530 replies to this topic

[to age or not to age]

Midas, I can confirm that NR and NMN both increase NAD, either alone does this. I agree with you about
possible unintended consequences of massive precursor dosing. And, in part 1 of my interview with SInclair
I raised that point, ie: if you reverse one component of aging, could the metabolism in effect be mismatched to itself.
In other words, as you suggested, we age gradually; must the reverse be carefully calibrated. Several scientists
have said to me that part of the reason mice can be affected by this or that compound is that, relative to humans,
they are more hearty with regard to dose. Humans might not survive the massive dosing mice receive in some
experiments.

[Kevnzworld]

Midas, I can confirm that NR and NMN both increase NAD, either alone does this. I agree with you about
possible unintended consequences of massive precursor dosing. And, in part 1 of my interview with SInclair
I raised that point, ie: if you reverse one component of aging, could the metabolism in effect be mismatched to itself.
In other words, as you suggested, we age gradually; must the reverse be carefully calibrated. Several scientists
have said to me that part of the reason mice can be affected by this or that compound is that, relative to humans,
they are more hearty with regard to dose. Humans might not survive the massive dosing mice receive in some
experiments.

I think dosing is the question. The mice in Sinclairs study received massive amounts of NMN to boost their NAD. Would 250 mg of NR really move the NAD needle?
It's becoming clear that NR combined with a Sirt1 activator like resveratrol could be a synergistic combination if issues like bioavailability and effective dosing were figured out.
Perhaps the former with ubiquinol, C60oo, and PQQ could be a powerful cocktail.

Edited by Kevnzworld, 04 April 2014 - 06:32 PM.

[to age or not to age]

Kevnzworld, I can confirm that, according to Lenny Guarente, the effect of combining a SIRT1 activator such as resveratrol with an NAD precursor
is more than additive, he used the word "multiple." With regard to bioavailability, without doing the tween 80 thing, micronized resveratrol
made into an emulsion increases bioavailability significantly. More to come on ingestion of NR.

[APBT]

Kevnzworld, I can confirm that, according to Lenny Guarente, the effect of combining a SIRT1 activator such as resveratrol with an NAD precursor
is more than additive, he used the word "multiple." With regard to bioavailability, without doing the tween 80 thing, micronized resveratrol
made into an emulsion increases bioavailability significantly. More to come on ingestion of NR.

There have been endless posts in the past on different emulsions with resveratrol, do you know which are the most effective for increasing bioavailability.
Yes, NR (Niagen) dosing is a huge question, if for no other reason than economics. Taking a human-scaled dose based on the Sinclair study, would be cost prohibitive (at least for me).
As a NAD+ precursor, niacin is inexpensive. The downside is the flushing, which, I'm probably the only one on the planet but, I kinda like it. Do you know if (comparable dose size) NA is similarly effective to NR as a NAD+ precursor?
I, for one, appreciate your contributions and acting as a sort of intermediary between us and the researchers you have access to.

[Ukko]

Kevnzworld, I can confirm that, according to Lenny Guarente, the effect of combining a SIRT1 activator such as resveratrol with an NAD precursor
is more than additive, he used the word "multiple." With regard to bioavailability, without doing the tween 80 thing, micronized resveratrol
made into an emulsion increases bioavailability significantly. More to come on ingestion of NR.

There have been endless posts in the past on different emulsions with resveratrol, do you know which are the most effective for increasing bioavailability.
Yes, NR (Niagen) dosing is a huge question, if for no other reason than economics. Taking a human-scaled dose based on the Sinclair study, would be cost prohibitive (at least for me).
As a NAD+ precursor, niacin is inexpensive. The downside is the flushing, which, I'm probably the only one on the planet but, I kinda like it. Do you know if (comparable dose size) NA is similarly effective to NR as a NAD+ precursor?
I, for one, appreciate your contributions and acting as a sort of intermediary between us and the researchers you have access to.

I'm with you. I find the niacin flush amusing and..almost...enjoyable. No big deal. But there are feedback mechanisms and circadian rhythm issues to worry about. But for the time being, my NAD+ upping stack is as follows:

- Niacin (free form)
- Nicotinamide riboside
- Glutamine (both free form and sustamine...shitloads of both)
- C3G
- Apigenin
- Resveratrol
- R Lipoic Acid
- Pterostilbene
- Quercetin
- IP6 (to enhance the bioavailability of the above)

Still alive

Edited by Ukko, 05 April 2014 - 02:45 AM.

[follies]

Ukko, how do you decide when to take each element of your stack and which ones should be taken together and which should be taken separately?

[midas]

- Niacin (free form)
- Nicotinamide riboside
- Glutamine (both free form and sustamine...shitloads of both)
- C3G
- Apigenin
- Resveratrol
- R Lipoic Acid
- Pterostilbene
- Quercetin
- IP6 (to enhance the bioavailability of the above)

Still alive

But the question is, do you feel any different than before you were taking any of these..Personally I have decided to add one thing at a time and see if I notice any changes over a period of time before using anything else.
I am a little concerned about some things that are listed on here that we do not know the contra indications of, and I would be worried about mixing the wrong compounds and doing more harm than good.
My main reason for being here is to help with a medical issue that I have and really don't want to be making anything worse.
I only take one supplement at the moment which is Q10, both Ubiquinone and Ubiquinol and I am 95% sure that it has helped with my condition as I have had a big change since using it. My Doctor cant explain the change and he is not even willing to discus the Q10 aspect of it, as it is not a recognised treatment in the UK

I have mentioned before that it might be advantageous if we knew how old we all are and if we are combating any illnesses with these compounds.

[Iporuru]

Ukko
In one of your previous posts you said you take 20 g of glutamine - how did you arrive at this dose?
Examine.com says: "The Observed Safety Limit of glutamine supplementation, of which is the highest amount one can take and be assured of no side effects, has been suggested as being 14g/d in supplemental form (above food intake).^[83] Higher levels than this have been tested and well tolerated, but there is not enough evidence to suggest that higher doses are completely free from harm over a lifetime of supplementation nor enough evidence to assume harm exists. Limited evidence suggests that 50-60g for a period of a few weeks is not associated with significant adverse effects.^[84][85]"

[Ukko]

Ukko, how do you decide when to take each element of your stack and which ones should be taken together and which should be taken separately?

I take the glutamine with my breakfast protein shake. The other NAD+ boosting supps I take around lunch at noon or so. Seems advisable in light of the circadian cycle aspects of it.

[Ukko]

Ukko
In one of your previous posts you said you take 20 g of glutamine - how did you arrive at this dose?
Examine.com says: "The Observed Safety Limit of glutamine supplementation, of which is the highest amount one can take and be assured of no side effects, has been suggested as being 14g/d in supplemental form (above food intake).^[83] Higher levels than this have been tested and well tolerated, but there is not enough evidence to suggest that higher doses are completely free from harm over a lifetime of supplementation nor enough evidence to assume harm exists. Limited evidence suggests that 50-60g for a period of a few weeks is not associated with significant adverse effects.^[84][85]"

Fairly random = 15-20g is a heaping table spoon. Sometimes I settle for just 10g of trans-alanyl-L-Glutamine aka Sustamine. Anyhow, Glutamine/L-glutamic acid is the most common amino acid in the human body. Good luck with trying to something LESS toxic yet bioactive.

- Niacin (free form)
- Nicotinamide riboside
- Glutamine (both free form and sustamine...shitloads of both)
- C3G
- Apigenin
- Resveratrol
- R Lipoic Acid
- Pterostilbene
- Quercetin
- IP6 (to enhance the bioavailability of the above)

Still alive

But the question is, do you feel any different than before you were taking any of these..Personally I have decided to add one thing at a time and see if I notice any changes over a period of time before using anything else.
I am a little concerned about some things that are listed on here that we do not know the contra indications of, and I would be worried about mixing the wrong compounds and doing more harm than good.
My main reason for being here is to help with a medical issue that I have and really don't want to be making anything worse.
I only take one supplement at the moment which is Q10, both Ubiquinone and Ubiquinol and I am 95% sure that it has helped with my condition as I have had a big change since using it. My Doctor cant explain the change and he is not even willing to discus the Q10 aspect of it, as it is not a recognised treatment in the UK

I have mentioned before that it might be advantageous if we knew how old we all are and if we are combating any illnesses with these compounds.

Medical conditions are a different beast altogether. For me as a "healthy yet aging" guy the NAD+ boosting stack is like 1/4 of the stuff I take.Then again, I glow in the dark

[APBT]

There's all kinds of interesting stuff (propaganda?) on the Biotiva site about their soon-to-be-released NAD+ precursor, MitoTrans.
https://www.biotivia..._antiaging.html

[midas]

There's all kinds of interesting stuff (propaganda?) on the Biotiva site about their soon-to-be-released NAD+ precursor, MitoTrans.
https://www.biotivia..._antiaging.html

And here is an interesting article from four years ago about the guy (James Betz) that owns Biotiva....He is still using the same BS (search Google Scholar, no evidence of his own ) to sell his products. Take the time to read the article, its worth it. http://www.wired.co....ll-hype-machine

MitoTrans is $479 for a months supply




I e-mailed Mr Betz and I posted about this a couple of weeks ago, post 199 here..
http://www.longecity...n/page__st__180

After reading that article I have no faith in this guys products. He is very evasive about what is actually in there, I strongly suspect it is NR

.

Edited by midas, 06 April 2014 - 04:42 AM.

[midas]

Some information about more research very interesting research with Nicotinamide Riboside....

 

http://medicalxpress...in-b3.html#nwlt

 

"These results are a breakthrough for understanding the mechanisms of human mitochondrial muscle diseases and for exploring the efficient treatment options for these progressive disorders of adults. They also highlight the potent role of niacin in guiding mitochondrial energy metabolism"

 

 

 

This is something else, not NR related, but also worth reading.......

 

http://medicalxpress...ers.html#inlRlv

Edited by midas, 08 April 2014 - 01:29 AM.

[midas]

And the same story from a different website.... http://www.scienceda...40407090403.htm

[APBT]

I thought I had a reasonable NAD+/Sirt1 regimen with 500 mg nicotinic acid (2x daily) + 580 mg magnesium salicylate (2x daily) + plenty of berries & black rice + mild calorie restriction / exercise.
 

 

 

Darryl

Is this still your current regimen?  Any changes?  Have you added NR?
 

[mikeinnaples]

Most bang for the buck supplements for upping NAD+?

 

Precursors

• NR
• NA

 

AMPK Inducers

• Exercise
• Aspirin, Resveratrol, Quercetin, ECGC, Curcumin, Anthocyanins, Garlic
• Metformin

CD38 Inhibition

• Quercetin
• Chrysanthemin (Cy3g)
• Apigenen

 

 

Seems like high dose Nicotinic Acid (NA) combined with Metformin, ECGC, Resveratrol, Quercetin, and a cost effective supplier of Cy3g maybe be the best all around approach with what we know so far. I am not sure NR really buys us anything over NA. In fact, you could supplement with everything I just mentioned for a month for the cost of the NR alone. To me the bigger issue I have is with the timing of the supplements. Reading the literature on circadian rhythm, it seems as though this is a pretty big deal as well.

 

Edit: If we are worried about methylation add in: methyl b12 / methylfolate / SAM-e / TMG ?

 

Edited by mikeinnaples, 10 April 2014 - 06:57 PM.

[LaViidaLocaa]

Most bang for the buck supplements for upping NAD+?
 
Precursors

• NR
• NA

 
AMPK Inducers

• Exercise
• Aspirin, Resveratrol, Quercetin, ECGC, Curcumin, Anthocyanins, Garlic
• Metformin

CD38 Inhibition

• Quercetin
• Chrysanthemin (Cy3g)
• Apigenen

 
 
Seems like high dose Nicotinic Acid (NA) combined with Metformin, ECGC, Resveratrol, Quercetin, and a cost effective supplier of Cy3g maybe be the best all around approach with what we know so far. I am not sure NR really buys us anything over NA. In fact, you could supplement with everything I just mentioned for a month for the cost of the NR alone. To me the bigger issue I have is with the timing of the supplements. Reading the literature on circadian rhythm, it seems as though this is a pretty big deal as well.
 
 

The timing of taking the supplements is indeed an interesting subject. I wonder if this has been taken into account in many studies, if any.
One question though: what 'cost-effective' suplier of C3G are you talking about? The ones I found were almost as expensive as NR itself? Unless you are talking about different doses?

[Kevnzworld]

Most bang for the buck supplements for upping NAD+?
 
Precursors

• NR
• NA

 
AMPK Inducers

• Exercise
• Aspirin, Resveratrol, Quercetin, ECGC, Curcumin, Anthocyanins, Garlic
• Metformin

CD38 Inhibition

• Quercetin
• Chrysanthemin (Cy3g)
• Apigenen

 
 
Seems like high dose Nicotinic Acid (NA) combined with Metformin, ECGC, Resveratrol, Quercetin, and a cost effective supplier of Cy3g maybe be the best all around approach with what we know so far. I am not sure NR really buys us anything over NA. In fact, you could supplement with everything I just mentioned for a month for the cost of the NR alone. To me the bigger issue I have is with the timing of the supplements. Reading the literature on circadian rhythm, it seems as though this is a pretty big deal as well.
 
Edit: If we are worried about methylation add in: methyl b12 / methylfolate / SAM-e / TMG ?
 

NR is a more direct and effective NAD inducer, and it activates Sirt1
http://embomolmed.em...403943.full.pdf
http://www.smart-pub...lifespan-part-i

The problem with Metformin and NSAIDs like aspirin is that they suppress NAD
http://www.sciencedi...006291X10001828

That being said, I do take Metformin and baby aspirin, but later in the day. I also take lower doses of NR later in the day, with the larger dose being early AM
It seems like resveratrol being a Sirt1 inducer is synergistic, so I doubled my dose to 200 mg.
The problem with cd38 inhibitors like anthrocyanins is bioavailability
It's a complex puzzle!

[mikeinnaples]

 

Most bang for the buck supplements for upping NAD+?
 
Precursors

• NR
• NA

 
AMPK Inducers

• Exercise
• Aspirin, Resveratrol, Quercetin, ECGC, Curcumin, Anthocyanins, Garlic
• Metformin

CD38 Inhibition

• Quercetin
• Chrysanthemin (Cy3g)
• Apigenen

 
 
Seems like high dose Nicotinic Acid (NA) combined with Metformin, ECGC, Resveratrol, Quercetin, and a cost effective supplier of Cy3g maybe be the best all around approach with what we know so far. I am not sure NR really buys us anything over NA. In fact, you could supplement with everything I just mentioned for a month for the cost of the NR alone. To me the bigger issue I have is with the timing of the supplements. Reading the literature on circadian rhythm, it seems as though this is a pretty big deal as well.
 
Edit: If we are worried about methylation add in: methyl b12 / methylfolate / SAM-e / TMG ?
 

NR is a more direct and effective NAD inducer, and it activates Sirt1
http://embomolmed.em...403943.full.pdf
http://www.smart-pub...lifespan-part-i

The problem with Metformin and NSAIDs like aspirin is that they suppress NAD
http://www.sciencedi...006291X10001828

That being said, I do take Metformin and baby aspirin, but later in the day. I also take lower doses of NR later in the day, with the larger dose being early AM
It seems like resveratrol being a Sirt1 inducer is synergistic, so I doubled my dose to 200 mg.
The problem with cd38 inhibitors like anthrocyanins is bioavailability
It's a complex puzzle!

 

 

Is NR more direct and more effective across the board? Consider price point at effective dosage too ....

 

http://www.ncbi.nlm....6313/figure/F1/

 

I am confused about this:

 

The problem with Metformin and NSAIDs like aspirin is that they suppress NAD
http://www.sciencedi...006291X10001828

 

The article said Metformin suppresses NAD(P)H Oxidase. Isn't that a good thing? That is not the same thing as NAD+ .....or am I missing something really big here in my understanding of this?

 

Edited by mikeinnaples, 10 April 2014 - 08:16 PM.

[APBT]

 

Is NR more direct and more effective across the board? Consider price point at effective dosage too .

 

http://www.ncbi.nlm....6313/figure/F1/

 

 

I've studied those graphs many times and thought the same thing. The mice were all dosed at 400 mg/kg/day of either NR, NMN or NA.

 

NA is close to on par with NR in most aspects of NAD+ content listed, and surpasses it markedly in the liver.  Certainly plain ole niacin is dirt cheap, if you can embrace the flush (as I do).

Edited by APBT, 10 April 2014 - 10:28 PM.

[midas]

 

 

Is NR more direct and more effective across the board? Consider price point at effective dosage too .

 

http://www.ncbi.nlm....6313/figure/F1/

 

 

I've studied those graphs many times and thought the same thing. The mice were all dosed at 400 mg/kg/day of either NR, NMN or NA.

 

NA is close to on par with NR in most aspects of NAD+ content listed, and surpasses it markedly in the liver.  Certainly plain ole niacin is dirt cheap, if you can embrace the flush (as I do).

 

 

 

Can you please explain to me why you got involved with the Niagen group buy if you are so confident that NA/Niacin is more or less just as efficient as NR and very inexpensive compared to NR.....I'm confused

Edited by midas, 10 April 2014 - 11:11 PM.

[Darryl]

APBT, on 08 April 2014 - 10:40 PM, said: Darryl, Is this still your current regimen?  Any changes?  Have you added NR?

 

I haven't added NR yet, but its intriguing. My understanding of NR is that its potentially an effective NAD⁺ precursor, but only in tissues that express NR kinase. In the oft cited (in this thread) 2012 Cantó study, NR increased NAD levels in mouse liver and muscle, but not in brain or white adipose tissue, and equal doses of NA worked better in liver and comparably in muscle. See Msg #77. No one has done studies on human NAD+ levels with high-dose precursors, which is a shame as relatively non-invasive tests would reveal how NAD⁺ levels in erythrocytes are affected.

 

The major advantage of NR is that it doesn't activate GPR109A, and hence doesn't cause flushing at high doses. However the flushing response to NA may be important in its blood lipid effects, and I have become accustomed to the slight sunburn feeling twice a day. I have learned not to take it before social outings, as the story behind my ruddy appearance is a long one.

 

Ukko above has a pretty comprehensive supplementation schedule including both NA and NR that makes a lot of sense for those willing to take a handful of supplements, but there are a lot of other pathways besides NAD⁺/Sirt1 that compete for my pill reminder case and budget.

 

Kevnzworld, on 10 Apr 2014 - 2:25 PM, said: The problem with Metformin and NSAIDs like aspirin is that they suppress NAD: http://www.sciencedi...006291X10001828

 

Read that abstract again. Metformin and NSAIDs suppress NADPH oxidase, which is a membrane bound enzyme that uses NADPH as fuel to generate superoxide (which is also responsible for much of the H₂O₂, nitric oxide and peroxynitrate radicals floating around). NAD⁺ and NADPH are chemically related, but are "fuels" for distinct sets of cellular enzymes. As NADPH oxidase is implicated in many diseases with inflammatory etiologies, its worth partially inhibiting.

 

 

Edited by Darryl, 10 April 2014 - 11:35 PM.

[APBT]

Can you please explain to me why you got involved with the Niagen group buy if you are so confident that NA/Niacin is more or less just as efficient as NR and very inexpensive compared to NR.....I'm confused

 

 

Well, I'd say confident is too strong a word.  But, to answer your question more directly, I primarily participated in the group buy based on the Sinclair study, the postings "to age or not to age" made WRT NR being a strong NAD precursor (as an example see post #331) and that the NA and NR molecules look quite different - hence the possibility they could work via different pathways or render different positive results, or may work synergistically together - stacking as it were.

My bigger question is, what's an effective dose of NR?  If it is equal to NA mg to mg, the results are similar and one can endure the flushing (I agree with Darryl's comment about not using NA before a social engagement), then NA is a veritable bargain.  Even the "experts" don't have all the answers. 

[midas]

 

Can you please explain to me why you got involved with the Niagen group buy if you are so confident that NA/Niacin is more or less just as efficient as NR and very inexpensive compared to NR.....I'm confused

 

 

Well, I'd say confident is too strong a word.  But, to answer your question more directly, I primarily participated in the group buy based on the Sinclair study, the postings "to age or not to age" made WRT NR being a strong NAD precursor (as an example see post #331) and that the NA and NR molecules look quite different - hence the possibility they could work via different pathways or render different positive results, or may work synergistically together - stacking as it were.

My bigger question is, what's an effective dose of NR?  If it is equal to NA mg to mg, the results are similar and one can endure the flushing (I agree with Darryl's comment about not using NA before a social engagement), then NA is a veritable bargain.  Even the "experts" don't have all the answers. 

 

 

Thanks for the come back on that....Where does Niacinamide come into the Niacin/NA/NR equation, or doesn't it?
 

[Darryl]

Where does Niacinamide come in

 

If you mean nicotinamide (yes I've made the same mistake countless times), for Sir2 (the yeast homolog of Sirt1),  

 

nicotinamide was the most potent inhibitor (IC₅₀ = 0.126 mM), while nicotinic acid (IC₅₀ = 250 mM) was the worst inhibitor, displaying almost a 2000-fold difference in efficiency

 

Schmidt, Manning T., et al. "Coenzyme specificity of Sir2 protein deacetylases: implications for physiological regulation." Journal of Biological Chemistry 279.38 (2004): 40122-40129.

 

Ie, it appears our biology uses nicotinamide, the major by-product of sirtuin deacetylation, PARP and CD-38 activity, as a negative feedback regulator for the sirtuins, defeating the purpose of the intervention. There's some speculation that this is why nicotinic acid has beneficial effects on blood lipids while nicotinamide doesn't, but so far this hasn't been substantiated by mechanistic studies.

Edited by Darryl, 11 April 2014 - 01:02 AM.

[to age or not to age]

I will post a video excerpt in the next few days in which Dr Guarente at MIT says on camera that both NMN and NR increase NAD, either one

does it alone.  'It's an emerging situation'  and  'being a natural product very likely to be safe'

In this whole realm, there are questions, and more questions.  One thing for sure though, these scientists absolutely

believe in the truth eventually winning out, of being determined. I'm speaking here about Guarente and Sinclair.  

[tunt01]

I will post a video excerpt in the next few days in which Dr Guarente at MIT says on camera that both NMN and NR increase NAD, either one

does it alone.  'It's an emerging situation'  and  'being a natural product very likely to be safe'

In this whole realm, there are questions, and more questions.  One thing for sure though, these scientists absolutely

believe in the truth eventually winning out, of being determined. I'm speaking here about Guarente and Sinclair.  

 

Guarente has always been mildly upbeat on things like Resveratrol but he would never personally take the stuff himself.  I'd be more curious if they are taking NMR with or with out resveratrol.  And if not, what kind of data are they waiting to see that make them take it?  At what point would they turn to their loved ones (wife, etc.) and say -- you should really take this all natural product.  

[1thoughtMaze1]

I will post a video excerpt in the next few days in which Dr Guarente at MIT says on camera that both NMN and NR increase NAD, either one
does it alone.  'It's an emerging situation'  and  'being a natural product very likely to be safe'
In this whole realm, there are questions, and more questions.  One thing for sure though, these scientists absolutely
believe in the truth eventually winning out, of being determined. I'm speaking here about Guarente and Sinclair.  

 
Guarente has always been mildly upbeat on things like Resveratrol but he would never personally take the stuff himself.  I'd be more curious if they are taking NMR with or with out resveratrol.  And if not, what kind of data are they waiting to see that make them take it?  At what point would they turn to their loved ones (wife, etc.) and say -- you should really take this all natural product.  

Haha nice

[to age or not to age]

To Prophets and Thoughtmaze1 - In the video clip I will post, Lenny Guarente says, among other things, that he takes resveratrol.

As a general comment, over the past 7+ years I have found that a number of scientists take compounds but will not go on the record 

admitting this.  I have been told that certain doctors are taking rapamycin, which has been proven to extend lifespan when given to older

animals.  These scientists feel that the public warnings about rapamycin -  because it decisively down regulates the immune

system (which is good when used in cases of organ transplants) are actually a broad brush.  Thus these doctors cycle it. This is the case for many of

compounds; namely, it's a dialing issue, because major pathways like mtor and the like wear white and black hats.  More to come.  I will

post the clip soon.  Right now I am busy watching the masters tournament.  

 

[to age or not to age]

One other thing, some scientists say they intend to take NR soon, which may mean that they are taking it now.  I don't have that

on camera so I can't publicly say anything.  Make no mistake, there are questions being worked out now, but we will know a lot

within the year. Big pharma is getting into this game, but I can't be specific at this time.