10 replies to this topic

[able]

New study finds higher dietary intake of NAD+ precursors reduced the risk of all causes of premature death, especially those related to cardiovascular diseases.

 

Below is from Rhonda Patricks post about this on foundmyfitness.

 

 

 

 

Nicotinamide adenine dinucleotide (NAD+) plays an essential role in multiple physiological processes, including energy metabolism, DNA repair, and immune activation. Cellular NAD+ production declines with age, however, and its depletion has been implicated in the onset and progression of a wide range of age-related conditions. Findings from a new study suggest that NAD+ is beneficial in treating heart failure with preserved ejection fraction.

The human study drew on nutritional and death rate data from a prospective, population-based survey of atherosclerosis among 40- to 79-year-old men and women. The data indicated that higher dietary intake of NAD+ precursors reduced the risk of all causes of premature death, especially those related to cardiovascular diseases. People who consumed more NAD+ precursors were also less likely to have high blood pressure. These findings held true even after taking into account other factors, including age, sex, smoking, diabetes, alcohol intake, body mass index, and total cholesterol.

These findings demonstrate that NAD+ precursors show promise as a means of treating heart failure with preserved ejection fraction. The FMF team has developed a collection of articles related to NAD+ and its precursors, nicotinamide mononucleotide and nicotinamide riboside.

• Link to study abstract.

 

[brundall]

So NAD+ precursors can extend healthspan by reducing risk of premature all cause death but probably don't extend lifespan according to yesterdays post. That's good enough for me and worth the cost of admission imo

[Guest]

Well, I can only draw from that blog post and the abstract, but it seems that it even could lower all cause mortality (it doesn't say directly). If the relationship can be replicated (it's an epidemological study).

 

You can even save on the cost of admission. The human observation part is referring to nicotinamide - not NR or NMN. People eating food sources rich in nicotinamide (fish, nuts, mushrooms) appear to have lower "premature death" compared to people not eating fish or nuts.

 

If this really means reduced total mortality: just buy nicotinamide for a fraction of the cost of NR or NMN

[rodentman]

So NAD+ precursors can extend healthspan by reducing risk of premature all cause death but probably don't extend lifespan according to yesterdays post. That's good enough for me and worth the cost of admission imo

 

The lifespan issue may be related to the CD38 issue.  I think a multi-pronged approach is probably a good idea, one that also focuses on nad+ boosting, senolytics and CD38 suppression.  Especially as we get older.

[able]

NAM has been shown to be beneficial in numerous studies.  

 

It has also been shown to be less beneficial than NR and NMN in other studies.

 

I'm pretty sure it has never been shown to be MORE benefit than NR or NMN in any research.

 

NAMPT is required to create NR/NMN from NAM, and is known as the rate limited step in the salvage process, thru which we get 85% of our NAD+.

 

The reason for NMN and NR is they bypass this bottleneck in salvage process.

 

So while NAM is dirt cheap and seems to have benefit for human health span, there is no reason to believe it is "as good" as NMN or NR for health, beyond the price.

 

 

Edited by able, 12 February 2021 - 10:02 PM.

[Guest]

In science nothing beats empirical evidence.

 

 

On a forum called "Longecity" this means:

 

a) actual disease outcomes; e.g. reduction in cardiovascular events, cancer cases or mortality of each

 

b) ideally positive lifespan effects

 

 

There is precious little data for NMN and not much for NR on either a) and b) in humans. Which makes it hard to tell if they would be indeed better than NAM - also considering potential bioavailability issues for practical dosing and potential feedback effects on endogenous NAD cycling.

 

The FMF blog posted a study that found an association between NAM consumption in food and "premature death" (and maybe lifespan.... I can't access the paper). That's not a trial, but an observational study, so all the usual disclaimers about causality apply. Nonetheless, it's the best there is (i.e. population statistics based on NAM consumption) in human data, barring some clinical trial of NR/NMN that report on actual disease outcomes instead of just biomarkers.

 

In addition there are controlled trials in mice, which you may or may not take serious - though undoubtedly Elysium and Chromadex would jump on any positive mice lifespan study as "proof" for NR/NMN.

 

 

To illustrate the situation with another molecule:

 

2-Deoxy-D-glucose and Glucosamine are both almost identical to glucose. 2DDG is the more potent molecule in terms of the primary effect - inhibition of glycolisis and activation of mitochondrial metabolism. It shows anti-tumor properties and is used in cancer trials. It activates autophagy.

 

Researchers in the field of hormesis and cancer assumed based on biomarkers, that it would perform better than glucosamine in lifespan trials. Surprisingly 2DDG did not only fail - but was toxic in long term application in mice. Glucosamine had less an effect on glycolisis and mitochondrial metabolism. But given in old age it still extended lifespan in mice.

 

In short: there is no replacement for the actual experiment to validate theoretical considerations

Edited by Guest, 13 February 2021 - 12:26 AM.

[MikeDC]

Could be due to Taurine intake.

[able]

 

 

In short: there is no replacement for the actual experiment to validate theoretical considerations

 

 

True.  

 

There are numerous experiments that found NAM was not effective when NMN or NR were in the same experiment.   That is not theoretical.

 

No research has found NAM more effective than NMN or NR.

 

I do agree that they have bioavailability problems and are mostly degraded to NAM, so the effects are often similar.

 

But there is a difference.  Especially when given by IV to bypass the bioavailability problem.  That is not theoretical either.

Edited by able, 14 February 2021 - 04:09 PM.

[Guest]

We have to be careful not to get too excited about biomarkers. While it can be an indicator to pursue further studies in mice and man, biomarkers alone still mean it's rather uncertain what the actual effect size will be on diseases (and longevity).

 

There are numerous studies looking at (short term) biomarkers and you are correct that their profile is more favorable than for NAM. So as an investigator this means focusing more attention on NR/NMN.

 

 

However, until we have more data on actual clinical outcomes - number of disease events/disease mortality or disease progression (in men, mice or maybe monkeys) - the jury is still out if it's a good idea:

 

a) to take NAD-boosters

 

b) at what dose and route of administration

 

 

Elysium (Sinclair) and Chromadex (Brenner) are marketing their products based on the assumption, that low dose oral intake is the way to go (based on their recommended intake).  I think any neutral observer would agree, that there is no strong argument for that based on data about disease pogression/events/mortality in mice or otherwise.

 

 

Don't get me wrong: I would LOVE if there is a compound, NAD precursors or something else, that I can pop a once-a-day-pill of, and get a lifespan or substantial disease modification benefit. I'm taking a number of pills already to optimize my chances for that. So I'm not "happy" that the NR (at the dose used) failed in the ITP trial. But given the vast amount of potential substances to take, we should be careful in scrutinizing claims about health or lifespan - particularly with rather costly things.

 

So as the mice at least didn't get a negative effects (the number one cause of death for lab mice is cancer - NR it seems didn't fuel that one), and if you have the funding, you can say you're doing that personal experiment in the hopes that there will be better data in the future. But be conscious about how preliminary the evidence is and open minded if it fails in the future.

[Phoebus]

So NAD+ precursors can extend healthspan by reducing risk of premature all cause death but probably don't extend lifespan according to yesterdays post. That's good enough for me and worth the cost of admission imo

 

 

They don't extend life span...in mice!

 

They might in humans, who knows? 

 

Also the study in the OP is about consuming nicotinamide, NOT NR and/or NMN, just an FYI 

Edited by Phoebus, 14 February 2021 - 06:28 PM.

[MikeDC]

I am pretty sure NR/NMN can extend lifespan in both mice and humans. The problem is the studies used a dose that is too high. The root cause is low bioavailability of NR and NMN. NRH will get better results.