2255 replies to this topic

[Bryan_S]

Nicotinamide riboside is uniquely and orally bioavailable in mice and humans

 

Here is one of the first peer reviews posted for the Brenner study.

 

http://www.nature.co...mms12948-s5.pdf

 

 

 

First human clinical trial for nicotinamide riboside

PUBLIC RELEASE: 10-OCT-2016

 

https://www.eurekale...h-fhc100616.php

 

 

 

Nicotinamide riboside is uniquely and orally bioavailable in mice and humans

http://www.nature.co...les/ncomms12948

Article | OPEN

Samuel A. J. Trammell, Mark S. Schmidt, Benjamin J. Weidemann, Philip Redpath, Frank Jaksch, Ryan W. Dellinger, Zhonggang Li, E. Dale Abel, Marie E. Migaud & Charles Brenner

Nature Communications 7, Article number: 12948 (2016)

doi:10.1038/ncomms12948

Download Citation

Diagnostic markersMetabolomics

Received: 30 January 2016

Accepted: 12 August 2016

Published online: 10 October 2016

 

Abstract

Nicotinamide riboside (NR) is in wide use as an NAD+ precursor vitamin. Here we determine the time and dose-dependent effects of NR on blood NAD+ metabolism in humans. We report that human blood NAD+ can rise as much as 2.7-fold with a single oral dose of NR in a pilot study of one individual, and that oral NR elevates mouse hepatic NAD+ with distinct and superior pharmacokinetics to those of nicotinic acid and nicotinamide. We further show that single doses of 100, 300 and 1,000 mg of NR produce dose-dependent increases in the blood NAD+ metabolome in the first clinical trial of NR pharmacokinetics in humans. We also report that nicotinic acid adenine dinucleotide (NAAD), which was not thought to be en route for the conversion of NR to NAD+, is formed from NR and discover that the rise in NAAD is a highly sensitive biomarker of effective NAD+ repletion.

 

OK guys here is the long awaited full Brenner study release.

 

Ray Kurzweil also commented:

http://www.kurzweila...namide-riboside

 

 

[Bryan_S]

The way I look at it, all of the time based dosage data off a single dose is not what we are seeking. I understand why researchers have to take an Oral Gavage approach or have human test subjects take a dose at a set time. I think the ad libitum feeding data is what you want to see long term effects. The first approach (Oral Gavage) which can help show base NAD levels before and time based increases is great if you want to see end to end ranges. It can also help detect a NAD ceiling if there is such a thing, which we all suspect. However the 2nd (ad libitum feeding) is how the long term rodent studies are performed and those that have produced some of the phenomenal results we've seen. In this example the animals are ingesting a little at a time thru water or feed. This is as close as you could get to a time released approach and it avoids the suspected NAD ceiling we've all been debating. Also across the day more NAD precursor can be administered without hitting this hypothetical saturation point. So if we are looking at raising our NAD to youthful levels around the clock, I want to see around the clock data reflecting a slow NAD repletion method like the ad libitum feeding.

 

So as everyone kicks around re-enforcing Circadian rhythms I would like to see raised NAD levels that remain RAISED and let the Circadian rhythms do what they will.

 

As always JMHO

[warner]

In this example the animals are ingesting a little at a time thru water or feed. ... So if we are looking at raising our NAD to youthful levels around the clock, I want to see around the clock data reflecting a slow NAD repletion method like the ad libitum feeding.

But is that true?  If, for example, you spread my NR dose evenly across my food and water intake, it would be far from uniform.  In fact, it would look more like taking several NR capsules across the day.  I don't know what the answer is, but an ad libitum dosing based on food and water may not be optimal.  (Do the mice drink at a uniform rate across the day and night?)

 

I think the summary of where we're at given by Oakman above is very good.  In particular, I'm interested at the moment in what the mechanism (if any) would be for NR supplementation to interfere with circadian-related suppression of breast and prostate cancer metastasis, as described here:

http://caloriesprope...-breast-cancer/

http://caloriesprope...rostate-cancer/

[Bryan_S]

So guys with a little LongeCity Admin encouragement I'm starting to think about who to talk with next. I'm reading comments from across the boards talking about CD38, NAD precursor bioavailability as to which one is best. This dosage question, which I do not think enough has been published. I see some human clinical trial data just around the corner and a ton of animal research suggesting all sorts of medical applications.

 

So priorities please! We all have our pet questions we want answered. However when you have researchers focusing their efforts on specific questions, those are the questions we can ask that will yield the best insights. If its not in their field I'll only get at best opinions. If we look at CD38 for instance the pioneering group who published in the spring has been very rooted in cancers for the last decade. Brenner for instance was not the researcher who was best suited for those questions. So with any of these researcher of interest I'll need to target those researchers who have expertise in the surrounding topics they've specialized in that have brought them to study NAD repletion and why.

 

So what are our must pressing questions so I can select a researcher of interest who's field of study makes then the expert?

[Bryan_S]

 

In this example the animals are ingesting a little at a time thru water or feed. ... So if we are looking at raising our NAD to youthful levels around the clock, I want to see around the clock data reflecting a slow NAD repletion method like the ad libitum feeding.

But is that true?  If, for example, you spread my NR dose evenly across my food and water intake, it would be far from uniform.  In fact, it would look more like taking several NR capsules across the day.  I don't know what the answer is, but an ad libitum dosing based on food and water may not be optimal.  (Do the mice drink at a uniform rate across the day and night?)

 

I think the summary of where we're at given by Oakman above is very good.  In particular, I'm interested at the moment in what the mechanism (if any) would be for NR supplementation to interfere with circadian-related suppression of breast and prostate cancer metastasis, as described here:

http://caloriesprope...-breast-cancer/

http://caloriesprope...rostate-cancer/

 

 

Not perfect not optimal but there are no time released preparations. I think there is still a lot of great data out there with questions that needed answered but absolutely nothing from a continuously released source like an IV or time released method. Ad libitum feeding is as close as it gets. These are the early days as Brenner suggested.

[normalizing]

hi i just read NR can regenerate liver and kidney cells, whats the best dose for this? as i read up to 500mg is well tolerated with most effect achieved around 300mg and above ok thank you

 

can someone answer me to this because i dont have the patience to read all that crap about longevity and nonsense you guys spew pages of ktnx

[normalizing]

or is this a flux? i keep checking google, it just has few sponsored review news. if someone can help me out on this ill be very thankful i dont wanna make a separate thread on it and i understand you guys dont care for things like generating liver or kidney cells but are more concentrated on some longivity benefits this supposedly enhances. either way, any help appreciated thanks!

[Bryan_S]

 

hi i just read NR can regenerate liver and kidney cells, whats the best dose for this? as i read up to 500mg is well tolerated with most effect achieved around 300mg and above ok thank you

 

 

can someone answer me to this please
 

 

 

Here is a recent study

http://www.nature.co...ature17184.html

http://mitochondrial...y-acute-injury/

 

https://www.ncbi.nlm...les/PMC3193667/

 

here is one on rejuvenation of stem cells, they touch on kidney.

https://www.scienced...60428152124.htm

 

http://science.scien...t/352/6292/1436

 

No human dose is referenced and this is a little early to be recommending a dose for diseases or the rejuvenation of organs. Lets not get to far ahead of the research.

Edited by Bryan_S, 04 November 2016 - 09:07 AM.

[Fafner55]

or is this a flux? i keep checking google, it just has few sponsored review news. if someone can help me out on this ill be very thankful i dont wanna make a separate thread on it and i understand you guys dont care for things like generating liver or kidney cells but are more concentrated on some longivity benefits this supposedly enhances. either way, any help appreciated thanks!

 

My recent post on another thread is relevant.

http://www.longecity...ndpost&p=794346

[bluemoon]

 

No human dose is referenced and this is a little early to be recommending a dose for diseases or the rejuvenation of organs. Lets not get to far ahead of the research.

 

 

But  I think there is enough evidence to take NR for rejuvenation as long as one remembers that the effect may be quite small in humans. You could always do what most of the 200,000 people taking NR do - take 250 mg until more is known. 

 

I'm curious if anything Brenner said changed Bryan_S' or anyone else's thinking on taking 1000 mg a day. 

[warner]

So what are our must pressing questions so I can select a researcher of interest who's field of study makes then the expert?

I assume NR would instantly lose GRAS status if it is found to promote any type of common cancer.

I would look for researchers who can address this risk, at least theoretically, if not experimentally.

Give us a good reason for thinking that existing breast, prostate, colon, etc., cancers will not be accelerated by typical doses of NR, as well as higher doses that might disrupt circadian rhythm (as evidenced by the insomnia reported by some users).

[stefan_001]

 

So what are our must pressing questions so I can select a researcher of interest who's field of study makes then the expert?

I assume NR would instantly lose GRAS status if it is found to promote any type of common cancer.

I would look for researchers who can address this risk, at least theoretically, if not experimentally.

Give us a good reason for thinking that existing breast, prostate, colon, etc., cancers will not be accelerated by typical doses of NR, as well as higher doses that might disrupt circadian rhythm (as evidenced by the insomnia reported by some users).

 

 

No serious researcher will answer those questions with strong statements

Edited by stefan_001, 04 November 2016 - 02:27 PM.

[warner]

No serious researcher will answer those questions with strong statements

Ahh... good you edited that.    I expect every serious researcher (good scientist) to speculate/hypothesize about all aspects of existence with which they have some familiarity.  Whether they do that publicly or not is more about politics than science.  I guess what you're saying is that not enough is known for any of them to have much to say at this point, but I'd like to hear them say that too, and suggest/explain what needs to be done to fix that.  Also interested in whether any cancer researchers themselves are taking NR, and how personally risky they think that might be.  The GRAS approval was done largely on the basis that NR is "just another B3 vitamin", but it's clearly more than that, so some caution seems wise.

Edited by warner, 04 November 2016 - 03:20 PM.

[Bryan_S]

Jobs / Job post

Post-doc/Associate Specialist - NAD+ Metabolism

PostDoc Position

Posted on 04 Nov 2016

https://www.research...-NAD_Metabolism

 

 

http://www.universit...nne-switzerland

Edited by Bryan_S, 05 November 2016 - 05:19 AM.

[Bryan_S]

 

 

No human dose is referenced and this is a little early to be recommending a dose for diseases or the rejuvenation of organs. Lets not get to far ahead of the research.

 

 

But  I think there is enough evidence to take NR for rejuvenation as long as one remembers that the effect may be quite small in humans. You could always do what most of the 200,000 people taking NR do - take 250 mg until more is known. 

 

I'm curious if anything Brenner said changed Bryan_S' or anyone else's thinking on taking 1000 mg a day. 

 

 

From a marketing standpoint Nicotinamide Riboside supplementation needs to be as simple as possible and once or twice a day is considered reasonable dosing. I clearly get that. It also takes a great deal of effort and handling of animals to give them doses at specific times so for long term study ad libitum feeding makes sense. But our bodies don't work on set dosage schedule and both the NR and NMN studies are indicating an optimum dosing witch is still a question. So if there is an optimum dose you'll only be hitting that dose once or twice a day and we have round the clock NAD demands. I certainly don't have a concrete answer for anyone but I still break my 1000 mg's up thru the day for now.

 

As always JMHO 

[bluemoon]

 

 

 

 

From a marketing standpoint Nicotinamide Riboside supplementation needs to be as simple as possible and once or twice a day is considered reasonable dosing. I clearly get that. It also takes a great deal of effort and handling of animals to give them doses at specific times so for long term study ad libitum feeding makes sense. But our bodies don't work on set dosage schedule and both the NR and NMN studies are indicating an optimum dosing witch is still a question. So if there is an optimum dose you'll only be hitting that dose once or twice a day and we have round the clock NAD demands. I certainly don't have a concrete answer for anyone but I still break my 1000 mg's up thru the day for now.

 

As always JMHO 

 

 

 

Ever since the Chromadex very small study on 100mg, 300mg and 1000mg for one day came out that showed NR was boosted NAD+ 30% at the low dose and 50% at both the 300mg and 1000mg, I wondered if that means 1000mg is not necessary. But since that doesn't last throughout the day at 300mg, maybe 500mg, 750mg or even 1000mg will be shown to be the healthier way to go. But it is also much more expensive than the 250mg most seem to be taking. I also wonder why Elysium markets Basis at 250mg - because that is what they think a good/ideal dosage is or because they don't expect to sell much if recommending 500mg.

 

I hope this will be known within a year, but I doubt it. I don't think the right dose of resveratrol has been concluded other than that many have gravitated toward either 250mg or 500mg a day while David Sinclair told the WaPo last year that he takes 1000mg powder with his cereal each morning.

[stefan_001]

 

 

 

 

From a marketing standpoint Nicotinamide Riboside supplementation needs to be as simple as possible and once or twice a day is considered reasonable dosing. I clearly get that. It also takes a great deal of effort and handling of animals to give them doses at specific times so for long term study ad libitum feeding makes sense. But our bodies don't work on set dosage schedule and both the NR and NMN studies are indicating an optimum dosing witch is still a question. So if there is an optimum dose you'll only be hitting that dose once or twice a day and we have round the clock NAD demands. I certainly don't have a concrete answer for anyone but I still break my 1000 mg's up thru the day for now.

 

As always JMHO 

 

 

 

Ever since the Chromadex very small study on 100mg, 300mg and 1000mg for one day came out that showed NR was boosted NAD+ 30% at the low dose and 50% at both the 300mg and 1000mg, I wondered if that means 1000mg is not necessary. But since that doesn't last throughout the day at 300mg, maybe 500mg, 750mg or even 1000mg will be shown to be the healthier way to go. But it is also much more expensive than the 250mg most seem to be taking. I also wonder why Elysium markets Basis at 250mg - because that is what they think a good/ideal dosage is or because they don't expect to sell much if recommending 500mg.

 

I hope this will be known within a year, but I doubt it. I don't think the right dose of resveratrol has been concluded other than that many have gravitated toward either 250mg or 500mg a day while David Sinclair told the WaPo last year that he takes 1000mg powder with his cereal each morning.

 

 

I think the reason may be here:
http://www.timelessl...side-published/

 

they concluded that the outcome of a toxicology study, with a FDA safety margin applied, leads to a "safe dose" of 288mg / day. I guess that all supplement sellers want to wash their hands in case there would be adverse effects and apply this. Or then its one of those coincidences......  Other reason maybe that the price becomes too high.

Edited by stefan_001, 04 November 2016 - 08:36 PM.

[Bryan_S]

 

I think the reason may be here:
http://www.timelessl...side-published/

 

they concluded that the outcome of a toxicology study, with a FDA safety margin applied, leads to a "safe dose" of 288mg / day. I guess that all supplement sellers want to wash their hands in case there would be adverse effects and apply this. Or then its one of those coincidences......  Other reason maybe that the price becomes too high.

 

 

True is all about reasonable safety margins with a little extra knocked off. We are going to debate dosage for some time without doubt. I also think the way this is priced is whats perceived as the maximum price they can charge and still grow sales. As far as the recommended dosage and how often we take it, they've got to keep the dosage simple at once or twice per day. Anything more than that would be a hassle for the average person. I'm not recommending anything, please do what you would on your own, I'm just giving my opinion on why I regiment the way I do. I think a time released version would be the way to go. Pure Opinion at this point.

Edited by Bryan_S, 05 November 2016 - 05:12 AM.

[normalizing]

 

 

hi i just read NR can regenerate liver and kidney cells, whats the best dose for this? as i read up to 500mg is well tolerated with most effect achieved around 300mg and above ok thank you

 

 

can someone answer me to this please
 

 

 

Here is a recent study

http://www.nature.co...ature17184.html

http://mitochondrial...y-acute-injury/

 

https://www.ncbi.nlm...les/PMC3193667/

 

here is one on rejuvenation of stem cells, they touch on kidney.

https://www.scienced...60428152124.htm

 

http://science.scien...t/352/6292/1436

 

No human dose is referenced and this is a little early to be recommending a dose for diseases or the rejuvenation of organs. Lets not get to far ahead of the research.

 

 

there is refferenced human dose it is in one article saying "Nicotinamide 250 mg capsules were given twice daily for 25 patients with serum phosphorus greater than 5 mg/dL and thrice daily for 5 patients with serum phosphorus greater than 8 mg/dL immediately after food for 8 weeks"

 

so thats 500mg a day, or up to 750mg a day. of course i dunno how to split into 250mg considering my tablets come as only 100mg each. im not going to cut a tiny pill into a tinier fragment, might as well take 500mg all together during the day

 

[normalizing]

 

or is this a flux? i keep checking google, it just has few sponsored review news. if someone can help me out on this ill be very thankful i dont wanna make a separate thread on it and i understand you guys dont care for things like generating liver or kidney cells but are more concentrated on some longivity benefits this supposedly enhances. either way, any help appreciated thanks!

 

My recent post on another thread is relevant.

http://www.longecity...ndpost&p=794346

 

 

i read this and i cannot believe one would need to take 4000mg of this stuff... i cannot find a single study suggesting such thing! im sure you dont do it yourself but you seem to think its a good idea to recommend it to people
 

[Harkijn]

Speaking of dosing:

 

The author here 

http://www.timelessl...ing-conclusion/

discusses research that we already were aware of. However, he differs with the authors on their conclusions about dosage and favors higher daily amounts.  Yes, this is about NMN. And mice. But the human data so far are rather scant.

[Oakman]

I hadn't seen this before, that Elysium Health has been conducting a study since January of its Basis > https://clinicaltria...how/NCT02678611

 

Some strange things about this trial are, and considering how Elysium is marketed, is that "Blood NAD+" levels are demoted to a Secondary Outcome, plus the rather benign Primary Outcome Measures. And last, the "Physiological Performance" levels tested for, seem to be those of nursing home patients, not reasonably healthy 60-80 yr olds, or is that really a reasonable exercise expectation for that age group in general? Does anyone on the forum belong to this study?

 

However, still might be interesting to get in on the tail end of this if you live near where it's happening: 

Locations 

Canada, Ontario KGK Synergize Inc.   London, Ontario, Canada, N6A 5R8
 

A Study to Evaluate Safety and Health Benefits of Basis™ Among Elderly (60 Years to 80 Years ) Subjects.

 

Primary Outcome Measures:

• Blood pressure [ Time Frame: 8 weeks ][ Designated as safety issue: Yes ]
  Assessment of blood pressure
• Safety Blood Parameters [ Time Frame: 8 weeks ][ Designated as safety issue: Yes ]
  Assessment of safety blood parameters: CBC, electrolytes (Na, K, Cl), kidney function (creatinine), liver function (AST, ALT, GGT and bilirubin)
• Heart Rate [ Time Frame: 8 weeks ][ Designated as safety issue: Yes ]
  Assessment of heart rate

Secondary Outcome Measures:

• Physiological Performance [ Time Frame: 8 weeks ][ Designated as safety issue: No ]
  6 Minute Walk Test
• Physiological Performance [ Time Frame: 8 weeks ][ Designated as safety issue: No ]
  30 Second Chair Stand Test
• Physiological Performance [ Time Frame: 8 weeks ][ Designated as safety issue: No ]
  Physical Activity Scale for the Elderly
• Body Weight [ Time Frame: 8 weeks ][ Designated as safety issue: No ]
• Blood Pressure [ Time Frame: 8 weeks ][ Designated as safety issue: No ]
• Serum Glucose [ Time Frame: 8 weeks ][ Designated as safety issue: No ]
• Lipid Profile [ Time Frame: 8 weeks ][ Designated as safety issue: No ]
• Quality of Life and Sleep Quality [ Time Frame: 8 weeks ][ Designated as safety issue: No ]
  Health Assessment Questionnaire
• Quality of Life and Sleep Quality [ Time Frame: 8 weeks ][ Designated as safety issue: No ]
  Older People's Quality of Life Questionnaires
• Blood NAD+ [ Time Frame: 8 weeks ][ Designated as safety issue: No ]

Other Outcome Measures:

• Expression Profile of Peripheral Blood Mononuclear Cells [ Time Frame: 8 weeks ][ Designated as safety issue: No ]
• Pain Assessment [ Time Frame: 8 weeks ][ Designated as safety issue: No ]
  VAS Pain Scale
• Endothelial Function [ Time Frame: 8 weeks ][ Designated as safety issue: No ]
  EndoPat

 

 

 

[Oakman]

_{Here's an eye-opener, if there ever was one. And it comes from many of those truly invested in aging research.}

 

This article appears in the August 22, 2016 issue of New York Magazine. I've excerpted a part that describes who is using the product. Not very encouraging, and actually quite disappointing really. If these guys don't really see a benefit in NR, what does that leave the rest of us to think? (bolding in the excerpt is mine)

 

http://nymag.com/sci...&GA=attribution

 

------------------------------

That day at the Elysium offices, advisory board member Jack Szostak, who won the Nobel Prize for Physiology or Medicine in 2009, was visiting, and we spoke in an empty space down the hall where the company would soon be expanding. Szostak has known Guarente for 30 years (“the yeast-genetics community, everybody knows everybody”), and his official role at Elysium is to keep an eye out for compounds that, like Basis, could target health maintenance rather than specific diseases. I asked him if he had any discomfort selling an unproven product. “To follow a large number of people for a long period of time is an expensive undertaking,” he observed.

 

This argument, that the cart had to be put before the horse in order to get the horse to move, is one I heard from several defenders of Elysium’s approach. But even advisory board member James Kirkland, who leads the Mayo Clinic’s Robert and Arlene Kogod Center on Aging, said, when asked about this concern, “I think that’s a good point.” Kaeberlein, Guarente’s former protégé, is sharper: “They have the legal right to market this compound to people without any real knowledge of what it’s going to do — good, bad, or indifferent — in the long run. Is it something they should be doing? I’m not qualified to make that moral argument. We each have our own view as a scientist what level of evidence do we need to feel comfortable staking our scientific reputation on that and making general recommendations to the general public. You can probably guess where my opinion is.”

 

For me, as that first month taking Basis ticked by, this question had become more than academic. This was true for many of these scientific advisers, and at least some of them are guinea-pigging themselves. Sir Richard Roberts, a 72-year-old Nobelist who also sits on Elysium’s board, says that both he and his wife take Basis. “The only thing I’ve noticed, and this was only because someone mentioned they’d noticed it too,” Sir Richard said, “the skin on my elbows, which I always noticed was pretty rough, was now much smoother.” Robert Nelsen, a leading biotech venture capitalist who has invested in Elysium and takes Basis, told me, “I feel younger than I am,” and said he can do more push-ups now. (Nelsen, who is 53, also takes metformin, despite not having diabetes. “My partners think I’m nuts,” he says.)

 

Then again, all these people are financially and reputationally incentivized to believe in Basis. Even Nelsen acknowledged he could be experiencing a placebo effect. I asked other scientists, outside Elysium’s orbit, whether they take the pill. Olshansky told me he takes nothing: He tries to exercise daily and watch what he eats. Kennedy, likewise, takes nothing: “I said I’m going to wait till I’m 50 before I start taking anything. I run, I try to keep my caloric level down, I manage stress.” Kaeberlein takes nothing but says he’s “getting more and more tempted to take rapamycin in a low dose.” Sinclair, who now co-directs a Glenn-funded center at Harvard, still takes resveratrol every day and also takes an NAD booster (he has his own biotech company, currently in stealth mode, focused on that booster).

 

Sinclair did say that Basis is “based on solid science” and, if he didn’t have his own NAD booster,  “he’d “strongly consider” taking it. Was I, then, on safe ground taking it? There was a long pause on Sinclair’s end of the line. “You’re never safe assuming anything,” he said.  "The results from studies indicate it should be safe.” And effective? Another pause. “I’d rather not say anything that definitive.”

 

My confidence waned. None of these scientists deemed Basis something they urgently need to be taking. Maybe it would help. Maybe it wouldn’t. Like Dylar, the black-market drug in Don DeLillo’s White Noise that cures the fear of death, the true payload of Basis and its coming wave of peers, whatever their physical benefits, may be a balm for existential terror. Side effects may include an obsession with death, reinforced every morning when you swallow your pill.

 

 

Edited by Oakman, 07 November 2016 - 03:31 PM.

[bluemoon]

  And last, the "Physiological Performance" levels tested for, seem to be those of nursing home patients, not reasonably healthy 60-80 yr olds, or is that really a reasonable exercise expectation for that age group in general? Does anyone on the forum belong to this study?   

 

There are only 120 people in the study, where 40 take 250mg, 40 take 500mg and 40 take a placebo. I'm glad the trial includes a twice as great as they currently recommend.

 

And the age group seems exactly who they should initially study, 60 to 80 year olds, those who are most likely to be healthy elderly and includes those in their 60s who are heading into the elderly range, that is 70+.

 

I hope they stick with their claim when Elysium was launched - that all results, favorable or not, would be put up on their website. 

[stefan_001]

Asking from Sinclair to say that NR is effective while he is busy spending investor money on something doing almost the same would not be a healthy "longevity" strategy for his startup company......

Edited by stefan_001, 07 November 2016 - 03:43 PM.

[Nate-2004]

 

This argument, that the cart had to be put before the horse in order to get the horse to move, is one I heard from several defenders of Elysium’s approach. But even advisory board member James Kirkland, who leads the Mayo Clinic’s Robert and Arlene Kogod Center on Aging, said, when asked about this concern, “I think that’s a good point.” Kaeberlein, Guarente’s former protégé, is sharper: “They have the legal right to market this compound to people without any real knowledge of what it’s going to do — good, bad, or indifferent — in the long run. Is it something they should be doing? I’m not qualified to make that moral argument. We each have our own view as a scientist what level of evidence do we need to feel comfortable staking our scientific reputation on that and making general recommendations to the general public. You can probably guess where my opinion is.”

 

For me, as that first month taking Basis ticked by, this question had become more than academic. This was true for many of these scientific advisers, and at least some of them are guinea-pigging themselves. Sir Richard Roberts, a 72-year-old Nobelist who also sits on Elysium’s board, says that both he and his wife take Basis. “The only thing I’ve noticed, and this was only because someone mentioned they’d noticed it too,” Sir Richard said, “the skin on my elbows, which I always noticed was pretty rough, was now much smoother.” Robert Nelsen, a leading biotech venture capitalist who has invested in Elysium and takes Basis, told me, “I feel younger than I am,” and said he can do more push-ups now. (Nelsen, who is 53, also takes metformin, despite not having diabetes. “My partners think I’m nuts,” he says.)

 

 

The FDA only approves medicine for the treatment of specific diseases and does not classify aging or prevention of a disease as cause for treatment. I find that to be a completely absurd stance to take but it looks like some of these guys ("my partners think I'm nuts") really buy into it. People have the right to put whatever they want into their own body without the approval of some authoritarian monopoly of force like the DEA or FDA. Is it ethical to sell snake oil? No, but it's really up to those selling it to risk their reputation and possible lawsuits and it's up to the buyer to educate themselves and be skeptical of what they're buying and aware of the risk they're taking as well, whether it's a Samsung product or a drug.

 

Nelson isn't crazy for taking metformin despite not having diabetes, these people are just indoctrinated by and have bought into an authoritarian system of rigid rules and regulations regarding what something can be used for or not used for, despite other possibilities. The FDA's magical seal of approval for what ____ can be taken for changes nothing.

 

There is a lot of positive evidence mounting for NR and it's all being posted on this thread. It's also getting cheaper from sources like HPN. For me, it's been worth it.

Edited by Nate-2004, 07 November 2016 - 03:53 PM.

[bluemoon]

It is unlikely that the New Yorker Magazine writer is old enough to feel benefits from NR.  

[trakker]

 

I hadn't seen this before, that Elysium Health has been conducting a study since January of its Basis > https://clinicaltria...how/NCT02678611

 

Some strange things about this trial are, and considering how Elysium is marketed, is that "Blood NAD+" levels are demoted to a Secondary Outcome, plus the rather benign Primary Outcome Measures. And last, the "Physiological Performance" levels tested for, seem to be those of nursing home patients, not reasonably healthy 60-80 yr olds, or is that really a reasonable exercise expectation for that age group in general? Does anyone on the forum belong to this study?

 

However, still might be interesting to get in on the tail end of this if you live near where it's happening: 

Locations 

Canada, Ontario KGK Synergize Inc.   London, Ontario, Canada, N6A 5R8
 

A Study to Evaluate Safety and Health Benefits of Basis™ Among Elderly (60 Years to 80 Years ) Subjects.

 

Primary Outcome Measures:

• Blood pressure [ Time Frame: 8 weeks ][ Designated as safety issue: Yes ]
  Assessment of blood pressure
• Safety Blood Parameters [ Time Frame: 8 weeks ][ Designated as safety issue: Yes ]
  Assessment of safety blood parameters: CBC, electrolytes (Na, K, Cl), kidney function (creatinine), liver function (AST, ALT, GGT and bilirubin)
• Heart Rate [ Time Frame: 8 weeks ][ Designated as safety issue: Yes ]
  Assessment of heart rate

Secondary Outcome Measures:

• Physiological Performance [ Time Frame: 8 weeks ][ Designated as safety issue: No ]
  6 Minute Walk Test
• Physiological Performance [ Time Frame: 8 weeks ][ Designated as safety issue: No ]
  30 Second Chair Stand Test
• Physiological Performance [ Time Frame: 8 weeks ][ Designated as safety issue: No ]
  Physical Activity Scale for the Elderly
• Body Weight [ Time Frame: 8 weeks ][ Designated as safety issue: No ]
• Blood Pressure [ Time Frame: 8 weeks ][ Designated as safety issue: No ]
• Serum Glucose [ Time Frame: 8 weeks ][ Designated as safety issue: No ]
• Lipid Profile [ Time Frame: 8 weeks ][ Designated as safety issue: No ]
• Quality of Life and Sleep Quality [ Time Frame: 8 weeks ][ Designated as safety issue: No ]
  Health Assessment Questionnaire
• Quality of Life and Sleep Quality [ Time Frame: 8 weeks ][ Designated as safety issue: No ]
  Older People's Quality of Life Questionnaires
• Blood NAD+ [ Time Frame: 8 weeks ][ Designated as safety issue: No ]

Other Outcome Measures:

• Expression Profile of Peripheral Blood Mononuclear Cells [ Time Frame: 8 weeks ][ Designated as safety issue: No ]
• Pain Assessment [ Time Frame: 8 weeks ][ Designated as safety issue: No ]
  VAS Pain Scale
• Endothelial Function [ Time Frame: 8 weeks ][ Designated as safety issue: No ]
  EndoPat

 

 

 

I believe this was completed in July, and we are just awaiting publication.

 

As to the question of NAD+ being a secondary endpoint.  They made safety their primary endpoints, which MUST be met of it is a valid product.  

 

Of course they want and expect to see blood NAD+ increase.  But they can claim it met primary endpoints quickly and issue press releases, while they evaluate and document all the secondary endpoint results.  

 

Of course, just my guess on why they designed that way.

 

I thought it was great they will have all the physical performance measures.  Super excited to see those results.

 

[Bryan_S]

Speaking of dosing:

 

The author here 

http://www.timelessl...ing-conclusion/

discusses research that we already were aware of. However, he differs with the authors on their conclusions about dosage and favors higher daily amounts.  Yes, this is about NMN. And mice. But the human data so far are rather scant.

 

Thank you harkijn

 

The conclusions in this authors blog speak to the dosing conversation we've had here. The human data thus far has not approached the near continues dosing we see in the animal studies. It troubles me when comparing sample times from one experiment to the other when suggesting bioavailability and dosing frequency. The NR study did a good job showing sample rates over a 24hr period showing the secondary boost. This NMN group is also about to hold a human trial as well to further a competitive product so the quicker the results the better the excitement. The NMN study did a more rapid sampling scale to show the initial onset of the NAD boost. We can draw conclusions from both studies and some of the data aligns but much is lacking. So in all the timelesslifemag author challenges a number of conclusions as do I. Since the initial NAD rise happens within the first 15 minutes for NMN who's to say it doesn't for NR and where the NMN data suggests the 100mg group vs the 300 mg group sees better results, does it really? I think the overall conclusion can be reached that more frequent dosing and the higher sustained blood serum levels produced the best results when you dig down.

 

In checking the https://clinicaltria...e&Search=Search I see some new trials (12 in all) but they all appear to be single or twice per/day dosing strategies. So if we wanted to see results similar to the ad libitum dosing its not in the cards at least for now.

 

Again JMHO 

[genji]

I’ve just recently joined this forum. I would like to comment briefly on the nicotinamide riboside and NAD+, sirtuin, etc., thread.

Maybe I missed something somewhere, but in the curated threadI’ve only seen  passing references to the extensive literature on well-studied negative effects of elevated NAD+ and sirtuin levels, especially in the case of cancer initiation, progression, and metastasis.

You certainly never find detailed discussions of this issue with Guarente or Sinclair or any of the others with deep nvolvement in selling NAD+ precursors or intermediates or putative sirtuin activators. How many hundreds of millions of dollars (!) did Sinclair make in pushing resveratrol by a little tweaking of the research?

But there are others outside this group who have published a long series of papers on NAD+ and cancer. 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. 

And all that means is that they have many, in some cases many hundreds, of contradictory effects in different parts of the body, in different tissues, and sometimes in different cellular compartments of the body, as is the well-known case of the sirtuins.

I could post a dozen or more links to papers on cancer and upregulated NAD+, which the Guarente or Sinclair types only mention quickly, and in passing, but as I understand it I can’t post links in the List yet as a new member. But a good place to start is with this review by Shackelford et al. published in _Genes and Cancer_ in 2013. It deals with Nicotinamide Phosphoribosyltransferase (Nampt). Nampt is part of the catalytic chain that produces nicotinamide mononucleotide, a key step in the synthesis of NAD+.

 

Here I just post the abstract, since I can’t apparently post links, but you can get the whole paper, which is open access, by putting the title into PubMed.

 

Also see the further warnings (esp. on p. 1213) about autoimmune activation and cancer involving NAD and its relatives in the 2015 review of NAD+ in _Science_ by Eric Verdin, of UCSF, who also has no financial interest (unlike the Sinclair or Guarente types) in research in this field: 

 

"NAD+ in aging, metabolism, and neurodegeneration,” Science. 2015 Dec 4;350(6265):1208-13. doi: 10.1126/science.aac4854

 

Best,

Genji

 

***************

 

Nicotinamide Phosphoribosyltransferase in Malignancy:A Review

Rodney E. Shackelford1, Kim Mayhall2, Nicole M. Maxwell3, Emad Kandil2, and Domenico Coppola4

Submitted 19-Jun-2013; accepted 26-Aug-2013

Abstract

Genes & Cancer
4(11-12) 447–456
DOI: 10.1177/1947601913507576

Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the rate-limiting step of nicotinamide adenine dinucleotide (NAD) synthesis. Both intracellular and extracellular Nampt (iNampt and eNampt) levels are increased in several human malignancies and some studies demonstrate increased iNampt in more aggressive/invasive tumors and in tumor metastases. Several different molecular targets have been identified that promote carcinogenesis following iNampt overexpression, including SirT1, CtBP, and PARP-1. Additionally, eNampt is elevated in several human cancers and is often associated with a higher tumor stage and worse prognoses. Here we review the roles of Nampt in malignancy, some of the known mechanisms by which it promotes carcinogenesis, and discuss the possibility of employing Nampt inhibitors in cancer treatment.

Keywords

nicotinamide phosphoribosyltransferase, nicotinamide adenine dinucleotide, human cancer