2284 replies to this topic

[ambivalent]

The kidney pain that was so severe, I nearly called for an ambulance, followed the day after stopping NR because of the new benchmark of extremity pain. The extremity pain is undoubtedly NR or N+R - I'd experienced this when just on NR as have others.

 

There is also a dizziness I've experienced when first taking NR which I knew to be the same dizziness frequently experienced 15-20 years prior when my blood-glucose was undoubtedly very high from an extremely sugar diet. I have no doubt that NR and possibly N+R are responsible for the extremity pain (incidentally my feet still felt 'bruised' even now ): it is way too strongly correlated. The uncertainty resided as to whether it was responsible for triggering kidney damage of which I've never experienced the like of.

 

The possibility that these two events are unrelated seems rather unlikely - it is a question of whether it was direct or indirect (such as stirring up kidney stones, say).

 

There can be a tendency to be bias against the obvious, because it is the smarter thing to do as we know people leap to connections; however, we can overcompensate too. My health has been excellent for years save histamine problems earlier this year exacerbated, but not caused by NR. I have had great benefits from NR and N+R too, in fact I felt incredible just a couple of days prior. 

 

 

We have evidence of ribose increasing glycated haemoglobin and NAM inducing glucose intolerance:

 

https://www.ncbi.nlm...mentation sirt1

 

In addition:

 

 

https://www.ncbi.nlm...pubmed/22559853

 

In hyperglycemia, the kidneys may play an exacerbating role by reabsorbing excess glucose, ultimately contributing to chronic hyperglycemia, which in turn contributes to chronic glycemic burden and the risk of microvascular consequences.

 

 

 

My diet had been poor recently which I suspect meant elevated levels of blood glucose were pushed higher, which is why perhaps others have been ok. Others have been fine. I'm not interested in banging on about this, I may well be an outlier, but I'd say it is extremely unlikely the problems I've experienced have not been NR, N+R related. 

[Turnbuckle]

The kidney pain that was so severe, I nearly called for an ambulance, followed the day after stopping NR because of the new benchmark of extremity pain. The extremity pain is undoubtedly NR or N+R - I'd experienced this when just on NR as have others.

 

There is also a dizziness I've experienced when first taking NR which I knew to be the same dizziness frequently experienced 15-20 years prior when my blood-glucose was undoubtedly very high from an extremely sugar diet. I have no doubt that NR and possibly N+R are responsible for the extremity pain (incidentally my feet still felt 'bruised' even now ): it is way too strongly correlated. The uncertainty resided as to whether it was responsible for triggering kidney damage of which I've never experienced the like of.

 

The possibility that these two events are unrelated seems rather unlikely - it is a question of whether it was direct or indirect (such as stirring up kidney stones, say).

 

 

 

If connected, could be the ribose. It appears that ribose can raise uric acid in some people, and that can produce UA stones.

[Nate-2004]

I understand. I'm actually back on the keto diet as I've figured out it played a strong synergistic role with MCT oil in diminishing my tremor significantly. It's an ultra low carb diet which may help you when experimenting with this protocol. Not sure.

[ambivalent]

re uric acid: I'm currently two days in to a fast. This morning, when I awoke, I belched and a moderate about of bile surfaced, it was extremely acidic. Not something I recall expereincing before to that degree.  I'll give some sodium bi-carb a go.

Edited by ambivalent, 01 November 2017 - 04:32 PM.

[Andey]

I'm currently two days in to a fast. This morning, when I awoke, I belched and a moderate about of bile surfaced, it was extremely acidic. Not something I recall expereincing before to that degree.  I'll give some sodium bi-carb a go.

   If you get dizzy on standing from sitting I would suggest to add a significant amount of plain salt. Dizziness is often experienced during fasts or keto diet because mineral excretion speedups a lot during ketosis. Esp if you are low on salt, to begin with. When you are low on electrolytes a lot of basic things start to go wrong very fast. 

[ambivalent]

 

I'm currently two days in to a fast. This morning, when I awoke, I belched and a moderate about of bile surfaced, it was extremely acidic. Not something I recall expereincing before to that degree.  I'll give some sodium bi-carb a go.

   If you get dizzy on standing from sitting I would suggest to add a significant amount of plain salt. Dizziness is often experienced during fasts or keto diet because mineral excretion speedups a lot during ketosis. Esp if you are low on salt, to begin with. When you are low on electrolytes a lot of basic things start to go wrong very fast. 

 

 

Andey: I'm not on the keto diet and I'm not currently experiencing the dizziness while fasting. But yes the salt tip is one I've heard of and will employ if I go deeper in. Thanks.

 

Nate: I will try this again, hopefully when recovered, but it will be in a very different context: lower doses and a background of fasting. I fasted regularly four 4 and a half years, partly as insurance policy for some of the riskier experimentation, not so last 6 months, which I believe could well have prevented this escalation. 

[ambivalent]

This has been day two of the fast, yesterday was fine but the pains have started this afternoon. If TB is right and it is uric acid then fasting may not be a great idea and might explain why the problem has increased today (even though presumably blood sugar levels will have dropped);

 

http://www.jbc.org/c.../2/521.full.pdf

[Nate-2004]

 

 

I'm currently two days in to a fast. This morning, when I awoke, I belched and a moderate about of bile surfaced, it was extremely acidic. Not something I recall expereincing before to that degree.  I'll give some sodium bi-carb a go.

   If you get dizzy on standing from sitting I would suggest to add a significant amount of plain salt. Dizziness is often experienced during fasts or keto diet because mineral excretion speedups a lot during ketosis. Esp if you are low on salt, to begin with. When you are low on electrolytes a lot of basic things start to go wrong very fast. 

 

 

Andey: I'm not on the keto diet and I'm not currently experiencing the dizziness while fasting. But yes the salt tip is one I've heard of and will employ if I go deeper in. Thanks.

 

Nate: I will try this again, hopefully when recovered, but it will be in a very different context: lower doses and a background of fasting. I fasted regularly four 4 and a half years, partly as insurance policy for some of the riskier experimentation, not so last 6 months, which I believe could well have prevented this escalation. 

 

 

Andey fasting will also put you in ketosis a lot faster than a keto diet and you will lose electrolytes so buy some potassium supplements (or eat tomatoes or avocatos) as well as chelated magnesium or magnesium citrate and yeah definitely take that with plenty of salt and water. I just salt a lot of the food I eat, salted roasted nuts help.

Edited by Nate-2004, 01 November 2017 - 06:28 PM.

[sthira]

The dizziness is pretty common. I drink more water, learn to slow down when moving from laying to seated to standing. Dizziness is definitely an annoying side effect of fasting; but when I weigh it against the potential benefits of fasting, it's pretty mild. I'm on day 7 right now, aiming for day 10, but I usually don't make it. Rereading Fung's site usually increases the wind beneath my wings.

[smithx]

What type of fasting are you guys doing? Straight fasting can be dangerous. Consider something like this:

A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan
http://www.cell.com/...4131(15)00224-7

Edited by smithx, 01 November 2017 - 08:26 PM.

[able]

Thanks smithx. I have seen that Low Carb and D-Ribose before in a couple threads here, and there did not seem to be long-term follow-up by the posters. I hope all their issues resolved, although the tie to D-Ribose might not be true. Who knows. (P.S. I have never gotten an inclination that you are a shill for stockholders.)

 

I am still curious if there are any Ketogenic or Low Carb members trying the protocol? Checking blood glucose?

 

I trust Turnbuckles opinion, and result reports. His theory, and personal experience are plenty. Past experience says that, he will report as contrary data or experience come to him. High integrity member.There have been plenty who are taking shots at this thread, maybe some should watch for awhile.

 

Heisok - We responded a bit on another thread about Keto - thought I'd update here as I am doing keto, NR, N+R, and other aspects of the TB protocol.

 

I'm almost 60 and in good shape.

 

Have been taking NR for 2 years, with good results.  I had more energy, especially in the gym.  Skin much improved - rosacea and blemishes gone, and much smoother.

 

Went Keto about 1 year ago.  Lost 20 pounds, back to high school weigh.  Huge improvement in energy, motivation, brain function.

 

Maybe 3 months ago, I modified exercise to HIIT 2 time a week, which was great.  

 

I do a kind of periodic fasting.  nothing but fats most days until evening where I eat keto dinner.  Timing exercise to be at most fasted state.

 

Bulletproof coffee for breakfast.  Exercise around noon, and avoid eating anything but fats for at least a couple hours to stimulate more ampk and BHB.  

 

Lastly, I started some of the TB protocol ideas 2 months ago.   Taking 1000mg NAM and 500mg Tryptophan in evenings.

Have experimented with N + R instead of NR, but haven't been able to tell any difference so far.

 

I do measure fasted glucose - around 85 most days.  Ribose kicks it up only 10 points, so not too concerned about it.

 

I am cycling my supplements and feel that really helps.  2 days taking Niacin and NR (or N+R) in mornings of exercise days.

1 or 2 days no exercise, taking sulforaphane instead of Niacin and NR.

 

I have no thoughts on fission/fusion, but think giving liver a break from NR and Niacin is probably good.   I sometimes skip the NAM on "rest" days, but am undecided about that.

 

Everything together is proving amazing.  I have the energy and motivation I had in my 20s.  

Edited by able, 01 November 2017 - 09:03 PM.

[sthira]

What type of fasting are you guys doing? Straight fasting can be dangerous. Consider something like this:

A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan
http://www.cell.com/...4131(15)00224-7

I agree. Unsupervised, prolonged water-only fasting isn't for everyone. Nor is enough evidence available in humans to recommend it; everyone researching fasting may agree we embark with eyes not wide shut. It's potentially risky behavior.

In support of your opinion, Dr. Longo, the chief researcher in the study you linked, echoes you repeatedly in conversation and in publications that unsupervised, prolonged water-only fasting can be unsafe. Safety first. Thus, he developed ProLon and FMD to help provide many of the benefits of water-fasting, perhaps more safely. His system is smart, but expensive. We may replicate it on our own, just research his ingredients, for far less hassle and money.

Meanwhile, some people can handle straight up, prolonged water only fasting, others, cannot and should not. The practice is gently eased into over time, with dedication; indeed, prolonged water-only fasting is a personal long term journey, and all along the way we weigh the risks against the benefits. We do what's perceived as best for ourselves, N=1, we're ignorant humans awaiting anti aging methods with more evidence. So fasting remains an example of personal self-experimentation.

I'd also point out that "not fasting" may be dangerous for certain individuals, too. Depends on the individual. The motivation behind prolonged, water-only fasting -- for me, anyway -- is not weigh-loss, T2 diabetes elimination, nor life extension. It's more along the (unstudied lines) of perhaps "manipulating mitochondrial dynamics," topic of this thread. Obviously I've no human data, evidence, or support for doing what may indeed be dangerous.

Meanwhile, here's pleasant read: https://idmprogram.c...history-part-i/

[Nate-2004]

First day of fission. I took 375 mg NR this morning and then N+R (1.5 hrs before gym) at about a 1.0 to 0.8 ratio of NAM to R respectively with berberine (AMPK). I did my usual calisthenic bodyweight workout, pushups, pullups, dips, one leg squats, leg curls, calf raises, which is naturally lower weight compared to weights. Now I'm kaput. I feel pumped but exhausted. I'll take fisetin later today as I left it at home.

 

I've changed to 4 days fusion with a very light amount of fusion on the 4th day, ended with 375mg NR, followed by 3 full days fission ended with some vitamin C before bed on the 3rd day. 

 

I can't wait to see how I feel over the next few days as I go back into fusion. Will report back.

 

Edited by Nate-2004, 02 November 2017 - 04:28 PM.

[able]

First day of fission. I took 375 mg NR this morning and then N+R (1.5 hrs before gym) at about a 1.0 to 0.8 ratio of NAM to R respectively with berberine (AMPK). I did my usual calisthenic bodyweight workout, pushups, pullups, dips, one leg squats, leg curls, calf raises, which is naturally lower weight compared to weights. Now I'm kaput. I feel pumped but exhausted. I'll take fisetin later today as I left it at home.

 

I've changed to 4 days fusion with a very light amount of fusion on the 4th day, ended with 375mg NR, followed by 3 full days fission ended with some vitamin C before bed on the 3rd day. 

 

I can't wait to see how I feel over the next few days as I go back into fusion. Will report back.

 

Nate - Are you cycling your nutrition at all in sync with the fission/fusion?

 

AMPK is most activated by HIIT exercise when blood glucose/ATP levels are low.  I feel that combination is extremely stimulating for me, so try to time it with fission days.

 

Also, have you tried exogenous ketones?   I like using those when already fasted, before my workouts, to really crank up the BHB.

Edited by able, 02 November 2017 - 07:05 PM.

[Nate-2004]

Able, I am doing my best to cycle nutrition but it's pretty tough to be perfect. There's a significant amount of stearic acid intake with keto. I take kale out of my smoothies if it's fission time since that adds sulforaphane. I am still trying to research other options for fission days with keto, and it's not gonna be easy... hell, it's not even easy without keto. Fasting is an option but I sometimes just don't have it in me to do that.

 

As for HIIT I've been doing that on fusion days because you get a lot more lactic acid buildup with HIIT, which induces biogenesis. I am ambivalent about whether I should stick to just resistance training during fusion or include HIIT. It's a tough call.

 

I thought about BHB but my ketones if I had to guess and I'll be blood testing later to confirm, are around 2.5 to 3.0 already. No need for BHB.

 

I forgot to add earlier that on fission days I'm applying to my face in the mornings, a small amount of NR mixed with DMSO, Urea, and Rosmarinic Acid (just mixed in the palm of my hand) and CeraVé hyaluronic acid with ceramides. DMSO may actually end up carrying it pretty deep, enough to enter the blood stream dermally. Who knows what effect this will have but every picture taken of me lately I'm looking a bit brighter and younger than I normally think I look. As always, this is just subjective, possibly placebo and possibly based on my mood. So here's hoping it restores some firmness. 

 

I was looking at old pictures of myself back when I was 30, I feel better now because I honestly don't look that different aside from the greying beard. 

 

 

Edited by Nate-2004, 02 November 2017 - 07:42 PM.

[Nate-2004]

I was reading up more on what we are trying to accomplish here. I thought I'd share this, while it doesn't talk about our protocol it does explain what's going on and what needs to be done, ultimately.

 

From: https://www.fightagi...t-mitochondria/

 

The SENS view of mitochondrial damage in aging starts with the fact that deletions accrue to mitochondrial DNA. When those deletions remove one or more of the thirteen genes necessary to the primary processes of energy generation, the mutant becomes either more able to replicate or more able to resist destruction by quality control processes. In some cases, the mutant strain takes over the cell and turns it into a dysfunctional exporter of harmful, reactive molecules. There are even mechanisms by which such broken mitochondria can be exported to surrounding cells, spreading the rot. We accumulate a small but significant population of these malfunctioning cells over the years, and this is one of the root causes of aging and age-related disease. It is a step on the way to the production of oxidized lipids, to pick one example of the downstream consequences, and that contributes to the progression of atherosclerosis.

The SENS approach to remediation involves gene therapy to produce backup copies of the necessary mitochondrial genes, ensuring that the supply of vital protein machinery isn't interrupted by genetic damage in mitochondria. Is it possible, however, to manipulate the existing machinery of mitochondrial quality control to ensure that mutants are reliably destroyed rather than slipping past the net? This is an open question, and good arguments can be made either way: one the one hand, the existing system is pretty comprehensive but still fails catastrophically, allowing mutant mitochondria to very quickly overtake their cells. It isn't clear that simply dialing up quality control activity is going to help at all. On the other hand, cells that are reprogrammed for pluripotency quite clearly rejuvenate their mitochondria. Answering this question is better achieved through action rather than debate: in this open access paper researchers demonstrate clearance of mutant mitochondria with large deletions from fly tissues via manipulation of existing quality control systems as a proof of principle. It isn't at all clear to me from reading the paper that the authors have created a mutant strain that deletes the important genes relevant to aging, however, and therein lies the vital detail. They have, however, created the basis for model organisms that could be used for further exploration of this topic, in a more efficient manner than has been possible in the past.

Quote:

Mitochondria are membrane-bound organelles present in many copies in most eukaryotic cells. The circular mitochondrial genome(mtDNA) encodes proteins necessary for oxidative phosphorylation, which generates the bulk of ATP in most cells. Individual mitochondria contain multiple copies of mtDNA, each of which is packaged into a structure known as a nucleoid, with primarily a single mtDNA per nucleoid. This multiplicity of genomes per cell, in conjunction with mtDNA's high mutation rate and limited repair capacity, often results in cells carrying mtDNA of different genotypes, a condition known as heteroplasmy. Recent studies suggest that 90% of individuals have some level of heteroplasmy, with 20% harbouring heteroplasmies that are implicated in disease. If the frequency of such a mutation reaches a threshold, pathology results. Heteroplasmy for deleterious mtDNA can also arise in somatic tissues during development and in adulthood. It accumulates throughout life, and is thought to contribute to diseases of aging. These observations emphasize the importance of devising ways to reduce heteroplasmy in vivo.

Mitochondria-targeted site-specific nucleases provide one way to decrease the levels of heteroplasmy. In this approach, a site-specific nuclease is engineered so as to bind and cleave a specific mutant version of the mtDNA genome, promoting its selective degradation. This approach has recently been used to decrease the levels of heteroplasmy in patient-derived cell lines, in oocytesand in single cell embryos. However, these methods are likely to be challenging to implement in the adult, as the nuclease being expressed is a non-self protein; many cells must be targeted without off target cleavage effects; and individuals may be heteroplasmic for multiple deleterious mutations. Here we seek to promote cell biological processes that normally regulate mtDNA quality as an alternative approach to decreasing heteroplasmy in adults.

Mitophagy serves as a form of quality control that promotes the selective removal of damaged mitochondria. In one important pathway, dysfunctional mitochondria are eliminated through a process dependent on PTEN-induced putative kinase 1 (PINK1) and Parkin, loss of which lead to familial forms of Parkinson's disease. Regardless, the fact that mutant mtDNA accumulates in individuals wild type for PINK1 and parkin during aging indicates that if PINK1- and Parkin-dependent mitophagy and/or other pathways promote mtDNA quality control, they are often not active or effective. To identify ways of reducing the mutant mtDNA load in somatic tissues, systems are needed in which a specific deleterious heteroplasmy can be induced in vivo and followed over time, ideally in post-mitotic cells so as to eliminate potential confounding effects associated with stochastic segregation during cell division, and differential cell proliferation and/or cell death. Current in vivo models are cumbersome and limited, but we describe the generation and use of a transgene-based system of heteroplasmy in post-mitotic muscle to identify conditions that result in the selective removal of mutant mtDNA.

We demonstrate that the load of deleterious mtDNA can be decreased through several different interventions. Genetic and chemical screens using such a model should prove useful in identifying molecules that can cleanse tissues of a deleterious genome, via known and unknown mitochondrial quality control pathways. The many tools for regulated spatial and temporal control of gene expression in Drosophila will allow such screens to be carried out in a variety of tissues and environmental contexts, including aging. Our results show that adult muscle has a significant but limited ability to remove mutant mtDNA utilizing genes required for autophagy, and that mutant mtDNA removal can be greatly stimulated in several ways: by limiting the ability of mitochondrial fragments to re-fuse with the network (decreasing Mfn levels), by limiting their ability to undergo repolarization through ATP synthasereversal (ATPIF1 expression), by increasing the tagging of mtDNA-bearing fragments (increasing PINK1 or Parkin levels), and by increasing the frequency with which these tagged fragments are degraded (activation of autophagy). These observations have important implications for new therapies for mitochondrial disease and diseases of aging.

Link: http://dx.doi.org/10.1038/ncomms13100

[PAMPAGUY]

Alive by Nature was my go to site for NR. Seems Chromadex cut them off. So rather than find a new source for NR, they have started selling NMN, and saying how superior it is to NR while playing up Dr. Sinclair.

http://alivebynature.com

[Turnbuckle]

Alive by Nature was my go to site for NR. Seems Chromadex cut them off. So rather than find a new source for NR, they have started selling NMN, and saying how superior it is to NR while playing up Dr. Sinclair.

http://alivebynature.com

 

Thanks for the link, Pampaguy. There's a wealth of information in there, and not just about NMN.

 

NMN is being sold at around $24/gram, and given that NMN is not orally available and the mice were getting 100-300 mg/kg per day, that seems an awfully expensive way to get N+R.

[able]

 

Alive by Nature was my go to site for NR. Seems Chromadex cut them off. So rather than find a new source for NR, they have started selling NMN, and saying how superior it is to NR while playing up Dr. Sinclair.

http://alivebynature.com

 

Thanks for the link, Pampaguy. There's a wealth of information in there, and not just about NMN.

 

NMN is being sold at around $24/gram, and given that NMN is not orally available and the mice were getting 100-300 mg/kg per day, that seems an awfully expensive way to get N+R.

 

 

How is that N+R?   All the charts/studies they show looks like NMN makes it through the stomach to different cells as NMN and NAD+ within 1/2 hour - hard to believe it goes thru NR/NAM that fast.

 

http://alivebynature.com/about-niagen/

 

It is expensive though - almost as much as basis.

[Nate-2004]

Convincing sales pitch. That NMN contains only 125 mg NMN along with 350mg of NAM, TRP, and NA. Why add other precursors?

[able]

A lot to wade through there, and kinda scattered presentation imo.

 

Seems they base it on fact that all the precursors raise NAD in liver, but important point is to reach other organs.  

 

Down near bottom of page they have their reason:

 

"Including NA and Tryptophan help elevate NAD+ levels in the liver to their maximum quickly, sparing NMN to be released into the bloodstream and make its way into tissues throughout the body much more effectively."

 

 

I'd like to try NMN myself if they didn't have those, as I already take most of those separately.  And, if price comes down.

Edited by able, 03 November 2017 - 01:09 PM.

[Turnbuckle]

I'm replying to able here as I'd accidentally posted to the NR experiences thread, where it is definitely off topic.

 

That NMN is broken down to NR/NAM  seems contradicted by later studies, particularly the long term mouse study where double labeled NMN makes its way to liver in 10 minutes and to muscle in 30 minutes

 

 

 

You also posted a plot of double labeled NMN from page 3 fig. C of this paper, and I don't know what to make of it as the y-axis is in arbitrary units and single-labeled NMN is not reported. If there is a great deal of single-labeled NMN, that would still be consistent with breakdown and reassembly. I expect, however, that a small amount of NMN is indeed being absorbed, and if the plot were extended out past 30 minutes, we would see a surge of NAM at 4+ hours as NMN is broken down, just as it is with NR.

Edited by Turnbuckle, 03 November 2017 - 02:50 PM.

[able]

 

I'm replying to able here as I'd accidentally posted to the NR experiences thread, where it is definitely off topic.

 

That NMN is broken down to NR/NAM  seems contradicted by later studies, particularly the long term mouse study where double labeled NMN makes its way to liver in 10 minutes and to muscle in 30 minutes

 

 

 

You also posted a plot of double labeled NMN from page 3 fig. C of this paper, and I don't know what to make of it as the y-axis is in arbitrary units and single-labeled NMN is not reported. If there is a great deal of single-labeled NMN, that would still be consistent with breakdown and reassembly. I expect, however, that a small amount of NMN is indeed being absorbed, and if the plot were extended out past 30 minutes, we would see a surge of NAM at 4+ hours as NMN is broken down, just as it is with NR.

 

Yes, it would be much better if they reported single-labeled NMN for sure.  

 

I can't quite get my head around why you say the NMN is broken down to NAM and would see a surge at 4 hours.

 

Another chart they used  (below) shows NMN in blood goes up 4-5x within 15 minutes, then drops back to baseline.   

 

NAD+ in TISSUE then elevates over next 15 minutes.   

 

Are you saying the liver soaks up the NMN from bloodstream and breaks it down to NAM, and the NAM is then making its way to tissue NAD+ over those 15 minutes?   

 

I guess that does agree somewhat with the Trammell paper that showed NAM fast acting but can't recall anything the shows how fast NAM increases NAD+ in tissues beyond the liver.

 

[Nate-2004]

So basically neither NR nor N+R is making it past the liver to the muscles or boosting NAD+ therein? 

 

Boosting NAD in the liver via NAM, NA and TRP seems like a nice idea for getting NMN past the liver but did they prove it actually works?

 

$49 for 60 125mg caps is pretty steep but if it *actually* works better it might be worthwhile. I dunno.

 

 

Edited by Nate-2004, 03 November 2017 - 03:53 PM.

[able]

So basically neither NR nor N+R is making it past the liver to the muscles or boosting NAD+ therein? 

 

Boosting NAD in the liver via NAM, NA and TRP seems like a nice idea for getting NMN past the liver but did they prove it actually works?

 

$49 for 60 125mg caps is pretty steep but if it *actually* works better it might be worthwhile. I dunno.

 

Sounds like yet another unproven theory to me.   Guess it would be nice if it does work though.

 

Certainly SOME NR and NAM make it to muscles to boost NAD.  Think the question is how much, and if it makes it as NR.

 

It sounds to me like NR is very briefly available in the bloodstream before the liver filters it out and it breaks down to NAM or used to increase NAD.  Which is why most studies do not detect any NR in blood, but the one on mice muscle found traces of NR in blood.

 

NAM will be dependent on Nampt to create NAD.  

 

They claim less Nampt as we age is one reason for decreased NAD+, but I haven't followed that research to see if I believe that, or if its all due to increased CD38 and PARP consuming NAD+.

 

If that is accurate, floating a lot of NAM in the blood might help some cells that have sufficient Nampt, but other cells might not be able to use NAM effectively which is why NMN or NR could be better IF available in the bloodstream. 

Edited by able, 03 November 2017 - 04:15 PM.

[PAMPAGUY]

Dr. Sinclair shows a bottle of NMN that is being used for his trial at Brigham and Women's in Boston in the following video.    It shows 500 mg., not the 125 mg contained in the Alive by Nature formula.  If they sold 500 mg of NMN it would be way too expensive for anyone to afford so they add all these other precursors which they say boosts the effect of a small dose of NMN.  I feel that we are going to find out that 125 mg NMN is not optimum. 

 

 

 

() at 33:23 on the tape.

Edited by PAMPAGUY, 03 November 2017 - 04:38 PM.

[PAMPAGUY]

In the last tape of Dr. Sinclair he held a bottle of NMN in his hand labeled as 500 mg NMN while describing the upcoming human trial at Brigham and Women's Hosp. in Boston.  I feel that 125 mg in Alive by Nature formula is probably not enough, and to justify the price they are adding all those other precursors. 

 

Having a problem posting the video, but if it doesn't come up properly then go to YOUTube and google Dr. Sinclair, and it is first tape on top.  See ()

 

at 33:23 on the tape.

[able]

Interesting find Pampaguy.

 

I see the Washington University study is using 2 capsules of 125 mg (250mg total) for 8 weeks, so that may be a good clue on what they think will be effective.

 

Wonder if Sinclair takes 500mg himself.  He certainly is light years ahead of Brenner in presentation skills.

 

https://clinicaltria...cond=nmn&rank=1

Edited by able, 03 November 2017 - 05:03 PM.

[PAMPAGUY]

There is a formula to convert murine dosages to human dosages.  I'm sure Dr. Sinclair is very aware that to reproduce similar results in humans that he got in mice you have to use a certain dosage.  That said, the first trial is a small trial to check the safety of the drug, so they could be trying the max dose for that purpose.  Remember, that Sinclair and his family have been on this for quite a while now and I'm sure have had many blood tests to check the NAD+ levels and the other parameters. 

 

I agree with you Brenner's presentation skills are very lacking.

[Turnbuckle]

 

 

I'm replying to able here as I'd accidentally posted to the NR experiences thread, where it is definitely off topic.

 

That NMN is broken down to NR/NAM  seems contradicted by later studies, particularly the long term mouse study where double labeled NMN makes its way to liver in 10 minutes and to muscle in 30 minutes

 

 

 

You also posted a plot of double labeled NMN from page 3 fig. C of this paper, and I don't know what to make of it as the y-axis is in arbitrary units and single-labeled NMN is not reported. If there is a great deal of single-labeled NMN, that would still be consistent with breakdown and reassembly. I expect, however, that a small amount of NMN is indeed being absorbed, and if the plot were extended out past 30 minutes, we would see a surge of NAM at 4+ hours as NMN is broken down, just as it is with NR.

 

Yes, it would be much better if they reported single-labeled NMN for sure.  

 

I can't quite get my head around why you say the NMN is broken down to NAM and would see a surge at 4 hours.

 

Another chart they used  (below) shows NMN in blood goes up 4-5x within 15 minutes, then drops back to baseline.   

 

NAD+ in TISSUE then elevates over next 15 minutes.   

 

Are you saying the liver soaks up the NMN from bloodstream and breaks it down to NAM, and the NAM is then making its way to tissue NAD+ over those 15 minutes?   

 

I guess that does agree somewhat with the Trammell paper that showed NAM fast acting but can't recall anything the shows how fast NAM increases NAD+ in tissues beyond the liver.

 

 

 

Given the very short time-frame, I suspect a small amount of NMN is absorbed through the stomach and the rest is broken down in the intestines. The study in this trial that found that NMN was converted to NR and NR to NAM. However, this experiment was by intestinal perfusion.

 

For stomach emptying in mice the exponential decay constant was 74 min...

http://onlinelibrary.../mrm.10207/full