18 replies to this topic

[PeaceAndProsperity]

NR (Nicotinamide riboside) is touted as being able to do something NA (nicotinic acid) can't do, increasing NAD in brain and muscle cells. But if NA converts to NR why would it not hold true that ultimately NA increases NAD in brain and muscle cells as NR does?

 

If NA only converts to nicotinamide and not NR itself (although NR is broken down to nicotinamide and riboside separately and taken up to be recombined) why should adding riboside to NA supplementation not work as taking nicotinamide together with riboside works to increase NR and ultimately NAD?

 

Do patents make NA useless for anything? Do patents make NA not do these things NR does?

[SearchHorizon]

What I read was that certain tissues have more enzymes that deal with a specific form of a Vitamin B3 in its conversion to NAD+. In particular, neurons carry enzyme for converting NR into NAD+, but lack enzymes for converting NAM or NA into NAD+.

 

Having said that, there has to be some cross-talk between different vitamin B3 salvage pathways. For example, some NAM should end up as NR before it is eventually broken down; similarly for other vitamin B3. Some NAM or NA would convert to NR and be carried into the nerve cells.

 

How much cross-talk there is between different pathways should depend on the efficiency of various Vitamin B3 salvage pathways (i.e., the amount converted into another B3 form) before its degradation. Given that we don't know, we'd like vitamin B3 to end up as the most bio-effective form (i.e., NR) as early as possible.

 

 

 

[PeaceAndProsperity]

This graph posted in this thread http://www.longecity...e-2#entry682735

directly shows that NA does increase muscle NAD

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[MikeDC]

The increase is only about 40% of NR.

[PeaceAndProsperity]

it looks to be close to nr's effects. why did you repeatedly claim that na does not increase muscle nad?

[MikeDC]

Niacin's effect is close to the vehicle in both muscle and liver.

[PeaceAndProsperity]

no that is nmn, na is dark gray and nmn is light gray

[MikeDC]

You are correct on this one. But millions take Niacin at high doses and don't have same effect as Niagen.

[PeaceAndProsperity]

Hundreds of thousands of people have taken NR and not had the positive effects on cardiovascular disease seen with NA. This doesn't even scratch the surface of the tens of other positive effects of NA.

 

The most common review for NR products is, "I'm on my third bottle of 500mg and can't tell if it's doing anything."

The second most common review is some idiot who claims he can physically see that he is getting younger although even the greedy patent holder with his fraudulent studies that conclude all sorts of lies claims it won't make you younger.

[MikeDC]

Keep trashing NR and promise never to take it. In the mean while we are getting benefits from NR.

[Florian E.]

Seems like he was kind of right concerning muscle tissue... according to this (https://www.ncbi.nlm...51433/table/T1/)

 

 

And here are some quotes from "ChromaDex: Response To The Claim Niagen Is Just 'Expensive Vitamin B3" interview (https://seekingalpha...sive-vitamin-b3)

 

 

 

Q: The article I asked you to read stated that "All three produce NAD+ in the human body." Please elaborate on this.

Q: What's the problem with niacin or nicotinamide as a NAD+ precursor?

 

CB: There are trillions of cells in the human body of many hundreds of cell types. For example, there are nerve cells, skeletal muscle cells, cardiac cells, several types of pancreatic cells, several types of blood cells, liver cells, etc. What makes a neuron a neuron and not a hepatocyte is the expression of neuronal genes. When we discovered NR as a vitamin, we discovered the NR pathway to NAD. The value proposition of NR depends on the unique ability of NR to maintain and boost NAD in every cell and tissue and, in particular, in tissues undergoing damage and stress.

There are only two steps in the NR pathway to NAD but there are two genes that can do the first step and three genes that can do the second step. The NR pathway never gets turned off. NRK1 is expressed in every cell and tissue, while NRK2 is turned on by cellular damage, particularly in skeletal and cardiac muscle. This means that people supplementing with NR are able to keep NAD levels high in stressed cells that specifically have the NR pathway turned on to deal with cellular stress. Supplementing with niacin and nicotinamide doesn't help because they don't feed into the NR pathway, which is turned on by stresses.

 

 

CB: There are three problems with niacin and two problems with nicotinamide, particularly at high doses.

First, niacin can't be used in lots of tissues because the niacin pathway is not on. The brain and skeletal muscle can't use niacin to boost NAD and these are two of the most important tissues that suffer the ravages of aging. Niacin also causes flushing at high doses and does not efficiently elevate mitochondrial NAD.

The nicotinamide pathway declines in aging, which means you would need ever higher doses to try to maintain your NAD. Second, at high doses, nicotinamide inhibits sirtuins, which is the opposite of NR. NR is a STAC that extends lifespan in model systems.

 

To my understanding one essential point is that NR can boost NAD even in damaged/stressed cells. And NMN is even better at this task. 

 

And i can remember some study graphics which showed different NAD+ levels by NA, NR and NMN, where NMN and NR NAD+ levels where way above NA. Unfortunately can't find it anymore.

 

I'm personally not sure what to think about all of that, at this point. Maybe, in the meanwhile, i just take NA, NR and NMN all together 

Edited by Florian E., 16 April 2017 - 02:47 PM.

[PeaceAndProsperity]

The issue is that there are a plethora of contradictory studies that literally each get to polar opposite results, and some clearly have financial gains in NR or NMN being shown as vastly superior.

Even if it is a 100-step process that uses the Adolph Goldberg pathway of NAD synthesis, if in the end NA has to become NR to make NAD or for another reason then what does it matter? Just take the 4g of NA and reap the other benefits. I could make sense out of why this wouldn't work but it clearly looks to be working.

 

Also, according to your study graph NR does not increase NAD in cells that NA does so in?

[MikeDC]

Niacin and Nicotinamide are metabolites of NR. Pathways for NR, NA, and Nicotinamide all contribute to NAD+ When you take NR.

[PeaceAndProsperity]

That makes no sense, NR is not converted back to NA. The conversion goes the other way. i know you are joking

[mikeinnaples]

Niacin and Nicotinamide are metabolites of NR. Pathways for NR, NA, and Nicotinamide all contribute to NAD+ When you take NR.

 

Just a little friendly advice and please take it as me being friendly.

 

In this thread you have absolutely completely misrepresented study results despite it being clearly shown for all to see. Even someone casually glancing at this (me) noticed it easily. You have also completely posted something inherently wrong. So given this, it is probably best to not be so aggressive when someone points that out. You absolutely have to expect that on these boards.

[mikeinnaples]

The issue is that there are a plethora of contradictory studies that literally each get to polar opposite results, and some clearly have financial gains in NR or NMN being shown as vastly superior.

 

I agree with this. There is some good literature and charts linked to on these very boards (you will have to use the forum search feature because I don't have the link handy) that show the pathways involved. The price and availability of NA is drastically different than NR, so the profit margin on NR is going to be significantly higher than that of a supplement readily available at your local pharmacy or grocery store.

 

With that said, note the difference:

 

NR->NMN->NAD

NA->NaMN->NaAD->NAD

NAM ->NMN->NAD

 

From NAD they all recycle the same, but I think the key to NR is the ribose. I am sure someone that actually works in the field can confirm or deny as I can only do my best to interpret publications and follow the people in the field on these boards that engage in these discussions.

 

Anyways, with that said .... there is enough literature to support NA actually working better in some cases than NR providing you can tolerate the flush as well as it being a viable much cheaper alternative to NR in a pinch. Also please note that flush free 'niacin' is not nicotinic acid. Me personally, I take BOTH. NR in the morning and NA in the evening. NA is cheap enough, I can barely flush up to 2g, and it has the lovely side affect of raising HDL in its pathway.

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[MikeDC]

Increasing NAD+ is not the only effect NR has probably. What determines which one is better is human studies. From experiences of taking NR in my family and my friends, I am pretty sure NR is much superior to NA and NAM. Do I want to try NA to save money? No. I consider NR as dirt cheap considering the effects it provides for me.

It is pointless to argue. If you believe in NA, take it. If you believe in NR, take it.

Edited by MikeDC, 18 April 2017 - 01:25 PM.

[mikeinnaples]

I am not sure where belief comes into anything, either the science supports something or it doesn't. Anecdote is all good and well but it serves no real purpose and the placebo affect is also very well documented. I am really not sure what you are adding to the conversation at this point other than acting as a cheerleader. If I wanted to take things on faith alone, I wouldn't be an atheist. I guess the question I have for you is why are you trying to hard to spread the gospel of NR ? You do realize that there is an entire thread that has been long running purely dedicated to anecdote right? Maybe you should keep the preaching there instead.

 

 

Edit:

 

To be clear, from one Mike to another, I am most certainly pro-NR, so take what I am telling you as from someone on your side.

Edited by mikeinnaples, 18 April 2017 - 02:26 PM.

[PeaceAndProsperity]

What's the difference between nmn and namn. What does "NaMN" stand for?