167 replies to this topic

[Turnbuckle]

 

NR -> NMN -> NAD->NAM

After that recycling so that can lead to single labelled NR

 

 

 

It can only lead to single labeled NR if NR is cleaved and reassembled.

[stefan_001]

NR -> NMN -> NAD->NAM

After that recycling so that can lead to single labelled NR

It can only lead to single labeled NR if NR is cleaved and reassembled.

Woops typo single labelled NAD+. Anyways for you it should not make a difference as you believe that reassembly path exists.

[Ovidus]

Dear Heisok, 

Thanks a lot for trying to get this back on track. 
How about we try and get this focused again on the main issues with a very simple question:

Can those who are using N + R (for whatever reason, whether because they are convinced it is better, lack of availability or whatever -really does not matter) tell us how much N and R respectively they have found to be ideal? 

[Turnbuckle]

 

 

NR -> NMN -> NAD->NAM

After that recycling so that can lead to single labelled NR

It can only lead to single labeled NR if NR is cleaved and reassembled.

Woops typo single labelled NAD+. Anyways for you it should not make a difference as you believe that reassembly path exists.

 

 

 

If you are now arguing the reassembly path exists (which you've already admitted on the previous page), then your argument is lost. Cells can make NR out of N+R. And if it is sufficient to erase almost all of the doubly labeled NAD+ by recycling NAD+, then it is perfectly sufficient to generate the same about of NAD+ from N+R to begin with.

[stefan_001]

Ok the thread starter and moderator wants to move to a "observational" discussion so with that I stop in this topic.

Edited by stefan_001, 19 September 2017 - 09:37 PM.

[MikeDC]

Look at the diagram on NAD+ recycling. Ribose is not involved in any step.
This topic was started to satisfy someone's ego. It will lead potential NR users into something that could be harmful since NAM inhibit Sirt1 and ribose increase glycation. Both will accelerate aging.

[Advocatus Diaboli]

The OP, Ovidus, in post #1 Question 1, asks: "Can those who have tried both and stuck with Nicotinamide + Ribose please chime in, because other than Turnbuckle I see nobody in that boat."

 

I've tried an earlier (not his current method) Turnbuckle protocol and the only effect I noticed was a transitory lowering of blood pressure, both systolic and diastolic, by about 15 and 10 mm, respectively (lasting about 4 hrs duration starting after about 1 hr post ingestion).

 

 

 

 

I'm currently trying HPN Niagen at 375mg/day (3x125mg) with no noticeable effects after 5 days. I will continue with whatever Turnbuckle protocol is current when my bottle of HPN Niagen is empty.

 

 

      

 

Edited by Advocatus Diaboli, 19 September 2017 - 11:09 PM.

[Advocatus Diaboli]

One thing I failed mention in post #67 is that the N+R tastes really nasty!  

 

[Nate-2004]

MikeDC made the only good point about glycation. If D-Ribose leads to glycation and NR is broken down into N+R in the gut then NR also leads to glycation. Taking N+R is definitely going to have a glycation problem if the referenced source he gave is true.

 

Turnbuckle, why do you think cells can create NR from N and R? I've yet to see a source on that or maybe I missed it in the sea of posts.

Edited by Nate-2004, 20 September 2017 - 04:18 PM.

[Harkijn]

Two days ago I repeated OP's invitation to users of N+R to come forward. No one ventured to describe ideas or experiences. Peculiar,  since even taking just ribose gives many people a 'lift'.

Those who feel they are swayed by assertions about N+R please also read my post #3 in this thread.....

[MikeDC]

Since D-Ribose is input to ATP production, a boost in energy is expected. But it doesn't mean that NAD+ and Sirt1 are increased.
We need both NAD+ and Sirt1 to increase to have anti aging effect.

[Advocatus Diaboli]

Re post #69

 

Nate, ribose causes glycation only in abnormally high doses. Quote from linked article:

 

"All the referenced studies demonstrated that D-Ribose can cause protein glycation (ribosylation), when D-Ribose is administered in high doses, with resulting damage to tissues."

 

"When D-Ribose is the sugar in the glycation process, as opposed to glucose or fructose, it is called ribosylation."

 

 

"The therapeutic dosage range simply cannot cause serum ribose concentrations to rise high enough to create ribosylation that was found in the laboratory studies."

 

 

[Harkijn]

Since D-Ribose is input to ATP production, a boost in energy is expected. But it doesn't mean that NAD+ and Sirt1 are increased.
We need both NAD+ and Sirt1 to increase to have anti aging effect.

Mike, you and someone else on this thread have made a lot of assertions. Lets put this at rest for the time being and ask N+R users if their experiences are better than NAM alone. Or whatever they want to comment on this issue.

[MikeDC]

The ribose from 250mg NR is extremely small compared to existing ribose in the cells. So if NR breaks down in the stomach, the only effect is from N. which means same dose of NR and N produce the same effect. We know this is not correct.

Not detecting NR in the blood may mean that NR is converted to NAD+ and other precursors when passing through liver.

[Harkijn]

Re post #69

 

Nate, ribose causes glycation only in abnormally high doses. Quote from linked article:

 

"All the referenced studies demonstrated that D-Ribose can cause protein glycation (ribosylation), when D-Ribose is administered in high doses, with resulting damage to tissues."

 

"When D-Ribose is the sugar in the glycation process, as opposed to glucose or fructose, it is called ribosylation."

 

 

"The therapeutic dosage range simply cannot cause serum ribose concentrations to rise high enough to create ribosylation that was found in the laboratory studies."

Says who?

[Nate-2004]

 

Since D-Ribose is input to ATP production, a boost in energy is expected. But it doesn't mean that NAD+ and Sirt1 are increased.
We need both NAD+ and Sirt1 to increase to have anti aging effect.

Mike, you and someone else on this thread have made a lot of assertions. Lets put this at rest for the time being and ask N+R users if their experiences are better than NAM alone. Or whatever they want to comment on this issue.

 

 

Subjective experiences and comparisons are best for the NR personal experiences thread, this thread is going nowhere because nobody can definitively say whether N+R results in NR and consequently a better increase in NAD+ than NR or NAM alone. There are literally no studies on this. The studies are certainly warranted in the midst of all the NR and NMN craze. So far nobody on this thread can answer the subject of the thread. There are two threads too, the one I started and this one. I imagine this got started because of the manipulating mitochondrial dynamics discussion.

 

I've got my personal experiences of NR which are positive, on that personal experiences thread. Though I'm currently doing the fission / fusion experiment so my regular intake has been changed to fission days only at 1000mg NR on those days. We shall see. My main concern is the movement disorder. If I see that improve considerably (especially considering this article) or other improvements then I'll know one thing is true. That I don't have to take it every day.

Edited by Nate-2004, 20 September 2017 - 05:42 PM.

[Advocatus Diaboli]

If whoever gave my post # 72 a "Needs references" had actually read the linked article they would have found the needed references. But, here they are, again:

 

http://www.lifeexten...ur-Life/Page-01

 

https://www.ncbi.nlm.../pubmed/1354276

 

https://www.ncbi.nlm...pubmed/22274132

 

https://www.ncbi.nlm...les/PMC3169629/

 

http://journals.plos...al.pone.0024623

 

https://www.ncbi.nlm.../pubmed/1901925

 

 

 

[Advocatus Diaboli]

@Harkijn, you wrote: "says who?" Read the article.

[Harkijn]

@Harkijn, you wrote: "says who?" Read the article.

Hi Advo, I did not rate your post 'Need ref' but it surely did  need references. I think all of us are glad that you decided to provide them. I for one will certainly check them. Thanks!

[Advocatus Diaboli]

@MikeDC re post #71 Here's a freebie for you.

@Nate, I reported a lowering of blood pressure in post #67, and Turnbuckle has mentioned it too. How about you?

@Harkijn post #79 "surely did  need references"

 

Well, I quoted some assertions in post #72. The reference for the quoted assertions was the link I provided in that post: " abnormally high doses ". So, I'm not sure why someone didn't consider the link that I gave as being a reference for the assertions that I listed. 

 

Clicking on that reference link I gave in post #72 shows that the assertions that I quoted are, indeed, in the link (i.e. a "reference" link) . The originator of the article, BioFoundations, provided 6 links within their article to substantiate their assertions about ribose, which I then listed in my post #77.

 

And, for the person who suggested that I need a reference for my post #77, here is one and here is another. (You probably won't get it, lol. But, if you need yet another reference (Yar) try this on for size. Boom! !).

[MikeDC]

This freebie I have read before. It listed NR and NMN as precursors and didn't list N+R.

https://www.ncbi.nlm...les/PMC4112140/

Anyone arguing for N+R should stop taking NR.

I don't need to lower my blood pressure. It is at 110/70 and never changed.

[Harkijn]

This freebie I have read before. It listed NR and NMN as precursors and didn't list N+R.
 

Yes, we discussed this study amply in 2014 in the Curated thread. Many other authors in the field have not deemed it worthwile to take N+R in consideration....

[Turnbuckle]

The ribose from 250mg NR is extremely small compared to existing ribose in the cells. So if NR breaks down in the stomach, the only effect is from N. which means same dose of NR and N produce the same effect. We know this is not correct.
 

 

You know this is not correct? How do you know? The direct comparison of NR to nicotinamide and nicotinic acid was done in mice at a very high dose, so the additional ribose would be a significant advantage. 

 

Look at Fig. 5b in this paper, where this comparison is made between mice given NR or NAM. Each data point represents 4 mice killed at that point, and only the livers were examined for NAD+.  NAD+ levels are not statistically different in 6 of 7 data points over the 12 hour period. Only at one point does it zoom up to twice that of NAM, and the whole story of NR being better than NAM vis-a-vis NAD+ is based on the livers of 4 mice at that singe hour at a dose of 185 mg/kg.

 

Although some mouse experiments have been done with IP administered NR at dosages of 1,000 mg kg−1 twice per day28, NR is active as an oral agent at a daily dose of 400 mg kg−1 by supplementation into food and demonstrated potent NAD+ boosting activity in the n=1 human experiment at 15 mg kg−1 (Fig. 2). On the basis of weight/surface area, the conversion between human adult dose and mouse dose is a factor of 12.3 (ref. 40), suggesting that mice should be administered 185 mg kg−1 to achieve comparable levels of supplementation with the human pilot experiment. We therefore designed a reverse translational experiment in which mice were administered 185 mg kg−1 of NR or the mole equivalent doses of Nam and NA by oral gavage. To ascertain the timecourse by which these vitamins boost the hepatic NAD+ metabolome without the complication of circadian oscillation of NAD+ metabolism17,18, we euthanized all mice at ∼2 pm. Thus, gavage was performed at 0.25, 1, 2, 4, 6, 8 and 12 h before tissue harvest. To stop metabolism synchronously, mouse livers were harvested by freeze-clamping. 

 

 

Another interesting point: NR is being sold with the claim it is closer on the pathway to NAD+ than other precursors, but if so, why isn't it faster in producing NAD+? In fact, from Fig. 5b referenced above, NR doesn't even get off baseline until hour 4, while niacin has already peaked and headed down. And NR doesn't match NAM until that point.

 

As shown in Fig. 5b, NA produced the least increase in hepatic NAD+ and also was 4–6 h faster than NR and Nam in kinetics of hepatic NAD+ accumulation.

 

 

The only way to explain such a large delay is that it has to be broken down first in the intestines, as previously shown in rats.

Edited by Turnbuckle, 21 September 2017 - 11:30 AM.

[MikeDC]

NR is bigger. So the absorption might take longer and take longer to get into cells.

At the end of the day, it is human experience and clinical trials that count. Get a few hundred people on Nicotinamide and observe the results. I am sold on NR both from science and personal experiences.

[Ovidus]

Subjective experiences and comparisons are best for the NR personal experiences thread, this thread is going nowhere because nobody can definitively say whether N+R results in NR and consequently a better increase in NAD+ than NR or NAM alone. There are literally no studies on this. 
........

I disagree with the first underlined sentence, precisely due to the accuracy of the second underlined sentence.

There are no studies that directly and satisfactorily compare N+R to NR. Therefore, all we here can do is go by personal experiences. Yes such experiences will be subjective and not scientific, but what else can be done? The indirect data at hand does not allow us to draw definitive conclusions.

 

So two questions

- Has anyone at all used both?
- Does anyone have any idea what a potential equivalent N+R would be (in terms of N and R dosages) that would replicate 250 mg of NR, which is the most common and label-recommended dose?

 

Thank you all

[stefan_001]

...mistake posting in wrong thread

Edited by stefan_001, 21 September 2017 - 09:48 PM.

[MikeDC]

I think it is the correct thread.

Using NRK1 liver-specific KO mice, we demonstrate that NRK1 is required to maintain hepatic NAD+ levels and mitochondrial function upon high-fat feeding

https://infoscience....h/record/229935

[MikeDC]

This means only NR can prevent mitochondrial disfunction upon high fat feeding. If NR becomes N+R, it will not be effective since NAMPT pathway is not sufficient to prevent high fat diet induced stress and provide sufficient NAD+.

[MikeDC]

"Here we show that nicotinamide riboside kinase 1 (NRK1) is necessary and rate-limiting for the use of exogenous NR and NMN for NAD(+) synthesis. Using genetic gain- and loss-of-function models, we further demonstrate that the role of NRK1 in driving NAD(+) synthesis from other NAD(+) precursors, such as nicotinamide or nicotinic acid, is dispensable"

This means that our body has negligible ability to synthesize NR from Nicotinamide or Niacin.

https://www.ncbi.nlm.../?i=2&from=nrk1

[MikeDC]

This study shows increasing NAD+ from NAMPT pathway doesn't improve muscle metabolic health. While NR studies show muscle metabolic health improved significantly. NMN showed 2 year old mice muscle turned into 3 month old in a few weeks. As suspected by many, there is a hidden benefit from NR beyond increasing NAD+.

http://m.jbc.org/con...290/3/1546.full