89 replies to this topic

[VP.]

https://www.nature.c...1514-017-0016-9
NRPT is a combination of nicotinamide riboside (NR), a nicotinamide adenine dinucleotide (NAD+) precursor vitamin found in milk, and pterostilbene (PT), a polyphenol found in blueberries. Here, we report this first-in-humans clinical trial designed to assess the safety and efficacy of a repeat dose of NRPT (commercially known as Basis). NRPT was evaluated in a randomized, double-blind, and placebo-controlled study in a population of 120 healthy adults between the ages of 60 and 80 years. The study consisted of three treatment arms: placebo, recommended dose of NRPT (NRPT 1X), and double dose of NRPT (NRPT 2X). All subjects took their blinded supplement daily for eight weeks. Analysis of NAD+ in whole blood demonstrated that NRPT significantly increases the concentration of NAD+ in a dose-dependent manner. NAD+ levels increased by approximately 40% in the NRPT 1X group and approximately 90% in the NRPT 2X group after 4 weeks as compared to placebo and baseline. Furthermore, this significant increase in NAD+levels was sustained throughout the entire 8-week trial. NAD+ levels did not increase for the placebo group during the trial. No serious adverse events were reported in this study. This study shows that a repeat dose of NRPT is a safe and effective way to increase NAD+ levels sustainably.
 
EDIT: VP, stefan, able: I trust that no one will object to my merging your topics or editing the title to avoid duplication and to be sure that this was clear to all and that those interested would see it. -MR

Edited by Michael, 27 November 2017 - 04:59 PM.

[stefan_001]

https://www.nature.c...1514-017-0016-9

 

Elysium Health study: NR + PT. From the days they got Niagen from Chromadex.

 

Edited by stefan_001, 27 November 2017 - 04:48 PM.

[able]

Thanks Michael.  Interested to hear your thoughts on these results.

 

Don't see much new yet - mostly confirms the top line results they posted about previously.  Overall, a bit disappointing to me.

 

250 Mg a day resulted in 40% NAD+ increase that was maintained throughout the study.

 

500 Mg  a day shows 90% increase of NAD+ at 30 days, but dropped back down to 55% at 60 days.

 

Am thinking  this is the news that pushed Chromadex stock up so much the last week.

 

https://www.nature.c...1514-017-0016-9

 

They did measure a lot more than just NAD+.  

 

Some improvement in mobility:

 

"the NRPT 2X group showed a significant within-group increase in mobility in both the 30-s chair test (Table S5) and the 6-min walk test"

 

Some improvement at lower dose that was not noted in 500 Mg per day dosage:

 

"diastolic blood pressure was significantly reduced at day 60 in the NRPT 1X group. This finding is consistent with an earlier small trial showing that pterostilbene alone caused a small decrease in diastolic blood pressure.29 

 

Second, the liver enzyme ALT showed a significant decrease in the NRPT 1X group at both day 30 and day 60"

 

 

 

 

But I was surprised to see not much change in BP, Glucose, Triglycerides and such. 

 

"there was no significant difference between groups in hematology and clinical chemistry parameters in participants"

 

"Levels of triglycerides within the NRPT 1X and NRPT 2X group showed no significant changes from baseline at day 30 or day 60"

 

"There were no changes in the liver function tests for any group"

 

 

Edited by able, 27 November 2017 - 05:06 PM.

[stefan_001]

This part poses some thinking:

 

Thus, we stratified the three treatment groups by BMI and reanalyzed the data (Table 4). Subjects in the NRPT 1X group with normal BMI (18–25) showed no significant increases in LDL cholesterol at day 30 or day 60. Subjects in the NRPT 2X group with normal BMI did show increases in LDL cholesterol at day 30 and day 60. Subjects in the overweight category (BMI 25–32) showed increases in LDL cholesterol at day 30 and day 60 in both the NRPT 1X and NRPT 2X groups. However, overweight subjects in the placebo group also showed a significant increase at day 60. Overall, these findings suggest a small but significant increase in cholesterol may occur at the normal dose of NRPT, at least for people with a higher than normal BMI.

 

NR has been mentioned as possible supplement to help combat obesity, this is not  entirely encouraging. At first view I would remove the PT for the higher BMI group.

Edited by stefan_001, 27 November 2017 - 05:07 PM.

[able]

This part poses some thinking:

 

Thus, we stratified the three treatment groups by BMI and reanalyzed the data (Table 4). Subjects in the NRPT 1X group with normal BMI (18–25) showed no significant increases in LDL cholesterol at day 30 or day 60. Subjects in the NRPT 2X group with normal BMI did show increases in LDL cholesterol at day 30 and day 60. Subjects in the overweight category (BMI 25–32) showed increases in LDL cholesterol at day 30 and day 60 in both the NRPT 1X and NRPT 2X groups. However, overweight subjects in the placebo group also showed a significant increase at day 60. Overall, these findings suggest a small but significant increase in cholesterol may occur at the normal dose of NRPT, at least for people with a higher than normal BMI.

 

NR has been mentioned as possible supplement to help combat obesity, this is not  entirely encouraging. At first view I would remove the PT for the higher BMI group.

 

Yes, that didn't sound good.  From results in other studies, I expected to see more improvements in cholesterol, tryglcerides, and such.

 

But in the discussion, authors point out the slight increase in LDL cholesterol may not be significant.

 

"One possibility is that NRPT 1X improves liver health (e.g., by reducing hepatocyte cell death) and the healthier liver shows improved functions, including modestly more synthesis of cholesterol. It is unclear if the small increase in LDL cholesterol is due to an increase in particle size, which would be benign with regards to cardiovascular health. As an example, omega-3-fatty acids raise LDL cholesterol via increases in particle size, but may be beneficial for cardiovascular health"

 

 

It seems the 500 Mg dosage shows some improvement in mobility, but also some increase in LDL, which may, or may not, but significant.

 

So do these results suggest if 250 or 500 Mg is a better dosage?

 

Personally, I could believe the Ptero might impact the LDL (as prior study hints).  Since I'm not taking Ptero, I'm happy to continue with 500 Mg NR for now.

Edited by able, 27 November 2017 - 05:35 PM.

[Heisok]

Able, at the end of your post you quoted this about the Liver:

 

"There were no changes in the liver function tests for any group"

 

They elaborated a little further along, and the ALT alone is a significant Liver function indicator to me.  Perhaps it indicates some healing?

 

"There were no changes in the liver function tests for any group (placebo, NRPT 1X, or NRPT 2X) except that a significant decrease was observed in the ALT (alanine transaminase) test at 30 and 60 days within the NRPT 1X as compared to baseline (Table 2). A similar trend that did not reach significance was also observed for AST (aspartate transaminase). Since the presence of liver enzymes in the blood indicates defects in liver health, the data suggest that NRPT 1X may improve liver function in healthy adults. We intend to pursue subsequent human studies to further investigate the role of NRPT on liver health."

 

Stefan_001, would you elaborate as to why you believe the following quote?

 

"NR has been mentioned as possible supplement to help combat obesity, this is not  entirely encouraging. At first view I would remove the PT for the higher BMI group."

 

 

 

 

 

Edited by Heisok, 27 November 2017 - 05:48 PM.

[Oakman]

"There was a robust 40% (NRPT 1X) and 90% (NRPT 2X) increase in NAD+ at day 30 over baseline, and this was fully sustained at day 60 in the NRPT 1X group and partially declined to 55% over baseline in the NRPT 2X group."

 

"It is not clear why the NRPT 2X group showed the partial decline at 60 days, but it is possible that extraordinarily high levels of NAD+ can induce homeostatic mechanisms to restrain further increases. One possible mechanism is induction of NAD+ degrading enzymes, such as CD38."

 

This is an excellent result in terms of protoclol cost and efficacy. A minimum dose of 250mg seems to provide significant benefits without the higher dose side effects. Perhaps an optimal dose is 300-375mg. 

 

"Second, the liver enzyme ALT showed a significant decrease in the NRPT 1X group at both day 30 and day 60. A second liver enzyme, AST, showed the same trend at both day 30 and day 60, which did not reach significance."

 

Again, an excellent result at lower dose and better than X2 dose.

 

"First, diastolic blood pressure was significantly reduced at day 60 in the NRPT 1X group. "

 

Ditto.

 

"With respect to mobility, the finding that NRPT 2X group demonstrated significant increase in both the 30-second chair stand and the 6-min walk test at 60 days suggests that prolonged supplementation with NRPT may support overall muscle health and/or energy in an older population."

 

The only positive really to come from the X2 dose. Would be helpful to know the base fitness level of participants to see if they are typical old people with limited fitness levels, or more active fit individuals.

 

Overall, not seeing how this could have produced better results for NR+Pterostilbene protocol. This will give great encouragement to future researchers to fine tune and expand on study parameters and lengthen study time, hopefully towards developing a longevity protocol.

[bluemoon]

But it would have been nice if 500 mg of NR and 100 mg of pterostilbine further improved mobility. Of course, Elysium didn't report details on mobility for either group.  in addition, we don't know what 125 mg of NR does for mobility. 

Edited by bluemoon, 27 November 2017 - 06:10 PM.

[able]

But it would have been nice if 500 mg of NR and 100 mg of pterostilbine further improved mobility. Of course, Elysium didn't report details on mobility for either group.  in addition, we don't know what 125 mg of NR does for mobility. 

 

I don't follow your reasoning.

 

250Mg didn't really improve mobility, so it seems doubtful 125 Mg would help.

 

For those not overweight it seems 500 Mg is a good bet.  

 

If you are worried about the slight increase in LDL, maybe 375 Mg is good as Oakman says.

 

Edited by able, 27 November 2017 - 06:21 PM.

[bluemoon]

 

I don't follow your reasoning.

 

250Mg didn't really improve mobility, so it seems doubtful 125 Mg would help.

 

For those not overweight it seems 500 Mg is a good bet.  

 

If you are worried about the slight increase in LDL, maybe 375 Mg is good as Oakman says.

 

 

Well that is embarrassing... I read that part too quickly and thought there was improvement in mobility with 250 mg as well. Then again, 125 mg could still help the liver but was not tested. 

 

Note that the trial doesn't indicate whether or not 500 mg doesn't increase NAD by just 40% or 45% in week 12. 

 

The mobility improvement may no longer be there after week 12 nor do we have any idea how much mobility improved at the 8 week mark. For now, it looks like 375 mg a day might improve mobility by some unknown amount for those 60 to 80 years old. At current TruNiagen prices, that is $2.00 a day. Other positive effects may be discovered but this trial sure doesn't seem like something that will get anyone under 50 to take it.    

[bluemoon]

 

This is an excellent result in terms of protoclol cost and efficacy. A minimum dose of 250mg seems to provide significant benefits without the higher dose side effects. Perhaps an optimal dose is 300-375mg. 

 

"Second, the liver enzyme ALT showed a significant decrease in the NRPT 1X group at both day 30 and day 60. A second liver enzyme, AST, showed the same trend at both day 30 and day 60, which did not reach significance."

 

Again, an excellent result at lower dose and better than X2 dose.

 

"First, diastolic blood pressure was significantly reduced at day 60 in the NRPT 1X group. "

 

Ditto.

 

"With respect to mobility, the finding that NRPT 2X group demonstrated significant increase in both the 30-second chair stand and the 6-min walk test at 60 days suggests that prolonged supplementation with NRPT may support overall muscle health and/or energy in an older population."

 

The only positive really to come from the X2 dose. Would be helpful to know the base fitness level of participants to see if they are typical old people with limited fitness levels, or more active fit individuals. 

 

250 mg doesn't realy do anything except improve ALT, and they didn't report by how much. "Significantly" doesn't mean "a lot" but instead means statistically sigificant.   

 

So if 250 mg of NR doesn't do anything to improve mobility but 500 mg does then again "significantly" doesn't mean "by a lot" in that case, either. It might, but so far Elysium isn't saying.  

[stefan_001]

This study raises more questions than answers. For example when was the last time participants took NR + PT before measurements. The paper says:

Clinic visits
Eligible volunteers returned to the clinic in the morning, after a 12-hour fast (no food or drink except water) for baseline assessments. A physical exam was conducted where weight was measured and BMI calculated. Resting blood pressure and heart rate measurements were also taken. Fasting blood samples were collected for fasting glucose, lipid panel, hs-CRP, CBC, electrolytes (Na, K, Cl), creatinine, AST, ALT, GGT, bilirubin, PBMC, and NAD+ analysis.

So does that fast include NR+PT? Everybody knows there is a rise and fall of NAD+ after NR ingestion and the peak comes after 8 hours. So what is really measured here?

[stefan_001]

Just checked who are the authors of the paper. Based on that I will not spend further time analyzing.

[bluemoon]

Just checked who are the authors of the paper. Based on that I will not spend further time analyzing.

Not a big fan of Guarente, eh?   Can you see any flaws in the study? 

 

These first results match what Brenner has said in the past year: 1) no single study is going to make NR popular over night and 2) it will become apparent over time that NR helps the oldest and/or those most  metabolistically out of whack from normal.   

 

NR still may be show to have positive effects on skin, hair and memory so that those under 55 may consider taking it. NR also may be shown next year or the next to improve the heart for those with conditions, so I think there are still reasons to be optimistic.

[Harkijn]

I also see reasons for optimism. Of course a strong improvement in tryglicerides would have been a great result, but I did not expect that. On the bright side: NAD+ can be raised over a 60 day period. We thought it would, but we did not know!

And, to name just an example,  among the Adverse Events  there is no mention of tendonitis or similar nerve conditions. As you may recall in the Personal Experiences thread here on LC a number of people (tentatively) attributed their tendonitis to taking NR.

[Fredrik]

I just like to point out something obvious before we jump to any conclusions on human nicotinamide riboside supplementation. This was NOT a randomized, double-blind, placebo-controlled study of nicotinamide riboside (NR) monotherapy in humans. It was a trial of nicotinamide riboside + pterostilbene.

 

Any effects of nicotinamide riboside on any of the biomarkers or outcomes in this group has been contaminated by the inclusion of pterostilbene, a xenobiotic polyphenol that in itself can have an effect on metabolic parameters. Pterostilbene can raise LDL and lower systolic and diastolic blood pressure (at 250 mg) in humans. Looking forward to coming trials of nicotinamide riboside monotherapy.

 

Reference

Riche DM, Riche KD, Blackshear CT, McEwen CL, Sherman JJ, Wofford MR, Griswold ME. Pterostilbene on metabolic parameters: a randomized, double-blind, and placebo-controlled trial. Evidence-Based Complementary and Alternative Medicine. 2014;2014.

 

Edited by Fredrik, 28 November 2017 - 01:39 PM.

[stefan_001]

 

Just checked who are the authors of the paper. Based on that I will not spend further time analyzing.

Not a big fan of Guarente, eh?   Can you see any flaws in the study? 

 

These first results match what Brenner has said in the past year: 1) no single study is going to make NR popular over night and 2) it will become apparent over time that NR helps the oldest and/or those most  metabolistically out of whack from normal.   

 

NR still may be show to have positive effects on skin, hair and memory so that those under 55 may consider taking it. NR also may be shown next year or the next to improve the heart for those with conditions, so I think there are still reasons to be optimistic.

 

 

Well the mentioned ahum researchers of the study include the CFO and CEO.....so you can be sure its selective data only. As mentioned several times by posters this study is distorted by the PT and they failed to show any benefits of the PT and were forced to explaining that. It was already unlikely but after this I dont think anybody else than EH will do research with PT+NR. The issue with the study itself is that it doesnt explain how they tackle the transcient aspect in the measurement. All we know is that the measurement was done minimally 12 hours after the last consumption. What does it really tell if NAD+ falls off faster in the double dose after a minimal 12 hours after ingestion? Does it also peak lower?

 

[Harkijn]

I agree with the PT as a thoroughly confounding factor.

About the measurements and the  rest of 'compliance ' : I think they were  just being realistic about what exertion and involvement you can expect from a group of (elderly) test persons.

Edited by Harkijn, 28 November 2017 - 04:54 PM.

[able]

Yes, the PT does muddy the waters in discerning the effect of NR alone.

 

I do agree it is positive that NAD+ remains elevated for 8 weeks.  But we already knew that as they pushed the top line results  out long ago.

 

What is new -  the improvement in mobility, and lack of improvement in other areas.   Perhaps 8 weeks isn't long enough for some things?

 

I was initially surprised that Chromadex stock seemed to respond so well to such news.

 

But now, I'm thinking, investors see no indication that PT provides a noticeable benefit.

 

And perhaps, big investors know, or believe, the soon to be published results on NR alone will be at least as good as these Basis results.

 

That's my hopeful  interpretation anyways.  

 

 

 

Edited by able, 28 November 2017 - 05:51 PM.

[bluemoon]

We also don't know if 500 mg of NR doesn't drop even lower past 55% increase to maybe 40% or 45% after eight weeks because the study didn't look at 12 or 18 weeks. Would the improved walking and chair tests results show no change after eight weeks? It seems strange that there were no positive results in this area when NAD+ levels rose to 40% but did at 90% down to 55%. 

 

 

[PAMPAGUY]

I have been taking 500 mg. NR for 16 weeks. At 71 yo, I have noticed a big improvement in energy such as walking. Most young people will not notice much until probably 60-65 when your energy and stamina accelerate downhill. I just dont get tired as quickly. Hell I was running 6K's all the time in my 50's. I can tell when my cells are processing oxygen more efficiently. This has improved taking NR. Also, I believe some things take much longer to see improvement. 8 wks is not long. NR is just one rung on the anti-ageing protocal.

[able]

We also don't know if 500 mg of NR doesn't drop even lower past 55% increase to maybe 40% or 45% after eight weeks because the study didn't look at 12 or 18 weeks. Would the improved walking and chair tests results show no change after eight weeks? It seems strange that there were no positive results in this area when NAD+ levels rose to 40% but did at 90% down to 55%. 

 

They measured 40,55, 90% NAD+ increase in blood - not all tissues.

 

Perhaps with the single dose (250Mg), Liver/blood NAD+ is elevated, but not much escapes to other tissues, whereas 500 Mg floods the system and a significant amount of NR makes it to muscle tissue.  

 

Pure conjecture of course.

Edited by able, 28 November 2017 - 07:56 PM.

[VP.]

I have been taking 500 mg. NR for 16 weeks. At 71 yo, I have noticed a big improvement in energy such as walking. Most young people will not notice much until probably 60-65 when your energy and stamina accelerate downhill. I just dont get tired as quickly. Hell I was running 6K's all the time in my 50's. I can tell when my cells are processing oxygen more efficiently. This has improved taking NR. Also, I believe some things take much longer to see improvement. 8 wks is not long. NR is just one rung on the anti-ageing protocal.

Isn't Rapamycin a confounding factor? Did you start taking NR at the same time as Rapa?

[PAMPAGUY]

Yes, I have been taking Rapa for 9 months. Has improved my Creatin, BPH, arthritic hip, but it never improved my energy. Noticed the energy improvement and clarity of mind once I started NR 1st August.

[warner]

We also don't know if 500 mg of NR doesn't drop even lower past 55% increase to maybe 40% or 45% after eight weeks because the study didn't look at 12 or 18 weeks. 

And even the low dose NAD levels were falling after 8 weeks (although not significantly).  It's probably a good bet that NAD levels will continue to fall with time (via "homeostatic mechanisms"), and that the lower they fall, and the longer this takes, the more screwed you will be if discontinuing supplementation.  This reminds me of testosterone supplementation that slowly shuts down one's own T production (and producing smaller testes), which can then leave you in an even more precarious state if T is discontinued.  Just another feature of NR supplementation that will need to be fully characterized.

[stefan_001]

 

We also don't know if 500 mg of NR doesn't drop even lower past 55% increase to maybe 40% or 45% after eight weeks because the study didn't look at 12 or 18 weeks. 

And even the low dose NAD levels were falling after 8 weeks (although not significantly).  It's probably a good bet that NAD levels will continue to fall with time (via "homeostatic mechanisms"), and that the lower they fall, and the longer this takes, the more screwed you will be if discontinuing supplementation.  This reminds me of testosterone supplementation that slowly shuts down one's own T production (and producing smaller testes), which can then leave you in an even more precarious state if T is discontinued.  Just another feature of NR supplementation that will need to be fully characterized.

 

 

I am using NR now for over 2.5 years, almost daily with couple breaks of a few weeks and neither theory of what you write is what I perceive. While anecdotal I am 100% sure NR keeps its effectiveness in all areas from fitness, mental, appearance. One indicator that I  track and has visual facts is hair line, which continuous to grow back at a very slow but consistent pace. I make every week pictures. Before NR it was rapidly retreating. And there are many more easy to track indicators. One of them a finger at my hand which started to go numb in winter with cold hands. Gone and in general I use gloves for cold hands less. Winter is starting here and hands and finger are good also this year.

 

I sometimes wrote about the recovering hair on my blog and has pictures:

http://www.timelessl...-be-the-reason/

 

But need to update it, because the effect stays also while only taking it orally.
 

Edited by stefan_001, 28 November 2017 - 09:22 PM.

[Heisok]

Stephen, I rated your post informative. Thanks. I have not documented, but have noticed some hair change. I started on NR early in it's release also.  Due to a few reasons, I have taken more breaks than you, but had not had any breaks longer than a couple days until about 3 to 6 months ago. Have been on a break for a few weeks recently.

 

Curious? Any comment about your protocol, which I will quote a part of, Stephen?

 

"Daily: Niagen, Pterostilbine, Ginkho Biloba"

"Rotating: Honokiol, Quercitin, Luteolin, Fisitin

 

 

"I am using NR now for over 2.5 years, almost daily with couple breaks of a few weeks and neither theory of what you write is what I perceive. While anecdotal I am 100% sure NR keeps its effectiveness in all areas from fitness, mental, appearance. One indicator that I  track and has visual facts is hair line, which continuous to grow back at a very slow but consistent pace. I make every week pictures. Before NR it was rapidly retreating. And there are many more easy to track indicators. One of them a finger at my hand which started to go numb in winter with cold hands. Gone and in general I use gloves for cold hands less. Winter is starting here and hands and finger are good also this year.

 

I sometimes wrote about the recovering hair on my blog and has pictures:

http://www.timelessl...-be-the-reason/

 

But need to update it, because the effect stays also while only taking it orally."

Edited by Heisok, 28 November 2017 - 10:50 PM.

[warner]

I am using NR now for over 2.5 years, almost daily with couple breaks of a few weeks and neither theory of what you write is what I perceive. While anecdotal I am 100% sure NR keeps its effectiveness in all areas from fitness, mental, appearance.

I was specifically referring to the situation where one has been taking NR for a lengthy period, with slowly declining NAD levels due to acclimation (of some sort), followed by an abrupt discontinuation.  Under such circumstances, the state you'd be in on discontinuation would very likely be worse (i.e., lower NAD levels) than before supplementation started, since your body would have shut down some fraction of its unsupplemented NAD production capacity over a long period, and the time it would take to recover from that is probably related to the time it took to acclimate to the NR in the first place (which is why I didn't like seeing that slow decline in NAD levels at both doses, suggesting a lengthy, complex process, perhaps not easily reversed).

 

Even in that situation, you still might be better off for having tried the NR (i.e., a net positive outcome).  Also, I'm not suggesting that the higher NAD levels return all the way to pre-supplementation levels, so none of this conflicts with your experience wherein you've only taken a few breaks from supplementation over a long period.  However, if you were to stop cold turkey, I'm suggesting that the following day, and probably for many days after that, you'd have an NAD deficit worse than before starting supplementation, although you may not notice that, depending on what you're measuring, and how long you refrain from the NR.

Edited by warner, 28 November 2017 - 11:34 PM.

[Michael]

Curious? Any comment about your protocol, which I will quote a part of, Stephen?

 

"Daily: Niagen, Pterostilbine, Ginkho Biloba"

"Rotating: Honokiol, Quercitin, Luteolin, Fisitin

 

"I am using NR now for over 2.5 years [...]

 

I sometimes wrote about the recovering hair on my blog and has pictures:

http://www.timelessl...-be-the-reason/

 

But need to update it, because the effect stays also while only taking it orally."

 

This thread is about the Elysium Basis trial; Stefan, if you opt to follow up, will you please start a new thread, or do so in the "Personal Experiences" thread (or do so on your blog and link from the latter)?

[stefan_001]

@heisok will reply bit longer later
@warner I have actually done that, stop cold turkey from 500mg for over 1 month. Reason being I had some kind of lung bacterial infection Inpicked up on an asian trip. I was wondering whether the NR might feed bacteria as they can synthesize it and that was the reason I could not get rid of it. But it made no difference and went on antibiotics next during which I stayed of the NR as well. I continued not using NR another 2 weeks after anti biotics. I was surprised how well things stayed up and only after a month or so I started feeling some old aging phenomena from the past coming back. To me its not clear how such NR resistance path could develop. The NRK path seems pretty solid and independent.

Edited by stefan_001, 28 November 2017 - 11:44 PM.