2255 replies to this topic

[Supierce]

Genji, the question of cancer does come up here fairly regularly. So far, we've seen little evidence that NR actually causes cancer, but there's the possibility that once started, cancer cells thrive on NAD+ as you describe. The consensus seems to be to stop NR and other NAD+ boosters at the first sign of cancer. Your point is well taken, though, so thank you!

Edited by Supierce, 07 November 2016 - 08:11 PM.

[genji]

Thanks, Supierce. But do note of course that elevated NAD+ levels have been correlated with all three major stages of cancer -- initiation, progression, and metastasis. Many cancers of course are not caught at an early stage. And once tumors have metastasized, there is so much genetic diversity in the tumors that death is pretty much assured.

 

I say all this admitting that I'm (for a month) experimenting with nicotinamide riboside myself. But I go into the experiment having read all the contravening literature. When you read papers by Sinclair or Guarente or their associates, you don't get these discussions, and as a researcher myself, that really angers me. 

 

Best,

Steve

[genji]

Addendum to my last post:

 

I don't want to wear out my welcome on this List almost as soon as I've joined. But I do want to point out that the literature linking upregulated NAD+ levels to initiation, progression, and metastasis of a wide range of cancers is large, not peripheral, and is rapidly growing. You just don't get references to that literature much in papers written by researchers with massive financial interests in pushing NAD+ as a supposed anti-aging elixir.

 

The involvement of NAD+ in cancer metabolism isn't at all surprising -- since NAD+ is a ubiquitous enzyme with a zillion different functions involving energy regulation (among many other things) in different tissues with wide variations of NAD+ appropriate levels in even different compartments of single cells.

 

Thinking that you can just rev things up systemically and reverse aging by "returning NAD+ to youthful levels" -- the same view once claimed about melatonin, and DHEA, and even anti-oxidants until a few years ago -- is biologically naive. Increased NAD+ levels in one cellular compartment or tissue might have beneficial effects, but raising those levels in different tissues or cellular compartments at the same time might kill you. 

 

That's the trouble with pleiotropic substances, or substances containing huge numbers of pleiotropic substances.

 

I could legitimately claim that cigarette smoking is protective against Parkinson's disease, and could maybe sell you on smoking for that reason -- just by forgetting to mention a few of cigarettes' less attractive carcinogenic features.  

 

The case isn't so different with NAD+, Elysium aside.

 

And any serious molecular biologist will know that, including Sinclair and Guarente. But the money speaks, just as it does with geneticists pushing so-called precision medicine while knowing that there is *never* real precision in molecular biology, just as there isn't in quantum mechanics, because in both stochastic processes rule.

 

In the last few days still another new paper has been accepted (in the journal _Pharmaceutical Research) on NAD+ and cancer -- underlining again the well-known links to researchers between a variety of cancers and NAD+.

 

The punchline of the paper? One powerful anti-cancer treatment might lie in blocking NAD+ synthesis (via the salvage pathway). Well, watch for what you wish for here too: safe homeostatic ratios of NAD+/NADH can be expected to differ in different tissues and cellular compartments, but block it in one and you will probably block it in all.  

 

Again, since I apparently can't post links yet on this List, I'll just give here the title and conclusion of the preprint, which I read earlier today.  And for now, on this topic, I'll fall silent at least for now.

 

Best wishes,

Genji

 

NAD+ salvage pathway in cancer metabolism and therapy

Barry E. Kennedy1, Tanveer Sharif1, Emma Martell1, Cathleen Dai1, Youra Kim2, Patrick W. K. Lee1,2, Shashi A. Gujar1,2,3

Departments of 1Microbiology & Immunology and 2Pathology, Dalhousie University, Halifax, NS, Canada; 3Centre for Innovative and Collaborative Health Systems Research, IWK Health Centre, Halifax, NS, Canada

 

Corresponding Author:

Shashi Gujar, DVM, PhD, MHA
Departments of Pathology, and Microbiology and Immunology Faculty of Medicine, Dalhousie University,
7P, Charles Tupper Building, 5850 College Street
Halifax, Nova Scotia, Canada B3H 1X5

 

ACCEPTED MANUSCRIPT

 

Conclusion (p. 22 of accepted manuscript at the publisher's site)

 

Inhibition of the NAD+ salvage pathway has been very successful in killing cancer cells in vitro and in vivo. Decreased NAD+ levels in cancer cells causes impaired energy metabolism and energy production and increased ROS production. The depletion of energy and increased ROS results in alteration of cell signals leading to decreased proliferation and an upregulation of autophagy and apoptosis, resulting in cell death. Additionally, DNA repair is inhibited by inhibition of the NAD+ salvage pathway, which prevents proliferation of cancer cells (summarized in Graphical abstract). Because cancer cells rely more on these pathways than non- cancerous cells, inhibition of the NAD+ salvage pathway had little effect on non-cancerous cells. However, these successes have not translated to clinical trials in humans and the reasons remain unknown. To better understand the lack of success in patients, recent studies have explored the effect of NAMPT inhibition in combination with other anti-cancer drugs on cancer cell growth. Often, these combinations targeting energy levels, DNA repair, and proliferation, synergistically improved cancer cell death, and are likely to be the future in this field. Additionally, there has been a huge interest in the involvement of the immune system in fighting cancer in vivo. The NAD+ salvage pathway is also essential for immune cell function and future work will be required to balance the positive effect of NAMPT inhibition on cancer cell death with the negative side effects of NAMPT inhibition on immune cell function. Overall, the NAD+ salvage pathway is a very intriguing target to prevent cancer cell proliferation and promote cancer cell death; however, further work will be required to understand the factors that will allow us to achieve better efficacy for these therapeutic options in clinical settings. 

 

 

[bluemoon]

In his presentation in Sydney in late 2014, Sinclair says at one point:

 

"This sounds all too good true to be true. Maybe MNM and NAD will cause cancer! Well, here's research from Lindsey's work: if you feed mice that develop liver cancer - on the left you can see these little dots are tumors that will kill a human pretty quickly. These are liver cancers and if you just put MNM in the drinking water of these mice for a few months, you can barely see any tumors. So this is not a tumor promoting molecule - at least in liver cancer."

 

So Sinclair has discussed cancer with respect to NMN and that slide he put up wasn't just in passing.

 

youtube, "scientists close to reversing aging" from 1:10:00 to 1:11:10

 

Genji, you wrote: "The problem with all these wishful-thinking anti-aging magic bullets (in the decades I’ve followed the field there has been a long list — the most hyped these days including metformin, rapamycin, NAD+ and its relatives, the sirtuins — is that all are intensively pleiotropic. "

 

So what were the supposed magic pills mentioned before 2004? I can only think of Pauling and Vitamin C. What are the others since you claim that there is a long list? Why do I have a feeling you won't be back to share with us your long list?

 

 

[Bryan_S]

Thanks Steve, for the most part we are looking at PARP and what depleted levels of NAD can do to cripple needed cellular repair processes thus bringing about cancers. The same can be said of CD38 as it consumes available NAD depriving other cellular functions. So far no adverse effects have been noted by researchers doing NAD repletion work and one human NAM study showed a reduction in skin cancers. 

 

Now there are interesting NAD depletion treatments assisting chemotherapy to fight certain cancers as you elude to above. But as we mention that this approach its also known to create secondary cancers by weakening the repair processes of healthy tissues, so its a catch 22 with known risks best discussed with the attending oncologist. Here is a related topic because this cancer approach effects PARP: Successes and Challenges of PARP Inhibitors in Cancer Therapy

 

If you want to read the arguments pro and con the following article focus's on cancer and NAD+. 

 

a SciTechnol journal Review ArticlePoljsak, J Clin Exp Oncol 2016, 5:4DOI: 10.4172/2324-9110.1000165 Journal of Clinical & Experimental OncologyAll articles published in Journal of Clinical & Experimental Oncology are the property of SciTechnol, and is protected by copyright laws. Copyright © 2016, SciTechnol, All Rights Reserved.International Publisher of Science, Technology and Medicine

 

NAD+ in Cancer Prevention and Treatment: Pros and Cons

 

If you are a researcher you know NAD+ has multiple cellular functions. Changes in NAD+ metabolism have been associated with several pathologies, including cancer. So we can circle this topic endlessly but we can all agree NAD+ has been shown as an important factor related to cancer formation and its prevention. So its a chicken and the egg question with evidence suggesting that its more preventive than not. These are the early days and why we embrace all research here.

 

Welcome aboard I hope you find some interesting reading here.

Edited by Bryan_S, 08 November 2016 - 07:09 PM.
link added

[Supierce]

Bluemoon, Genji is raising a legitimate point. His/her post above mentions metformin, rapamycin, sirtuin activators in general (I assume resveratrol and Pterostilbene), antioxidants, melatonin and DHEA. Another that comes to mind is acetyl-l-carnitine. Most appear to be fairly safe when taken in sane amounts, but the issue is still worth discussing.

[bluemoon]

Of course it is worth discussing. But he made a statement that I've heard others make that they nor he can support: "The potential magic pills have been around for decades" when I have heard of nothing until resveratrol as a potential health booster in 2003. Genji said there was a long list. OK, let's try to flll in just a short list

of just five. I'll go first:

 

1. vitamin C

2. Wheaties, the breakfast of champions

3. Coke adds life, so have a Coke and a smile

4.

5.

 

But I can't even get up to 5 

[genji]

Genji, you wrote: "The problem with all these wishful-thinking anti-aging magic bullets (in the decades I’ve followed the field there has been a long list — the most hyped these days including metformin, rapamycin, NAD+ and its relatives, the sirtuins — is that all are intensively pleiotropic. "

 

So what were the supposed magic pills mentioned before 2004? I can only think of Pauling and Vitamin C. What are the others since you claim that there is a long list? Why do I have a feeling you won't be back to share with us your long list?

Putative anti-aging "magic bullets" go back way before 2004. That was the way that melatonin was presented by the italian researcher Walter Pierpaoli in a long series of peer-reviewed papers and then a best-selling book in the early 1990s. For one influential paper, see Pierpaoli, "The pineal gland as ontogenetic scanner of reproduction, immunity, and aging. The aging clock," Ann N Y Acad Sci. 1994 Nov 25;741:46-9. 

 

And then later in the 1990s that was the way that DHEA was discussed by a long list of researchers including above all the late William Regelson, of the Medical College of Virginia. He wrote his first paper on DHEA and aging in 1988. He and Pierpaoli in fact also co-authored a best seller together on melatonin, when it was first promoted as a miraculous anti-aging pill, In _The Melatonin Miracle: Nature's Age Reversing, Disease Fighting, Sex-Enhancing Hormone_, in the mid 1990s. Great title, and it is still apparently in print.

 

Please note that both Pierpaoli and Regelson were much published researchers, and their work was taken very seriously at the time. I remember working carefully through a special issue of the Annals of the New York Academy of Sciences devoted to DHEA as an anti-aging elixir. It was published in 1988. 

 

And long before that, of course, and long after too, in the wake of Harman's free radical theory of aging, formulated in the 1950s, there were many dozens of serious papers written on anti-oxidants as anti-aging pills, supposedly reinvigorating mitochondria overwhelmed during aging by damaging free radicals. That model really only has been killed off by work in recent years by Michael Ristow and others on the critical importance of ROS signaling in healthy aging. See e.g. Ristow and Schmeisser, "Mitohormesis, promoting health and lifespan by increased levels of reactive oxygen speciies (ROS)," 2014.

 

You mention Linus Pauling and vitamin C. A recent paper by James Watson -- admittedly not the nicest researcher on the planet -- ridicules Pauling for taking a reported 12 grams a day while dying of prostate cancer in a 2012 paper, "Oxidants, antioxidants, and the current incurability of cancer." One of Watson's points: that it may be time to consider anti-oxidants not as anti-aging or anti-cancer agents but as promoters of cancer:

 

At the time of his death from prostate cancer in 1994, at the age of 93, Linus was taking 12 g of vitamin C every day. In light of the recent data strongly hinting that much of late-stage cancer’s untreatability may arise from its possession of too many antioxidants, the time has come to seriously ask whether antioxidant use much more likely causes than prevents cancer. 

 

So i don't know if that qualifies in your eyes as a "long list." But there is no doubt that there were a number of previous putative anti-aging "magic bullets" that long preceded resveratrol, sirtuins, NAD+, rapamycin, metformin, etc. And the term "magic bullet" (magische Kugel) in this sense of course goes back to Paul Ehrlich's work over 100 years ago. 

 

Please note that I'm not attacking anti-aging medicine. I'm just suggesting a little more skepticism than exists at present in the NAD+ hyped world, fueled by huge amounts of money.

 

Full disclosure: i used melatonin on the 90s, used to dump tons of anti-oxidants in my body, still use DHEA (though not as a putative anti-aging elixir), and cautiously have experimented with NAD+ precursors and intermediates. But the deeper I go into the molecular biology the more i am convinced that behavioral anti-aging interventions are safer and potentially more effective.

 

I take the field seriously. But do note the interesting suggestions that most of the highly visible scientific names on the Elysium Scientific Board reportedly don't use NAD+ intermediates themselves. That does suggest something is odd here, I think.

 

Best,

Genji

[Nate-2004]

That previous attempts at slowing, stopping or reversing aging have failed in the past does not mean that present and future attempts will also fail. It's certainly wise to be skeptical, but it doesn't follow. There's always failure on the way to success, it's how you get there.  I'm assuming that NR and Resveratrol have been the closest we've come so far in addition to other future possibilities like CRISPR. I'm hoping that Moore's law applies to science and progress as much as it does technology, if only governments would get out of the way.

Edited by Nate-2004, 08 November 2016 - 04:30 AM.

[bluemoon]

"So i don't know if that qualifies in your eyes as a "long list."

 

Correct, it does not not but will happily add what you wrote to the growing list below:

 

 

1. vitamin C

2. Wheaties, the breakfast of champions

3. Coke adds life, so have a Coke and a smile

4. the melatonin miracle

5.  

 

All we need is one more to make 5.  

 

By the way, I don't recall an increase in cancer among the many who have taken metformin and rapamycin over the decades.  I thought lower for rapamycin but maybe it was metformin.

 

Also, what is your source for the Nobel Laureates on Elysium's Scientific board not taking NR themselves?  

 

Edited by bluemoon, 08 November 2016 - 05:18 AM.

[genji]

Hi bluemoon,

 

I wrote a serious answer to your post and then closed the window by accident. But maybe that's for the best.

 

This is advertised as a curated list, which normally means one involving discussions of published research. I'm only interested in the science, not rhetorical debate.

 

it is indisputable that there was a long string of proposed antiaging magic bullets way before resveratrol appeared on the scene -- long even before (say) Harman's work on antioxidants appeared in the 1950s (which had absolutely nothing to do with Pauling's work on vitamin c), or Regelson's work on DHEA in the 1980s, or even before Ehrlich's proposed "magische Kugel" at the turn of the 20th century. 

 

Take a look sometime at the heated discussions in the 1880s and 90s of Brown-Sequard's claims that injections of fluids from the testicles of guinea pigs and dogs led to rejuvenation and extended life.

 

And that debate hardly ended in the 1890s: There is of course still a huge would-be rejuvenation market in an updated form using synthetic testosterone. For discussion, see e.g., G. Matfin, "The rejuvenation of testosterone: philosopher's stone or Brown-Séquard Elixir?"  Ther Adv Endocrinol Metab. 2010 Aug;1(4):151-4. doi: 10.1177/2042018810385052.

 

And please do take Wheaties off your list. The gliadin portions of Wheaties will upregulate zonulin, increase gut permeability and low-grade chronic inflammation, and most likely shorten and not extend life. See any number of Fasano's studies here.

 

And maybe lighten up a bit as well? You are welcome to think of NAD+ as an Elixir of Life, just as Brown-Séquard viewed crushed pig testicles, but stress also upregulates low-grade inflammation and can kill you.

 

Cheers: i really just wanted to discuss some serious evidence,

Genji

[bluemoon]

Genji, you are going back to 1890? Do you think potential health pills of today of which there are at least five have much to do with where the science was at before there were more than a hundred cars on the road?

 

 

1. fluids from pig and dog testicles - 1880s 

2. antioxidants - 1950s

2. Coke adds life, so have a Coke and a smile - 1970s

4. Vitamin C - 1970s

5. DHEA - 1980s

 

OK, we made it to 5, but I don't consider that a long list, especially when one is a soft drink.

 

 Has anyone read or heard that  Elysium's science advisory board doesn't take Basis?  

Edited by bluemoon, 08 November 2016 - 08:31 AM.

[tunt01]

Stop derailing this thread from NAD+, NR and its mechanistic behavior to some meandering walk through time back to the days of ponce de leon.  Discuss the merits of Genji's comments on NAD+ and metabolism, and not nitpick at whether or not his history on DHEA, Vitamin C, and other ancillary issues is accurate.  

 

This isn't a thread about "fluid from pig and dog testicles".  

 

 

[bluemoon]

Hold it, Genji is the one who gave the history lesson on dog testicles in the 1890s, not me. He made three major claims including that these potential health pills have been discussed for decades and had a long list but could only add one to my vitamin C.  

 

Genji's next claim was about cancer, and I knew I had heard either rapmycin or metformin seemed to reduce it among those taking for decades and on a quick search found this:   "Not only has it been good for transplant patients, but derivatives of Rapamycin have also been effectively used for various kinds of kidney, lung and breast cancers." That isn't the same as preventing cancer in the first place, of course.

 

Then he put out a rumor he declined to back up: most of the six Nobel laureates nor other high profile scientists on Elysiums' advisory board: "But do note the interesting suggestions that most of the highly visible scientific names on the Elysium Scientific Board reportedly don't use NAD+ intermediates themselves. That does suggest something is odd here, I think."

 

That is interesting if he can back up that claim but so far he hasn't. 

[Harkijn]

  Discuss the merits of Genji's comments on NAD+ and metabolism

I totally agree. Genji, please keep posting and/or answering questions about your views on NAD+. We won't get any useful results unless every now and then someone ruffles our feathers, so to speak. Your comments about raising NAD+ levels anytime anywhere touch on a longstanding unease about this on my part.

[stefan_001]

 

  Discuss the merits of Genji's comments on NAD+ and metabolism

I totally agree. Genji, please keep posting and/or answering questions about your views on NAD+. We won't get any useful results unless every now and then someone ruffles our feathers, so to speak. Your comments about raising NAD+ levels anytime anywhere touch on a longstanding unease about this on my part.

 

 

The cancer topic is an interesting one. But personally I see a difference between what helps to kill cancer versus what helps it to get started. SIRT1 is also known as a tumor promoter, which would mean that calorie restriction, so not eating, would help cancer.......Regardless its an important topic and research and clarity into it is welcome

[Nate-2004]

SIRT1 is a tumor *promoter*?!?!

[Bryan_S]

 

The cancer topic is an interesting one. But personally I see a difference between what helps to kill cancer versus what helps it to get started. SIRT1 is also known as a tumor promoter, which would mean that calorie restriction, so not eating, would help cancer.......Regardless its an important topic and research and clarity into it is welcome

 

Here are the calorie restriction links:

https://www.ncbi.nlm...pubmed/23966420

https://www.fightagi...ncer-therapies/

Cancer as a metabolic disease

http://www.sciencedi...05272810006857/

I'll stop here because the list goes on and the research supports activating these pathways.

 

Interesting how easily we're encouraged to question our beliefs. Before it was about feeding pathogens now its about feeding cancers. So in light of the bumper crop of peer reviewed published research recently I do have to question the motivations to dilute the conversation here. I'm here to find the latest published papers, talk about the research and when we get up a good head of steam we seem to get another dose of fear mongering. So if there is an interest in derailing the conversation here I'll be watching for the off topic indicator so we don't go to far astray. So people please rank the posts. If the opinions are not supported I expect to see them ranked as such.

Edited by Bryan_S, 08 November 2016 - 06:13 PM.

[tunt01]

SIRT1 is a tumor *promoter*?!?!

 

 

Of the many things that SIRT1 deacetylates, one of them is p53 an important checkpoint for cancer and cell cycle arrest.  Knowing that NAD+ oscillates over the course of a day, It seems risky to me to give the middle finger to mother nature and our epigenetic machinery and just ramp up NAD+ to high levels in perpetuity.  SIRT1 can be pro-oncogenic.  SOURCE

 

 

I think SIRT1 can be a tumor promoter, but I've not flushed it out enough.  I share Genji's concern.

[midas]

 

 So if there is an interest in derailing the conversation here I'll be watching for the off topic indicator so we don't go to far astray. So people please rank the posts. If the opinions are not supported I expect to see them ranked as such.

 

 

To be honest I would be expecting big pharma to start sticking their nose in sooner or later. Because the way the NR research seems to be heading big pharma looks like its in for a kicking in a few different areas...So new members that seem to be overly negative are always going to be suspicious to me.....

 

And just an uneducated observation on the NAD/NR cancer thing, by far the vast majority of cancers hit in later life, NAD declines with age....Just sayin!

[stefan_001]

 

 

  Discuss the merits of Genji's comments on NAD+ and metabolism

I totally agree. Genji, please keep posting and/or answering questions about your views on NAD+. We won't get any useful results unless every now and then someone ruffles our feathers, so to speak. Your comments about raising NAD+ levels anytime anywhere touch on a longstanding unease about this on my part.

 

 

The cancer topic is an interesting one. But personally I see a difference between what helps to kill cancer versus what helps it to get started. SIRT1 is also known as a tumor promoter, which would mean that calorie restriction, so not eating, would help cancer.......Regardless its an important topic and research and clarity into it is welcome

 

 

 

All dont take my post in the wrong way please. It was simply meant to add perspective to the topic. We all know that if you eat less you dont get cancer. BTW I thought most people were familiar with the SIRT1 discussion regarding cancer. Everything that has a role in healthy cells in some way has a role in cancer cells so each enzyme that maybe good for a healthy cell can be a kill target to get rid of cancer. Here a good article on the SIRT1 that describes the yes/no arguments...:

 

http://www.sciencedi...570963910001159

NAD⁺-dependent Class III histone deacetylase SIRT1 is a multiple function protein critically involved in stress responses, cellular metabolism and aging through deacetylating a variety of substrates including p53, forkhead-box transcription factors, PGC-1α, NF-κB, Ku70 and histones. The first discovered non-histone target of SIRT1, p53, is suggested to play a central role in SIRT1-mediated functions in tumorigenesis and senescence. SIRT1 was originally considered to be a potential tumor promoter since it negatively regulates the tumor suppressor p53 and other tumor suppressors. There is new evidence that SIRT1 acts as a tumor suppressor based on its role in negatively regulating β-catenin and survivin. This review provides an overview of current knowledge of SIRT1-p53 signaling and controversies regarding the functions of SIRT1 in tumorigenesis.

Edited by stefan_001, 08 November 2016 - 08:15 PM.

[stefan_001]

 

 

The cancer topic is an interesting one. But personally I see a difference between what helps to kill cancer versus what helps it to get started. SIRT1 is also known as a tumor promoter, which would mean that calorie restriction, so not eating, would help cancer.......Regardless its an important topic and research and clarity into it is welcome

 

Here are the calorie restriction links:

https://www.ncbi.nlm...pubmed/23966420

https://www.fightagi...ncer-therapies/

Cancer as a metabolic disease

http://www.sciencedi...05272810006857/

I'll stop here because the list goes on and the research supports activating these pathways.

 

Interesting how easily we're encouraged to question our beliefs. Before it was about feeding pathogens now its about feeding cancers. So in light of the bumper crop of peer reviewed published research recently I do have to question the motivations to dilute the conversation here. I'm here to find the latest published papers, talk about the research and when we get up a good head of steam we seem to get another dose of fear mongering. So if there is an interest in derailing the conversation here I'll be watching for the off topic indicator so we don't go to far astray. So people please rank the posts. If the opinions are not supported I expect to see them ranked as such.

 

a bit over reacting?

[Bryan_S]

a bit over reacting?

 

stefan_001, Not to you, the second half of that was to the the board in general. As far as I know we are good and I have no problem with your posts. As the moderator I'll support these parallel discussions as long as it doesn't run amuck and I view our readers rankings as an indicator.

[stefan_001]

Ok got it

Edited by stefan_001, 08 November 2016 - 09:02 PM.

[Oakman]

A robust discussion of cancer and NAD+ levels is very pertinent IMO. As the facts in this matter are far from certain at this point, it only makes sense to look at NAD+ supplementation considering all possible outcomes. I've noted this cancer possibility since I started taking NR, as I've had a small brush with cancer (BCC surgically removed) some years ago. It was not fun, and any cancer is certainly not something I want to be encouraging.

 

Because of that, and being 67, I have added Quercetin (as "EMIQ") and Apigenin, with my NR dose, for some weeks now. They do appear to be very symbiotic acting supplements with NR.

 

Happily, both serve a two fold purpose re: NAD+.  First, they are CD38 inhibitors*, and as CD38 levels rise sharply as we age**, and consume NAD+, they should help keep NAD+ levels from being overly suppressed. Second, they are both shown to possess anti-cancer characteristics***, and IF, IN FACT, heightened NAD+ levels due to supplementation are found to encourage cancers, these compounds could offer some anti-cancer protection. 

 

I'd rather be proactive and potentially prevent disease, than be in reactive mode trying to cure disease.  All with a bonus of higher NAD+ levels with less NR supplementation.

 

* Flavonoid Apigenin Is an Inhibitor of the NAD+ ase CD38 - Implications for Cellular NAD+ Metabolism, Protein Acetylation, and Treatment of Metabolic Syndrome >  https://dash.harvard....pdf?sequence=1

 

** CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction >   http://www.cell.com/...4131(16)30224-8

 

*** A general overview of Cytotoxicity of dietary flavonoids on different human cancer types > https://www.ncbi.nlm...les/PMC4127821/

[Harkijn]

IMO it is the very essence of this board that we permanently challenge our beliefs. Only doubt and discussion will bring us forward. Issues like the pathogens and the present discussion  will not be resolved in the short term.  We should see them  as items on a list that is checked every time a new piece of research data comes in.  Keep up the good work Bryan, I think we all realize how much effort you put into this.

[mrkosh1]

I tremendously doubt that any specific compound found in nature without human modification will have a high level of anti-aging potential. When I say a high level, I mean the ability to literally transform someone's body backwards to a younger state, inside and out. At this time, my guess is that NR may have some ability, over time, to reverse aging in those with serious disease conditions and to a lesser extent in "healthier" humans. If we are going to try and stick with natural compounds that are reasonably simple to acquire, then we're going to need to utilize "stacks" or "combinations" of these substances to produce synergistic effects.

 

You see, if a sixty year individual can take a supplement and reverse gene expression to that of a twenty year old, that may not be enough (even over a period of months or years) to do more than slow or slightly reverse the LIFETIME of damage that has accumulated in his body. To do that, he'd need even stronger agents to push his gene expression and natural repair mechanisms even further. Perhaps all the way to the amazing regenerative levels of an INFANT!

 

If Chromadex and other companies could acquire the funding, I think testing combinations of NAD+ and Sirt boosting compounds for even more pronounced effects would yield the best results. Of course pushing these natural systems to VERY high levels may cause unintentional side effects or even some harm to the body. But the truth is that thousands and thousands of people have been taking NR for months or years now, and if NR was inducing rapid age reversal we would have heard about it. Instead, we here a lot of stories of reversal of disease conditions and more modest anti-aging potential -- even if stronger than most other supplements.

 

The first NR "stack" I'd be tempted to try would be Nicontinamide Riboside plus R Alpha Lipoid Acid plus Acetyl L Carnitine. My hunch is that if this stack was tested on a group of fifty elderly people for a month compared to an NR alone and a control group, the stack would yield better results.

[Oakman]

   ....  

 

The first NR "stack" I'd be tempted to try would be Nicontinamide Riboside plus R Alpha Lipoid Acid plus Acetyl L Carnitine. My hunch is that if this stack was tested on a group of fifty elderly people for a month compared to an NR alone and a control group, the stack would yield better results.

 

Good thought that. I added ALC to my general health stack that included R-ALA maybe 6 months ago, then began my longevity stack with NR + pterostilbene in August, w/PQQ, EMIQ & Apigenin added recently. Not being the personal experience thread, suffice to say I'd like to think everything I take has benefits, but neither NR nor any one other thing added has turned back the hands of time just yet, maybe slowed it a bit... ​  but how would I tell? A study w/wo might show differences - would be fun to see exactly what. 

[stefan_001]

I tremendously doubt that any specific compound found in nature without human modification will have a high level of anti-aging potential. When I say a high level, I mean the ability to literally transform someone's body backwards to a younger state, inside and out. At this time, my guess is that NR may have some ability, over time, to reverse aging in those with serious disease conditions and to a lesser extent in "healthier" humans. If we are going to try and stick with natural compounds that are reasonably simple to acquire, then we're going to need to utilize "stacks" or "combinations" of these substances to produce synergistic effects.

 

You see, if a sixty year individual can take a supplement and reverse gene expression to that of a twenty year old, that may not be enough (even over a period of months or years) to do more than slow or slightly reverse the LIFETIME of damage that has accumulated in his body. To do that, he'd need even stronger agents to push his gene expression and natural repair mechanisms even further. Perhaps all the way to the amazing regenerative levels of an INFANT!

 

If Chromadex and other companies could acquire the funding, I think testing combinations of NAD+ and Sirt boosting compounds for even more pronounced effects would yield the best results. Of course pushing these natural systems to VERY high levels may cause unintentional side effects or even some harm to the body. But the truth is that thousands and thousands of people have been taking NR for months or years now, and if NR was inducing rapid age reversal we would have heard about it. Instead, we here a lot of stories of reversal of disease conditions and more modest anti-aging potential -- even if stronger than most other supplements.

 

The first NR "stack" I'd be tempted to try would be Nicontinamide Riboside plus R Alpha Lipoid Acid plus Acetyl L Carnitine. My hunch is that if this stack was tested on a group of fifty elderly people for a month compared to an NR alone and a control group, the stack would yield better results.

 

Personally when I look in the mirror, how I feel, energy, mind I am clearly in a better shape. I have no doubt about that at all. 

[Nate-2004]

 

I tremendously doubt that any specific compound found in nature without human modification will have a high level of anti-aging potential. When I say a high level, I mean the ability to literally transform someone's body backwards to a younger state, inside and out. At this time, my guess is that NR may have some ability, over time, to reverse aging in those with serious disease conditions and to a lesser extent in "healthier" humans. If we are going to try and stick with natural compounds that are reasonably simple to acquire, then we're going to need to utilize "stacks" or "combinations" of these substances to produce synergistic effects.

 

You see, if a sixty year individual can take a supplement and reverse gene expression to that of a twenty year old, that may not be enough (even over a period of months or years) to do more than slow or slightly reverse the LIFETIME of damage that has accumulated in his body. To do that, he'd need even stronger agents to push his gene expression and natural repair mechanisms even further. Perhaps all the way to the amazing regenerative levels of an INFANT!

 

If Chromadex and other companies could acquire the funding, I think testing combinations of NAD+ and Sirt boosting compounds for even more pronounced effects would yield the best results. Of course pushing these natural systems to VERY high levels may cause unintentional side effects or even some harm to the body. But the truth is that thousands and thousands of people have been taking NR for months or years now, and if NR was inducing rapid age reversal we would have heard about it. Instead, we here a lot of stories of reversal of disease conditions and more modest anti-aging potential -- even if stronger than most other supplements.

 

The first NR "stack" I'd be tempted to try would be Nicontinamide Riboside plus R Alpha Lipoid Acid plus Acetyl L Carnitine. My hunch is that if this stack was tested on a group of fifty elderly people for a month compared to an NR alone and a control group, the stack would yield better results.

 

Personally when I look in the mirror, how I feel, energy, mind I am clearly in a better shape. I have no doubt about that at all. 

 

 

This makes sense and I agree with Stefan as well.

 

Also I've already been trying that exact stack for a month in addition to MK-677 and creatine mrkosh1. I'm actually getting some pretty incredible results from it. My lower back pain of 7 years is finally gone, despite my awful mattress which I finally broke down and decided to replace with a tuft and needle. I still wake up with lower back pain but it's gone the instant I get out of bed and gone for the rest of the day. The painlessness has stood out like a sore thumb and I keep expecting to feel it when I do certain things and when I don't, it's like, whoa wtf. Still taking it easy. I lifted more in squats this time than I have in years but I didn't go too far with it.

Edited by Nate-2004, 11 November 2016 - 02:28 PM.