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NAD+ Sublingual vs NMN Sublingual

nmn nad+ nad

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#1 Forever21

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Posted 26 September 2019 - 03:47 AM


I made a mistake and ordered NAD+ Sublingual instead of my regular NMN Sublingual. What's the difference between the two really?



#2 Oakman

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Posted 26 September 2019 - 01:50 PM

Briefly from my understanding ...NMN is a precursor to NAD+, NAD+ is the thing itself. Precursors helping the body produce its own NAD+.  Whereas NAD+ has a very short term existence in the body that very quickly dissipates, that is why it is best to let the body create its own as needed rather than supplementing directly. The only place NAD+ itself seems to apply and perhaps be effective, is nasal as it can cross into the brain and effect it, whereas other administration methods can't easily do that.  

 

BTW I have some of the NAD+ nasal spray (free sample from a generous vendor), and can't get the hang of nasal delivery (yuck) so have tried sublingual with it, with no noticeable effect.

 

It doesn't seem very cost or results effective, IMHO.



#3 Forever21

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Posted 26 September 2019 - 02:56 PM

Briefly from my understanding ...NMN is a precursor to NAD+, NAD+ is the thing itself. Precursors helping the body produce its own NAD+.  Whereas NAD+ has a very short term existence in the body that very quickly dissipates, that is why it is best to let the body create its own as needed rather than supplementing directly. The only place NAD+ itself seems to apply and perhaps be effective, is nasal as it can cross into the brain and effect it, whereas other administration methods can't easily do that.  

 

BTW I have some of the NAD+ nasal spray (free sample from a generous vendor), and can't get the hang of nasal delivery (yuck) so have tried sublingual with it, with no noticeable effect.

 

It doesn't seem very cost or results effective, IMHO.

 

 

So I bought nothing. Air.

 

What do you use again? NMN? Sublingual?



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#4 able

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Posted 26 September 2019 - 02:58 PM

Research shows NAD+ enters some cells as NAD+, while others it needs to be converted to NMN, NR, NAM or something else to enter cells.

 

Look at the charts below from the recent study of NAD+ IV in humans.

 

The big news was that for 2 hours, NAD+ or any other metabolites were nowhere to be found.  It was quickly changed to something that is used by some cells somewhere.

 

But after that, from hours 2 -8 , NAD+, NMN, NAM, and ADPR  were ALL elevated around 400% or so.

 

 

So I'm guessing there is a lot of overlap in their effect.

 

I have been taking both (as powder) for at least 6 months.  For me, the NAD+ has much more noticable stimulative effect, but can't tell much difference otherwise.

 

fnagi-11-00257-g001.jpg


Edited by able, 26 September 2019 - 03:01 PM.

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#5 Oakman

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Posted 26 September 2019 - 04:15 PM

So I bought nothing. Air.

 

What do you use again? NMN? Sublingual?

 

300 mg Niagen daily in the AM, thern typically every other day NMN pre exercise and during exercise. For that, 300-400 mg powder sublingual before starting, then x4-6 of 100 mg sublingual over the course of 2-3 hrs endurance cycling. My performance is increasing significantly week over week, I'm hoping NR+NMN is at least part of the reason, other than just the training.

 

Again, if you can stand the NAD+ nasal administration, it does seem according to studies to have an effect in mice/rats, but I can't find any human results (not surprised).

 

Mouse > https://www.ncbi.nlm...pubmed/19298759

 

IV in humans seems to be the best > https://www.dazeddig...t-bionad-clinic

https://www.fda.gov/...113016/download

 

Pill commercial site fueling the hope that it works> https://nadovim.com/...ty-and-formula/


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#6 able

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Posted 28 September 2019 - 06:36 PM

Dr Sinclair tweets about another study showing NAD+ has no problem entering cells and helping stave off heart disease (in mice).

 

 

What’s weird is they treated cells with NAD, a large molecule that is not believed to get into most cells (like NAD precursors can). Yet NAD reduced senescent “zombie cell” formation. Perhaps NAD was imported. Perhaps it was degraded & imported. Either way, something’s up. Ideas?

 

 

 

 

https://twitter.com/...382554116268033


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#7 Andey

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Posted 28 September 2019 - 09:19 PM

Dr Sinclair tweets about another study showing NAD+ has no problem entering cells and helping stave off heart disease (in mice).

 

 

 

 

https://twitter.com/...382554116268033

 

BTW Charles Brenner posted an interesting rant about SIRT-s, implying that Sinclair is good in generating hype but not much else.

https://twitter.com/...780237972774912

I am starting to like the guy), whether right he or wrong he gives a different perspective to think about


Edited by Andey, 28 September 2019 - 09:27 PM.

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#8 aribadabar

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Posted 01 October 2019 - 10:31 PM

BTW Charles Brenner posted an interesting rant about SIRT-s, implying that Sinclair is good in generating hype but not much else.

https://twitter.com/...780237972774912

I am starting to like the guy), whether right he or wrong he gives a different perspective to think about

 

Brenner is not any different - a biased NR huckster trying to explain away NR's purported benefits whereas study after study shows NR is not doing all that much IN HUMANS.


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#9 joesixpack

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Posted 02 October 2019 - 01:54 AM

Brenner is not any different - a biased NR huckster trying to explain away NR's purported benefits whereas study after study shows NR is not doing all that much IN HUMANS.

 

Please explain how Brenner is explaining "away the benefits", while "study after study shows NR is not doing all that much in HUMANS."

 

Also, which studies show no effect?



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#10 aribadabar

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Posted 02 October 2019 - 05:11 AM

Please explain how Brenner is explaining "away the benefits", while "study after study shows NR is not doing all that much in HUMANS."

 

Also, which studies show no effect?

 

As a co-author of this shameful attempt at misdirection , I think he quite deserved my depiction of him.

 

That study as well as the following showing that NR is not really doing much:

https://academic.oup...8/2/343/5051210

https://www.nature.c...467-018-03421-7

https://link.springe...394-019-01919-4


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#11 joesixpack

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Posted 03 October 2019 - 12:30 AM

As a co-author of this shameful attempt at misdirection , I think he quite deserved my depiction of him.

 

That study as well as the following showing that NR is not really doing much:

https://academic.oup...8/2/343/5051210

https://www.nature.c...467-018-03421-7

https://link.springe...394-019-01919-4

 

Thanks for the response, but it did not reveal studies that show NR does next to nothing for humans. I have reviewed the articles and cut and pasted the abstracts from each.

 

The first one, is a review of animal studies that concludes that NR supplementation may play a positive role iin nsulin sensitivity and fatty liver.

 

The second suggests that NAD+ precursors  may improve cardiovascular and other physiological functions with aging in humans.

 

The third suggests that NR supplementation would likely benefit older individuals.

 

So, again, what studies show that NR supplementation show no benefits? I am not arguing, I am just asking.

 

 

https://academic.oup...8/2/343/5051210

 

Animal studies suggest a positive role for nicotinamide riboside (NR) on insulin sensitivity and hepatic steatosis in models of obesity and type 2 diabetes. NR, an NAD+ precursor, is a member of the vitamin B-3 family now available as an over-the-counter supplement. Although data from preclinical trials appear consistent, potential effects and safety need to be evaluated in human clinical trials.

 

 

https://www.nature.c...467-018-03421-7

 

Nicotinamide adenine dinucleotide (NAD+) has emerged as a critical co-substrate for enzymes involved in the beneficial effects of regular calorie restriction on healthspan. As such, the use of NAD+ precursors to augment NAD+ bioavailability has been proposed as a strategy for improving cardiovascular and other physiological functions with aging in humans. Here we provide the evidence in a 2 × 6-week randomized, double-blind, placebo-controlled, crossover clinical trial that chronic supplementation with the NAD+ precursor vitamin, nicotinamide riboside (NR), is well tolerated and effectively stimulates NAD+ metabolism in healthy middle-aged and older adults. Our results also provide initial insight into the effects of chronic NR supplementation on physiological function in humans, and suggest that, in particular, future clinical trials should further assess the potential benefits of NR for reducing blood pressure and arterial stiffness in this group.

 

 

 

https://link.springe...394-019-01919-4

 

Older individuals suffer from low NADH levels. We have previously shown that nicotinamide riboside [NR; a NAD(P)(H) precursor] administration impaired exercise performance in young rats. It has been suggested that supplementation of redox agents exerts ergogenic effect only in deficient individuals. We hypothesized that old individuals would more likely benefit from NR supplementation. We investigated the effect of acute NR supplementation on redox homeostasis and physical performance in young and old individuals.


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#12 aribadabar

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Posted 03 October 2019 - 01:54 AM

Thanks for the response, but it did not reveal studies that show NR does next to nothing for humans. I have reviewed the articles and cut and pasted the abstracts from each.

 

The first one, is a review of animal studies that concludes that NR supplementation may play a positive role iin nsulin sensitivity and fatty liver.

 

The second suggests that NAD+ precursors  may improve cardiovascular and other physiological functions with aging in humans.

 

The third suggests that NR supplementation would likely benefit older individuals.

 

So, again, what studies show that NR supplementation show no benefits? I am not arguing, I am just asking.

 

 

https://academic.oup...8/2/343/5051210

 

Animal studies suggest a positive role for nicotinamide riboside (NR) on insulin sensitivity and hepatic steatosis in models of obesity and type 2 diabetes. NR, an NAD+ precursor, is a member of the vitamin B-3 family now available as an over-the-counter supplement. Although data from preclinical trials appear consistent, potential effects and safety need to be evaluated in human clinical trials.

 

 

https://www.nature.c...467-018-03421-7

 

Nicotinamide adenine dinucleotide (NAD+) has emerged as a critical co-substrate for enzymes involved in the beneficial effects of regular calorie restriction on healthspan. As such, the use of NAD+ precursors to augment NAD+ bioavailability has been proposed as a strategy for improving cardiovascular and other physiological functions with aging in humans. Here we provide the evidence in a 2 × 6-week randomized, double-blind, placebo-controlled, crossover clinical trial that chronic supplementation with the NAD+ precursor vitamin, nicotinamide riboside (NR), is well tolerated and effectively stimulates NAD+ metabolism in healthy middle-aged and older adults. Our results also provide initial insight into the effects of chronic NR supplementation on physiological function in humans, and suggest that, in particular, future clinical trials should further assess the potential benefits of NR for reducing blood pressure and arterial stiffness in this group.

 

 

 

https://link.springe...394-019-01919-4

 

Older individuals suffer from low NADH levels. We have previously shown that nicotinamide riboside [NR; a NAD(P)(H) precursor] administration impaired exercise performance in young rats. It has been suggested that supplementation of redox agents exerts ergogenic effect only in deficient individuals. We hypothesized that old individuals would more likely benefit from NR supplementation. We investigated the effect of acute NR supplementation on redox homeostasis and physical performance in young and old individuals.

 

 

Let's quote the relevant findings from each of the linked studies, shall we?

 

Study #1:

 

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. No serious adverse events due to NR supplementation were observed and safety blood tests were normal.

 

Study #2:

 

 

Effect of NR on indicators of cardiovascular health

Supplementation with NR tended to lower mean systolic (SBP; mean change = −3.9 mmHg; one-sided 95% CI (−∞, −0.058)) and diastolic (DBP; mean change = −2.0 mmHg; one-sided 95% CI (−∞, −0.26)) blood pressure (BP) in all subjects as a group (Fig. 3a–c); however, these comparisons were not statistically significant after correction for multiple comparisons. Because the risk of cardiovascular events is greatly increased in individuals with above-normal baseline BP36, we performed a follow-up analysis to compare the effect of NR on BP in the participants with BP in the normal range (SBP/DBP < 120/80 mmHg; N = 11) vs. those with BP in the elevated/stage I hypertension range (SBP, 120–139 mmHg; DBP, 80–89 mmHg; N = 13) based on recently updated guidelines37. Of particular note, mean SBP was 9 mmHg lower after NR vs. placebo in individuals with elevated/stage I hypertension, whereas no change was observed in subjects with initial SBP in the normal range (Fig. 3d). Because this post-hoc subgroup analysis was exploratory, no statistical inferences can be made.

We also observed a trend towards a reduction in the mean carotid-femoral pulse wave velocity (PWV) with NR supplementation, the clinical “gold standard” measure of the stiffness of the aorta38, and a strong independent risk factor for incident cardiovascular events with aging and age-related diseases (Fig. 4a; mean change = −41.5 m s−1; one-sided 95% CI (−∞, −4.8)). However, this reduction was not statistically significant after correction for multiple comparisons. Similar to our exploratory analysis of BP, NR supplementation tended to lower aortic stiffness (carotid-femoral PWV) more in individuals with higher baseline BP (Fig. 4b), although no statistical inferences were made for this post-hoc comparison. No effect of NR was observed on ultrasound-determined carotid artery compliance (Fig. 4c) or brachial artery flow-mediated dilation, a measure of vascular endothelial function 

 

 

Study #3:

 

 

At rest, old individuals exhibited lower erythrocyte NAD(P)H levels, higher urine F2-isoprostanes and lower erythrocyte glutathione levels compared to young (P < 0.05). NR supplementation increased NADH (51% young; 59% old) and NADPH (32% young; 38% old) levels in both groups (P < 0.05), decreased F2-isoprostanes by 18% (P < 0.05), and tended to increase glutathione (P = 0.078) only in the old. NR supplementation did not affect VO2max and concentric peak torque, but improved isometric peak torque by 8% (P = 0.048) and the fatigue index by 15% (P = 0.012) in the old. In contrast, NR supplementation did not exert any redox or physiological effect in the young.

 

This sounds a lot like "not that much" to me in tangible effects for a healthy person not in their senior years (70+). One of the main NR marketing points is for improving athletic performance in active (young) adults which it demonstrably did not.


Edited by aribadabar, 03 October 2019 - 01:59 AM.

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#13 joesixpack

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Posted 03 October 2019 - 04:18 PM

Let's quote the relevant findings from each of the linked studies, shall we?

 

Study #1:

 

Study #2:

 

 

Study #3:

 

This sounds a lot like "not that much" to me in tangible effects for a healthy person not in their senior years (70+). One of the main NR marketing points is for improving athletic performance in active (young) adults which it demonstrably did not.

 

Again, thanks for the response and your explanation above. 

 

I am 70, and have experienced many of the positive effects noted in the studies. I agree that NR is probably not going to do much for a healthy, young person, in its current form.


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#14 Mind

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Posted 04 October 2019 - 10:56 PM

A podcast relevant to the NR/NMN discussion.







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