71 replies to this topic

[Fredrik]

But if your cholesterol is 250, it will improve. All my friends with very high LDL and triglycerides got great improvements.

 

What is you published source of data (no, "all your friends" is not a valid source) that supports a claim of reduction in cholesterol in humans?

 

In the second human clinical trial of NR they looked at cholesterol and there was NO reduction in LDL or total cholesterol, but an unwanted increase in triglycerides was found.

 

Further, there was NO beneficial effects of NR on any of the following:

 

"Results: Insulin sensitivity, endogenous glucose production, and glucose disposal and oxidation were not improved by NR supplementation. Similarly, NR supplementation had no effect on resting energy expenditure, lipolysis, oxidation of lipids, or body composition."

 

 

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1. Dollerup OL, Christensen B, Svart M, Schmidt MS, Sulek K, Ringgaard S, Stødkilde-Jørgensen H, Møller N, Brenner C, Treebak JT, Jessen N. A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects. The American journal of clinical nutrition. 2018 Jul 10;108(2):343-53.

Edited by Fredrik, 17 November 2018 - 12:33 PM.

[MikeDC]

What about 129?
It won't improve?

129 LDL or total cholesterol?
If it is 129 LDL, it will improve. 129 total is too low.

What NR does is to help biomarkers return to normal range.

[Fredrik]

What NR does is to help biomarkers return to normal range.

 

 

MikeDC, in what human clinical trial of NR has cholesterol returned to "a normal range"?

 

You have provided zero references to your claim of cholesterol reduction in humans with NR supplementation but I have provided you with a high dose NR trial that showed NO change in cholesterol or any other biomarkers.

 

https://www.longecit...ndpost&p=862922

 

What is it you do not understand, or are you just refusing to answer because you have no answers? You are just posting anecdotal claims from you and your friends.

 

 

Edited by Fredrik, 17 November 2018 - 01:14 PM.

[MikeDC]

Yes, I have enough anecdotal evidence to claim. We are only at the start of clinical trials. Don’t make conclusions too early. NR is the best anti aging drug ever invented. Believe it or not is your choice. Time will tell.

[Fredrik]

Don’t make conclusions too early. NR is the best anti aging drug ever invented. Believe it or not is your choice. Time will tell.

 

Good that you finally admit to having no published proof whatsoever to your claims that NR can "...help biomarkers return to normal range" or that NR can "lower a high cholesterol" in humans. None of which is true as of 17 November 2018.

 

I am only making conclusion on available data and that will change as new data is generated. Unlike you I have not made my mind up at all. I still own some shares in Chromadex, but that does not make me rely on some future trials and possible future positive result that does not currently exist. 

 

Saying that: "NR is the best anti aging drug ever invented." like you just said IS hyperbole and making conclusions too early.

Edited by Fredrik, 17 November 2018 - 06:58 PM.

[stefan_001]

@Fredrik

 

Being he devils advocate here. When @Mike says "NR is the best anti aging drug ever invented" he does not say it does a lot. So if you disagree with the statement you must be of the view and understanding, based available data that you have studied, that there is a better drug? Which drug is that?

Edited by stefan_001, 18 November 2018 - 01:42 PM.

[Oakman]

@Fredrik

 

Being he devils advocate here. When @Mike says "NR is the best anti aging drug ever invented" he does not say it does a lot. So if you disagree with the statement you must be of the view and understanding, based available data that you have studied, that there is a better drug? Which drug is that?

 

Just because someone disagrees with the statement "NR is the best anti aging drug ever invented", doesn't mean they have the opinion you state. What if there is not any "..best anti-aging drug...?"

 

And really... "Is there any (human) anti aging drug?" I can't think of a proven one.

[Harkijn]

Don't bother folks, these two are straining to f*rt into one candle. Nothing  of value remains except burned buttocks...

[Fredrik]

@Fredrik

 

Being he devils advocate here. When @Mike says "NR is the best anti aging drug ever invented" he does not say it does a lot. So if you disagree with the statement you must be of the view and understanding, based available data that you have studied, that there is a better drug? Which drug is that?

 

Well, I am not the one making fantastical claims so the burden of evidence is on the one who does. I have never said that a anti aging drug exists at all (it does not, metformin seems to be the first potential one in a clinical trial even if they can not call it anti aging since FDA does not see aging as a treatable diagnosis yet).

 

You have to ask MikeDC proof of why "NR is the best anti aging drug invented". Of course, no one invented NR but nature. It was discovered, but that is just a minor thing wrong in these fantastical statements.

Edited by Fredrik, 18 November 2018 - 06:24 PM.

[Fredrik]

Just because someone disagrees with the statement "NR is the best anti aging drug ever invented", doesn't mean they have the opinion you state. What if there is not any "..best anti-aging drug...?"

 

And really... "Is there any (human) anti aging drug?" I can't think of a proven one.

 

Agree! Thank you Oakman for posting that. I disagree with the statement "NR is an anti aging drug". There is no human anti aging drug. Potential candidates like metformin, low dose pulse dosing of rapamycin and NMN-derivatives etc yes. But none of these are FDA approved to treat aging.

Edited by Fredrik, 18 November 2018 - 06:36 PM.

[Fredrik]

Don't bother folks, these two are straining to f*rt into one candle. Nothing  of value remains except burned buttocks...

 

Maybe But now you have added that missing value to the discussion. Because I have never heard the expression "straining to fart into one candle". Now I can make myself better understood when talking to english natives abroad. I will think of you whenever I use that expression. Thank you.

Edited by Fredrik, 18 November 2018 - 06:45 PM.

[able]

I find this a bit irritating.  We are desperate for any research comparing NMN/NR/NAD+.  Dr Sinclair drops this bit of info below in a tweet:

 

 

"Fits with my lab’s unpublished studies in mice comparing NMN to NR. NMN increased endurance in 20-22 month old mice but NR didn’t at same dose. Needs repeating. Were the rats in this study young or old?"

 

https://twitter.com/...378895615623168

 

It certainly sounds like they have done some direct comparisons.  Publish them!

 

I get the impression Dr Sinclair doesn't have the same pressure to publish results that others might have, and  can  hold the info to further his myriad business interests without divulging anything to possible competitors.

Edited by able, 20 November 2018 - 03:55 AM.

[MikeDC]

Two studies show NR raises more NAD+ in muscle than NMN.
NMN IV barely raised any NAD+ in the muscles which may imply the effect of Oral NMN in muscle is mediated through NAM.

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[able]

Two studies show NR raises more NAD+ in muscle than NMN.
NMN IV barely raised any NAD+ in the muscles which may imply the effect of Oral NMN in muscle is mediated through NAM.

 

 

Yes, that is why I say it would really help for Dr Sinclair to publish his research showing NMN improves endurance, while NR does not.

 

As you say below, it is the results that we really care most about, not the pathways.  

 

 

Ling liu’s Paper showed baseline NR is much higher than baseline NMN. She showed majority of NR and NMN were broken down before reaching liver. But it doesn’t exlude small amount of NR reaching liver and blood stream. In the end what count is health benefit. NR has shown more benefit than NAM in both studies and user experiences.

 

 

It is curious that NMN doesn't raise NAD+ levels in muscle very well.  I thought that would result in little effect on muscle.  But later studies of performance show it seems to have exceptional effect on muscle and endurance.

 

Perhaps that is due to the growth of blood vessels - actual new blood vessel growth in very old animals - that support muscle growth, and not dependent on elevating NAD+ in the muscle itself?  

 

Whatever the reason, as you say, it is the results that matter.  NMN has shown great results for endurance in the Sinclair study in Mar 2018. 

 

"After two months, the mice had increased muscular blood flow, enhanced physical performance and endurance and the old mice became as fit and strong as young mice"

 

I have pointed out numerous times that NR has not yet shown any such dramatic results.  

 

Sinclair says he has unpublished results showing superior results from NMN vs NR  in head to head study, so yes, it would be nice to see those.

 

Until then, I know we can count on you to keep cherry picking data and praying that Dr Sinclair is flat out lying.

Edited by able, 20 November 2018 - 09:01 PM.

[MikeDC]

Even Sinclair has not found mechanism of action for NMN other than NAD+. I give him credit for picking interesting studies that attract people’s attention. If NR is used in the same study, it will do better.

[stefan_001]

Given the amount of people that use NMN and have reported here its probably safe to conclude the mouse result of sinclair that @able quotes doesn't translate to humans.

If you go through the personal experience threads you find for both NMN and NR statements of perceived improved performance but neither jumps out with hard numbers.

I personally think it is more interesting to learn for what areas NAD+ boosting doesnt help how these can be tackled. NAD+ for me is baseline, whats next.

[Heisok]

Hi Stefan,

 

Stefan, lack of data in personal experiences is not cause to conclude anything either way about the NMN mouse study. It will have to stand on its own. I can find very few NMN personal experiences on Longecity. I also think some might have kept taking NR at least for awhile. Oakman shared bicycling data, and Warner shared some weight loss data; but I am not sure which threads as posts get spread out. If I remember correctly, Warner hypothesized that some fitness gains might be related to weight loss.

 

LawrenceW shared bloodwork information, and their personal experience related to fitness, but no hard exercise data. Hard exercise data possibly related to NMN might show up once Alive by Nature finishes their tests with "athletes" Will this be100% conclusive? Not scientifically as a clinical trial might be. https://www.longecit...ad/#entry844369

 

I would like to see labwork from males of their various hormone levels pre and post NR and NMN.

 

Does your last sentence refer to which areas of the body are shown to get NAD+ boosted? If so,I agree that NAD+ levels as a baseline are surely a way to go.

 

 

Edited by Heisok, 21 November 2018 - 08:18 PM.

[Fredrik]

I find this a bit irritating.  We are desperate for any research comparing NMN/NR/NAD+.  Dr Sinclair drops this bit of info below in a tweet:

 

 

"Fits with my lab’s unpublished studies in mice comparing NMN to NR. NMN increased endurance in 20-22 month old mice but NR didn’t at same dose. Needs repeating. Were the rats in this study young or old?"

 

https://twitter.com/...378895615623168

 

It certainly sounds like they have done some direct comparisons.  Publish them!

 

I get the impression Dr Sinclair doesn't have the same pressure to publish results that others might have, and  can  hold the info to further his myriad business interests without divulging anything to possible competitors.

 

You missed Dr Sinclairs follow up tweet that NMN did not increase endurance in 4 month old mice either. They used younger mice in the NR study compared to the NMN so you can not compare them.

 

Dr David Sinclair:

 

"Ok. They were young 4 month old rats. That makes sense. We dont see benefits of NMN on endurance of 4 month old mice either. Curious what Johan Auwerx who did first NR mouse endurance study thinks."

 

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Edited by Fredrik, 22 November 2018 - 11:53 PM.

[MikeDC]

The Greece research who published the two papers saying NR reduces exercise performance is nuts. His results are not statistically significant. He should also emphasize “young mice” in the study title. Not sure why he wants to prove that NR is not good.

[able]

You missed Dr Sinclairs follow up tweet that NMN did not increase endurance in 4 month old mice either. They used younger mice in the NR study compared to the NMN so you can not compare them.

 

Dr David Sinclair:

 

"Ok. They were young 4 month old rats. That makes sense. We dont see benefits of NMN on endurance of 4 month old mice either. Curious what Johan Auwerx who did first NR mouse endurance study thinks."

 

Screenshot 2018-11-23 at 00.56.27.png

 

@Fredrik  - I didn't miss that follow on tweet, but found it irrelevant.  I actually agree with MikeDC, that a  study on  exercise performance on young ( 4 month old) mice wouldn't be expected to show improvement from NR.   As many have agreed here  for a few years now - fairly meaningless.

 

I was just ignoring it to focus on the recent news -  his mention of unpublished results that compared exercise performance in OLD mice given NMN or NR.  An entirely different matter.

[Fredrik]

@Fredrik  - I didn't miss that follow on tweet, but found it irrelevant.  I actually agree with MikeDC, that a  study on  exercise performance on young ( 4 month old) mice wouldn't be expected to show improvement from NR.   As many have agreed here  for a few years now - fairly meaningless.

 

I was just ignoring it to focus on the recent news -  his mention of unpublished results that compared exercise performance in OLD mice given NMN or NR.  An entirely different matter.

 

Ok. For for completeness sake both of Dr Sinclairs quotes is now up here and readers in the thread can decide themselves which statements from him is irrelevant and to be ignored.

 

David Sinclair‏ @davidasinclair

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David Sinclair Retweeted Mike Landers

Fits with my lab’s unpublished studies in mice comparing NMN to NR. NMN increased endurance in 20-22 month old mice but NR didn’t at same dose. Needs repeating. Were the rats in this study young or old?

 

 

David Sinclair‏ @davidasinclair

FollowingFollowing @davidasinclair

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David Sinclair Retweeted Mike Landers

Ok. They were young 4 month old rats. That makes sense. We dont see benefits of NMN on endurance of 4 month old mice either. Curious what Johan Auwerx who did first NR mouse endurance study thinks.

 

 

 

Edited by Fredrik, 23 November 2018 - 12:31 PM.

[Harkijn]

It's my personal longevity strategy to stay away from Facebook, Twitter, Reddit etc., but since you , able and fredrik, navigate those waters, would not it be a good idea to ask Sinclair directly about more specifics on the comparison  NR/NMN in old mice? He seems rather keen on communicating with the public and may very  well drop a few crumbs for us to pick up....

[male_1978]

If you want to compare NR to NMN i just want to point out that a molecule of NMN has a higher mass (334)  than a molecule of NR (255).
 

One gram of NR contains hence more molecules that one gram of NMN. Doses in studies however are calculated in grams.

 

So if you compare 1g of NMN to 1g of NR you are not really comparing which molecule is more effective. NMN is one metabolic step closer to the product, but you have less molecules and can get less NAD+ out of it.

 

Its always more difficult to draw conclusions from an experiment, if two basic parameters are changed at the same time (depending on what you want to know of course).

 

 

 

[MikeDC]

NMN is one step closer than NR to NAD+ inside cells. When you take NMN, it needs to convert to NR before entering cells. So NMN is actually one step further than NR to NAD+.

Ling Liu’s Paper made it very clear that NR is a better precursor than NMN. NR levels in the blood is higher than NMN even before any supplementation.

[able]

NMN is one step closer than NR to NAD+ inside cells. When you take NMN, it needs to convert to NR before entering cells. So NMN is actually one step further than NR to NAD+.

Ling Liu’s Paper made it very clear that NR is a better precursor than NMN. NR levels in the blood is higher than NMN even before any supplementation.

 

 

No, the primary finding in Ling Liu's research was that oral NR and NMN do not make it out of the liver intact.

 

It also showed that NR elevates NAD+ similar  amount  to NMN in liver and kidney, but much more in muscle.

 

That did make me think NR would be much more effective in muscle, until Dr Sinclairs study came out the very next month showing NMN nearly doubled the endurance in old mice, making them similar to young mice, and resulted in new blood vessel growth.

 

Please show some study where NR has similar benefit in muscle or endurance.

 

In fact, before you make broad statements like "made it very clear that NR is a better precursor than NMN", please show any study where NR showed superior benefits than NMN.   

[MikeDC]

You don’t know what you are talking about. NR or NMN don’t make it out of liver has nothing to do with NMN need to convert to NR before entering cells. If IV NMN can’t make it into muscles, why do you think oral NMN will be better than NAM?

[able]

The Sinclair research I referenced shows NMN has a huge benefit in restoring blood vessel growth.  Decreased blood flow is a major cause of sarcopenia (muscle wasting), as well as a big impact on numerous other aging problems (Parkinsons, Alzheimers, Heart disease)

 

It seems that the blood vessel growth benefits muscle/endurance.

 

I don't doubt that we will find NR has unique benefits from NMN and likely better in some situations.  I just haven't seen the research yet.

 

You make a very broad claim that NR is clearly superior precursor to NMN.  Please reference any study that shows NR has such benefit, or any greater benefit than NMN, to back up your claims.

 

 

Edited by able, 29 November 2018 - 06:48 PM.

[MikeDC]

Study this carefully. There is small amount of intact oral NR that gets inside liver cells. There is close to zero intact oral NMN gets inside liver cells. This means NMN is not expected to deliver better results compared to NAM while NR could deliver better results from the small amount of Intact NR that can enter liver cells.

Even though intact NR can’t reach organs other liver. The increased circulating NAD+ and NR in the plasma will provide similar benefits. The researchers have ignored this effect. Liver is a source of NAD+ precursors for other organs. Ling LIU only pointed out NAM and ignored NAD+ and NR.

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Edited by MikeDC, 29 November 2018 - 06:51 PM.

[able]

Yes, that shows that both have a bioavailability problem, and raises the question why Chromadex cant come up with a sublingual or other delivery method to address it.

 

But you know very well that NMN does reach liver and tissues outside the liver intact.  In case you forget, this chart from the mills long term research shows double labelled NMN reaching blood plasma in minutes, liver in 10 minutes, and muscle in 30 minutes.

 

Still waiting for your reference on ANY study showing more benefit with NR vs NMN, to justify your claim it is clearly superior.

 

 

 

 

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[MikeDC]

This study was misleading. It gaves you the impression that most NMN were absorbed within 35 mins. The data from Ling Liu’s Paper showed that most of the absorption of NMN and NR is after 45 mins. To reconcile the two studies, initially small amounts of NMN were absorbed intact through the lymphatic system and enter blood stream. The majority of NMN were absorbed later and most are hydrolysed into NAM before entering liver.

Edited by MikeDC, 29 November 2018 - 08:13 PM.