2255 replies to this topic

[Smedvick]

I’m having difficulty reconciling two ideas:  1. NA has been used for 70 years in therapeutic doses to treat hyperlipoidemia, and 2. NA  increases homocysteine levels and therefore the risk of cardiovascular disease. 

 

On the surface it seems that if NA did cause elevated cardiovascular risk, it would have been observed decades ago. 

[lumia]

Should I seriously request mods' intervention?

[Logic]

 

This paper has me rethinking Nam, NA and NR:
http://sci-hub.bz/10...161209787185823

(NB http://sci-hub.bz for free access to research papers)

It would seem that NA is converted into Nam by the liver and its only when one doses above what the liver can handle that one gets NA into cells directly.
Also interesting is the NAD+ increase seen from Nam at the right dosage...

The only study looking at what happens to NR taken orally  shows it to be slowly broken down to N and R at/by the gut lining.
(There was, IIRC, some tantalizing hints that this is 'standard procedure' for getting things through linings and membranes etc and that the two are rejoined on the other side....??)

That said; the only available evidence points to NR being nothing more than a Nicotinamide and D-Ribose slow release pill.
 

Everyone here seems more or less oblivious to the pivotal role Ribose play in the synthesis of NAD+ and ATP in both the de-novo and salvage pathways and the long time time and large amount of energy it takes for the body to produce its own.  A quick Pubmed search for the effects of D-Ribose supplementation will give you very similar results to those seen in NAD+ boosting papers.

 

The problem with D-Ribose is that its very reactive in the Advanced Glycation Endproduct forming dept, so the slow release is key!

If the above hypothesis holds; alternate/cheaper forms of slow release Nam, NA and D-ribose should have the same effect as NR..?


Slow release Ribose:
This may be as simple as taking riboflavin = vit B2.
http://www.longecity...as-a-nootropic/
RiboCeine may be another alternative. (expensive)
http://www.longecity...athione-by-300/

Slow release Niacin:
Inositol Hexanicotinate (Blocks autophagy. http://www.longecity...crophagy/page-3 )
Chromium Polynicotinate.

I haven't tried this yet.  Hopefully someone here might and report back.

Hi y'all young whippersnappers out there, one of the links Logic posted is about snorting from capsules. Been there, done that. This here grizzled guy says: don't snort fillers and stuff unless you want live shorter.

 

 

 

I was thinking the same thing Harkijin.
I find the effect experienced by those posting there interesting and expound on my NA + R hypothesis in that thread.

I don't know if you saw my... 'dangerous and irresponsible'  link to intranasal B3 in that thread?

http://www.longecity...axing/?p=781763

I can't help wondering at the effect of taking both intranasally may be and whether we may be missing something by not skipping the stomach and liver metabolism..?

On the other hand; the placebo effect of 'snarfing a line' may be the main reason for the effects experienced.

[Logic]

 

This paper has me rethinking Nam, NA and NR:
http://sci-hub.bz/10...161209787185823

(NB http://sci-hub.bz for free access to research papers)

It would seem that NA is converted into Nam by the liver and its only when one doses above what the liver can handle that one gets NA into cells directly.
Also interesting is the NAD+ increase seen from Nam at the right dosage...

The only study looking at what happens to NR taken orally  shows it to be slowly broken down to N and R at/by the gut lining.
(There was, IIRC, some tantalizing hints that this is 'standard procedure' for getting things through linings and membranes etc and that the two are rejoined on the other side....??)

That said; the only available evidence points to NR being nothing more than a Nicotinamide and D-Ribose slow release pill.
 

Everyone here seems more or less oblivious to the pivotal role Ribose play in the synthesis of NAD+ and ATP in both the de-novo and salvage pathways and the long time time and large amount of energy it takes for the body to produce its own.  A quick Pubmed search for the effects of D-Ribose supplementation will give you very similar results to those seen in NAD+ boosting papers.

 
The problem with D-Ribose is that its very reactive in the Advanced Glycation Endproduct forming dept, so the slow release is key!

If the above hypothesis holds; alternate/cheaper forms of slow release Nam, NA and D-ribose should have the same effect as NR..?


Slow release Ribose:
This may be as simple as taking riboflavin = vit B2.
http://www.longecity...as-a-nootropic/
RiboCeine may be another alternative. (expensive)
http://www.longecity...athione-by-300/

Slow release Niacin:
Inositol Hexanicotinate (Blocks autophagy. http://www.longecity...crophagy/page-3 )
Chromium Polynicotinate.

I haven't tried this yet.  Hopefully someone here might and report back.

 

 
Interesting Logic,
 
However, I dont see where its stated that niacin will be converted into nicotinamide. Normally thats the opposite that could occur.

 

 

From the study:

 

...Small doses of nicotinic acid will be largely con-verted  to  NAD+  in  the  intestine  and  liver  and  quantifiable  levels of nicotinic acid may not appear in the systemic blood. The subsequent release of nicotinamide into the blood stream will  be  dependent  on  some  form  of  NAD  glycohydrolase  or  ADP-ribosylation  activity  in  small  intestine  and  liver  cells...

 

...We  have  observed  this  in  a  rat  model  with  high  oral  doses  of  nicotinamide.  The  usual  dietary  content  of  niacin  for  rats  is  30  mg/kg  diet.  When  nicotinamide  was  fed  at  1  g/kg  of  diet,  liver  NAD+  was  increased  by  50%  and  basal  poly(ADP-ribose)  was  increased  2-fold,  indicating  that  this  dose  of  nicotinamide  acts  more  to  enhance  substrate  pools  than  to  inhibit  PARP-1  [6].  However,  when  these  rats  were  treated with a hepatocarcinogen to enhance PARP-1 activity, high  nicotinamide-fed  rats  and  controls  displayed  the  same  increase  in  poly(ADP-ribose)  content,  although  high  nico-tinic   acid   supplementation   did   support   higher   levels   of   poly(ADP-ribose)  formation  than  control  or  high  nicotina-mide supplemented rats [6]. Thus, high nicotinamide feeding significantly  enhanced  basal  poly(ADP-ribose)  formation,  but  appeared  to  marginally  limit  carcinogen-induced  PARP-1  activity...

 

All this study confirm that all precursor looks bad way to increase NAD+ since you will expose yourself then to homocysteine etc. And curently there is no data performed on the safety profile of NR, especially looking at the its methylation mechanism. Thats really bad especially when all studies show the need to use large dose for both NA and NR.
 
I take niacin in low dose along a multi vitamine to insure i also get the B6, B9 (as folate), and B12. So I also get quiet large dose of B2 (riboflavin). But since riboflavin would loose its D-Ribose only after it has enter the cell, Im not sure its relevant isnt ? Because we need the ribose pool prior to enter the cell. There is study that confirm such pool however and NR will be produced with niacinamide.

...Nicotinamide  supplementation  may  also  disrupt  single  carbon  metabolism.  We  found  in  a  rat  model  that  nicotinamide  supplementation  worsened  liver  fat  accumulation  in  choline  deficient  rats,  and  that  increased  poly(ADP-ribose)  accumulation  occurred  with  a  combination  of  low  choline  and high dietary nicotinamide [36]. This would appear to be due  to  the  use  of  methyl  groups  in  nicotinamide  excretion  [37], and the methyl depleting effect of nicotinamide dosing should  be  considered  in  the  interpretation  of  basic  research  and considered as a side effect in clinical treatments...

 

A very interesting thread on methylation etc.

...Folic acid should be avoided if you have the genetic mutation which reduces the ability to convert it (60% of the world's population have this mutation)...

http://www.longecity...ndpost&p=609889

http://forums.phoeni...l-basics.10138/

[Nate-2004]

I’m having difficulty reconciling two ideas:  1. NA has been used for 70 years in therapeutic doses to treat hyperlipoidemia, and 2. NA  increases homocysteine levels and therefore the risk of cardiovascular disease. 

 

On the surface it seems that if NA did cause elevated cardiovascular risk, it would have been observed decades ago. 

 

Maybe I'm drawing the wrong conclusion but if B12 and B6 are enough to help prevent undermethylation when taking Na, then wouldn't it be the case that the amount of Na you intake should be directly proportional (in relative measure) to the amount of B12 and B6 you take in combination? For instance if I up my intake of Na from 50mg to 500mg then I should increase my B12 from 1000mcg to 10,000mcg or would that be too much? Then at least you'd avoid the homocysteine problem that comes from being undermethylated and the B3 would prevent overmethylation, keeping it in balance.

 

I could be totally understanding this all incorrectly but this is just having spent 3 hrs just learning about it today.

[stefan_001]

 

Tom, for me your motivation remains to be seen:

- You are promoting beta-lapachone as the better alternative for NAD booster. You did that in this discussion and you have now dedicated a seperate discussion to that

- You seem not concerned about safety data for BL in similar intensity as NR

- You have a website dedicated to BL

- and in the other thread you try to sell it for 250USD / gram

 

Hi Everyone,

I think I got a good source for pure beta-lapachone. Knowing the dosage on mice and if we take like 4 times less, it would mean around 1g per month per persons.

The price would be 250$ per grams without shipping fees. I know its a lot but much less than TA65 crap or the current price for beta lapachone on the market.. I think also no need to use it daily, a transitent use can be ok.

So anyone interested in ?

 

ps: its also interesting that in short succession Brain get 2 x unfriendly as feedbacks to his post and you get very fast after your post 2 positive feedbacks......

 

Hey Stefan ! What you say is really unfair.. I dont speak about beta lapachone here anymore, and I wanted to use it first for myself.. If you make a quick research yourself you will see how hard it is to found a source cheaper for BL, and if you have a trusty one, then please come to the thread and share. I never hidden myself to own and write some blog and I really dont see the problem and the link with this discussion ?

 

here is my list: asc2p.com (for ascorbic acid 2phosphate, the only vit C that enter the cell and truly stable), beta-lapachone.com, pterostilbene.com, oh.. and nicotinamide-riboside.net ! and some others, I ill add soon for instance : honokiol.net.. spermidine.net etc.. I could hide that but I dont see why ? whats the wrong with you ?

 

Please get back to the topic and science.. today I see only attack. I should maybe just ask where to buy NR or what ?

 

So Tom I visited your website nicotinamide-riboside.net. It sounds like a paid promotion and not at all in line with all the concerns you voice here. So which Tom should we believe? Or you forgot to update it recently? Quite surprising that with all these health concerns you see in NR you more or less promote and entice people to use it in your website in other words putting there health at risk. No disclaimers, no recommendation to use low dose and so on. I guess then the website was made before BL? 

 

I added some screenshots to my post. Love the tittle "Nicotinamide Riboside: Key to Life". Other great quotes:

- "when ingested nicotininamide riboside is directly converted into NAD+"

- "Nicotinamide riboside supplements may be the only way to practically boost NAD+ in the body"

- "Nicotinamide riboside is unique  in being able to promote NAD+ synthesis"

- "when researchers gave NR to normal mice....they particularly noticed an increase in NAD+ in the liver"

- And my favorite given the discussion here: "supplementation with Nicotonic Acid does not shorten lifespan nor does it lengthen lifespan or increase levels of NAD+"

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Edited by stefan_001, 12 July 2016 - 07:13 AM.

[Tom Andre F. (ex shinobi)]

Nice off topic stefan ! U could just have noted these blogs are old and none of these are updated... I wanted even help from anyone interested to edit contenr and make each topic more easy to understand but im not even sure if NR blog deserve some more energy given the facts posted here. I will wait for facts no personal attack.
U should not believe me or anyone else but only the data i copy pasted in this thread. Im glad at least some person are looking into the methyl concern here now. You the only one who prefer spend time into terrible stupid off topic. I will not reply to you poluting here anymore

[stefan_001]

Nice off topic stefan ! U could just have noted these blogs are old and none of these are updated... I wanted even help from anyone interested to edit contenr and make each topic more easy to understand but im not even sure if NR blog deserve some more energy given the facts posted here. I will wait for facts no personal attack.
U should not believe me or anyone else but only the data i copy pasted in this thread. Im glad at least some person are looking into the methyl concern here now. You the only one who prefer spend time into terrible stupid off topic. I will not reply to you poluting here anymore

 

So you are leaving the blog up? Well then I cannot take your strong statements here serious. 

Edited by stefan_001, 12 July 2016 - 08:06 AM.

[Tom Andre F. (ex shinobi)]

 

 

From the study:

 

...Small doses of nicotinic acid will be largely con-verted  to  NAD+  in  the  intestine  and  liver  and  quantifiable  levels of nicotinic acid may not appear in the systemic blood. The subsequent release of nicotinamide into the blood stream will  be  dependent  on  some  form  of  NAD  glycohydrolase  or  ADP-ribosylation  activity  in  small  intestine  and  liver  cells...

 

...We  have  observed  this  in  a  rat  model  with  high  oral  doses  of  nicotinamide.  The  usual  dietary  content  of  niacin  for  rats  is  30  mg/kg  diet.  When  nicotinamide  was  fed  at  1  g/kg  of  diet,  liver  NAD+  was  increased  by  50%  and  basal  poly(ADP-ribose)  was  increased  2-fold,  indicating  that  this  dose  of  nicotinamide  acts  more  to  enhance  substrate  pools  than  to  inhibit  PARP-1  [6].  However,  when  these  rats  were  treated with a hepatocarcinogen to enhance PARP-1 activity, high  nicotinamide-fed  rats  and  controls  displayed  the  same  increase  in  poly(ADP-ribose)  content,  although  high  nico-tinic   acid   supplementation   did   support   higher   levels   of   poly(ADP-ribose)  formation  than  control  or  high  nicotina-mide supplemented rats [6]. Thus, high nicotinamide feeding significantly  enhanced  basal  poly(ADP-ribose)  formation,  but  appeared  to  marginally  limit  carcinogen-induced  PARP-1  activity...

 

All this study confirm that all precursor looks bad way to increase NAD+ since you will expose yourself then to homocysteine etc. And curently there is no data performed on the safety profile of NR, especially looking at the its methylation mechanism. Thats really bad especially when all studies show the need to use large dose for both NA and NR.
 
I take niacin in low dose along a multi vitamine to insure i also get the B6, B9 (as folate), and B12. So I also get quiet large dose of B2 (riboflavin). But since riboflavin would loose its D-Ribose only after it has enter the cell, Im not sure its relevant isnt ? Because we need the ribose pool prior to enter the cell. There is study that confirm such pool however and NR will be produced with niacinamide.

...Nicotinamide  supplementation  may  also  disrupt  single  carbon  metabolism.  We  found  in  a  rat  model  that  nicotinamide  supplementation  worsened  liver  fat  accumulation  in  choline  deficient  rats,  and  that  increased  poly(ADP-ribose)  accumulation  occurred  with  a  combination  of  low  choline  and high dietary nicotinamide [36]. This would appear to be due  to  the  use  of  methyl  groups  in  nicotinamide  excretion  [37], and the methyl depleting effect of nicotinamide dosing should  be  considered  in  the  interpretation  of  basic  research  and considered as a side effect in clinical treatments...

 

A very interesting thread on methylation etc.

...Folic acid should be avoided if you have the genetic mutation which reduces the ability to convert it (60% of the world's population have this mutation)...

http://www.longecity...ndpost&p=609889

http://forums.phoeni...l-basics.10138/

 

 

yeah so nicotinamide in the indirect way : converted from NAD+, its the release. Thats why as the study and the others state, NA is better to increase NAD+ than nicotinamide as we see in raw score, but whatever happen we should be concerned about nicotinamide. If increased dosage comes the problem with methylation as its the case with all unmethylated substrate seen there will occur: homocysteine will be high as low choline and betaine.

 

For folic acid, thats why most now recomend the min / max of 400mcg per day. We also have to choose folate: 5-methyltetrahydrofolate / 5-MTHF and not folic acid.

 

https://chriskresser...-vs-folic-acid/

 

and http://mthfr.net/for...ng-info-anyone/ (see second comment here that explain the root)

 

when looking to the full loop the axis: B3 / B6 / folate / B12 is compulsory and have to come in balance as it control histidine, homocysteine, methionine, glutamate... We just cant only focus on NAD+ anymore.

 

If we take too much nicotinamide compared with the others B vitamines that are dose limited or above what one can process, then methyl problem will occur. I will stay on my low dose as homocysteine is much more a concern for me than NAD+

[stefan_001]

there are some previous discussions on the absorption of NR. There is a separate thread on that:

http://www.longecity...absorbed/page-1

 

An interesting quote from that thread wrt homocysteine:

Kevnzworld

•  
• Registered User
• 829 posts
• 269 ₮

• Location:Los Angeles

Posted 08 August 2014 - 07:17 PM

Primal, on 08 Aug 2014 - 6:43 PM, said:

As I previously posted, my homocysteine actually declined slightly after taking 750mg NR and 100mg NA daily. 7.2 to 6.4 I haven't added any additional methyl donators .
Somebody, I believe it was SmithX wondered about NR supplementation and thyroid health.
My TSH dropped from 2.4 to 1.

 

[Tom Andre F. (ex shinobi)]

 

there are some previous discussions on the absorption of NR. There is a separate thread on that:

http://www.longecity...absorbed/page-1

 

An interesting quote from that thread wrt homocysteine:

Kevnzworld

•  
• Registered User
• 829 posts
• 269 ₮

• Location:Los Angeles

Posted 08 August 2014 - 07:17 PM

Primal, on 08 Aug 2014 - 6:43 PM, said:

As I previously posted, my homocysteine actually declined slightly after taking 750mg NR and 100mg NA daily. 7.2 to 6.4 I haven't added any additional methyl donators .
Somebody, I believe it was SmithX wondered about NR supplementation and thyroid health.
My TSH dropped from 2.4 to 1.

 

 

I do now remember this thread, and its crazy that most the question here awas already discussed in 2014. I do not understand why we still not have now in 2016 the pharmakokinetics study about niagen.. anyone has info about that ?

 

Regarding Kevnworld dosage we do not have much info here, his age, duration of the supplementation, others supplements, diet etc.. What we know is that 750mg NR means around 325mg nicotinamide + 100mg NA. Maybe he can handle this dosage very well on the long run, maybe this dosage is low, maybe this dosage is just below the limit he can achieve for now and have a good iNampt / eNampt ratio, etc

 

I think (but we dont have more data) that we can handle such dosage and that we have to use others B vitamins especially to handle the pathway explained. Some persons use large dose niacin (such as 1g per day) without problem at all. Problem is its not the case for everyone and unlike what studies explain us (the problem comes with large dose), some members here experienced high homocysteine (or blood sugar problem) with much lower dosage of B3s.

 

I think BigLabRat and Primal made some good points in this thread. We need studies that can show low dose can be enough for the NAD+ boosting effect we all look here, else the more we use NR / NA, AND the more frequent we expose ourselves to the problem listed there and there

 

[Nate-2004]

 

 

there are some previous discussions on the absorption of NR. There is a separate thread on that:

http://www.longecity...absorbed/page-1

 

An interesting quote from that thread wrt homocysteine:

Kevnzworld

•  
• Registered User
• 829 posts
• 269 ₮

• Location:Los Angeles

Posted 08 August 2014 - 07:17 PM

Primal, on 08 Aug 2014 - 6:43 PM, said:

As I previously posted, my homocysteine actually declined slightly after taking 750mg NR and 100mg NA daily. 7.2 to 6.4 I haven't added any additional methyl donators .
Somebody, I believe it was SmithX wondered about NR supplementation and thyroid health.
My TSH dropped from 2.4 to 1.

 

 

I do now remember this thread, and its crazy that most the question here awas already discussed in 2014. I do not understand why we still not have now in 2016 the pharmakokinetics study about niagen.. anyone has info about that ?

 

Regarding Kevnworld dosage we do not have much info here, his age, duration of the supplementation, others supplements, diet etc.. What we know is that 750mg NR means around 325mg nicotinamide + 100mg NA. Maybe he can handle this dosage very well on the long run, maybe this dosage is low, maybe this dosage is just below the limit he can achieve for now and have a good iNampt / eNampt ratio, etc

 

I think (but we dont have more data) that we can handle such dosage and that we have to use others B vitamins especially to handle the pathway explained. Some persons use large dose niacin (such as 1g per day) without problem at all. Problem is its not the case for everyone and unlike what studies explain us (the problem comes with large dose), some members here experienced high homocysteine (or blood sugar problem) with much lower dosage of B3s.

 

I think BigLabRat and Primal made some good points in this thread. We need studies that can show low dose can be enough for the NAD+ boosting effect we all look here, else the more we use NR / NA, AND the more frequent we expose ourselves to the problem listed there and there

 

 

 

 

Is there some way to test whether you're undermethylated or overmethylated?

[Smedvick]

http://www.nature.co...ll/nm.4132.html

 

Another avenue? 

[ceridwen]

@Nate2004 get genetically tested

[Bryan_S]

Niagen, Nicotinamide Riboside Side Effects vs. NAD+ Benefits

 

Superfoodly

July 8, 2016

 

OK its time to get back to the core of what I do here which is post the latest research and articles surrounding NAD Repletion/Boosting. Somehow that effort has been sidelined and its time to return to what has been the core of this thread.

 

A balanced article appeared in Superfoodly. While its contents are not new it does review comments from forums like ours on LongeCity and the latest academic and medical studies.

 

"With those caveats said, it appears the hype – as least as of to date – is justified, given the many promising studies so far suggesting its ability to increase NAD+ levels. However further research and clinical trials will be needed to verify whether or not the benefits are what many researchers suspect them to be."

[Nate-2004]

@Nate2004 get genetically tested

 

This would not address my current state after taking NR or Na or B6 and B12 in a complex. I'd like to know what I am currently at, not what I have a genetic tendency towards being.  However I'd love to know that as well. Which report on 23 and Me is related to this?

Edited by Nate-2004, 12 July 2016 - 06:44 PM.

[Bryan_S]

NAD+ metabolism: Bioenergetics, signaling and manipulation for therapy.

Biochim Biophys Acta. 2016 Jun 29. pii: S1570-9639(16)30123-6. doi: 10.1016/j.bbapap.2016.06.014. [Epub ahead of print]

http://www.ncbi.nlm....pubmed/27374990

 

Abstract

We survey the historical development of scientific knowledge surrounding Vitamin B3, and describe the active metabolite forms of Vitamin B3, the pyridine dinucleotides NAD+ and NADP+ which are essential to cellular processes of energy metabolism, cell protection and biosynthesis. The study of NAD+ has become reinvigorated by new understandings that dynamics within NAD+ metabolism trigger major signaling processes coupled to effectors (sirtuins, PARPs, and CD38) that reprogram cellular metabolism using NAD+ as an effector substrate. Cellular adaptations include stimulation of mitochondrial biogenesis, a process fundamental to adjusting cellular and tissue physiology to reduced nutrient availability and/or increased energy demand. Several metabolic pathways converge to NAD+, including tryptophan-derived de novo pathways, nicotinamide salvage pathways, nicotinic acid salvage and nucleoside salvage pathways incorporating nicotinamide riboside and nicotinic acid riboside. Key discoveries highlight a therapeutic potential for targeting NAD+ biosynthetic pathways for treatment of human diseases. A recent emergence of understanding that NAD+ homeostasis is vulnerable to aging and disease processes has stimulated testing to determine if replenishment or augmentation of cellular or tissue NAD+ can have ameliorative effects on aging or disease phenotypes. This experimental approach has provided several proof of concept successes demonstrating that replenishment or augmentation of NAD+ concentrations can provide ameliorative or curative benefits. Thus NAD+ metabolic pathways can provide key biomarkers and parameters for assessing and modulating organism health.

 

Keywords

Nicotinamide Adenine Dinucleotide; Nicotinamide riboside; Tryptophan; Vitamin B3; Nicotinic acid riboside; NADH

[Nate-2004]

 

Niagen, Nicotinamide Riboside Side Effects vs. NAD+ Benefits

 

Superfoodly

July 8, 2016

 

OK its time to get back to the core of what I do here which is post the latest research and articles surrounding NAD Repletion/Boosting. Somehow that effort has been sidelined and its time to return to what has been the core of this thread.

 

A balanced article appeared in Superfoodly. While its contents are not new it does review comments from forums like ours on LongeCity and the latest academic and medical studies.

 

"With those caveats said, it appears the hype – as least as of to date – is justified, given the many promising studies so far suggesting its ability to increase NAD+ levels. However further research and clinical trials will be needed to verify whether or not the benefits are what many researchers suspect them to be."

 

 

From the article:

 

What is the difference between resveratrol and nicotinamide riboside? Both are believed to sirtuin inhibitors, but they operate in different ways.

 

Was this a typo? Inhibitors?

Edited by Nate-2004, 12 July 2016 - 06:53 PM.

[Tom Andre F. (ex shinobi)]

 

 

Niagen, Nicotinamide Riboside Side Effects vs. NAD+ Benefits

 

Superfoodly

July 8, 2016

 

OK its time to get back to the core of what I do here which is post the latest research and articles surrounding NAD Repletion/Boosting. Somehow that effort has been sidelined and its time to return to what has been the core of this thread.

 

A balanced article appeared in Superfoodly. While its contents are not new it does review comments from forums like ours on LongeCity and the latest academic and medical studies.

 

"With those caveats said, it appears the hype – as least as of to date – is justified, given the many promising studies so far suggesting its ability to increase NAD+ levels. However further research and clinical trials will be needed to verify whether or not the benefits are what many researchers suspect them to be."

 

 

From the article:

 

What is the difference between resveratrol and nicotinamide riboside? Both are believed to sirtuin inhibitors, but they operate in different ways.

 

Was this a typo? Inhibitors?

 

 

its an error and the author seems to have some others:

 

"Is nicotinic acid the same as nicotinamide? No. The difference is that nicotinic acid is a precursor to nicotinamide." -> wrong, this is the opposite

 

"nicotinamide is that it generally doesn’t carry the nasty side effects associated with a niacin supplement overdose, such as unbalanced uric acid levels, skin flush, rapid heart beat, abdominal pain, and more (8). This is because those side effects are caused by the conversion process." -> wrong !

 

"Only some nicotinic acid converts to nicotinamide. From that, a tiny fraction converts to NAD. In other words, niacin is two conversions away from NAD while nicotinamide is only one" wrong again ! the author totally "forgot" the preiss handler pathway that is not Nampt dependent and seems to think nicotinic acid has to be converted into Nam prior to NAD+..

 

+ all the studies including the one given by Logic that show nicotinic acid is far better to increase NAD+ level than nicotinamide.

 

From that I stoped to read more, with all respect, its clear he does not know about what he speak about.

 

[Nate-2004]

1. "Is nicotinic acid the same as nicotinamide? No. The difference is that nicotinic acid is a precursor to nicotinamide." -> wrong, this is the opposite

 

2. "nicotinamide is that it generally doesn’t carry the nasty side effects associated with a niacin supplement overdose, such as unbalanced uric acid levels, skin flush, rapid heart beat, abdominal pain, and more (8). This is because those side effects are caused by the conversion process." -> wrong !

 

3. "Only some nicotinic acid converts to nicotinamide. From that, a tiny fraction converts to NAD. In other words, niacin is two conversions away from NAD while nicotinamide is only one" wrong again ! the author totally "forgot" the preiss handler pathway that is not Nampt dependent and seems to think nicotinic acid has to be converted into Nam prior to NAD+..

 

4. + all the studies including the one given by Logic that show nicotinic acid is far better to increase NAD+ level than nicotinamide.

 

1. It is? I was under the same impression that Na is a precursor to NAM. Have I been wrong all this time?

2. What's wrong with that statement in particular? I found it interesting that he attributed the flush effect to overdose.

3. Is it true that only a tiny fraction is converted to NAM? This may answer my first question above.

4. Given #3 do you think that Logic's suggestion of nasal delivery (much easier by spray than by snorting) bypass the liver's conversion to NAM?

Edited by Nate-2004, 12 July 2016 - 07:13 PM.

[Bryan_S]

 

From the article:

 

What is the difference between resveratrol and nicotinamide riboside? Both are believed to sirtuin inhibitors, but they operate in different ways.

 

Was this a typo? Inhibitors?

 

 

I think so.

 

He also glossed over some other parts here in the conversion overview.

 

Nam is an eventual product of Na after its been thru about 4 or so steps.

Edited by Bryan_S, 12 July 2016 - 07:23 PM.
image added

[Tom Andre F. (ex shinobi)]

 

1. "Is nicotinic acid the same as nicotinamide? No. The difference is that nicotinic acid is a precursor to nicotinamide." -> wrong, this is the opposite

 

2. "nicotinamide is that it generally doesn’t carry the nasty side effects associated with a niacin supplement overdose, such as unbalanced uric acid levels, skin flush, rapid heart beat, abdominal pain, and more (8). This is because those side effects are caused by the conversion process." -> wrong !

 

3. "Only some nicotinic acid converts to nicotinamide. From that, a tiny fraction converts to NAD. In other words, niacin is two conversions away from NAD while nicotinamide is only one" wrong again ! the author totally "forgot" the preiss handler pathway that is not Nampt dependent and seems to think nicotinic acid has to be converted into Nam prior to NAD+..

 

4. + all the studies including the one given by Logic that show nicotinic acid is far better to increase NAD+ level than nicotinamide.

 

1. It is? I was under the same impression that Na is a precursor to NAM. Have I been wrong all this time?

2. What's wrong with that statement in particular? I found it interesting that he attributed the flush effect to overdose.

3. Is it true that only a tiny fraction is converted to NAM? This may answer my first question above.

4. Given #3 do you think that Logic's suggestion of nasal delivery (much easier by spray than by snorting) bypass the liver's conversion to NAM?

 

 

1. No, this is the opposite due to bacterial nicotinamidase. However the thing is NAD+ is converted into Nam due to NAD+ consuming enzymes such as CD34 we discussed here. Ref: http://www.schulenbe...rticles/NAD.pdf

2. the flush for niacin is due to GPR109A activation of epidermal Langerhans cells and keratinocytes. This is an effect that is only found using niacin. NR or Nam does not cause that. GPR109A activation is proven beneficial however ref: https://www.ncbi.nlm...les/PMC1297235/ and http://molpharm.aspe...ntent/70/6/1844

3. yeah see point 1

4. I really dont know

 

Edited by Tom Andre F. (ex shinobi), 12 July 2016 - 07:36 PM.

[Bryan_S]

Research shows sirtuins regulated by NAD+ concentration, no direct NAD/NADH ratio influence

July 9, 2016

http://www.timelessl...atio-influence/

 

Timeless life mag points to a study published in March

Investigating the Sensitivity of NAD+-dependent Sirtuin Deacylation Activities to NADH.

http://www.ncbi.nlm....pubmed/26861872

http://www.jbc.org/content/291/13/7128

 

"Abstract

Protein lysine posttranslational modification by an increasing number of different acyl groups is becoming appreciated as a regulatory mechanism in cellular biology. Sirtuins are class III histone deacylases that use NAD(+)as a co-substrate during amide bond hydrolysis. Several studies have described the sirtuins as sensors of the NAD(+)/NADH ratio, but it has not been formally tested for all the mammalian sirtuinsin vitro To address this problem, we first synthesized a wide variety of peptide-based probes, which were used to identify the range of hydrolytic activities of human sirtuins. These probes included aliphatic ϵ-N-acyllysine modifications with hydrocarbon lengths ranging from formyl (C1) to palmitoyl (C16) as well as negatively charged dicarboxyl-derived modifications. In addition to the well established activities of the sirtuins, "long chain" acyllysine modifications were also shown to be prone to hydrolytic cleavage by SIRT1-3 and SIRT6, supporting recent findings. We then tested the ability of NADH, ADP-ribose, and nicotinamide to inhibit these NAD(+)-dependent deacylase activities of the sirtuins. In the commonly used 7-amino-4-methylcoumarin-coupled fluorescence-based assay, the fluorophore has significant spectral overlap with NADH and therefore cannot be used to measure inhibition by NADH. Therefore, we turned to an HPLC-MS-based assay to directly monitor the conversion of acylated peptides to their deacylated forms. All tested sirtuin deacylase activities showed sensitivity to NADH in this assay. However, the inhibitory concentrations of NADH in these assays are far greater than the predicted concentrations of NADH in cells; therefore, our data indicate that NADH is unlikely to inhibit sirtuinsin vivo These data suggest a re-evaluation of the sirtuins as direct sensors of the NAD(+)/NADH ratio. 

© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

KEYWORDS: 

acetylation; fatty acid; histone deacetylase (HDAC); lysine myristoylation; lysine palmitoylation; nicotinamide adenine dinucleotide (NAD+); nicotinamide adenine dinucleotide (NADH); post-translational modification (PTM); protein acylation; sirtuin"

[Bryan_S]

Emerging Therapies for Mitochondrial Disorders

Helen Nightingale; Gerald Pfeffer; David Bargiela; Rita Horvath; Patrick F. Chinnery

Disclosures

 

Brain. 2016;139(6):1633-1648. 

http://www.medscape....rticle/864814_5

 

"Small Molecule Pharmaceuticals

 

Future pharmaceutical development focusing on disease-specific or patient-specific molecular targets aimed at boosting residual mitochondrial function is likely to be more successful than previous approaches, which were generally based on a non-specific bypass or amelioration of defective components of the respiratory chain.

 

Modulating NAD+ Bioavailability

 

The balance between NAD+ and NADH is crucial to the process of oxidative phosphorylation. With increased NAD+ bioavailability enhancing oxidative phosphorylation. Indeed NAD+ supplementation with nicotinamide riboside has produced promising biochemical and clinical improvements in two mitochondrial myopathy murine models; a nuclear gene (Sco2) knockout/knockin mouse (Cerutti et al., 2014), and the Deletor mouse possessing a nuclear gene mutation resulting in mtDNA deletions (Khan et al., 2014)."

Edited by Bryan_S, 12 July 2016 - 07:58 PM.

[Harkijn]

 

Niagen, Nicotinamide Riboside Side Effects vs. NAD+ Benefits

 

Superfoodly

July 8, 2016

 

OK its time to get back to the core of what I do here which is post the latest research and articles surrounding NAD Repletion/Boosting. Somehow that effort has been sidelined and its time to return to what has been the core of this thread.

 

A balanced article appeared in Superfoodly. While its contents are not new it does review comments from forums like ours on LongeCity and the latest academic and medical studies.

 

"With those caveats said, it appears the hype – as least as of to date – is justified, given the many promising studies so far suggesting its ability to increase NAD+ levels. However further research and clinical trials will be needed to verify whether or not the benefits are what many researchers suspect them to be."

 

This article mentions aspartic acid as an NAD precursor. Is this correct, or another mistake by the author? I read up on aspartic acid but cannot find any reference  to NAD sofar. If it is a precursor  there might be some useful synergy between taking NR and taking magnesium aspartaat. Any ideas?

 

Edit: spelling mistake.

Edited by harkijn, 13 July 2016 - 11:26 AM.

[Bryan_S]

 

 

Niagen, Nicotinamide Riboside Side Effects vs. NAD+ Benefits

 

Superfoodly

July 8, 2016

 

OK its time to get back to the core of what I do here which is post the latest research and articles surrounding NAD Repletion/Boosting. Somehow that effort has been sidelined and its time to return to what has been the core of this thread.

 

A balanced article appeared in Superfoodly. While its contents are not new it does review comments from forums like ours on LongeCity and the latest academic and medical studies.

 

"With those caveats said, it appears the hype – as least as of to date – is justified, given the many promising studies so far suggesting its ability to increase NAD+ levels. However further research and clinical trials will be needed to verify whether or not the benefits are what many researchers suspect them to be."

 

This article mentions aspartic acid as an NAD precursor. Is this correct, or another mistake by the author? I read up on aspartic acid but cannot find any reference  to NAD sofar. If it is a precursor  there might be some useful synergy between taking NR and taking magnesium aspartaat. Any ideas?

 

Edit: spelling mistake.

 

 

Bacterial NAD precursor

NR was first described in 1944 as a growth factor, termed Factor V, for Haemophilus influenza, a bacterium that lives in and depends on blood. Factor V, purified from blood was shown to exist in three forms: NAD+, NMN and NR. NR was the compound that led to the most rapid growth of this bacterium.[6] Notably, H. influenza cannot grow on nicotinic acid, nicotinamide, tryptophan or aspartic acid, which were the previously known precursors of NAD+.[7]

 

 

De Novo Pathways in Humans Microbes and Bacteria

The de novo pathway in most bacteria and plants starts from aspartate. The aspartate pathway is anaerobic, and molecular oxygen is not required (Kurnasov et al., 2003). The reaction of aspartate and dihydroxyacetone-phosphate leads to efficient synthesis of QA, catalyzed by aspartate oxidase and QA synthase (Fig. 2). Alternatively, yeast, humans, and some bacterial microbes make QA via an aerobic pathway from tryptophan (Kurnasov et al., 2003). Molecular oxygen as a substrate oxidizes tryptophan to downstream metabolites of the kynurenine pathway, 3-hydroxyanthranilate, and finally QA (Fig. 3) (Kurnasov et al., 2003). The respective de novo pathways are important sources of vitamin B₃ in most bacteria and in humans. In humans, 1 of 67 mg of tryptophan eventually ends up as nicotinamide if another B₃ source is not available in the diet (Fukuwatari et al., 2004).

[Harkijn]

Thank you, will start reading!

[Bryan_S]

10th World Congress on Polyphenols Applications: Porto Polyphenols 2016

Effects of marginal dietary vitamin B3 levels on metabolic flexibility and anti-oxidant response in mice exposed to a high fat diet.

Maria, HEGEMAN (1), Wenbiao, SHI (1), Jing, TANG (1), Dorien, VAN DARTEL (1), Hans, SWARTS (1), Jaap, KEIJER (1)

 

1: Wageningen University, Wageningen, the Netherlands, Netherlands

 

"Abstract

Objective: Nicotinamide adenine dinucleotide (NAD+) preserves cellular redox state and basal energy metabolism. Maintenance of NAD+ levels is dependent on dietary vitamin B3 levels, which is a NAD+ precursor. Although it is evident that severe vitamin B3 deficiency causes disease, little is known on the physiological consequences of marginal vitamin B3 levels. Therefore, the effects of marginal dietary vitamin B3 levels on metabolic flexibility and anti-oxidant response were studied.

 

Methods: Adult male mice were exposed to a HFD containing 5 or 30 mg nicotinamide riboside (NR) per kg diet. Body weight, lean mass, fat mass and feed intake were measured weekly. After 14 weeks, metabolic flexibility was assessed with a fasting and refeeding challenge using indirect calorimetry. After 15 weeks, the anti-oxidant response was determined in epididymal white adipose tissue.

 

Results: Whole body physiological parameters were not affected by dietary NR. Upon a fasting and refeeding challenge, the delta respiratory exchange ratio (ΔRER) was higher when comparing 30 to 5 mg/kg NR. Expression levels of anti-oxidant genes were enhanced in the 30 mg/kg group compared to the 5 mg/kg group.

 

Conclusion: Current results suggest that 30 mg/kg NR increases metabolic flexibility and anti-oxidant levels compared to 5 mg/kg NR."

 

 

Our Friend at TimelessLife reviewed the study @ Low dose Nicotinamide Riboside improves metabolic health and anti-oxidant response in mice

[Nate-2004]

 

10th World Congress on Polyphenols Applications: Porto Polyphenols 2016

Effects of marginal dietary vitamin B3 levels on metabolic flexibility and anti-oxidant response in mice exposed to a high fat diet.

Maria, HEGEMAN (1), Wenbiao, SHI (1), Jing, TANG (1), Dorien, VAN DARTEL (1), Hans, SWARTS (1), Jaap, KEIJER (1)

 

1: Wageningen University, Wageningen, the Netherlands, Netherlands

 

"Abstract

Objective: Nicotinamide adenine dinucleotide (NAD+) preserves cellular redox state and basal energy metabolism. Maintenance of NAD+ levels is dependent on dietary vitamin B3 levels, which is a NAD+ precursor. Although it is evident that severe vitamin B3 deficiency causes disease, little is known on the physiological consequences of marginal vitamin B3 levels. Therefore, the effects of marginal dietary vitamin B3 levels on metabolic flexibility and anti-oxidant response were studied.

 

Methods: Adult male mice were exposed to a HFD containing 5 or 30 mg nicotinamide riboside (NR) per kg diet. Body weight, lean mass, fat mass and feed intake were measured weekly. After 14 weeks, metabolic flexibility was assessed with a fasting and refeeding challenge using indirect calorimetry. After 15 weeks, the anti-oxidant response was determined in epididymal white adipose tissue.

 

Results: Whole body physiological parameters were not affected by dietary NR. Upon a fasting and refeeding challenge, the delta respiratory exchange ratio (ΔRER) was higher when comparing 30 to 5 mg/kg NR. Expression levels of anti-oxidant genes were enhanced in the 30 mg/kg group compared to the 5 mg/kg group.

 

Conclusion: Current results suggest that 30 mg/kg NR increases metabolic flexibility and anti-oxidant levels compared to 5 mg/kg NR."

 

 

Our Friend at TimelessLife reviewed the study @ Low dose Nicotinamide Riboside improves metabolic health and anti-oxidant response in mice

 

 

Yet another article suggesting a significantly higher dose than what's on the bottle to achieve results. Why does the title of his article say "low dose"? That's 2,340mg for me at 78kg.

 

EDIT: Ooops, I forgot the formula Stefan mentions below. I'm 78kg so that would be 180mg, so nm it is low dose.

Edited by Nate-2004, 14 July 2016 - 04:51 PM.

[stefan_001]

 

 

10th World Congress on Polyphenols Applications: Porto Polyphenols 2016

Effects of marginal dietary vitamin B3 levels on metabolic flexibility and anti-oxidant response in mice exposed to a high fat diet.

Maria, HEGEMAN (1), Wenbiao, SHI (1), Jing, TANG (1), Dorien, VAN DARTEL (1), Hans, SWARTS (1), Jaap, KEIJER (1)

 

1: Wageningen University, Wageningen, the Netherlands, Netherlands

 

"Abstract

Objective: Nicotinamide adenine dinucleotide (NAD+) preserves cellular redox state and basal energy metabolism. Maintenance of NAD+ levels is dependent on dietary vitamin B3 levels, which is a NAD+ precursor. Although it is evident that severe vitamin B3 deficiency causes disease, little is known on the physiological consequences of marginal vitamin B3 levels. Therefore, the effects of marginal dietary vitamin B3 levels on metabolic flexibility and anti-oxidant response were studied.

 

Methods: Adult male mice were exposed to a HFD containing 5 or 30 mg nicotinamide riboside (NR) per kg diet. Body weight, lean mass, fat mass and feed intake were measured weekly. After 14 weeks, metabolic flexibility was assessed with a fasting and refeeding challenge using indirect calorimetry. After 15 weeks, the anti-oxidant response was determined in epididymal white adipose tissue.

 

Results: Whole body physiological parameters were not affected by dietary NR. Upon a fasting and refeeding challenge, the delta respiratory exchange ratio (ΔRER) was higher when comparing 30 to 5 mg/kg NR. Expression levels of anti-oxidant genes were enhanced in the 30 mg/kg group compared to the 5 mg/kg group.

 

Conclusion: Current results suggest that 30 mg/kg NR increases metabolic flexibility and anti-oxidant levels compared to 5 mg/kg NR."

 

 

Our Friend at TimelessLife reviewed the study @ Low dose Nicotinamide Riboside improves metabolic health and anti-oxidant response in mice

 

 

Yet another article suggesting a significantly higher dose than what's on the bottle to achieve results. Why does the title of his article say "low dose"? That's 2,340mg for me at 78kg.

 

you forget the conversion from mice to humans according to:

 

Our Friend at TimelessLife reviewed the study @ Low dose Nicotinamide Riboside improves metabolic health and anti-oxidant response in mice

 

"approximately 170mg daily nicotinamide riboside dosing for a person weighing 70kg"

 

 

Edited by stefan_001, 14 July 2016 - 04:37 PM.