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Dr. Sinclair about the epigenome, NAD, NR, NMN

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#31 Oakman

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Posted 19 August 2018 - 02:34 AM

Here is the link to the study about H2S boosting

 

http://sci-hub.tw/10...ell.2018.02.008

 

"treated for 4 weeks with NMN and/or H2S precursors (NaHS and GYY4137)" 

 

This is apparently what led to the surprising results they got in this study. The question is, what can we do to replicate this to get the equivalent of NaH2S  for ourselves while taking NMN? Neither of these precursor compounds appear very human friendly, best I can tell, but I'm no chemist either. 

 

All I can come up with are possibly MSM and Taurine, but I can't find they produce NaHS in the body, but they are sulfur containing compounds and can be taken in relatively large (gram) amounts. Would they help? I don't have any idea.

 

Anybody?



#32 able

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Posted 19 August 2018 - 03:05 AM

"treated for 4 weeks with NMN and/or H2S precursors (NaHS and GYY4137)" 

 

This is apparently what led to the surprising results they got in this study. The question is, what can we do to replicate this to get the equivalent of NaH2S  for ourselves while taking NMN? Neither of these precursor compounds appear very human friendly, best I can tell, but I'm no chemist either. 

 

All I can come up with are possibly MSM and Taurine, but I can't find they produce NaHS in the body, but they are sulfur containing compounds and can be taken in relatively large (gram) amounts. Would they help? I don't have any idea.

 

Anybody?

 

 

I thought the results were very impressive just by using NMN -  80% increase in endurance, and new capillary growth.

 

 

"NMN restored the number of capillaries and capillary density of the old mice to those typically seen in young mice (Figures 6B and S6D). Resting muscle perfusion (Figures 6C and S6E) and soluble oxygen (sO2) levels were significantly higher in NMN-treated mice compared to controls (Figure 6D). Mitochon- drial protein and activity levels and other muscle properties re- mained unaltered (Figures S6F–S6L). NMN supplementation dramatically increased home-cage oxygen consumption (Fig- ure S6M), but the most striking effect was a 56%–80% improve- ment in endurance, with lower post-exercise blood lactate (Fig- ures 6E and 6F; Movie S5)."

 

Adding NaHS resulted in more NAD+ and more endurance, but wasn't required for the impressive results.  

 

"Mice treated with NMN had 1.6-fold increase in time and distance run compared to untreated mice (Figure 7H), while the combination of NMN with NaHS treatment doubled their endurance."

 

 

It sounds like the NaHS provided some additional benefit, but an increase from 1.6 to 2.0 in endurance isn't really that huge a difference, is it?



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#33 Nate-2004

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Posted 19 August 2018 - 03:14 AM

Every time I start taking NR again I feel a lot of zing, for quite a while, then I take time off, a month or two, take it again and zing.



#34 Kentavr

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Posted 19 August 2018 - 04:07 AM

"treated for 4 weeks with NMN and/or H2S precursors (NaHS and GYY4137)" 

 

This is apparently what led to the surprising results they got in this study. The question is, what can we do to replicate this to get the equivalent of NaH2S  for ourselves while taking NMN? Neither of these precursor compounds appear very human friendly, best I can tell, but I'm no chemist either. 

 

All I can come up with are possibly MSM and Taurine, but I can't find they produce NaHS in the body, but they are sulfur containing compounds and can be taken in relatively large (gram) amounts. Would they help? I don't have any idea.

 

Anybody?

 

I think the answer is here:

 

http://www.forbes.ru...t-serovodorodom (news in Russian)

 

https://www.ncbi.nlm...pubmed/30026406 

 

Scientists brought a substance that releases hydrogen sulphide into the mitochondria (using the Skulachev ion - triphenylphosphonium).
Perhaps they will be able to develop this drug for several years.
 
 
By the way:
I guess we can achieve synergy with SkQ1. It should go on sale in 2020-2021.

Edited by Kentavr, 19 August 2018 - 04:12 AM.


#35 Harkijn

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Posted 19 August 2018 - 06:01 AM

"treated for 4 weeks with NMN and/or H2S precursors (NaHS and GYY4137)" 

 

This is apparently what led to the surprising results they got in this study. The question is, what can we do to replicate this to get the equivalent of NaH2S  for ourselves while taking NMN? Neither of these precursor compounds appear very human friendly, best I can tell, but I'm no chemist either. 

 

All I can come up with are possibly MSM and Taurine, but I can't find they produce NaHS in the body, but they are sulfur containing compounds and can be taken in relatively large (gram) amounts. Would they help? I don't have any idea.

 

Anybody?

Here we have arrived at a paradox pointed out in manyy LC threads already:

It seems that H2S production is boosted by sulfur amino acid restriction:

 

https://www.ncbi.nlm...les/PMC4297538/


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#36 stefan_001

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Posted 19 August 2018 - 11:36 AM

The mentioned tiredness I have also experienced but it went off again. My best guess is that NAD+ boosting influences the circadian clock and if NAD+ levels start to fluctuate in a wrong pattern you shift the rhythm.

 

Its interesting that many observe an immediate energy boost from NMN. I am not sure that is an anti-aging property. If the NMN is used for energy boosting then what is left for SIRTs etc? I never expected an immediate energy boost from NR but a gradual improvement in health or at minimum a stabilizing body. The NR that hopefully enters the bloodstream from sublingual administration that I do I hope gets consumed by cells that have thee NRKs upregulated - so cells that are in some sorts of trouble. If it is used as energy boost then there are many substances that can help.


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#37 LawrenceW

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Posted 19 August 2018 - 02:49 PM

"The mentioned tiredness I have also experienced but it went off again. My best guess is that NAD+ boosting influences the circadian clock and if NAD+ levels start to fluctuate in a wrong pattern you shift the rhythm."

 

 

 

 

 "If it is used as energy boost then there are many substances that can help."

 

 

I agree with your best guess on synchronizing to the rhythms. Personally, I take my first dose when I wake up and the second batch at 2 or 3 in the afternoon.

 

I disagree with your other assertion.  The way I look at it is that the NMN does a lot of things internally that you don't feel but do show up in the blood tests weeks or months later. As the pickup in energy is almost immediate and felt, I use this as an indicator for when I change or alter my regimen.  I use the energy pickup as an indicator that the dose or delivery method of NMN is working and therefore doing the rest of the things that I expect will be confirmed by the blood tests in the future. The pickup in energy is a nice additional benefit, but definitely not the primary reason that I take NMN.



#38 Oakman

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Posted 19 August 2018 - 03:17 PM

I thought the results were very impressive just by using NMN -  80% increase in endurance, and new capillary growth.

 

 

"NMN restored the number of capillaries and capillary density of the old mice to those typically seen in young mice (Figures 6B and S6D). Resting muscle perfusion (Figures 6C and S6E) and soluble oxygen (sO2) levels were significantly higher in NMN-treated mice compared to controls (Figure 6D). Mitochon- drial protein and activity levels and other muscle properties re- mained unaltered (Figures S6F–S6L). NMN supplementation dramatically increased home-cage oxygen consumption (Fig- ure S6M), but the most striking effect was a 56%–80% improve- ment in endurance, with lower post-exercise blood lactate (Fig- ures 6E and 6F; Movie S5)."

 

Adding NaHS resulted in more NAD+ and more endurance, but wasn't required for the impressive results.  

 

"Mice treated with NMN had 1.6-fold increase in time and distance run compared to untreated mice (Figure 7H), while the combination of NMN with NaHS treatment doubled their endurance."

 

 

It sounds like the NaHS provided some additional benefit, but an increase from 1.6 to 2.0 in endurance isn't really that huge a difference, is it?

 

From 1.6x to 2.0x endurance is a 25% increase. So, say if I was cycling, perhaps I wouldn't hit the 'wall' at 30 miles (which I do currently), but instead at 37.5 miles.  I would term that a HUGE difference  :)


Edited by Oakman, 19 August 2018 - 03:17 PM.

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#39 able

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Posted 19 August 2018 - 03:48 PM

Sure, makes sense.  What I meant was, from zero to 1.6X is  4x the increase as from 1.6 to 2.0x.

 

I would like that extra "oopmph" for sure, but will settle for a 1.6x increase in endurance for now.



#40 Oakman

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Posted 19 August 2018 - 04:17 PM

^ I believe that your math is a bit off. Control group is x1 and so double the endurance is 100% increase, or x 2. Therefore 1.6x the endurance of control is 60% increase. Check out the low and high intensity graphs (Fig 6) in the study mentioned. Regardless, I get your point,, and 60% improvement is nothing to sneeze at!



#41 able

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Posted 19 August 2018 - 04:29 PM

right, good point.

 



#42 Brian Valerie

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Posted 19 August 2018 - 07:20 PM

Another interesting NAD+ thread!  Does anyone know of any evidence for contraindication in taking NR and NMN simultaneously?  That's what I'm doing (cycling about 2 days off per week) based on the preliminary evidence of their different times of onset, half-lives, manners of absorption, modes of action, and resulting NAD+ concentrations in varying tissues and organs.  Any thoughts on this?  Thanks!  



#43 Phoebus

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Posted 19 August 2018 - 07:22 PM

The question is, what can we do to replicate this to get the equivalent of NaH2S  for ourselves while taking NMN? 

Anybody?

 

relevant info here

 

https://www.longecit...e-mitochondria/

 

garlic, cysteine, and supplements that increase Ach all ratchet up H2S 



#44 Brian Valerie

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Posted 22 August 2018 - 06:19 PM

One more thought on a possible advantage in taking both NMN and NR simultaneously is that if one is taking the sublingual NMN, but NR po, perhaps these two different manners of ingestion would also help in covering the bases, so to speak.


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#45 Oakman

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Posted 22 August 2018 - 08:28 PM

One more thought on a possible advantage in taking both NMN and NR simultaneously is that if one is taking the sublingual NMN, but NR po, perhaps these two different manners of ingestion would also help in covering the bases, so to speak.

 

Agreed. Esp. as NR oral takes about 6 hrs to elevate NAD+ blood levels, which is just too slow and unpredictable for 'right-now' enhancement. Whereas sublingual NMN is apparently up and working in the body in 20 min or so. If there was a sublingual NR we could compare, but I don't think there is, unfortunately. Is Chromadex missing out, or do they know it doesn't help NR absorption? We just don't know.

 

The best combo may be oral NR to maintain an increased 'background level' of NAD+ taken once or twice daily, while the sublingual NMN could also do that, but uniquely provides an NAD+ boost on-demand.


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#46 able

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Posted 22 August 2018 - 08:46 PM

Agreed. Esp. as NR oral takes about 6 hrs to elevate NAD+ blood levels, which is just too slow and unpredictable for 'right-now' enhancement. Whereas sublingual NMN is apparently up and working in the body in 20 min or so. If there was a sublingual NR we could compare, but I don't think there is, unfortunately. Is Chromadex missing out, or do they know it doesn't help NR absorption? We just don't know.

 

The best combo may be oral NR to maintain an increased 'background level' of NAD+ taken once or twice daily, while the sublingual NMN could also do that, but uniquely provides an NAD+ boost on-demand.

 

Definitely makes sense to me.  I have done that sporadically and  what I plan on doing soon.  Only reason I haven't done that regularly is, I wanted to test out the effect of sublingual NMN by itself for a bit longer.

 

Some NR users like Stefan have noted that NR also is more effective sublingual.  I'm sure Chromadex knows and is looking at that, but unfortunately, the salt added to stabilize it makes it unpalatable.  They need to reformulate asap.


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#47 johnross47

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Posted 23 August 2018 - 07:37 PM

Sorry   :|?

 

Based on recent research, I would not advise you to drink coffee:

 

http://www.dailymail...tudy-shows.html

 

I am now reviewing its use

 

Based on years of research I would not advise you tp read the Daily Mail. One study found that at least 80% of their science reports was wrong.


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#48 PAMPAGUY

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Posted 24 August 2018 - 03:27 PM

 



#49 PAMPAGUY

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Posted 24 August 2018 - 03:31 PM

I think alivebynature does the public a disservice by selling NMN at less than 500 mg. capsules which is the most effective dose according to Dr. Sinclair.  They got cut off by Chromadex and went into selling NMN while discounting the effectiveness of NR. Did a complete turnaround.  They do good research, but cannot afford to sell NMN in the proper dose as the cost would be too high for the public to pay.


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#50 able

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Posted 24 August 2018 - 05:30 PM

I have never seen Dr Sinclair make any mention of "cost effectiveness" in his personal NMN dosage.

 

He used to say he took 500 mg a day, and now says that is 750 Mg a day for himself and his father.

 

Alivebynature sells 125 mg tablets and a 12 gram jar of powder.   They recommend multiple smaller doses as being more effective - for a  total  of  500-1,500 mg a day.  


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#51 PAMPAGUY

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Posted 24 August 2018 - 07:17 PM

I have never seen Dr Sinclair make any mention of "cost effectiveness" in his personal NMN dosage.

 

He used to say he took 500 mg a day, and now says that is 750 Mg a day for himself and his father.

 

Alivebynature sells 125 mg tablets and a 12 gram jar of powder.   They recommend multiple smaller doses as being more effective - for a  total  of  500-1,500 mg a day. 

I agree that Dr. Sinclair never said what it would cost to use NMN.  Why should he with his weaIth,  also have never heard him say that NMN is better than NR or N+R.  His name is on NR trials, with good results.  I personally can afford appx $300 a month to use the powder and take a 500 mg dose daily, but most people cannot.  Alivebynature advertises right on there package that the normal dose is 200mg daily.  I personally take N+R and have had wonderful results.  I believe all of us would like nothing better than a head to head trial of NMN, NR, N+R, but will never happen.  Worst thing that can happen to Pharmaceutical business is a cheap substitute for there product that works as good.  Sinclair said he had 25 people ready for the 2nd phase of his trial of NMN and ready to start next month.  Probably adding hydrogen sulfide (H 2 S) to boost effectiveness, and to give them a proprietary drug to sell to the public, and undercut Alivebynature or sell it to them.

 

There is so much hype about NAD+ precussors that the buying public has a very difficult time telling the truth from the marketing hype.


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#52 Kentavr

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Posted 24 August 2018 - 09:46 PM

Good presentation. Interestingly when asked about NR, he said it boosts NAD but is somewhat unstable , that’s why it should be refrigerated
He and his dad take NMN, 500 mg, resveratrol 1000 mg and Metformin. 800mg?
He hinted at as of a yet unpublished study showing life extension in mice with NMN.

 

It is clear why he takes metformin: NMN does not protect against type 2 diabetes, and metformin protects.
This was clear from the result of the analysis of LawrenceW (see this topic, # 22):
 
 
I do not understand the following:
 
Why does Sinclair's father eat as much resveratrol (1000 mg)?
Does he not know that resveratrol increases the level of estrogen in the body? It binds to both alpha and beta estrogen receptors
Could not he have chosen safer flavonoid?  :laugh:

 


Edited by Kentavr, 24 August 2018 - 09:51 PM.

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#53 LawrenceW

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Posted 24 August 2018 - 10:07 PM

 

It is clear why he takes metformin: NMN does not protect against type 2 diabetes, and metformin protects.
This was clear from the result of the analysis of LawrenceW (see this topic, # 22):
 

 

 

Kentavr.

 

Unfortunately, post #22 of the above referenced post was by MikeDC.  He completely misread my results in post #1 which were:

 

"On Dec. 7, after almost 3 months on the 1,600mg twice-per-day NMN regimen, I went in for blood tests. My doctor was very pleased to see that my previous HgbA1c reading of 6.4 had reduced to a 5.8. She commented that if my HgbA1c came back up to 6.0, or if I quit taking NMN, then I would have to get started on Metformin immediately."

 

My GP found that my NMN regimen controlled my A1C very nicely and found no need to put me on Metformin.

 

Lawrence


Edited by LawrenceW, 24 August 2018 - 10:15 PM.

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#54 Cocoblue

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Posted 09 September 2018 - 01:38 PM

"treated for 4 weeks with NMN and/or H2S precursors (NaHS and GYY4137)" 

 

This is apparently what led to the surprising results they got in this study. The question is, what can we do to replicate this to get the equivalent of NaH2S  for ourselves while taking NMN? Neither of these precursor compounds appear very human friendly, best I can tell, but I'm no chemist either. 

 

All I can come up with are possibly MSM and Taurine, but I can't find they produce NaHS in the body, but they are sulfur containing compounds and can be taken in relatively large (gram) amounts. Would they help? I don't have any idea.

 

Anybody?

 

 

Hi 

 

I am reading up atm on H2S precursors and instinctively thought about Sinclairs history in this area so checked to see whether reservatrol might be linked to the stimulation of H2S and it appears there is some research to indicate that reservatrol induces H2S. 


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#55 Oakman

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Posted 09 September 2018 - 06:21 PM

That would be great, as I take R already. For my part, I came up with pretty much nothing, save allicin perhaps. 



#56 Phoebus

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Posted 09 September 2018 - 06:32 PM

That would be great, as I take R already. For my part, I came up with pretty much nothing, save allicin perhaps. 

 

 

here 

 

https://www.longecit...e-mitochondria/

 

and 

 

https://www.ncbi.nlm...les/PMC5471864/

 

and 

 

https://www.ncbi.nlm...les/PMC2084282/


Edited by Phoebus, 09 September 2018 - 06:35 PM.

  • Informative x 1

#57 Oakman

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Posted 09 September 2018 - 09:40 PM

 

Thanks Phoebus, your references helped bring together thoughts on a regimen I've be working on :)  

 

So:

 

NAC, Taurine, and DATS, for it potential to increase H2S. I already take NAC, Taurine, and garlic extract, but I'll get some diallyl trisulfide to be sure. Combined with a recipe for NFR1 & NFR2 enhancement, that could theoretically make the NMN  (and NR) I take most effective for both NAD+ production and cardiovascular health. Excellent!



#58 Phoebus

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Posted 09 September 2018 - 11:02 PM

 Combined with a recipe for NFR1 & NFR2 enhancement,

 

what is this recipe may i ask? 



#59 Oakman

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Posted 10 September 2018 - 01:19 AM

what is this recipe may i ask? 

 

There is a company LifeVantage that markets two supplement cocktails. Not too sure about the company itself, nevertheless they patented a supplement called NRF2, and have a supporting study that showed NRF2 upregulation. Their NRF1 came later. I make my own capsules, so I'm doing something loosely based on those and see any differences with NR/NMN, if I see any changes/improvements. I have the ingredients, so easy to do.

 

INGREDIENTS Milk Thistle extract, Bacopa extract, Ashwagandha powder, Culinary Matcha Green Tea, UltraCur

 

INGREDIENTS Acetyl-L-Carnitine, Quercetin, GSE, Alpha Lipoic Acid, Coenzyme CQ10, Rhodiola Rosea
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#60 stefan_001

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Posted 10 September 2018 - 07:38 AM

I have been using Milk Thistle on a rotating bases because of studies like this:

 

http://www.mdpi.com/.../9/10/1086/html

Silibinin Restores NAD+ Levels and Induces the SIRT1/AMPK Pathway in Non-Alcoholic Fatty Liver

 

Tuarine I have added since some months as well, some early postive indications - but more time needed

 







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