46 replies to this topic

[Phoebus]

I haven't done the math but per mg nicotinamide is about 1/10 the price of NR/NMN

 

It also raises NAD+ although exactly how much and how it compares to NR/NMN I cant say. 

 

https://www.ncbi.nlm...pubmed/10566977

 

but you could take 3x the amount compared to NR/NMN and it would still be cheaper. So really why bother with NR/NMN at all and just stick to nicotinamide? 

[tunt01]

Inhibits SIRT1, which is exactly what you don't want.

 

EDIT:

 

Why is this even in dispute?  It's one thing if you don't want to inhibit SIRT1, that may be understandable.  But Nicotinamide definitely inhibits it.

 

 

 

Evidence that SIRT1 activity contributes to excitotoxic neuronal death. a SIRT1 deacetylase activities in cell extracts of neurons that had been exposed to the indicated concentrations of resveratrol or nicotinamide for 2 h. b Immunoblot showing SIRT1 levels in cortical neurons that had been treated for 2 h with the indicated concentrations of nicotinamide and sirtinol. c-e Survival of cortical neurons in cultures that had been treated with the indicated concentrations of sirtinol, NAD, NADH, or resveratrol, and then exposed to glutamate/NMDA for 24 h. f NAD+ levels in cortical neurons that had been treated with indicated concentration of resveratrol for 24 h. Values are the mean and SD of determinations made in at least four separate cultures. *P< 0.05, **P < 0.01

 

 

 

Liu, D., Gharavi, R., Pitta, M., Gleichmann, M., & Mattson, M. (2009). Nicotinamide Prevents NAD+ Depletion and Protects Neurons Against Excitotoxicity and Cerebral Ischemia: NAD+ Consumption by SIRT1 may Endanger Energetically Compromised Neurons. Neuromolecular Medicine, 11(1), 28-42. doi:10.1007/s12017-009-8058-1

Edited by tunt01, 28 May 2018 - 01:42 AM.

[Phoebus]

Inhibits SIRT1, which is exactly what you don't want.

 oh, I see, did not know that 

[aribadabar]

Inhibits SIRT1, which is exactly what you don't want.

 

EDIT:

 

Why is this even in dispute?  It's one thing if you don't want to inhibit SIRT1, that may be understandable.  But Nicotinamide definitely inhibits it.

 

 

 

 

Liu, D., Gharavi, R., Pitta, M., Gleichmann, M., & Mattson, M. (2009). Nicotinamide Prevents NAD+ Depletion and Protects Neurons Against Excitotoxicity and Cerebral Ischemia: NAD+ Consumption by SIRT1 may Endanger Energetically Compromised Neurons. Neuromolecular Medicine, 11(1), 28-42. doi:10.1007/s12017-009-8058-1

 

Are these concentrations achievable in humans taking normal doses of NAM (< 2g) ?

[MikeDC]

In the Trammel paper, NR caused much higher NAD+ consumption flux than NAM.  

[SearchHorizon]

I'm not sure if you want chronic activation of SIRT1. Activating SIRT1 raises cortisol. This makes sense, if you consider the fact that cortisol is a stress-handling hormone and SIRT1 is associated with stress.  Chronic production of cortisol usually spells trouble. Thus, there is the possibility that chronic activation of SIRT1 may not be what one wants.

 

NAM's SIRT1's inhibition is transitory, which is what you'd want.

[Harkijn]

I'm not sure if you want chronic activation of SIRT1. Activating SIRT1 raises cortisol. This makes sense, if you consider the fact that cortisol is a stress-handling hormone and SIRT1 is associated with stress.  Chronic production of cortisol usually spells trouble. Thus, there is the possibility that chronic activation of SIRT1 may not be what one wants.

 

NAM's SIRT1's inhibition is transitory, which is what you'd want.

A short discussion of this topic wiith references for further reading can be found here:

https://www.research..._until_it_stops

 

So, yes transitory but  3 to 4 hours after every supplementation was found far too long in discussions elsewhere on LC.

[SearchHorizon]

A short discussion of this topic wiith references for further reading can be found here:

https://www.research..._until_it_stops

 

So, yes transitory but  3 to 4 hours after every supplementation was found far too long in discussions elsewhere on LC.

 

IMO, that depends on the timing of and the protocol associated with NAM administration over a 24 hour period.

 

Ideally, one'd want SIRT1 inhibition during and after eating dinner (post-prandial period) when the body is in a regenerative mode. This post-prandial period can take 8-12 hours. So if you take niacinamide just before dinner, it should amplify the effects of eating (and regeneration) since SIRT1 is inhibited. As the body passes from the post-prandial mode to the fasting mode (overnight), the niacinamide and fasting should strongly activate SIRT1.

 

This scheme should work exceptionally well for those who practice 20/4 fast-feed time-restricted feeding.

[SearchHorizon]

Also, here is a link to an abstract that talks about limited inhibition of SIRT1 by NAM.

 

https://www.ncbi.nlm...pubmed/28417163

Edited by SearchHorizon, 15 October 2018 - 07:15 AM.

[Fredrik]

This 2018 paper argues that nicotinamide increase SIRT1 activity in cells and activates autophagy and mitophagy. Reference 18. in this paper is the same as has been discussed in this thread.

 

 

Nicotinamide (NAM), an amide form of vitamin B3, is a potent inhibitor of sirtuins, a family of NAD⁺-dependent deacetylases. The sirtuin family proteins, of which SIRT1 is the best known, play critical roles in cellular and organismal health and longevity (17), and NAM has been predicted to negatively affect cell viability. However, in cells NAM is rapidly converted to NAD⁺ through a salvage pathway, and therefore treatment with NAM has been found to increase SIRT1 activity (18). As a result, NAM appears to protect cells against oxidative stress in a number of studies, including ours. For example, administration of 5 mM NAM caused a decrease in mitochondrial superoxide levels and resulted in substantial extension of proliferative potential in normal fibroblasts (19). The treated cells showed a decrease in mitochondria content but an increase in their quality as evidenced by lower levels of ROS generation and oxidative damage to mitochondrial proteins. These changes might be due at least in part to activation of autophagy (and mitophagy) through SIRT1 mobilization driven by the NAM-induced increases in the NAD⁺/NADH ratio (20).

 

 

http://www.ijstemcel...ge=13&year=2018

 

18. Hwang, ES, and Song, SB (2017). Nicotinamide is an inhibitor of SIRT1 in vitro, but can be a stimulator in cells. Cell Mol Life Sci. 74, 3347-3362.

 

 

19. Kang, HT, Lee, HI, and Hwang, ES (2006). Nicotinamide extends replicative lifespan of human cells. Aging Cell. 5, 423-436.

 

 

20. Jang, SY, Kang, HT, and Hwang, ES (2012). Nicotinamide-induced mitophagy: event mediated by high NAD+/NADH ratio and SIRT1 protein activation. J Biol Chem. 287, 19304-19314.

  

[MikeDC]

This paper shows human plasma NAD+ goes down with age and NAM goes up with age.
https://www.ncbi.nlm...from=plasma nad

[MikeDC]

Nicotinamide make it worse for rat with Parkinson disease.
There is another paper that shows NR ameliorate Parkinson disease in flies.

https://onlinelibrar....1111/jnc.14599

[MikeDC]

Finally, mice were fed with ethanol diet added with 200 mg/kg NAM to serve as a SirT1 inhibitor. We found that SirT1 was significantly decreased in NAM- fed mice (Fig. S8A). NAM indeed exacerbated lipid accumulation in the hepatocytes and also exaggerated levels of serum ALT, AST, and hepatic MDA induced by ethanol (Fig. S8B-D). Although NAM reversed the reduced NAD+ levels by ethanol, the level of ATP was much lower in the NAM group (Fig. S8E). This data confirmed in vivo that inhibition of SirT1 is one key step for the formation of ALD.


https://www.ncbi.nlm...72/#!po=54.8077

NAM does increase NAD+. But the positive effect of increased NAD+ is more than compensated by NAM inhibition of Sirt1. I am not going to dig up other papers that show NR worked in brain and heart white NAM didn’t.

Edited by MikeDC, 15 October 2018 - 01:56 PM.

[SearchHorizon]

This paper shows human plasma NAD+ goes down with age and NAM goes up with age.
https://www.ncbi.nlm...from=plasma nad

 

You have to consider that NAMPT goes down with age - so, you'd expect NAM to go up with age.  By loading up with NAM even more, you are just moving the point of chemical equilibrium, at which you have higher NAD+.

Edited by SearchHorizon, 16 October 2018 - 02:12 AM.

[Nate-2004]

As I've asked and argued in other threads, the goal should be to boost NAMPT, that would be ideal. NAD+ falls not just because there are more NAD+ consumers but also because NAMPT activity drops. Maybe it can't keep up with demand? I don't know why the focus hasn't been on attempting to do this instead.

 

The only thing that for sure boosts NAMPT is exercise, there may be other things though. If I'm taking NMN or NR I'm going to exercise that day. Excess NAM is going to mess things up and possibly further dysregulate the cycle.

[MikeDC]

H2S has the effect of boosting NAMPT. I think it was mentioned in Sinclair’s paper on NMN and H2S. Taking Taurine will increase H2S and other benefits.

[Harkijn]

As I've asked and argued in other threads, the goal should be to boost NAMPT, that would be ideal. NAD+ falls not just because there are more NAD+ consumers but also because NAMPT activity drops. Maybe it can't keep up with demand? I don't know why the focus hasn't been on attempting to do this instead.

 

The only thing that for sure boosts NAMPT is exercise, there may be other things though. If I'm taking NMN or NR I'm going to exercise that day. Excess NAM is going to mess things up and possibly further dysregulate the cycle.

Coudn't agrree with you more.

A recent LC thread relevant here is:

https://www.longecit...ase-activation/

Since a few weeks I take my NR together with resveratrol, garlic and NAC with promising results.

[QuestforLife]

Another way to raise NAMPT is troxerutin. (or at least cancel out the effects of having lots of oxidized lipids in your blood)

 

https://www.ncbi.nlm...pubmed/25026599

 

(full text on sci-hub)

 

[QuestforLife]

Re: NAD inhibiting SIRT, this IS a temporary effect - which is used so that PARP can unwind and repair DNA without letting the SIRTUINS start curling it up again. It does this by using up NAD and producing NAM at those locations. But of course once NAMPT has recovered that NAM is once again available to be recycled into NAD. 

[MikeDC]

Another way to raise NAMPT is troxerutin. (or at least cancel out the effects of having lots of oxidized lipids in your blood)

https://www.ncbi.nlm...pubmed/25026599

(full text on sci-hub)

Side effects are associated with almost all natural and synthetic molecules. Intervening in our body’s chemical processes is extremely hard. Increasing NAMPT might be okay. But decreasing PARP1 might not.

The beauty of NR is it is a molecular our body already use and our body needs more when we are older.

[SearchHorizon]

The beauty of NR is it is a molecular our body already use and our body needs more when we are older.

 

Except that most of NR consumed is converted into NAM when it is in the blood stream. 

 

Probably only 5% of orally administered NR survives the gut.

[MikeDC]

Except that most of NR consumed is converted into NAM when it is in the blood stream.

Probably only 5% of orally administered NR survives the gut.

We don’t know if it is 5% or 10%. But we do know 250 mg NR daily provided great health benefits that NAM doesn’t. We also know NR was effective at preventing liver, heart and brain damage that NAM doesn’t. (I am not going to digg up the papers this time)
The low bioavailability of oral NR just shows the potential of NR is much more than we are getting now. Someday, we will get a better formulation of NR that provide much greater benefits.

[able]

We don’t know if it is 5% or 10%. But we do know 250 mg NR daily provided great health benefits that NAM doesn’t. We also know NR was effective at preventing liver, heart and brain damage that NAM doesn’t. (I am not going to digg up the papers this time)
The low bioavailability of oral NR just shows the potential of NR is much more than we are getting now. Someday, we will get a better formulation of NR that provide much greater benefits.

 

Or 2% or 3%.

 

We know that when given to mice in drinking water, it is more effective than NAM

 

But so far, there is little or no evidence that it does more than NAM when humans take NR capsules.  I believe it does, but we have no proof yet.

 

We do NOT know that 250 mg NR provides great health benefits.  

 

Edited by able, 17 October 2018 - 02:43 PM.

[MikeDC]

Or 2% or 3%.

We know that when given to mice in drinking water, it is more effective than NAM

But so far, there is little or no evidence that it does more than NAM when humans take NR capsules. I believe it does, but we have no proof yet.

We do NOT know that 250 mg NR provides great health benefits.

The 200,000 people that are taking NR obviously do get more benefits than NAM. Otherwise why would they pay so much more money for it? Clinical trials show evidence that NR reduces blood pressure and fatty liver. They need to design larger trials to show statistically significant results obviously. But the evidence is there.

[QuestforLife]

Do we have a clinical trial (for mice or humans) comparing NR with NAM as a positive control?

[MikeDC]

Do we have a clinical trial (for mice or humans) comparing NR with NAM as a positive control?

I am not going to list all the references.
1. NR increased NAD+ consumption more than NAM and Niacin
2. NR prevented alcoholic liver enjury while NAM didn’t
3. NR protected the heart while NAM didn’t
4. NR improves Huntington’s while NAM make it worse.

[MikeDC]

There is also an article saying we are consuming too much meat that contains NAM. This over nutrition is damaging our health.

[Pirateer]

Howdy all,

 

Could you take Nicotinamide (NAM) sublingually and get the same benefit you do with sublingual NMN/NR/ABNs new NAD powder? I'm all for reducing cost. To cut costs I tried Pau d'arco with it's beta lapachone and it didn't react well with me for some reason. I currently do sublingual NR and NMN and hopefully soon NAD. Sublingual administration seems to have more bang for buck also.

 

Cheers.

[Phoebus]

Howdy all,

 

Could you take Nicotinamide (NAM) sublingually and get the same benefit you do with sublingual NMN/NR/ABNs new NAD powder? 

 

 

no

[Pirateer]

Phoebus:

I haven't done the math but per mg nicotinamide is about 1/10 the price of NR/NMN

It also raises NAD+ although exactly how much and how it compares to NR/NMN I cant say.

https://www.ncbi.nlm...pubmed/10566977

but you could take 3x the amount compared to NR/NMN and it would still be cheaper. So really why bother with NR/NMN at all and just stick to nicotinamide?

 

Pirateer:

Could you take Nicotinamide (NAM) sublingually and get the same benefit you do with sublingual NMN/NR/ABNs new NAD powder?

Phoebus:
no


So you've changed your mind and now believe that NAM doesn't raise NAD+ despite being cheaper? Why the change of mind?