2255 replies to this topic

[bluemoon]

 

And a few more quotes if not interested in registering with Seeking Alpha:

 

Brenner:  Nicotinamide and niacin can't substitute for NR because they aren't used in all of the same cells and they don't produce the same results. The best example of these compounds not being equivalent is with respect to glycemic control. Nicotinamide and niacin promote insulin insensitivity (which is bad), while NR promotes insulin sensitivity (which staves off type 2 diabetes). So you should not believe anyone who says that the three compounds are equivalent.

 

 

Brenner:  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.

 

 

Brenner:  Basically, we are talking about yeast, flies, worms and rodents - systems in which scientists have total control over the genetics, environment and diet and can carefully look at results. In yeast, nicotinamide shortens lifespan. NR extends yeast lifespan even when they are on a high sugar diet.  In mice and people, both nicotinamide and niacin can induce insulin resistance, which is a precursor to diabetes. NR promotes insulin sensitivity and resistance to diabetic neuropathy.

 

 

Brenner:  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. 

[Harkijn]

The HELDA researchers are very positive!  that's good for my motivation!

What I had missed sofar in reading up on NR is that you can apparently heat it without loss of quality....

[midas]

Promoting NAD+ metabolism: A new target for treating degenerative disease

 

http://search.inform...5396;res=IELNZC

[midas]

I have no access to this but someone here might...

 

http://journals.lww...._and.99320.aspx

 

Nicotinamide riboside, a form of vitamin B3 and NAD+ precursor, relieves the nociceptive and aversive dimensions of paclitaxel-induced peripheral neuropathy in female rats.

[Harkijn]

It's not accessible for me either, perhaps it is too early. That's a pity because the abstract is very promising: 50% more NAD+ in the blood of NR treated rats...

[Bryan_S]

 

I have no access to this but someone here might...

 

http://journals.lww...._and.99320.aspx

 

Nicotinamide riboside, a form of vitamin B3 and NAD+ precursor, relieves the nociceptive and aversive dimensions of paclitaxel-induced peripheral neuropathy in female rats.

 

 

It looks like it hasn't gotten much distribution yet maybe soon.

 

 

Abstract

Injury to sensory afferents may contribute to the peripheral neuropathies that develop after administration of chemotherapeutic agents. Manipulations that increase levels of nicotinamide adenine dinucleotide (NAD+) can protect against neuronal injury. This study examined whether nicotinamide riboside (NR), a third form of vitamin B3 and precursor of NAD+, diminishes tactile hypersensitivity and place escape-avoidance behaviors in a rodent model of paclitaxel-induced peripheral neuropathy. Female Sprague-Dawley rats received three intravenous injections of 6.6 mg/kg paclitaxel over five days. Daily oral administration of 200 mg/kg NR beginning seven days before paclitaxel treatment and continuing for another 24 days prevented the development of tactile hypersensitivity and blunted place escape-avoidance behaviors. These effects were sustained after a two-week washout period. This dose of NR increased blood levels of NAD+ by 50%, did not interfere with the myelosuppressive effects of paclitaxel, and did not produce adverse locomotor effects. Treatment with 200 mg/kg NR for three weeks after paclitaxel reversed the well-established tactile hypersensitivity in a subset of rats and blunted place-escape behaviors. Pretreatment with 100 mg/kg p.o. acetyl-Lcarnitine (ALCAR) did not prevent paclitaxel-induced tactile hypersensitivity or blunt place-escape behaviors. ALCAR by itself produced tactile hypersensitivity. These findings suggest that agents that increase NAD+, a critical co-factor for mitochondrial oxidative phosphorylation systems and cellular redox systems involved with fuel utilization and energy metabolism, represent a novel therapeutic approach for relief of chemotherapy-induced peripheral neuropathies. As NR is a vitamin B3 precursor of NAD+ and a nutritional supplement, clinical tests of this hypothesis may be accelerated.

© 2017 International Association for the Study of Pain

[Synaptik]

Just wondering if anyone is taking high doses of apeginin along with your NR. It sounds like a perfect combination.

 

Not only is apeginin an mTor inhibitor like rapamycin, which in itself slows down the aging process like caloric restriction, it's also a potent CD38 inhibitor as well. NADese CD38 increasingly consumes more NAD+ in the mitochondria as people age, leading to degenerative problems and aging-related decline.

 

I still take regular 500g x 2 daily niacin, along with multiple hour steeped green + chamomile tea (apeginin), so I thought I would share this information with other in case they weren't aware. I would love to try the NR though once I can!

 

Anyhow, seems like strong steeped 2 or 3 bags of chamomile tea would be a great (and dirt cheap) adjunct to the NR therapy.

 

BTW, green tea (ECGC) is an mTor inhibitor as well, so the NR/NA greent tea and chamomile are could be a very potent anti-aging combo.

 

Cheers.

[Vastmandana]

Just wondering if anyone is taking high doses of apeginin along with your NR. It sounds like a perfect combination.

 

Not only is apeginin an mTor inhibitor like rapamycin, which in itself slows down the aging process like caloric restriction, it's also a potent CD38 inhibitor as well. NADese CD38 increasingly consumes more NAD+ in the mitochondria as people age, leading to degenerative problems and aging-related decline.

 

I still take regular 500g x 2 daily niacin, along with multiple hour steeped green + chamomile tea (apeginin), so I thought I would share this information with other in case they weren't aware. I would love to try the NR though once I can!

 

Anyhow, seems like strong steeped 2 or 3 bags of chamomile tea would be a great (and dirt cheap) adjunct to the NR therapy.

 

BTW, green tea (ECGC) is an mTor inhibitor as well, so the NR/NA greent tea and chamomile are could be a very potent anti-aging combo.

 

Cheers.

Yep! Along with gallons of high quality yummy Jasmine green tea per day (well, lots...laced with neurmag powder... love it!) I also recently added 100mg Apigenin and 100mg fisetin along with my 1g NR and a zillion other things.  Exciting stuff on both fronts! And since they're flavonoid polyphenols, the price is reasonable.

 

Seeking Alpha sucks big donky dicks... have requested removal from their stupid email blasts to no avail... will try again.

 

 

Edited by Vastmandana, 05 February 2017 - 08:58 AM.

[normalizing]

uhm guys, why keep mentioning silly oral route treatments for NAD, when i found that people can IV NAD+ with success; http://www.nadtreatmentcenter.com/

 

yes, its treatment center for addictions that people swear helps them, but it can also help anyone really who is seeking NAD+ boost without spending so much money on pills which barely have any long lasting effect. from a person i spoke at that center, it seems she noticed positive results only from IV treatment something you can do at home which sucks

Edited by hazy, 09 February 2017 - 04:07 AM.

[mrkosh1]

All of that NAD+ will have to be converted into NR before it can enter cells. Since NR is taken into the bloodstream so well by oral administration, I see little benefit in taking an IV of NAD+ that then has to be converted to NR. If anything, an NR IV with sulforaphane and/or alpha lipoic acid to boost NQO1 would be very interesting.

[midas]

uhm guys, why keep mentioning silly oral route treatments for NAD, when i found that people can IV NAD+ with success; http://www.nadtreatmentcenter.com/

 

yes, its treatment center for addictions that people swear helps them, but it can also help anyone really who is seeking NAD+ boost without spending so much money on pills which barely have any long lasting effect. from a person i spoke at that center, it seems she noticed positive results only from IV treatment something you can do at home which sucks

 

I really dont think that would be a good idea .

 

And I agree with mrcosh1's post above..

[mrkosh1]

Question. Is the increased level of CD38 being produced in elderly people serving an actual purpose; for example, could the CD38 be struggling to effect some sort of cellular repair that has been caused by aging? Or is the increased level of CD38 pointless and only harmful to an organism?

 

[Nate-2004]

Question. Is the increased level of CD38 being produced in elderly people serving an actual purpose; for example, could the CD38 be struggling to effect some sort of cellular repair that has been caused by aging? Or is the increased level of CD38 pointless and only harmful to an organism?

 

I'm no expert but based on what I've read so far on that it's not serving any good purpose, it's actually just an effect of increased inflammation and in this case it's from SASP.

[normalizing]

All of that NAD+ will have to be converted into NR before it can enter cells. Since NR is taken into the bloodstream so well by oral administration, I see little benefit in taking an IV of NAD+ that then has to be converted to NR. If anything, an NR IV with sulforaphane and/or alpha lipoic acid to boost NQO1 would be very interesting.

 

well, the whole IV NAD+ is for people who have abused drugs and alcohol like me and are actually proven scientifically to be depleted unlike most of you guys who just wanna live forever. and you know what,  I AM using NR and there is zero effect. so basically, NR doesn't really help orally at all!

[mrkosh1]

If NR orally doesn't help, I really don't think that IV NAD+ would help, because the NAD+ would simply be converted to NR before it entered your cells. However, if the NAD+ IV bag contained a cocktail of other ingredients (one company offering NAD+ IVs had a whole list of added vitamins and supplements) then the OTHER ingredients (maybe combined with the NR) might be producing some of the effect. For example, on one website I found, the IV had methyl donors and other B vitamins. A possibility could be that for your specific biology NR could be depleting methyl donors and taking B12 at the same time could make a difference. Personally, I'd try a combination of much cheaper oral supplements with a good safety history before getting an IV of NAD+. Also, you could try combining a few supplements that could be synergistic. For example, I've never tried NR due to finances, but R-Alpha Lipoic Acid seemed to give me an energy boost. R-Alpha Lipoic Acid induces NRF2 which then activates NQO1 which boosts the NAD+ to spent NADH ratio by recycling NADH. I'm not a doctor or a pharmacist, but if I were in your case I might try a combo of NR, R-Alpha Lipoic Acid, and safe doses of B vitamins.

 

Another question. Have you tried fasting? I suffer from a poor diet and often have bad blood sugar swings. If I fast for a day or go on a very low carb diet for a day or two, my mind seems to clear up and I feel more stable mentally. I don't know if this would work for you, but fasting also boosts the ratio of NAD+. Exercise does as well. How often do you go out and go for a LONG walk? I know when I'm very depressed, if I force myself to walk a few miles and come back home I feel better.

[Nate-2004]

All of that NAD+ will have to be converted into NR before it can enter cells. Since NR is taken into the bloodstream so well by oral administration, I see little benefit in taking an IV of NAD+ that then has to be converted to NR. If anything, an NR IV with sulforaphane and/or alpha lipoic acid to boost NQO1 would be very interesting.

well, the whole IV NAD+ is for people who have abused drugs and alcohol like me and are actually proven scientifically to be depleted unlike most of you guys who just wanna live forever. and you know what, I AM using NR and there is zero effect. so basically, NR doesn't really help orally at all!

First off how old are you? Second, what are you expecting it to do?

[Vastmandana]

I can't  resist the tongue and cheek comment...  I think you're  a bit  "hazy"  coming off all the drugs and all...

 

Apparently you haven't bothered to review the 60 pages thread and all its data... You'll just go with ur gut... "Science is 4 sissies" some say!   

 

Edited by Vastmandana, 10 February 2017 - 10:34 AM.

[Bryan_S]

Role of NAD+ and mitochondrial sirtuins in cardiac and renal diseases

http://www.nature.co...eph.2017.5.html

 

Abstract

 

The coenzyme nicotinamide adenine dinucleotide (NAD+) has key roles in the regulation of redox status and energy metabolism. NAD+ depletion is emerging as a major contributor to the pathogenesis of cardiac and renal diseases and NAD+ repletion strategies have shown therapeutic potential as a means to restore healthy metabolism and physiological function. The pleotropic roles of NAD+ enable several possible avenues by which repletion of this coenzyme could have therapeutic efficacy. In particular, NAD+ functions as a co-substrate in deacylation reactions carried out by the sirtuin family of enzymes. These NAD+-dependent deacylases control several aspects of metabolism and a wealth of data suggests that boosting sirtuin activity via NAD+ supplementation might be a promising therapy for cardiac and renal pathologies. This Review summarizes the role of NAD+ metabolism in the heart and kidney, and highlights the mitochondrial sirtuins as mediators of some of the beneficial effects of NAD+-boosting therapies in preclinical animal models. We surmise that modulating the NAD+–sirtuin axis is a clinically relevant approach to develop new therapies for cardiac and renal diseases.

[Bryan_S]

 

I can't  resist the tongue and cheek comment...  I think you're  a bit  "hazy"  coming off all the drugs and all...

 

Apparently you haven't bothered to review the 60 pages thread and all its data... You'll just go with ur gut... "Science is 4 sissies" some say!   

 

 

Good Point!

 

This is a research thread and yes there are 60-pages of academic research postings prior to this one that says NAD repletion works. Some of the comments above would be better placed in the experience thread.

 

The IV approach might have some merit but as we all know NAD will be reduced to NR at the cell membrane anyway. Still I would like to see clinical data to see how intracellular levels respond.

 

Let's say an elderly patient is admitted to a hospital following a stroke. We've seen data supporting the idea that increasing NAD thru NR administration can save nerve tissue. So given that an IV is pretty standard protocol wouldn't it make sense to add a NAD precursor to the IV to bolster the recovery of nerve tissue?

 

As always JMHO

[Bryan_S]

The heat shock factor HSF1 juggles protein quality control and metabolic regulation

 

Carles Cantó

DOI: 10.1083/jcb.201701093 | Published February 9, 2017

http://jcb.rupress.o...8/jcb.201701093

 

Abstract

 

Transcriptional regulators often act as central hubs to integrate multiple nutrient and stress signals. In this issue, Qiao et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201607091)demonstrate how heat shock factor 1 (HSF1) uncouples metabolic control from proteostatic regulation and unveils HSF1 as a critical transcriptional regulator of NAD+ metabolism.

 

See

"If all the phenotypes of HSF1-deficient livers derive from an NAD+ crisis, it should be expected that recovering NAD+ levels would reverse the phenotypes of HSF1-null hepatocytes. To test this hypothesis, Qiao et al. (2017) performed a series of elegant experiments using Nampt-independent NAD+ precursors, such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). The treatment with either NR or NMN was enough to fully rescue intracellular NAD+ levels, mitochondrial respiration, and ATP levels in HSF1-deficient hepatocytes. Further, NR also improved hepatic glucose production capacity in HSF knockout mice, based on pyruvate tolerance tests. These experiments certified the relevance of NAD+ as the central element driving the metabolic decline caused by HSF1 deficiency. Overall, the work of Qiao et al. (2017) shows that HSF1 depletion affects the transcriptional regulation of Nampt levels. Lower amounts of Nampt lead to lower amounts of NAD+, which in turn dampen sirtuin activity and thereby mitochondrial biogenesis and oxidative capacity (Fig. 1)."

 

[Nate-2004]

 

The heat shock factor HSF1 juggles protein quality control and metabolic regulation

 

Carles Cantó

DOI: 10.1083/jcb.201701093 | Published February 9, 2017

http://jcb.rupress.o...8/jcb.201701093

 

Abstract

 

Transcriptional regulators often act as central hubs to integrate multiple nutrient and stress signals. In this issue, Qiao et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201607091)demonstrate how heat shock factor 1 (HSF1) uncouples metabolic control from proteostatic regulation and unveils HSF1 as a critical transcriptional regulator of NAD+ metabolism.

 

See

"If all the phenotypes of HSF1-deficient livers derive from an NAD+ crisis, it should be expected that recovering NAD+ levels would reverse the phenotypes of HSF1-null hepatocytes. To test this hypothesis, Qiao et al. (2017) performed a series of elegant experiments using Nampt-independent NAD+ precursors, such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). The treatment with either NR or NMN was enough to fully rescue intracellular NAD+ levels, mitochondrial respiration, and ATP levels in HSF1-deficient hepatocytes. Further, NR also improved hepatic glucose production capacity in HSF knockout mice, based on pyruvate tolerance tests. These experiments certified the relevance of NAD+ as the central element driving the metabolic decline caused by HSF1 deficiency. Overall, the work of Qiao et al. (2017) shows that HSF1 depletion affects the transcriptional regulation of Nampt levels. Lower amounts of Nampt lead to lower amounts of NAD+, which in turn dampen sirtuin activity and thereby mitochondrial biogenesis and oxidative capacity (Fig. 1)."

 

 

Bryan can you explain this one? I've been interested in heat shock proteins and sauna use lately (not to mention sulforaphane) and I'm wondering if there's synergy with NR.

Edited by Nate-2004, 10 February 2017 - 05:58 PM.

[normalizing]

 

I can't  resist the tongue and cheek comment...  I think you're  a bit  "hazy"  coming off all the drugs and all...

 

Apparently you haven't bothered to review the 60 pages thread and all its data... You'll just go with ur gut... "Science is 4 sissies" some say!   

 

 

i did review the studies but how does that work for me specifically? science is not "4 sissies" as you put it, but so generic the way things are done in science, not personalized and it doesnt concern the individual and their own complexity in the matter therefore i can be entertained by science, it can either discourage or encourage me, but its likely never to really affect me personally to an extraordinary effect

[Journey2016]

Im going for Nad+ iv in a few weeks for addiction, ive read far to many good things from many places, i respond very well to NR

Maybe try listening and reading the comments on this link then comment.. would be good to hear your views then..

Link

https://bengreenfiel...07/what-is-nad/

[Journey2016]

Also why is no one here mire interested in looking into the nad+ nasal products? Im told that when using it as a nasal its far more effective than NR tabs, and this was from a US lab that make both.

[Bryan_S]

Also why is no one here mire interested in looking into the nad+ nasal products? Im told that when using it as a nasal its far more effective than NR tabs, and this was from a US lab that make both.

 

NR is stabilized as a salt. When hydrated in an H2o solution it begins to break down after about 6 hours. "Stability analyses showed that when Niagen was dissolved in water, NR was stable up to 6 h at room temperature and 7 days at 2–8 C. " So from an IV or nasal spray perspective you have limited shelf life unless used right away. This was and still is the whole idea behind the Procter and Gamble Chromadex agreement they are partnering on a liquid version for food, beverage, skin care, sports nutrition, and pharmaceutical products. Also keep in mind the products we buy in capsule form often contains Silica Powder. So making aqueous preparations from this as your base wouldn't be recommended as a nasal spray but could be added to drinks and food eaten shortly after preparation.

 

As always JMHO  

[normalizing]

Im going for Nad+ iv in a few weeks for addiction, ive read far to many good things from many places, i respond very well to NR

Maybe try listening and reading the comments on this link then comment.. would be good to hear your views then..

Link

https://bengreenfiel...07/what-is-nad/

 

what does respond well to NR mean? do you feel something specific or you respond well meaning no side effects

[normalizing]

i have to ask, did anyone pay attention to this one; https://en.wikipedia.org/wiki/Butein seems quite interesting for NAD

[Harkijn]

i have to ask, did anyone pay attention to this one; https://en.wikipedia.org/wiki/Butein seems quite interesting for NAD

Yes, I read up on buteine some time ago when I found it included in this guy's list:

 

https://selfhacked.c...-health-issues/

 

I think it's an interesting phenol but so are all substances on the list. My personal conclusion is to eat plant-based with many (fresh) herbs ad spices included. And of course take NR.....

[Journey2016]

Im going for Nad+ iv in a few weeks for addiction, ive read far to many good things from many places, i respond very well to NR

Maybe try listening and reading the comments on this link then comment.. would be good to hear your views then..

Link

https://bengreenfiel...07/what-is-nad/

what does respond well to NR mean? do you feel something specific or you respond well meaning no side effects

Respond well- huge energy boost, well being, feel good.. happy.. huge impact of drug craving..

[normalizing]

 

 

Im going for Nad+ iv in a few weeks for addiction, ive read far to many good things from many places, i respond very well to NR

Maybe try listening and reading the comments on this link then comment.. would be good to hear your views then..

Link

https://bengreenfiel...07/what-is-nad/

what does respond well to NR mean? do you feel something specific or you respond well meaning no side effects

Respond well- huge energy boost, well being, feel good.. happy.. huge impact of drug craving..

 

 

 

interesting. i have drug problem too and i didnt notice helping me with this at all and also i dont get mood boost or physical energy at all. im taking 300mg switched to 400mg thinking extra 100 might help, but nothing really. maybe its best to just go low dose 100mg and hope for the best?