2255 replies to this topic

[stefan_001]

 

What I am somewhat on the fence for and I believe similar for you, is more in frequency and amount going to be better? The 12 hour interval I am also doing to ensure that a down regulation mechanism, if there is any, may not have a chance to develop. The evening dose under the thinking that sleep is a good repair window and may be a period where the body uses supplements effectively. I don't have scientific fact for that. Overall I am seeing NR as the base layer supplement  to keep the body healthy. Ontop, exercise, supplements to be used to trigger additional improvement which can now be fueled by the larger NAD+ pool. So how big should and can the NAD+ pool be made so all processes can be served.

 

Stefan

 

I don't necessarily believe more is better. I believe there is a certain saturation point which has yet to be identified and is different for all of us. I don't think we can push NAD levels higher than when we were young and at some point even with repeated conditioning and exersize our utilization curve will top out and adding more NAD precursors beyond that would be a waste of money.

 

I believe the most cost efficient approach is to break the daily dosage into evenly timed applications thru the day to stay near our maximum saturation point. If the ChromaDex/Brenner study was correct and the 300mg and 1000mg dosages produced an identical 50% NAD rise then there is a rate limiting process along the path. I think its tied to our utilization. If this is indeed true than surpassing the 300mg dosage has diminishing returns the higher you push the dosage because the unused portion will be eliminated thru the kidney's. As blood serum levels fall we have the opportunity supplement again to keep us near our saturation point. I believe its truly a use it our lose it scenario.

 

I liken the whole situation to a bucket with a leak. The older we get the bigger the leak. Fill the bucket to much and the excess splashes out. So in this scenario the amount needed differs with age and our infirmity's which helps drive demand beyond what's recycled and this recycle process gets worse with age.

 

So much like you I see the NAD precursors as a base supplement because we have this recycling/salvaging issue that diminishes our available NAD pool with age. But having said that there is also the theory that our NAD demand just raises with age. Either way the NAD pool needs supplementation to meet demand. 

 

Down regulation mechanism. Hum . . . we know the whole NAD process is driven via feed back loops so yes there are several down regulation mechanisms. However NAD is central to your respiratory metabolism so its how our cell breaths and I don't see that being cut off. I look at this as a supply and demand scenario. Excess Nicotinamide along with the NAD NADH ratio from our NAD reactions tells the cell I'm nutritionally satisfied and this begins to inhibit Sirtuin processes that ramp down NAD production. Once those (NAM) levels eventually fall the Sirtuin activities become more active again. There are other sensors at work as well but together when NAD falls low enough those enzymes to produce more become active again.

 

Sleep is a good repair window but lets also consider our circadian rhythm and NAD is a central signaling metabolite. I thought this way as you and dosed prior to sleep but found many nights I had the urge to read and it wasn't putting me to sleep. This told me I was fooling my body into thinking to was time to be mentally active. So I'm now trying to respect this part of my cycle and compliment it with the sedative effects of Nicotinamide (Nam) instead of stimulating myself with (NR).

 

To each their own.

 

 

The press release also stated that:

"Average maximal increases in blood NAD+ were approximately 30% at the 100 mg dose and approximately 50% at the higher doses. Increases in blood NAD+ tended to be sustained for longer times at higher doses"

 

which correlates that there is absorption rate limit. Interestingly however it also indicates that NR then apparently keeps circulating till its needed so in that sense the evenly spread timing is good but may not need to be overly accurate and excretion speed not that high. Well either way multeple dosing seems a good approach.

 

Now you forced me to read about circadian rhythm :-)

 

 

 

 

[stefan_001]

Thanks for the great efforts on all posters parts. It does help others decision making. Also, I specifically thank you, Bryan_S for your warning in post 152 about the dump and absorb sublingual method; and the dangers of inhalation, especially from excipients.

 

Are there any group deals going on, or suggestions about where to get the best prices? Currenly at 100 mg once per day. Would like to double that.

 

Please remember to mention your observations of the effects in the personal experience thread.
 

[works4you2]

Thanks for the great efforts on all posters parts. It does help others decision making. Also, I specifically thank you, Bryan_S for your warning in post 152 about the dump and absorb sublingual method; and the dangers of inhalation, especially from excipients.

 

Are there any group deals going on, or suggestions about where to get the best prices? Currenly at 100 mg once per day. Would like to double that.

 

I buy my Niagen from LCR they had a special for 40% off on Niagen during the boxing week for 6 bottles, they also told me that once you lock up a price they will respect it for life. So far so good!

I also know for a fact that if you buy 24 bottles at once they will make you an even better deal close to $20 for 30 x 250 mg bottles of NR.

I usually take 2 Niagen a day one first thing in the morning and a second one at 4 pm, around 1 hour before having supper.

Is there a reason why you guys buy from HPN in stead of LCR? Just Curious!

 

I have been taking 500 mg of Nicotinamide (Nam) before bed time for 3 moths now, sleeping great so far! Easy to get out of the bed and waking up energized.

 

Bryan_S I was wondering what dosage of Niacinamide (Nam) are you taking at bed time?

 

Thank you all for making this great threat, and wish you all healthier and prosperous 2016!

[Heisok]

I purchased through HPN. Thanks for the information.

 

Stefan_001, when I increase my dose, I will try to figure out if I notice any changes. It is not always obvious, and I will not be doing a controlled experiment where I cut back on other supplements. I plan to go from 100 mgs to 350 mgs. The 2 125 mg doses with the sublingual method.

[Bryan_S]

 

I had purchased some product from one of the other venders and they claimed "Niagen™ is comprised of 100% Nicotinamide Riboside, or NR" They also stated "and does not use any “fillers or binders.” well after coughing up a lung and dissolving their product in water the Silica powder remnants remained. So as I said buyer beware. There are trusted venders and there are those who will tell you want you want to hear. That vender is extremely aggressive in their marketing and after a confrontation he recanted after I threatened to expose the deception and they claimed they would change their formulation to match the advertising but by then any trust had been broken. I cant stand being lied to. The vender you just bought from "HPN" has modified their product to accommodate the sublingual users on our board and they've been responsive to our needs all along and they currently run three different discounts for us. We will see another big discount on or around February 15th but they are running a continuous discount for smaller orders for our members all the time.

 

Now you forced me to read about circadian rhythm :-)

 

Sorry' guess I read too much but NAD is a major circadian player and it gets us going in the morning and wanes towards the end of the day. We can complement this cycle or go against the grain, its our choice. But if this is the case maybe we have an opportunity to tackle jet lag to some degree. It would be interesting to hear from any of our members if NR helped them re-set their circadian clock after a big trip or at least get past the first rough day.

 

Bryan_S I was wondering what dosage of Niacinamide (Nam) are you taking at bed time?

 

2000mg of (NAM) but as previously stated in posts months ago if I could afford to take 100% (NR) I would. Currently I take 1000mg's of (NR) broken up thru the day and I add 2000mg of (NAM) before bed. 

Edited by Bryan_S, 11 January 2016 - 07:04 AM.

[Bryan_S]

With regard to mitochondrial bio-genesis has anyone considered PQQ in light of recent developments in NAD research? I'm unqualified to comment but I've been reading along and there is an interesting post here suggesting a connection with AMPK. PQQ seemed to fall out of favor with the nootropic crowd but the new research surrounding mitochondrial underpinnings may have some relevance?

 

Marty alternative methods have been discussed but when you head upstream you encounter a NAD deficit at the biochemical head waters. AMPK helps drive the expression of the NAD enzyme NAMPT but if you don't have the NAD precursors waiting in the wings ready to process it's like beating a dead horse.  So this is why we are focused on the NAD boosting, its hoped the downstream processes will mend themselves after the NAD cycle is restored with sufficient resources.  

Edited by Bryan_S, 11 January 2016 - 07:41 AM.

[sthira]

Thanks, Bryan for your info about sublingual use of Niagen. I've taken many bottles of it and have never noticed anything. So on your cue, I split open a few caps yesterday and this morning, and now I do think I may notice something like drinking half a cup of coffee. Maybe? Is this what people feel when taking Niagen -- caffeine-like effects? I'm doing the same sublingual with pterostilbene together with Niagen.

[Bryan_S]

Thanks, Bryan for your info about sublingual use of Niagen. I've taken many bottles of it and have never noticed anything. So on your cue, I split open a few caps yesterday and this morning, and now I do think I may notice something like drinking half a cup of coffee. Maybe? Is this what people feel when taking Niagen -- caffeine-like effects? I'm doing the same sublingual with pterostilbene together with Niagen.

 

Its not like caffein to me but I do feel more energy and mental clarity. You know that dull foggy feeling in the morning after waking up? After I put a capsules worth under my tongue within 10-15 minutes my attention and reading comprehension seems to improve. I've compared this to mornings where I wait and don't dose right away so I know there is something happening. I don't know how else to communicate that feeling. I've found I do drink less coffee overall and a little sip every now and then when I need coffee now goes a long way for me.

[Bryan_S]

Ischemic Brain Injury Is Mediated by the Activation of Poly(ADP-Ribose )Polymerase 

 

OK here is another article investigating NAD depletion in stroke scenarios. This article was made public posted on Dec 13, 2015 but I believe its a bit older. 

 

http://jcb.sagepub.c...1143.full.pdf  

[Bryan_S]

Dr. Charles Brenner was recently interviewed by Dr. Kazuo Tzubota, President of the Japanese Society of Anti-Aging Medicine, on the topic of NAD, nicotinamide riboside supplementation and aging. The interview was published in the Society’s magazine Anti-Aging Medicine

 

http://www.medicine....ingMedicine.pdf

[stefan_001]

Dr. Charles Brenner was recently interviewed by Dr. Kazuo Tzubota, President of the Japanese Society of Anti-Aging Medicine, on the topic of NAD, nicotinamide riboside supplementation and aging. The interview was published in the Society’s magazine Anti-Aging Medicine

http://www.medicine....ingMedicine.pdf

Nice find. If it's a recent picture in the document he looks in good shape for a 54 year old. Perhaps we need to ask him what supplements he uses....

[Bryan_S]

 

Dr. Charles Brenner was recently interviewed by Dr. Kazuo Tzubota, President of the Japanese Society of Anti-Aging Medicine, on the topic of NAD, nicotinamide riboside supplementation and aging. The interview was published in the Society’s magazine Anti-Aging Medicine

http://www.medicine....ingMedicine.pdf

Nice find. If it's a recent picture in the document he looks in good shape for a 54 year old. Perhaps we need to ask him what supplements he uses....

 

 

Nice history lesson about our overall NAD understanding from the beginning of the 20th century touching on NAD glycohydrolases, thru Arthur Harden and into our current understanding of the NAD consuming enzymes called sirtuins, poly(ADP-ribose)polymerase(PARP), and cyclic ADP-ribose synthetases.

 

He infers how much NAD is needed, but is rather vague about its overall demand saying; "it depends on cell state. When DNA is damaged in the cell and single strand breaks are generated, then PARP is activated" he doesn't pin it down exactly but we understand from past papers that PARP can give rise to a hugh NAD demand. He duck tails this into our understanding about some cancers where PARP inhibitors are being used in chemotherapy treatments. However for a healthy person he outlines the risks of PARP inhibitors and the DNA damage that can manifest by their use.

 

He talks about Shin-ichiro Imai and I think the discussion on the equivalency of NMN and NR was pretty enlightening. Both NAD precursors can get you there (NMN and NR are going to be largely bioequivalent) but the thought was NMN must be broken down at the cell membrane (dephosphorylation) to NR and reassembled upon entering the cell were NMRK1 / NMRK2 are put to work.

 

"Kazuo Tsubota I see. Is there any evidence that nicotinamide riboside kinase is not decreasing with aging like NAMPT?

Charles Brenner That’s a very interesting point. NMN inside the cell is a very important metabolite because evidence suggests it’s the metabolite that has to be formed in the cytoplasm in order to elevate mitochondrial NAD. As you know, mitochondrial metabolism is very important in fuel utilization, anti-aging, and prevention of diseases. As Dr. Imai has shown, NAMPT expression declines in aging. And interestingly, nicotinamide riboside kinase 2 expression is increased as a function of a number of stresses.

Kazuo Tsubota Is it like a compensation mechanism?

Charles Brenner Nicotinamide riboside kinase 2 is increased in a number of muscular, cardiac, and neurological stress situations, suggesting that particular cells are looking for NR in order to replenish their NAD. Thus, if NAMPT is declining and nicotinamide riboside kinase 1 and/or 2 expression is maintained or even increased in some circumstances, those are the conditions that may inform the beneficial uses of NR. 

Kazuo Tsubota Thank you very much."

 

So if Brenner's analogy is correct, as NAMPT levels fall with aging the cell looks for NR sources and increases production of NMRK1 / NMRK2 to compensate and replenish the NAD pool. If so I would expect there is a cell signaling mechanism calling for additional NR to be exported from cells with adequate NAD reserves to spare?

 

Didn't we review an article about "In vivo Monitoring of Transcriptional Dynamics After Lower-Limb Muscle Injury Enables Quantitative Classification of Healing" Where Nicotinamide Riboside Kinase Nmrk2 increased after muscle tissue injury? Makes me wonder if Nicotinamide Riboside might be an innate NAD precursor exported to the extra cellular spaces to aid other tissues in need? Also seems that I remember nicotinamide riboside is exported by yeast cells and this benefits the well being of local cell community. I wonder if this process was conserved and passed into mammalian cell lines? 

Edited by Bryan_S, 14 January 2016 - 08:28 AM.

[super-human]

Hello All NR Folks,

 

In the last number of weeks I have been trying to find out from Live Cell Research what it is they are using in their Niagen pill that they sell. Yes I know that all you all are just supporting HPR folks but just stay with me for a couple of seconds.

 

I have sent numerous notes to the LCR folks on three levels and not one of them has received a response. They include Bill the founder, their new showman Dr McClain and their information email. I AM A REPEAT PAYING CUSTOMER and I just have one question. What the heck are they selling to me? Chromadex seems to have gone a different way with their marketing so I am concerned about what I am feeding to my family by way of supplements. I am disturbed and concerned!!!!!!!!!!

 

LiveCell seems to be just a BS promotional scamming front for god knows what ingredients. Who does not respond to a sincere information request from a repeat customer?

 

EVERYONE. Please stop and think about this and if you are a customer of theirs ask the question of what you are getting. So far they have deemed my inquiry as unimportant or too perhaps too close to home to answer... 

 

My only reason for posting this not is because I am honestly frightened that Live Cell Research is pumping and dumping god knows what as NR into the marketplace and me and my family  (that includes an 8 year old) are being potentially harmed.

 

I am hugely disappointed in them.

 

Super

[docmaas]

In of the threads, more than a year ago, when the topic was how can we tell it's niagen most of the products using niagen had text on their labels saying so.  LCR was an exception but someone, I don't recall who, said that Chromadex had verified that LCR was indeed a niagen reseller.

 

I've never been comfortable with LCR and have always bought from HPN simply because I don't like the way they LCN pushes their products.  

 

Maybe it's time to ask Chromadex again.

 

Mike

Hello All NR Folks,

 

In the last number of weeks I have been trying to find out from Live Cell Research what it is they are using in their Niagen pill that they sell. Yes I know that all you all are just supporting HPR folks but just stay with me for a couple of seconds.

 

I have sent numerous notes to the LCR folks on three levels and not one of them has received a response. They include Bill the founder, their new showman Dr McClain and their information email. I AM A REPEAT PAYING CUSTOMER and I just have one question. What the heck are they selling to me? Chromadex seems to have gone a different way with their marketing so I am concerned about what I am feeding to my family by way of supplements. I am disturbed and concerned!!!!!!!!!!

 

LiveCell seems to be just a BS promotional scamming front for god knows what ingredients. Who does not respond to a sincere information request from a repeat customer?

 

EVERYONE. Please stop and think about this and if you are a customer of theirs ask the question of what you are getting. So far they have deemed my inquiry as unimportant or too perhaps too close to home to answer... 

 

My only reason for posting this not is because I am honestly frightened that Live Cell Research is pumping and dumping god knows what as NR into the marketplace and me and my family  (that includes an 8 year old) are being potentially harmed.

 

I am hugely disappointed in them.

 

Super

 

[midas]

I have said a similar thing about LCR more than once on here, everything about them just stinks to me. And to be honest it doesn't really matter what Chromadex say about LCR, they may well be supplying them but they have no control over what is actually ending up in the product from LCR.....The only two suppliers I have any time for are HPN and Elysium Health.

[stefan_001]

me and my family (that includes an 8 year old) are being potentially harmed.

8 year old....NR supplementation....That's a good idea??

[stefan_001]

So if Brenner's analogy is correct, as NAMPT levels fall with aging the cell looks for NR sources and increases production of NMRK1 / NMRK2 to compensate and replenish the NAD pool. If so I would expect there is a cell signaling mechanism calling for additional NR to be exported from cells with adequate NAD reserves to spare?

Didn't we review an article about "In vivo Monitoring of Transcriptional Dynamics After Lower-Limb Muscle Injury Enables Quantitative Classification of Healing" Where Nicotinamide Riboside Kinase Nmrk2 increased after muscle tissue injury? Makes me wonder if Nicotinamide Riboside might be an innate NAD precursor exported to the extra cellular spaces to aid other tissues in need? Also seems that I remember nicotinamide riboside is exported by yeast cells and this benefits the well being of local cell community. I wonder if this process was conserved and passed into mammalian cell lines?

This sounds like a possible theory, it would mean that the body has a build in back up system for situation where NAMPT mediated NAD supply falls short. That also means NR supplementation would be even more a hack than I thought - an apparently working hack. It begs the questions why does aging cause NAMPT decrease but spares the nmrk1/2 activity.

Edited by stefan_001, 16 January 2016 - 07:44 PM.

[super-human]

My point being that you do not know who is taking the suppliants (the case of an immuno-compromised senior could even be worse) so it is incumbent on the purveyor of these drugs to be forthright and responsive to their customers.

 

LCR is not being either and frankly if they do not start they should be investigated and be criminally charged for their fraudulent practices.  False advertising is still a crime and they are dealing with peoples health.

[stefan_001]

My point being that you do not know who is taking the suppliants (the case of an immuno-compromised senior could even be worse) so it is incumbent on the purveyor of these drugs to be forthright and responsive to their customers.

LCR is not being either and frankly if they do not start they should be investigated and be criminally charged for their fraudulent practices. False advertising is still a crime and they are dealing with peoples health.

Sure fully agree with that. I had a similar situation with Supersmart the only seller of NR in Europe after pressing them where they got the stuff it went from we make it ourself to it is secret so I switched immediately to US supplier.

Edited by stefan_001, 16 January 2016 - 07:35 PM.

[Bryan_S]

 

So if Brenner's analogy is correct, as NAMPT levels fall with aging the cell looks for NR sources and increases production of NMRK1 / NMRK2 to compensate and replenish the NAD pool. If so I would expect there is a cell signaling mechanism calling for additional NR to be exported from cells with adequate NAD reserves to spare?

Didn't we review an article about "In vivo Monitoring of Transcriptional Dynamics After Lower-Limb Muscle Injury Enables Quantitative Classification of Healing" Where Nicotinamide Riboside Kinase Nmrk2 increased after muscle tissue injury? Makes me wonder if Nicotinamide Riboside might be an innate NAD precursor exported to the extra cellular spaces to aid other tissues in need? Also seems that I remember nicotinamide riboside is exported by yeast cells and this benefits the well being of local cell community. I wonder if this process was conserved and passed into mammalian cell lines?

This sounds like a possible theory, it would mean that the body has a build in back up system for situation where NAMPT mediated NAD supply falls short. That also means NR supplementation would be even more a hack than I thought - an apparently working hack. It begs the questions why does aging cause NAMPT decrease but spares the nmrk1/2 activity.

 

 

This is a guess but some cells have a high metabolism i.e. muscle cells, cardiac tissue and neurons to name a few. It could be tissues functioning at a lower energy states can contribute to those higher energy cells in need. The muscle injury experiment hints at a symbiotic relationship so this might be a secondary path when the NAMPT can't keep up with cellular NAD demand.

[Bryan_S]

http://Niagen.ORGhtt...h.com/about.php

My point being that you do not know who is taking the suppliants (the case of an immuno-compromised senior could even be worse) so it is incumbent on the purveyor of these drugs to be forthright and responsive to their customers.

 

LCR is not being either and frankly if they do not start they should be investigated and be criminally charged for their fraudulent practices.  False advertising is still a crime and they are dealing with peoples health.

 

super-human,

 

Don't get me going, there are enough venders currently packaging Niagen that if one isn't meeting your needs purchase from the next.

 

Do this, ask for copies or a link to the documentation generated by their independent third party testing facility. If enough of you ask they'll be forced to post or send you their purity reports from the summer of 2014 on. Now I'm not interested in one arbitrary report from Jan. 2016, I want to see the last 12 months or more because these independent testing claims have been unsubstantiated. They claim to have every batch tested but where is all this independent documentation?  support@livecellresearch.com

 

"How do I know Live Cell Research products are pure?

 

Live Cell Research is committed to producing high-quality supplements without any synthetic binders or fillers. Our ingredients are derived from only the purest and most sustainable sources we can find, and we work hard to keep them that way through every step of the production process. To ensure the quality of each individual bottle, we have every batch tested by an independent third party testing facility." Multiple marketing listings

 

As far as truthfulness, check the ingredients across all of their other products for comparison because they likely use the same encapsulation equipment and process's for all of their products and to change that requires a capital investment.

 

Certain binders and fillers are the norm for the encapsulation process its just some are not acceptable for our sublingual users. In general the FDA approved excipients are fine if left undisturbed in the capsule and swallowed. I suspect but cant be sure they are still using certain ingredients still listed on their other products and never ceased the silica powder process because it costs money to change this one detail. I would like to be proven wrong but at a time in 2014 when they were claiming to not use silica powder they in fact were and promised to cease the practice after being confronted.

 

Back to the fillers, Rice Bran and Micro-crystalline cellulose are the 2 accepted organic fillers. I have no problem with either but keep in mind Rice Bran is an accepted-known-filler but they claim to not use "any fillers" so there is a conflict in their statements without looking very deep. We know today they don't supply 100% Niagen in their capsules as they claimed in 2014 because of the rice bran and there is no 3rd party documentation made available to confirm other factors such as microbial count or purity.

 

Now we all accept this kind of testing costs money. In fact I don't really care what FDA approved excipients they use as long as the the target market isn't our sublingual users. I know if I'd spent the money they have claimed on testing I'd publicly flaunt those assurance results because they are the type of thing that sells product assurance and they convey safety.

 

What we need is the testing Labs number and I'll gladly make the inquiry because I cant find it anywhere on their website. They should at least publish who they might be using because this is a big selling point.

 

Just review the last pages of their thread and see how they moved on when the simpler questions got increasingly difficult. I kind of feel they set up house among our established users to win over our group buy users but they didn't expect we'd have the depth of product questions we did.

 

Either they have the 3rd party testing paperwork or they don't but either way you'll have an answer indicating their truth in marketing if they choose to ignore the document request or if they openly share the last 1 year, 5 months of lab work. http://www.longecity...research/page-4

 

I'd like to find out they are doing as they claim. I'm a stickler for details and hope they publish their testing results covering the months they've made these claims. Our sublingual users are my main concern, I really don't care how they handle their product if they are making it friendly for those users and provide formula change verification. The 3rd party testing is a separate issue and if they've made the investment as claimed they should be proud to make those documents public.

 

Update Jan. 23rd 2016: I've thrown a few questions their way and have begun to monitor their website for a link to their 3rd party results. If I hear anything informative back from LCR I'll post it here. If anyone else receives a response please PM me.

 

Update Jan 31st 2016: I regret to inform everyone that I was contacted by a fellow interested party who eventually did receive a response concerning LCR's third party verification. As for me, my emails and personal messages to Ethan Furman and LCR proper have gone unanswered. Their response "Unfortunately, our third party laboratory does not allow us to release any of their information." They are dodging a major marketing point advertised since the summer of 2014. This response would infer they are not allowing public access to verify their claims. I can only say at this point is if you were considering buying this product Buyer Beware.

 

As mentioned above LCR's 3rd party testing is marketed as a public safety assurance claim, however at this date it can not be confirmed to be true and this creates substantial truth in marketing doubt. I would suggest if you are a Live Cell Research customer or wish to be one contact them directly and ask them to make available their 3rd party safety assurance documents. Contact Live Cell Research If anyone else receives verification either way please let me know?

 

Update March 6th 2016: LCR is still deflecting inquires concerning their advertised "Lab Certification" and verification about their "independent third party testing." As far as what is true or not I suspect after weeks of waiting for a response both these claims are FALSE. As to ingredients and purity your guess is as good as mine. If they are unwilling to verify their advertised safety assurance claims I doubt they care what kind of review we give them here concerning their other claims. They've recently embarked on a new advertising path using a non-commercial .ORG domain to promote their sales. See Niagen.ORG There isn't a fast and hard rule about registering under this non-profit domain anymore like there was in the old days, I just think this further speaks to their business ethics or lack thereof. 

Edited by Bryan_S, 06 March 2016 - 05:21 PM.
Update Jan 31st 2016, Update March 6th 2016

[Bryan_S]

Mitochondrial SIRT3 Mediates Adaptive Responses of Neurons to Exercise and Metabolic and Excitatory Challenges

 

Volume 23, Issue 1, p128–142, 12 January 2016

 

http://www.cell.com/...4131(15)00529-X

 

 

Highlights

•Exercise and glutamatergic signaling induce SIRT3 expression in cortical neurons

• •SIRT3 deacetylates SOD2 and cyclophilin D in neuronal mitochondria
• •SIRT3 prevents neuronal death in mouse models of epilepsy and Huntington’s disease
• •SIRT3 mediates adaptive responses of neurons to excitotoxic and metabolic stress

 

Abstract

The impact of mitochondrial protein acetylation status on neuronal function and vulnerability to neurological disorders is unknown. Here we show that the mitochondrial protein deacetylase SIRT3 mediates adaptive responses of neurons to bioenergetic, oxidative, and excitatory stress. Cortical neurons lacking SIRT3 exhibit heightened sensitivity to glutamate-induced calcium overload and excitotoxicity and oxidative and mitochondrial stress; AAV-mediated Sirt3 gene delivery restores neuronal stress resistance. In models relevant to Huntington's disease and epilepsy, Sirt3(-/-) mice exhibit increased vulnerability of striatal and hippocampal neurons, respectively. SIRT3 deficiency results in hyperacetylation of several mitochondrial proteins, including superoxide dismutase 2 and cyclophilin D. Running wheel exercise increases the expression of Sirt3 in hippocampal neurons, which is mediated by excitatory glutamatergic neurotransmission and is essential for mitochondrial protein acetylation homeostasis and the neuroprotective effects of running. Our findings suggest that SIRT3 plays pivotal roles in adaptive responses of neurons to physiological challenges and resistance to degeneration.

Edited by Bryan_S, 24 January 2016 - 06:50 PM.

[Bryan_S]

AIHM President’s Choice No. 65: Nicotinamide (Vitamin B3) for Chemoprevention of Nonmelanoma Skin Cancer

https://aihm.org/pub...tinamide-no-65/

Dec 27, 2015

 

Dr. Mimi Guarneri, MD relates the NAM/NAD/DNA repair aspects of its action.

 

Along these lines other research has sought to identify better NAD boosters. Oncogene-induced NAD+ depletion in tumorigenesis in this study Nicotinamide Riboside is investigated in Oncogene-induced cancers.

 

"Next, using global quantitative transcriptomic and proteomic analysis, we demonstrate that prior to DNA damage, URI downregulates the L-tryptophan/kynurenine catabolism pathway and thus, leads to the inhibition of de novo NAD+ synthesis. The decrease in total NAD+ levels consequently provokes DNA damage (Figure). Although it remains unclear how decreased in NAD+ concentrations causes genotoxic stress, preliminary results indicate that the DNA repair protein poly-ADP-ribose polymerase (PARP) activity may be affected. We do not completely exclude that NAD+ depletion may affect Sirts activity. Furthermore, because NAD+ is a cofactor for inosine monophosphate dehydrogenase implicated in dNTPs synthesis, NAD+ deficits can also lead to insufficient dNTP production that may contribute to DNA damage during high replication. Replenishing the NAD+ levels by nicotinamide riboside (NR), a derivative of vitamin B3, prevented and abolished DNA damage and aggressive tumor formation [5].

Based on previous observations and extending our work to other oncogenes known to induce tumors on the basis of DNA damage, we demonstrate that c-Myc expression in pancreas induced NAD+ depletion through a net reduction in tryptophan catabolism. Enzymes implicated in tryptophan degradation are downregulated by c-Myc over-expression. NAD+ depletion is apparently involved in the formation of pancreatic tumors. Importantly, these tumors could be tackled when NAD+ levels were enhanced by NR supplementation [5]. We propose that NAD+ depletion is a common molecular mechanistic basis for oncogene-induced DNA damage and tumor development.

NR seems therefore to be an efficient therapy for the treatment of various cancers in which predictive and prognostic factors can be identified as oncogene-associated genotoxic stress. Clinical trials with NR for treatment of such cancers are under consideration. However, developing a methodological screen to find more efficient and stable NAD+ “boosters” and, understanding the mechanisms of NAD+ depletion-dependent DNA damage would offer a broad spectrum of new possibilities to decisively prevent and cure cancer in human beings. The development of drug discovery platform based on screening of new compounds that enable to abolish DNA damage by increasing NAD+ levels can thus be an exciting investment in the war against cancer."

 

Perhaps its not at all surprising because we've seen other studies indicating this strategy works.

 

Derivative of vitamin B3 prevents liver cancer in mice

[Kirito]

I found this to be a pretty good read: http://www.medicine....ingMedicine.pdf

[Bryan_S]

Administration of Nicotinamide Mononucleotide in the Treatment of Disease

http://patents.justi...ent/20160022712

 

Looks like Shin-ichiro has been busy covering the bases. Its a pretty broad patent application covering the administration of Nicotinamide Mononucleotide NMN.  

[bluemoon]

Administration of Nicotinamide Mononucleotide in the Treatment of Disease

http://patents.justi...ent/20160022712

 

Looks like Shin-ichiro has been busy covering the bases. Its a pretty broad patent application covering the administration of Nicotinamide Mononucleotide NMN.  

 

Without getting into speculation, could you speculate what you think this may mean for the sale of NMN? 

[Bryan_S]

Without getting into speculation, could you speculate what you think this may mean for the sale of NMN? 

 

As a precursor I think it's on par with NR.

 

It seems to be most effective if injected, as is both NAD or NADH.

 

From research it appears to be reduced to NR like NAD at the cell membrane.

 

So as a hospital IV drip it appears interesting but I guess NR could also play the same roll.

 

The question; is it cheaper to produce and sell than NR? We know it is a slightly more complicated molecule. I'd say more research needs to be uncovered about its oral bioavailability. Along the lines of your question I remember someone advertising Nicotinamide Mononucleotide a year ago but given the above it didn't succeed or it wasn't the molecule advertised and was withdrawn.

 

Since Nicotinamide Mononucleotide is on par with Nicotinamide Riboside anything I find on it I'll relate on this forum. Cost wise I don't think there is an advantage and its oral bioavailability still needs to be tested against NR.

Edited by Bryan_S, 03 February 2016 - 01:21 AM.

[Tom Andre F. (ex shinobi)]

I will make a blog article about NAD+ again because I spoke again with leading researching of anti aging field (the one who made the NQO1 study and showed mice live longer using BL than CR group) and he is formal: NR, NMN and CoQ can exert effects on the NAD+/NADH ratio but the difference is duration of action comparing with for instance BL. And here we can connect the dots with the pharmacokinetics bryan pointed out. NR is break down or metabolized shortly while BL is long lasting and this part is VERY important.

 

The researcher think this is critical for the frequent and transitent increase of NAD+/NADH ratio.

 

Another thing interesting is that the NQO1 gene is not expressed in a similar way depending of our origin : asian or white people for instance.

 

Finally another thing is that in korea many of his team and including him and some of his family supplemented themselve using BL with some person reporting beneficial effect.

 

What about make a topic to speak in a more general way about NAD+ ?  because i think we still need to consider an holisitic approach to speak about that theme

 

 

Edited by Tom Andre F. (ex shinobi), 03 February 2016 - 03:03 PM.

[Alex_G]

Forgive me for my ignorance, but what is BL ?

[Logic]

What about make a topic to speak in a more general way about NAD+ ?  because i think we still need to consider an holisitic approach to speak about that theme

 

Good idea as there are a number of ways of increasing NAD+ that the NR disciples here don't want in the bible!  

 

BL = Beta-Lacaphone

1st mention here?:

http://www.longecity...beta-lacaphone/

 

Toms  Blog:

http://www.beta-lapachone.com/