wikipedia.org/wiki/Meldonium#Physio-pharmacology https://en.wikipedia.org/wiki/Meldonium#Physio-pharmacology This drug decrease beta-oxidation and increase the ratio of glucose consumption. As you can see e.g. on the wikipedia page, the rethoric behind mildronate sounds too very positive except many of the statements pro ALCAR/Mildronate are contradictory, in direct opposition. So either there is an explanatory factor that resolve the contradictions, either one or the other do actually significant harm, despite both having backing scientific evidence of improving health. This topic is major since those are the most potent mechanics toward mitochondria bioenergetics regulation, which is a major way to improve your lifespan/healthspan and even cognition. The issue is that the quality of the dicussion/research needed to elucidate those issues is above the level found on online forums and no paper directly address the question, so I am stuck in uncertainty.
  - chillingeffect 4y ago
    Nmn is generally said w b fast-mimicking. In me it leads to collagen generation, soft skin, much faster than fasting or hyper-green drinks. ...if that helps your question...
  - LinuxBender 4y ago
    I wish I knew someone that had a lot of knowledge of ALCAR. As someone that takes many different supplements, consumes no sugar, does IF, remains mostly keto+, the one supplement I can't seem to take is ALCAR. It makes me feel "ill" for about 24 hours. It's hard to even describe the feeling. Just an overwhelming feeling that something is very wrong and generally just "feel like crap" for a day. I feel relief after a good full nights sleep which suggests to me that my brain is clearing the compound or a byproduct of it but that is just a theory.
    - SemanticStrengh 4y ago
      Hmm that seems like a pretty rare side effects, at least I've never seen it reported on reddit. (Although some people have insomnia/palpitations which can be explained by e.g. TMAO) Maybe ALCAR makes your body consume not enough sugar but that seems unlikely. > that is just a theory well if you try to not sleep or only have a short night duration I think the result would be similar. The half life of ALCAR is ~17h so after 24h you no longer have a pharmacologically relevant dose, assuming you take as low as 500mg. BTW I recently discovered the organelle https://en.wikipedia.org/wiki/Peroxisome https://en.wikipedia.org/wiki/Peroxisome which is actually important in lipid (and therefore glucose) and oxidative metabolism
      - LinuxBender 4y ago
        The glucose theory may be a good one to test out. I consume almost no glucose in my diet and I take several supplements that effectively also reduce gluconeogenesis. I also use Berberine. I will try a few different methods to boost either glucose or ketones in the brain prior to experimenting with ALCAR again.

xvector 4y ago

Is an elevation of NAD levels desirable? (Why?)

TaylorAlexander 4y ago
It seems it is an anti aging treatment and may help reduce aging related diseases.
faluzure 4y ago
Your NAD levels decrease as you age. Returning NAD+ levels to a more youthful state is one of the things researchers are experimenting with to reduce the effects of aging. Quoted from https://www.nmn.com/precursors/what-is-nad https://www.nmn.com/precursors/what-is-nad "NAD+ works as a shuttle bus, transferring electrons from one molecule to another within cells to carry out all sorts of reactions and processes. With its molecular counterpart, NADH, this vital molecule participates in various metabolic reactions that generate our cell’s energy."

faluzure 4y ago

Nice. More NMN studies are a good thing. I've been taking 250mg every morning and I feel like I have more energy, but I'm not convinced it's not a placebo effect.

rhexs 4y ago

I’ve been taking flush niacin, which I believe has the same effect at a much lower cost. Flush is really only annoying the first day.

Andys 4y ago
Flush niacin has been the only thing which has reliably improved my "long covid" symptoms.
- SemanticStrengh 4y ago
  You should consider doing a cycle of magnesium lthreonate for its potent synaptothrophic properties
- fnordpiglet 4y ago
  Try L Citruline. It easily passes the gut and readily converts to arginine which is a strong vasoprotector. Covid damages the lining of blood vessels. My belief is long covid is a redirection of free arginine to extensive vascular system damage and inflammation. At the minimum, it worked like a miracle for my long covid, YMMV. (Placebo possible of course, but citruline is used for body building as an energy and performance enhancer so the improvement in energy and thought clarity isn’t unexpected and has been shown to be beneficial in sickle cell which causes low free arginine due to the shape of the red cell irritating the lining of the blood vessels https://pubmed.ncbi.nlm.nih.gov/11688916/ https://pubmed.ncbi.nlm.nih.gov/11688916/)
  - dr_kiszonka 4y ago
    Were you taking 0.1 g/kg? How long was your treatment?
    - fnordpiglet 4y ago
      Yes. A few months but I felt results immediately, like within 30 minutes. I checked with my doctor first and she had no anxiety about trying it - she said any excess beyond what my body can manage would be immediately urinated out and citrulline is plentiful in the body.

elihu 4y ago

Interesting. 15 test and 15 control subjects for 3 months seems like a pretty small-scale study to definitively declare something safe, but maybe that's normal procedure for them? I assume the FDA is the final arbiter of what's safe and what isn't, but do they have a position? Or is this in the nebulous world of vitamin and mineral supplements that they don't regulate?

deleted 4y ago
[deleted]
DennisP 4y ago
If other commenters are correct that NMN accelerates preexisting cancers, then 15 test subjects would only have caught that effect if at least one happened to have cancer at the time.
mrguyorama 4y ago
The FDA does not really police supplements.

thelazydogsback 4y ago

Note that this study shows that supplements increase _blood serum_ levels of NAD, not concentrations inside the cell and mitochondria where it counts. So I'd say that without further qualification, this study shows safety more than efficacy. The role (if any) of exogenous NAD precursor supplementation is still a topic of debate, and there's a lot of money in selling these formulations. FWIW, I personally take NAD precursors because they likely do no damage (other than to the wallet), and they possibly do some small amount of good. There are plenty of other supplements I'd spend my money before NAD precursors. (And of course diet and exercise outweigh them all for most...)

SubiculumCode 4y ago
Is it generally available to buy?
- WraithM 4y ago
  You can get NMN at most supplement places. NootropicsDepot sells it for example.
- thelazydogsback 4y ago
  Sure - you can find many NR and NMN supplements on AMZN for example. NMN has gained popularity over NR, I believe mostly due to longer shelf life. Elysium and TruNiagen are two famous brands, that IIR were sueing each other at some point? I take another/cheaper NMN supplement. Caveat emptor - there's really no way to tell what you're getting from many of these - and even if you're getting pure ingredients, the jury is still out.
  - criddell 4y ago
    For the past couple of years I’ve been taking Nicotinamide Riboside I buy on Amazon and it has basically eliminated inflammation and pain I used to get in my hands, wrists, and sometimes elbows. FWIW, I’m going to be 52 this year.
- faluzure 4y ago

gauravphoenix 4y ago

Do note conflict of interest: >YU, YF, TaS, and ToS were employees of Mitsubishi Corporation Life Sciences Limited and prepared NMN and the placebo

deleted 4y ago

[deleted]

bearjaws 4y ago

Just a heads up about NAD, its not recommended to take NAD if you or your family has a known history of cancer (primarily at younger ages <50). While it does not itself cause cancer, it accelerates cancer growth and thus can make catching it early less likely. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315198/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315198/

DennisP 4y ago
That sounds like a plausible reason for evolution to have given us lower NAD levels when we're older.
- deleted 4y ago
  [deleted]
- evo_9 4y ago
  - cpfohl 4y ago
    I have no doubt that you’re making these claims in good faith, but currently the score is 1 citation to 0…
  - thelazydogsback 4y ago
    Most things that increase normal cellular growth by stimulating the mtor pathway and IGF production, etc., will also increase abnormal cellular growth - including things like, well, eating - esp. carbs/sugar and protein. It's certainly possible that a marked increase in NAD _could_ increase the growth of certain types of cancers, but I'd think this effect would be swamped by other factors. As for "medical doctors" -- unless the MD in question is a (sports) nutrition specialist, perhaps oncologist, _and_ has graduated in the last few years or spends many hours a week keeping up with research that is accelerating every week, there's a good chance an intelligent consumer of podcasts/blogs/reddit/books is a better source of info on this topic. (Which is why I had to tell my MD why I wanted to take Metforin.) Not knocking MD's - but most simply don't have the time for this sort of thing the way practices are set up now.