2255 replies to this topic

[Journey2016]

You tube has many clips of peoples view after Nad IV

Worth a look just to get a better picture

https://m.youtube.co...h?v=AgehQhK8twQ

[Nate-2004]

For one thing NAD+ getting "into the body" vs getting "into the cell" are two completely different things. Hell, getting some things past the blood brain barrier is a challenge that only now is being resolved by expensive High Frequency Ultrasound machines. For another, that people report positive benefits about something says nothing to the truth or falsehood of any given claim. The placebo effect is often a major factor in things like this. So is bias. This is why science sorts these things out through large sample sizes, controls, p values, independent replication as well as in vitro analysis. 

 

Did you know that in one study on adverse childhood experiences (ACE) they actually found that the survey itself caused a positive change in mood and a relief from traumatic history?  Even if you don't have an illness, simply visiting the doctor and having him check you out can have positive effects on mood and feelings of well being.

 

So whether you're getting a coffee enema or a NAD+ IV, acupuncture or a massage, and then you feel better, does nothing to support the veracity of claims made about whatever procedure is being done. Testimonial evidence is often flimsy and only a queue for someone to perform actual scientific research.

 

As frustrated as I am by the lack of science and research funding, hesitation around human study, false ethics, and even more so by the ivory tower corruption of the entire incentives system when it comes to how research is conducted, funded, published, orchestrated, etc, we should still remain skeptical about things... Optimistically and open mindedly skeptical, but skeptical.

Edited by Nate-2004, 01 April 2017 - 03:13 PM.

[soulprogrammer]

Why this human trial is not mentioned in aboutnr? I think it is pretty important too.

 

Safety and Tolerability of the Nutritional Supplement, Nicotinamide Riboside, in Systolic Heart Failure
Tian, Rong    O'Brien, Kevin Douglas   
University of Washington, Seattle, WA, United States

 

Public Health Relevance

The goal of this research project is to develop innovative approaches for heart failure care by translating the laboratory findings in mitochondrial biology and function. We will test a strategy of protecting the heart from mitochondrial dysfunction by increasing NAD+ level in patients with heart failure via dietary supplementation of nicotinamide riboside (NR). The proposed study will determine the safety and tolerability of NR in heart failurepatients.

 

 

http://grantome.com/...R21-HL126209-01

 

 

 

 

Edited by soulprogrammer, 01 April 2017 - 04:40 PM.

[soulprogrammer]

Wait, I use the website to search for Nicotinamide Riboside, it showed a lot of results??

 

Why so many grants given for NR research? Are the research currently ongoing or cancel? Or all these actually old research completed?

 

 

http://grantome.com/...namide riboside

 

NIH 2016
R21 CA Phase II Trial of Nicotinamide Riboside for Relief of Taxane-Induced Sensory Neuropathy
Hammond, Donna L.; Thomas, Alexandra / University of Iowa $232,181 NIH 2017
R01 NS NAD, PGC-1alpha and SIRT3 as Therapeutics Targets for Huntington's Disease
Beal, M Flint / Weill Medical College of Cornell University $333,702 NIH 2015
R21 HL Safety and Tolerability of the Nutritional Supplement, Nicotinamide Riboside, in Systolic Heart Failure
O'Brien, Kevin Douglas; Tian, Rong / University of Washington $231,750 NIH 2015
R21 HL Safety and Tolerability of the Nutritional Supplement, Nicotinamide Riboside, in Systolic Heart Failure
O'Brien, Kevin Douglas; Tian, Rong / University of Washington $115,873 NIH 2016
R01  Nicotinamide Riboside and NAD+: Modulation of Sirtuins and Reactive Oxygen
Sauve, Anthony A. / Weill Medical College of Cornell University   NIH 2016
R01 DK NAD+ and SIRT1 Regulate Mitochondrial Function in Diabetic Neuropathy
Russell, James W. / University of Maryland Baltimore $413,528 NIH 2016
R01 NS NAD, PGC-1alpha and SIRT3 as Therapeutics Targets for Huntington's Disease
Beal, M Flint / Weill Medical College of Cornell University $333,702 NIH 2016
R01 GM Understanding the Regulatioin of NAD+Homeostasis and Signaling
Lin, Su-Ju / University of California Davis $310,097 NIH 2015
R01 GM Nicotinamide Riboside and NAD+: Modulation of Sirtuins and Reactive Oxygen
Sauve, Anthony A. / Weill Medical College of Cornell University $322,050 NIH 2016
K01 GM Metabolomic Biomarkers of a Nutritional Intervention to Prevent Weight Gain
Grossmann, Ruth Elizabeth / University of Iowa $154,683 NIH 2016
R01  Targeting NAD Metabolism to Improve Glucose Homeostasis in Obesity and Aging
Baur, Joseph A. / University of Pennsylvania   NIH 2016
ZIA  Mitochondrial DNA Repair Processes In Oxidative Stress And Aging
Bohr, Vilhelm A. / Aging   NIH 2016
P01  Modulating Energy Metabolism as a Therapeutic Approach for Alzheimer's Disease
Beal, M Flint / Winifred Masterson Burke Med Research Institute   NIH 2015
R01 NS NAD, PGC-1alpha and SIRT3 as Therapeutics Targets for Huntington's Disease
Beal, M Flint / Weill Medical College of Cornell University $370,781

 

[bluemoon]

Why this human trial is not mentioned in aboutnr? I think it is pretty important too.

 

Safety and Tolerability of the Nutritional Supplement, Nicotinamide Riboside, in Systolic Heart Failure
Tian, Rong    O'Brien, Kevin Douglas   
University of Washington, Seattle, WA, United States

 

 

This study has been mentioned here a couple of times. It isn't clear if the trial is under way or how much NR is used. I don't see it listed under the official list of trials that Bryan_S has put up.   

[Michael]

I had spent the last 18months or so looking into IV NAD+ for addiction, if it did not work then why are there so manny success storys and online videos of people saying how its changed them, brain fog gone, mental clarity , energy,wellbeing and no cravings ect

The reason why we have medical science — and the reason why respectable doctors no longer bleed people for infections, give people hepatotoxic and nephrotoxic creosote bush to ineffectually "treat" tuberculosis, administer Ayurvedic herbal concoctions intentionally compounded with heavy metals, or drill holes in their patients' skulls to deal with seizures — is that we figured out that anecdotes aren't evidence and that biological plausibility is an important criterion for scientific credibility. Many patients swore that "liberation therapy" was a miracle cure for MS. Scientific testing says it isn't. Many patients swear Hulda Clark's electric parasite zappers cured their cancers. Most of them didn't have cancer in the first place. Stanislaw Burzynski can point to patients who will swear that antineoplastons cured their inoperable disease:it doesn't (really).
 

Somthing i did have some to some degree when i first started on NR but it dropped down a few levels after 2 weeks ans just keeps me on a low level - positive , energetic feeling.

 
A sense of energy, improved mood, better sleep, sense of well-being, and relief from pain are the kinds of subjective responses that are most susceptible to placebo and Hawthorne effects.

Edited by Michael, 01 April 2017 - 06:48 PM.

[Andey]

 

 
A sense of energy, improved mood, better sleep, and relief from pain are the kinds of subjective responses that are most susceptible to placebo and Hawthorne effects.

 

Good point )

It also important though to remember that using a placebo effect is very beneficial.

In some cases expensive drugs with serious side effects are only 10-20% more effective than a placebo. 

 

And its always a possibility that some of those therapies that you mention as faux are actually working. We just dont know and nobody is interested enough to prove it. tDCS and PEMF for example are also forms of zapping and they really works and proven. Some mobility exercises are more effective than surgeries. You could not market and sell exercise or china sucking cups therapy etc.

  I often look on what drugs and therapies professional athletes use because its very little bullshit there. Same thing for industrial veterinary medicine. Its where marketing dont work, its either working or not.

[ambivalent]

 

I had spent the last 18months or so looking into IV NAD+ for addiction, if it did not work then why are there so manny success storys and online videos of people saying how its changed them, brain fog gone, mental clarity , energy,wellbeing and no cravings ect

The reason why we have medical science — and the reason why respectable doctors no longer bleed people for infections, give people hepatotoxic and nephrotoxic creosote bush to ineffectually "treat" tuberculosis, administer Ayurvedic herbal concoctions intentionally compounded with heavy metals, or drill holes in their patients' skulls to deal with seizures — is that we figured out that anecdotes aren't evidence and that biological plausibility is an important criterion for scientific credibility. Many patients swore that "liberation therapy" was a miracle cure for MS. Scientific testing says it isn't. Many patients swear Hulda Clark's electric parasite zappers cured their cancers. Most of them didn't have cancer in the first place. Stanislaw Burzynski can point to patients who will swear that antineoplastons cured their inoperable disease:it doesn't (really).
 

Somthing i did have some to some degree when i first started on NR but it dropped down a few levels after 2 weeks ans just keeps me on a low level - positive , energetic feeling.

 
A sense of energy, improved mood, better sleep, sense of well-being, and relief from pain are the kinds of subjective responses that are most susceptible to placebo and Hawthorne effects.

 

​'is that we figured out that anecdotes aren't evidence':

 

this is not true, they are simply not proof.

 

Suppose you and a few in your community reasoned a particular supplement would be beneficial for some condition you or someone close to you had. Others administered it before you and flagged it to have very dramatically worsened conditions. You subsequently administer the dose: the same response occurred in your subject as in others.

 

Would you claim in defence to have no evidence that this would happen? Of course not.

 

Anecdotes are evidence, in so much that they measure and reduce uncertainty but they seldom establish proof. In law we know that evidence is submittable without it being of itself proof.

[Florian E.]

I have put some of the doubts to a well reapected nad clinic in the US and the reply i got was

"You would think, but that isn't what we see clinically. IV and seems to penetrate the nervous system more than NR. Could 't explain it more than that"

Maybe expecting a better responce for spending a huge amount of money. But my u understanding and view based on huge online research is that people are getting huge benafits and results from flooding there system via IV.

 

I also mailed a dozen of drip clinics yesterday and asked them if their IV NAD would only increase extracellular NAD+ or also intracellular NAD+

First reply i got so far was:

 

"It's very hard to measure intracellular or extracellular NAD+ levels. In fact I can't think of a lab that does that. We can measure indirectly oxidative phosphorylation (ATP production in the electron transport chain inside mitochondria) indexes. One would be the pyruvate:lactate ratio. If this improves then we know the mitochondria are functioning more efficiently and the NAD+ is working."

 

Is anyone able to evaluate this indirect measurement ?

[Journey2016]

I have put some of the doubts to a well reapected nad clinic in the US and the reply i got was

"You would think, but that isn't what we see clinically. IV and seems to penetrate the nervous system more than NR. Could 't explain it more than that"

Maybe expecting a better responce for spending a huge amount of money. But my u understanding and view based on huge online research is that people are getting huge benafits and results from flooding there system via IV.

I also mailed a dozen of drip clinics yesterday and asked them if their IV NAD would only increase extracellular NAD+ or also intracellular NAD+
First reply i got so far was:

"It's very hard to measure intracellular or extracellular NAD+ levels. In fact I can't think of a lab that does that. We can measure indirectly oxidative phosphorylation (ATP production in the electron transport chain inside mitochondria) indexes. One would be the pyruvate:lactate ratio. If this improves then we know the mitochondria are functioning more efficiently and the NAD+ is working."

Is anyone able to evaluate this indirect measurement ?

I was so passed on this info


While a mammalian mitochondrial transporter for NAD+ has not yet been identified a recent study indicated that exogenous NAD can cross the plasma membrane and elevate mitochondrial NAD levels in mammalian cells enhancing mitochondrial oxygen consumption and ATP production suggesting that mitochondrial NAD transport mechanism/s do exist and that mitochondria can rapidly increase its NAD pool when the cytoplasmic availability of NAD increases.
See Pittelli M, Felici R, Pitozzi V, Giovannelli L, Bigagli E, Cialdai F, Romano
G, Moroni F, Chiarugi A (2011) Pharmacological effects of exogenous
NAD on mitochondrial bioenergetics, DNA repair, and apoptosis. Mol
Pharmacol 80:1136-1146. doi:10.1124/mol.111.073916mol.111.073916

[MikeDC]

This is about NAD transport from cytoplasm into Mitochandria.
Cytoplasm is inside a cell membrane

[Journey2016]

I have also been passed on this link for NAD nasal

https://goo.gl/forms/V2eHmVWd9TwhCN5n2

[Michael]

 

I was so passed on this info

While a mammalian mitochondrial transporter for NAD+ has not yet been identified a recent study indicated that exogenous NAD can cross the plasma membrane and elevate mitochondrial NAD levels in mammalian cells enhancing mitochondrial oxygen consumption and ATP production suggesting that mitochondrial NAD transport mechanism/s do exist and that mitochondria can rapidly increase its NAD pool when the cytoplasmic availability of NAD increases.
See Pittelli M, Felici R, Pitozzi V, Giovannelli L, Bigagli E, Cialdai F, Romano
G, Moroni F, Chiarugi A (2011) Pharmacological effects of exogenous
NAD on mitochondrial bioenergetics, DNA repair, and apoptosis. Mol
Pharmacol 80:1136-1146. doi:10.1124/mol.111.073916

 
This is about NAD transport from cytoplasm into Mitochandria.

 

No (or at least, not exclusively): they are reporting that NAD+ crosses the plasma (cell) membrane as well as being transported from the cytoplasm into mt once it gets there:
 

Here, we report that intracellular NAD contents increased upon exposure of cell lines or primary cultures to exogenous NAD (eNAD). NAD precursors [nicotinamide, NMN, NR] could not reproduce the effects of eNAD, and they were not found in the incubating medium containing eNAD, thereby suggesting direct cellular eNAD uptake.
 

 
We found that in mitochondria of cells exposed to eNAD, NAD and NADH as well as oxygen consumption and ATP production were increased. Conversely, DNA repair, a well known NAD-dependent process, was unaltered upon eNAD exposure. We also report that eNAD conferred significant cytoprotection from apoptosis triggered by staurosporine, C2-ceramide, or N-methyl-N′-nitro-N-nitrosoguanidine. In particular, eNAD reduced staurosporine-induced loss of mitochondrial membrane potential and ensuing caspase activation. ...

 

 
I've not read the paper and therefore can't offer a view on how strongly I think they've proved this.

Edited by Michael, 18 June 2019 - 06:42 PM.
https image

[MikeDC]

https://www.ncbi.nlm...ubmed/16720381/

This paper also says NAD+ can cross cell membrane. If NAD can cross cell membrane, NMN can too.

There is a serious contraversy about this.

[NRvsNMN]

Hi, I am Korean. i joined LongeCity today.  

 

i was searching NMN and found a company which recently bought a mass production method of NMN from a professor of a university.

 

i dont know about the production efficiency of that    but the company bought it at about 5M dollars in December 2016. 

 

i hope the price of NMN to go down in the near future.

 

 

instead of NMN, i ordered NR.  i am going to take 250mg of NR everyday.

 

 

 

 

Do you want to know the name of the company? this company is located in Korea.

 

the name is aribio.

 

http://www.dhnews.co...tml?idxno=67359   -  news about the deal of 5M.

 

http://www.aribio.com   -     homepage of  the company

 

this company is not listed on Korea stock market yet.

 

 

[midas]

 

 

http://www.dhnews.co...tml?idxno=67359   -  news about the deal of 5M.

 

 

 

Using a full page translator I see no mention of NMN or a University professor in that link?

 

 

(SNN), resveratrol, glutathione (GSH), and glutathione (GSH), which utilize AriBio Co., Ltd. and ' 5-aminolevulinate (ALA), etc.) '.

The technology transfer agreement with the technology developed by the research team of Professor Lee Jung-Kook of Sogang University was carried out on the 27th.

This technology was supported by the future convergence technology Pioneer business, which is being held in the future. As technology transfer, royalty fees include fixed-rate technical fee of 500 million won, sales proceeds of 5 billion won, and Gyeongsang royalties, totaling W5.5 billion.

This technique can produce a biosynthetic reaction module module by immobilizing the enzymes involved in the biosynthesis process, and produce the desired high value-added substance through combination with the optic device host reaction module. In addition, when additional additional high-value-added materials are desired, a separate biosynthetic module module can be manufactured, and the high-value-added material can be produced through a combination with the optic device cluster reaction module.

Professor Lee Jung-kook of Sogang University said, "The technology to utilize the optic device follicles for mass production of high value-added materials is an innovative source technology that overcomes the shortcomings of productivity reduction in bio-application using synthetic biology. Wide range. " In addition, he said, "The transfer of the technology is meaningful in realizing the technology of solar energy which is the ultimate energy source of the next generation in the industrial sector in the early stage."

"By securing high-value-added mass production platform technology using optical device cans, we will enter the next-generation natural product raw materials market in earnest," said Sung Su-hyun, representative director of ArioBio. "In particular, we are developing cosmetics based on total anti- aging substances, I expect a great synergy effect. "

Edited by midas, 02 April 2017 - 09:33 PM.

[bluemoon]

 

 
A sense of energy, improved mood, better sleep, sense of well-being, and relief from pain are the kinds of subjective responses that are most susceptible to placebo and Hawthorne effects.

 

 

The New Yorker recently quoted Guarante about what Basis has done for him:

 

 

There are no clinical data yet that Basis does anything useful in humans, so, when I visited Guarente in his office at M.I.T., I asked if he’d noticed any effects from taking it. “I have,” he said. He glanced at Elysium’s P.R. person. “Can I say it? It is O.K.?” She gave a calibrated nod, and he said, “My fingernails grow faster.” And what does that mean? “I don’t know. But something.”

 

 

There! That ain't a placebo effect! Finally ironclad proof that NR extends longev....finger nails.

[NRvsNMN]

 

http://www.dhnews.co...tml?idxno=67359   -  news about the deal of 5M.

 

Using a full page translator I see no mention of NMN or a University professor in that link?

 

 

(SNN), resveratrol, glutathione (GSH), and glutathione (GSH), which utilize AriBio Co., Ltd. and ' 5-aminolevulinate (ALA), etc.) '.

The technology transfer agreement with the technology developed by the research team of Professor Lee Jung-Kook of Sogang University was carried out on the 27th.

This technology was supported by the future convergence technology Pioneer business, which is being held in the future. As technology transfer, royalty fees include fixed-rate technical fee of 500 million won, sales proceeds of 5 billion won, and Gyeongsang royalties, totaling W5.5 billion.

 

 

i think there are some errors in the translator.  and  you don't need to translate the news and can see nicotinamide mononucleotide(NMN) written by english 

You didn't translate this sentence.  

 

서강대학교 산학협력단(단장 이희성)이 ㈜아리바이오(대표  성수현)와 ‘광기구 소낭’을 활용한 ‘고부가가치 물질(nicotinamide mononucleotide(NMN), resveratrol, glutathione (GSH), 5-aminolevulinate (ALA) 등)’의 대량생산 기술 이전 계약을 체결했다.   

 

 

 

Professor Lee jung-kook of sogang University developed the technology.

 

 

 

Edited by Michael, 03 April 2017 - 02:32 PM.

[MikeDC]

Younger skin, better metabolic parameters, and ataxia cure are not placedo effects.

[Bryan_S]

What's the confusion "Extracellular NMN dephosphorylates to NR" to cross the cell membrane. This is the most recent info I can find. 
 
NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells
https://brenner.lab....Ratajczak16.pdf
 
"Irrespective of the circulating NMN concentration, our work indicates that NMN dephosphorylation to NR constitutes a critical step in order to act as an exogenous NAD+ precursor. This is sustained by several studies suggesting that the extracellular receptor CD73 could act as a potential NR-releasing enzyme15. CD73 possesses pyrophosphates and 50 -ectonucleotidase activities that enable the utilization of extracellular NAD+ and NMN by converting them to NR, which would then enter the cell for NAD+ synthesis15. In line with this, CD73 silencing blocks the use of NMN as an extracellular NADþ precursor17. Our NRK1 gain- and loss-of-function models provide further evidence that NMN is extracellularly dephosphorylated to NR for its utilization as a NAD+ precursor. If NMN were directly incorporated into the cell, its conversion to NAD+ would only require NMNAT and not depend upon NRK1 activity. These data, together with our data on CMP inhibition and kinetic studies using tracer compounds, provide compelling evidence for the extracellular conversion of NMN to NR for subsequent conversion to NAD+ through the NRK pathway. Though yeast cells express a dedicated NR transporter35, most of the evidence suggests that mammalian cells rely upon equilibrative nucleoside transporters (ENTs) to import NR16,17. Inhibition of ENTs also largely prevented NR- induced NAD+ synthesis in our F3T3-NRK1 cells (Supplemen- try Fig. 5a). Accordingly, NMN was unable to generate NAD+ when ENTs where pharmacologically blocked16,17, indicating that NMN extracellular dephosphorylation is not a side reaction occurring concomitant with NMN direct transport but is the exclusive pathway for utilization of extracellular NMN in NAD+ synthesis."
 
​It appears extracellular NAD will be metabolized it just doesn't take the most efficient path but it's not wasted. Now think about where  extracellular NAD would come from naturally? Also why might it be useful? This article suggests it might be used to signal injury. https://www.ncbi.nlm...les/PMC2096762/
 
One thing for sure it doesn't normally stay intact thru the digestive track and our biggest source of NAD is red meat. NAM is the most prevalent result of meats digestion.
 
I tend to think of NAD+ and its derivatives as intra- and extra-cellular Ca2+-mobilizing molecules. In that realm it's a cell signaling agent most possibly for injury. http://www.biochemj....ontent/382/3/E5
 

 
Extracellular NAD(P) metabolism and leukocyte trafficking
http://www.nature.co...ll/nri1705.html
 
So our friend CD38 is showing its head again. Remember CD38 increases with age and cell senescence. So the roll of extracellular NAD has a purpose. It does different things in different locations. Just keep the relationships in mind. Eventually NAD levels are going to crash which is why we all read these studies looking for answers.
 

 
There is much more to this story which is fascinating, keep in mind NR has 2 paths. One NRK1 is available in all cells and NRK2 is expressed in injured cells particularly in skeletal and cardiac muscle.
 
there are other studies
https://www.ncbi.nlm...les/PMC4109396/
 
 
As always JMHO

Edited by Michael, 18 June 2019 - 05:52 PM.
https for images

[midas]

 

 

 

 

http://www.dhnews.co...tml?idxno=67359   -  news about the deal of 5M.

 

 

 

 

 

i think there are some errors in the translator.  and  you don't need to translate the news and can see nicotinamide mononucleotide(NMN) written by english 

You didn't translate this sentence.  

 

서강대학교 산학협력단(단장 이희성)이 ㈜아리바이오(대표  성수현)와 ‘광기구 소낭’을 활용한 ‘고부가가치 물질(nicotinamide mononucleotide(NMN), resveratrol, glutathione (GSH), 5-aminolevulinate (ALA) 등)’의 대량생산 기술 이전 계약을 체결했다.   

 

 

 

Professor Lee jung-kook of sogang University developed the technology.

 

 

Ah, thank you, yes the translator I used missed it....

[soulprogrammer]

Nicotinamide Phosphoribosyltransferase in Smooth Muscle Cells Maintains Genome

Integrity, Resists Aortic Medial Degeneration and Is Suppressed in Human Thoracic

Aortic Aneurysm Disease

 

Alanna Watson1,3, Zengxuan Nong1, Hao Yin1, Caroline O’Neil1, Stephanie Fox5, Brittany Balint4, Linrui

Guo5, Oberdan Leo8, Michael W. A. Chu5, Robert Gros1,6, J. Geoffrey Pickering1,2,3,4

1Robarts Research Institute; 2Departments of Medicine (Cardiology); 3Biochemistry; 4Medical

Biophysics; 5Surgery, 6Department of Physiology and Pharmacology, The University of Western Ontario,

London Health Sciences Centre, London, Canada, and; 8Department of Molecular Biology, Université

Libre de Bruxelles, Gosselies, Belgium

 

 

Can someone please read this paper and explain in simple human layman language? So hard to understand, so many technical jargons? In the paper, it mentioned about NR, not a lot though, so does NR improve Human Thoracic Aortic Aneurysm Disease or what??

 

 

 

Edited by soulprogrammer, 03 April 2017 - 05:56 AM.

[MikeDC]

The oaper says the disease and the NAMPT concentration has inverse correlation. Which means the disease Coorelation with low NAD+. Niagen might be able to prevent and cure the disease. But it was not tested

[soulprogrammer]

What about this picture? Can you explain what does it means/imply? Gosh, I wish I have a medical degree...

 

Edited by soulprogrammer, 03 April 2017 - 12:23 PM.

[MikeDC]

I think A says after NAMPT gene is deleted, DNA damage is more severe.
B says NR increases DNA repair ability. There is little DNA repair ability with NAMPT gene deleted. But NR can rescue it. The injection of agiotension ii caused a big response of DNA repair

Edited by MikeDC, 03 April 2017 - 12:37 PM.

[PeaceAndProsperity]

I think A says after NAMPT gene is deleted, DNA damage is more severe.
B says NR increases DNA repair ability. There is little DNA repair ability with NAMPT gene deleted. But NR can rescue it. The injection of agiotension ii caused a big response of DNA repair

Who would have thought that vitamin B3 was such a powerful vitamin?

 

[Michael]

I think A says after NAMPT gene is deleted, DNA damage is more severe.
B says NR increases DNA repair ability. There is little DNA repair ability with NAMPT gene deleted. But NR can rescue it. The injection of agiotension ii caused a big response of DNA repair

 

Sort of, but that's a somewhat extreme case of burying the lede.

 

People who follow NAD biology or the NR/NMN literature will know that NAMPT is the enzyme that converts nicotinamide to NMN, allowing NAD+ synthesis in the cell. The abstract says "Ascending aortas from patients with dilated aortopathy were immunostained for NAMPT, revealing an inverse relationship between [Vascular smooth muscle cells (SMC)] NAMPT content and aortic diameter." consistent with a role for NAMPT in maintaining SMC integrity and thus preventing aortic aneurism. Consistent with this, mice with the Nampt gene specifically knocked out in their SMCs suffered mildly dilated aortas, and "a 43% reduction in NAD⁺ in the media. Infusion of angiotensin II led to aortic medial hemorrhage and dissection." This is what you'd expect: AngII increases BP and arterial stiffness. The SMCs showed evidence premature senescence, which would clarify why their aortas are so vulnerable.

 

Figure A shows that deleting NAMPT leads to more background DNA damage, as you say — damage that is worsened in normal and especially KO SMC when AngII is infused. (I'm not clear if this is in vitro with cells from the SMC-KO mice or in vivo: I haven't seen the full text).

 

Fig. B is about the level of poly(ADP)ribose synthesis, a marker of the early stages of DNA repair by PARP1, an NAD+ dependent enzyme. The left hand of the graph indicates that NR doesn't change things much under baseline conditions in normal or KO cells, presumably because there's not much background DNA damage to repair. But when AngII is infused (right), there is a very large spike in PAR synthesis in normal cells, indicating that PARP1 is active in trying to repair single-strand breaks — but not in the knockout cells, presumably because without NAMPT they can't synthesize the NAD+ that PARP1 needs to do its job. Adding NR to the medium (I'm assuming that this is in vitro: again, I've not seen the paper) restores the ability of PARP1 to begin the repair process in NAMPT KO cells, presumably by providing it with the NAD+ it needs to work by allowing NMN synthesis by NRK1, bypassing NAMPT.

[Bryan_S]

 

I think A says after NAMPT gene is deleted, DNA damage is more severe.
B says NR increases DNA repair ability. There is little DNA repair ability with NAMPT gene deleted. But NR can rescue it. The injection of agiotension ii caused a big response of DNA repair

Who would have thought that vitamin B3 was such a powerful vitamin?

 

 

PeaceAndProsperity, this is a teachable moment and not specifically aimed at you. You may very well have advanced degrees in biochemistry and I don't want to disrespect those who I hope will become contributors. But yes B3 is a powerful vitamin.

 

B3 was one of the first vitamins to be used to fortify foods. This condition of Pellagra is rarely seen today. The visible lesions were do mainly to the inability to cope with UV damage. (See the The New England Journal of Medicine on B3)  Remember PARP1, with little to no B3, DNA repair falls to the wayside. PARP1 is a direct NAD consumer. Also see (Houtkooper et al., 2010) But energy comes from other sources, for different processes, and is needed in different forms. The calories you eat, the breath of air you take, these come together to produce almost all the ATP you need to run the engine of life. ATP is your cellular currency fueling a multitude of functions. B3 itself does not do these things but it's a NAD+ precursor and it does the work through the respiration of your electron transport chain.

 

Have you ever done the math? How Many ATPs Can One Glucose Molecule Yield?

 

Breaking down glucose to carbon dioxide can yield as many as 36 ATPs, mostly from chemiosmotic phosphorylation at the electron transport chain.

 

Is this the only way to make ATP?

 

How many ATP molecules per glucose does fermentation produce? You know we retain both aerobic and anaerobic paths to ATP. Once upon a time in the distant past life existed without reactive Oxygen, we can still find examples today. In fact Oxygen was a poison to early life. It still posses issues to us today but we've evolved repair mechanisms to combat Oxygens damage. The strategy to produce energy in Oxygen free environments is still apart of us and is still used today. Both play a role in day to day energy production and utilization.

 

Fermentation . . . Only TWO ATP molecules per glucose, so which method is more efficient? Have you ever watched children at play and wondered what was fueling all that activity? I'll tell you this it wasn't fermentation but this is still our backup system for when we over exceed our energy production thru Aerobic respiration. See video

 

I make these points to the board without singling out any one person because if this is truly an interest of yours, grab a copy of "Molecular and Cell Biology for Dummies." really. I don't mean this in a disparaging way. I have a buddy who is a genetic engineer. After 2-years of asking him the most mundane questions he forced me to get a copy and wouldn't talk to me again until I read it. Turns out after I started reading I couldn't stop.

 

The only way you can keep up with this biochem forum, YES this is a biochemistry forum but please don't be frightened. All you have to do is to read and ground yourself or pile thru the Brightstorm videos. Your fellow board members aren't going to digest and regurgitate all the data for you, some self assembly is required to understand the papers we post. So for those who are lurkers and those who take a chance and post here exposing themselves to an unknown classroom, understanding Nicotinamide Riboside's role and why it's attracting such academic interest requires some basic biochem knowledge.

 

So lets all read up and find the real jewels coming out of this new area of research. I hope some of you will be sparked to embark in some self study and come back and point out some really cool insights these researchers are suggesting about NAD repletion. 

 

As always JMHO

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Edited by Bryan_S, 03 April 2017 - 06:21 PM.
Links added

[bluemoon]

 

 

I make these points to the board without singling out any one person because if this is truly an interest of yours, grab a copy of "Molecular and Cell Biology for Dummies." really. I don't mean this in a disparaging way. I have a buddy who is a genetic engineer. After 2-years of asking him the most mundane questions he forced me to get a copy and wouldn't talk to me again until I read it. Turns out after I started reading I couldn't stop. 

 

 

Well this is a coincidence! I just ordered Molecular and Cellular Biology for Dummies last week after looking at a few pages on Amazon. I took Bio 101 25 years ago and finally decided to devote some time learning more. The Dummies series has a large range of difficulty and could easily be called "For the Curious" series.   

[Bryan_S]

Its like the crib notes of Molecular and Cellular Biology. There are still volumes of information to be learned between the lines.