2255 replies to this topic

[Bryan_S]

Tom we are essentially saying the same things but our native languages might mix up the meaning.

 

"poor patient compliance" has been a known Niacin issue. I agree (Na) should be used as a control but I don't design the experiments. Let's consider the up coming human trial for nicotinamide riboside on Minnesota College Football Players. Now could this same trial be conducted with Niacin? Sure, but at (750 mg/day for 12 weeks) patient compliance will be key and no one can say "I can't stand the flush." Also consider "The timed-release tablets and capsules may have fewer side effects than regular niacin. However, the timed-release versions are more likely to cause liver damage." So when something as important as TBI is finally going to be investigated with NAD boosting would you stop this study in favor of Niacin? I say let the data commence and we can associate the (NR) results to (Na) because no one else is considering a high profile traumatic brain injury study for Niacin.

[stefan_001]

 

And as we can see indeed for instance: in brain NR decreased a bit the sirtuins activity but increased it in the muscles. Thats why again we should see NA as control and should never rely on NR to completely help as an NAD+ boosting. 

 

 

 

Tom, you are quite focused on finding flaws in NR results. You are citing as reason to look at NA because NR in this study it showed slightly lower SIRT levels. But you must be aware that NA is a well known SIRT inhibitor. As you cited the brain example here a study that makes the point:

 

Nicotinamide restores cognition in AD transgenic mice via a mechanism involving sirtuin inhibition and selective reduction of Thr231-phosphotau http://www.ncbi.nlm....les/PMC2617713/

 

Just to be clear I can see benefits of taking NA but I dont see why we need to mix that with the opportunities that NR offfers. The substances are different, they convert via different paths so its logical they will also have different biological impacts. For me this discussion is to see where the research wrt NR leads. NR is an opportunity that has not yet reached its full potential and I hope in this place we focus on that. Also I am interested to understand how the NR can be augmented. I am not so much interested in NA as augmentation for more NAD+ boost but into other factors e.g. CD38. So from my side we stop this conparison of NA to NR. 

 

With a thank you to dr, Brenner here the best overview picture I have seen for the various pathways and tissue specificities and with that I sign off from the thread for a while as it takes more of my time than I wish and have available with all this debating:

 

Attached Files

•  pathways2.JPG   84.09KB   2 downloads

Edited by stefan_001, 08 July 2016 - 07:41 AM.

[Tom Andre F. (ex shinobi)]

Tom we are essentially saying the same things but our native languages might mix up the meaning.

 

"poor patient compliance" has been a known Niacin issue. I agree (Na) should be used as a control but I don't design the experiments. Let's consider the up coming human trial for nicotinamide riboside on Minnesota College Football Players. Now could this same trial be conducted with Niacin? Sure, but at (750 mg/day for 12 weeks) patient compliance will be key and no one can say "I can't stand the flush." Also consider "The timed-release tablets and capsules may have fewer side effects than regular niacin. However, the timed-release versions are more likely to cause liver damage." So when something as important as TBI is finally going to be investigated with NAD boosting would you stop this study in favor of Niacin? I say let the data commence and we can associate the (NR) results to (Na) because no one else is considering a high profile traumatic brain injury study for Niacin.

 

Bryan, I just moderate what you say about niacin being a "poor patient compliance". In your link they do not cover the topic at all unlike what did lifeextension with Dr. William Davis cardiologist (but he is one of the many people that believe the flush is actually what show people its working :

 

http://www.lifeexten...7/3/atd/Page-01 :

 

Niacin’s safety record is equally impressive. However, a brief foray into the use of very-slow-release niacin preparations in the 1980s taught us an important lesson: niacin is very safe, if the liver is exposed to it for only a few hours at a time. Niacin is, after all, just vitamin B3. However, 24-hour, day-after-day exposure to niacin over an extended period can be toxic to the liver. Thus, the very-slow-release niacin preparations that yielded sustained, high blood levels of niacin caused liver toxicity in 10-20% of people who used these preparations in the 1980s. Unfortunately, this learning experience left some physicians fearful of recommending niacin to their patients. For this reason, very-slow-release niacin should be avoided.

There are two safe forms of niacin:

• Immediate-release/crystalline niacin is available as a nutritional supplement and is inexpensive and effective. The niacin in each table is released immediately and usually provokes a “hot flush,” a warm, itchy feeling of the skin. For this reason, starting at small doses, such as 250 mg, can be helpful. The dose can be increased gradually (by 250 mg every four weeks) to achieve the desired amount. Doses greater than 500 mg per day should be used only under medical supervision. Some people take their niacin in small doses, three or four times daily, to spread out the dose. This could be unsafe, and I recommend that patients never take immediate-release niacin more than twice a day.
• Extended-release niacin is a time-release preparation, but does not act as slowly as slow-release niacin. This makes it safer than the slow-release preparations that can cause liver side effects. Extended-release niacin also provokes fewer hot flushes than immediate-release niacin. An example is Slo-Niacin®, which is sold over the counter. Niaspan® is an extended-release niacin preparation sold as a prescription drug.

By contrast, slow-release niacin preparations reduce the hot-flush effect by releasing niacin over an extended period of 12 hours or longer. Most of these preparations are unsafe and I do not recommend them

 

and here: http://www.lifeexten...ews?NewsID=4436 : Extended Release Niacin Reduces Cardiovascular Inflammatory Marker Lp-PLA2-diaDexus' PLAC® Test Measures Key Enzyme to Help Guide Treatment Decisions

 

Also, the 750mg NR means around 325mg NA

 

Finally, you recomended NR as large dose and very frequently : I also wanted to mitigated that since we could most likely see same problem that you point for NA

 

 

 

And as we can see indeed for instance: in brain NR decreased a bit the sirtuins activity but increased it in the muscles. Thats why again we should see NA as control and should never rely on NR to completely help as an NAD+ boosting. 

 

 

 

Tom, you are quite focused on finding flaws in NR results. You are citing as reason to look at NA because NR in this study it showed slightly lower SIRT levels. But you must be aware that NA is a well known SIRT inhibitor. As you cited the brain example here a study that makes the point:

 

Nicotinamide restores cognition in AD transgenic mice via a mechanism involving sirtuin inhibition and selective reduction of Thr231-phosphotau http://www.ncbi.nlm....les/PMC2617713/

 

Just to be clear I can see benefits of taking NA but I dont see why we need to mix that with the opportunities that NR offfers. The substances are different, they convert via different paths so its logical they will also have different biological impacts. For me this discussion is to see where the research wrt NR leads. NR is an opportunity that has not yet reached its full potential and I hope in this place we focus on that. Also I am interested to understand how the NR can be augmented. I am not so much interested in NA as augmentation for more NAD+ boost but into other factors e.g. CD38. So from my side we stop this conparison of NA to NR. 

 

 

Stefan, your study use nicotinamide not nicotinic acid

 

however you not volontary explained the Nate 2004 concernmaybe: why pterostilbene did not activated sirt1 in AD mice but worked on another path

 

And to reply to your post, I think precursor should be taken cautiously and maybe not on a regular use with a B complex along, and that we should move on more sexy way such as beta-lapachone or TFAM

 

EDIT: and yes, this picture from a study I already quoted to you a few page ago now, summary very well the NR limit and when you use the other salvage info from the study you see NA has less limit in the other hand since it will be converted also to NA riboside to use finally also the path of NR.

 

To boost NAD+ in the full body using only NR is a poor strategy, thats fact

Edited by Tom Andre F. (ex shinobi), 08 July 2016 - 07:57 AM.

[stefan_001]

 

 

 

 

 

 

 

And as we can see indeed for instance: in brain NR decreased a bit the sirtuins activity but increased it in the muscles. Thats why again we should see NA as control and should never rely on NR to completely help as an NAD+ boosting. 

 

 

 

Tom, you are quite focused on finding flaws in NR results. You are citing as reason to look at NA because NR in this study it showed slightly lower SIRT levels. But you must be aware that NA is a well known SIRT inhibitor. As you cited the brain example here a study that makes the point:

 

Nicotinamide restores cognition in AD transgenic mice via a mechanism involving sirtuin inhibition and selective reduction of Thr231-phosphotau http://www.ncbi.nlm....les/PMC2617713/

 

Just to be clear I can see benefits of taking NA but I dont see why we need to mix that with the opportunities that NR offfers. The substances are different, they convert via different paths so its logical they will also have different biological impacts. For me this discussion is to see where the research wrt NR leads. NR is an opportunity that has not yet reached its full potential and I hope in this place we focus on that. Also I am interested to understand how the NR can be augmented. I am not so much interested in NA as augmentation for more NAD+ boost but into other factors e.g. CD38. So from my side we stop this conparison of NA to NR. 

 

 

Stefan, your study use nicotinamide not nicotinic acid

 

 

 

ah yes thats true this is a NAM study, anyways now I am off. Btw dont forget to explain this one:

 

----------------

Posted Yesterday, 09:16 PM

Tom Andre F. (ex shinobi), on 07 Jul 2016 - 7:25 PM, said:

 

Furthermore, NR is probably also a methyl consumer, so even if no flush, one would have to take B6, B9 and B12 with it is the case for all B3s

 

 

 

Well NR is not niacinamide, its niacinamide(nicotinamide) riboside which means it has already a ribose sugar bonded to it. It cannot not work like niacinamide.

Edited by stefan_001, Yesterday, 09:17 PM.

-----------------------------------------------

 

[Tom Andre F. (ex shinobi)]

 

 

Well NR is not niacinamide, its niacinamide(nicotinamide) riboside which means it has already a ribose sugar bonded to it. It cannot not work like niacinamide.

Edited by stefan_001, Yesterday, 09:17 PM.

-----------------------------------------------

 

 

I supposed you mean the opposite ?

 

Well I dont see why the Ribose would make it work different regarding methylation. Still the process remain unclear, or at least I didnt found much studies about it, so I would play cautious and take it along other B vitamins known to keep in check your methyl and then your homocysteine. But would love to see more data here.

 

The over and under methylation can be regulated if we take the B3 along B6, B9 and B12

 

 

[Kirito]

Found this interesting:

 

Niacin receptor activation improves human microvascular endothelial cell angiogenic function during lipotoxicity.

http://www.ncbi.nlm....pubmed/25463108

 

"Although both niacin and NMN improved HMVEC tube formation during palmitate overload, only NMN increased cellular NAD(+) and SIRT1 activity."

[Logic]

I think I will wait until a proper direct genetic solution arrives rather than waste my money on supplements I am yet to see concrete evidence work in humans. Sure some mouse studies are interesting and I work in mouse testing so I know that translation is not always a given. I will take the supplement vendors advice in the article and wait. Certainly not interested in paying the ridiculous prices these companies charge for things I can source directly from my suppliers at factory cost especially given the human data is not reliable at this time. 

 

As I have previously said I think there is more mileage with tackling the root of the problem eg, NFKB, CD38 and chronic inflammation via senolytics and other robust approaches. I will collect NAD/NADH data in our current study and we will soon find out if reducing CD38 allows the NAD/NADH ratio to bounce back, that is what is really important here, that ratio is critical. 

 

I agree, but think the sources of increased inflammation are easier to treat than gene editing and treatable today:

 

Compared to their decreases in the model group, berberine administration restored the relative level of Bifidobacteria (2.16 ± 0.63 vs. 0.50 ± 0.08, P < 0.01) and the ratio of Bacteroidetes/ Firmicutes (0.76 ± 0.26 vs. 0.39 ± 0.11, P < 0.01), respectively, in the treatment groups. Microbiota restoration led to significant reductions in body weight, serum levels of lipids, glucose, insulin, and homeostasis model assessment of insulin resistance. Improvements were also observed in the serum transaminase activity and nonalcoholic fatty liver disease activity score, which demonstrated the attenuation of NASH. Mechanically, expression levels of CD14, IL-1, IL-6 and TNF-α were statistically down-regulated (treatment group vs model group, P < 0.01).

http://www.ncbi.nlm....pubmed/26923892

 

Treatment with 40 mg/kg berberine significantly increased the survival rate of mice challenged with Salmonella typhimurium (LT2), but berberine show no effects in bacteriostasis. Further study indicated that treatment with 0.20 g/kg berberine markedly increased the survival rate of mice challenged with 2 EU/ml bacterial endotoxin (LPS) and postpone the death time of the dead mice. Moreover, pretreatment with 0.05 g/kg berberine significantly lower the increasing temperature of rabbits challenged with LPS. The studies of molecular mechanism demonstrated that Berberine was able to bind to the TLR4/MD-2 receptor, and presented higher affinity in comparison with LPS. Furthermore, berberine could significantly suppressed the increasing expression of NF-κB, IL-6, TNFα, and IFNβ in the RAW264.7 challenged with LPS.

http://www.ncbi.nlm....les/PMC3946165/

 

Accumulating evidence suggests that the gut microbiota is an important factor in mediating the development of obesity-related metabolic disorders, including type 2 diabetes. Metformin and berberine, two clinically effective drugs for treating diabetes, have recently been shown to exert their actions through modulating the gut microbiota. In this study, we demonstrated that metformin and berberine similarly shifted the overall structure of the gut microbiota in rats. Both drugs showed reverting effects on the high-fat diet-induced structural changes of gut microbiota. The diversity of gut microbiota was significantly reduced by both berberine- and metformin-treatments. Nearest shrunken centroids analysis identified 134 operational taxonomic units (OTUs) responding to the treatments, which showed close associations with the changes of obese phenotypes. Sixty out of the 134 OTUs were decreased by both drugs, while those belonging to putative short-chain fatty acids (SCFA)-producing bacteria, including Allobaculum, Bacteriodes, Blautia, Butyricoccus, and Phascolarctobacterium, were markedly increased by both berberine and, to a lesser extent, metformin. Taken together, our findings suggest that berberine and metformin showed similarity in modulating the gut microbiota, including the enrichment of SCFA-producing bacteria and reduction of microbial diversity, which may contribute to their beneficial effects to the host.
http://www.ncbi.nlm....pubmed/26396057

 

All thx to Lumia's thread here:
http://www.longecity...and-probiotics/

NB:  The other herbs discussed and the need for probiotics.

 

As mentioned before:

• The gut, the barrier between us and near instant death by septicemia, has a turnover of just 5 days.
• This means that it ages faster than the rest of us, becoming ever more leaky, allowing toxins, pathogens and possibly even improperly digested foodstuffs through.
• It also becomes more dysbiotic with age, speeding up this aging faster than the rest of us effect.
• Telomere length probably becomes an issue far sooner at a cell turnover of just 5 days.
• The stem and progenitor cells replacing the senescent gut cells are located closeby enough to benefit from oral telomerase activators: http://www.ncbi.nlm....les/PMC2965634/

More info/proof here:

http://www.longecity...g-in-zebrafish/

 

For those daring enough to venture off this NR reservation:  

• AGEs are the other main reason for inflammation.
• AGE formation is catalysed (greatly speeded up to beyond the natural rate of clearance..?) by the accumulating of Iron, copper, etc and heavy metals...
• All AGE blockers and breakers are chelators..!?

Edited by Logic, 08 July 2016 - 10:41 AM.

[Nate-2004]

I agree, but think the sources of increased inflammation are easier to treat than gene editing and treatable today:

 

Compared to their decreases in the model group, berberine administration restored the relative level of Bifidobacteria (2.16 ± 0.63 vs. 0.50 ± 0.08, P < 0.01) and the ratio of Bacteroidetes/ Firmicutes (0.76 ± 0.26 vs. 0.39 ± 0.11, P < 0.01), respectively, in the treatment groups. Microbiota restoration led to significant reductions in body weight, serum levels of lipids, glucose, insulin, and homeostasis model assessment of insulin resistance. Improvements were also observed in the serum transaminase activity and nonalcoholic fatty liver disease activity score, which demonstrated the attenuation of NASH. Mechanically, expression levels of CD14, IL-1, IL-6 and TNF-α were statistically down-regulated (treatment group vs model group, P < 0.01).

http://www.ncbi.nlm....pubmed/26923892

 

Treatment with 40 mg/kg berberine significantly increased the survival rate of mice challenged with Salmonella typhimurium (LT2), but berberine show no effects in bacteriostasis. Further study indicated that treatment with 0.20 g/kg berberine markedly increased the survival rate of mice challenged with 2 EU/ml bacterial endotoxin (LPS) and postpone the death time of the dead mice. Moreover, pretreatment with 0.05 g/kg berberine significantly lower the increasing temperature of rabbits challenged with LPS. The studies of molecular mechanism demonstrated that Berberine was able to bind to the TLR4/MD-2 receptor, and presented higher affinity in comparison with LPS. Furthermore, berberine could significantly suppressed the increasing expression of NF-κB, IL-6, TNFα, and IFNβ in the RAW264.7 challenged with LPS.

http://www.ncbi.nlm....les/PMC3946165/

 

Accumulating evidence suggests that the gut microbiota is an important factor in mediating the development of obesity-related metabolic disorders, including type 2 diabetes. Metformin and berberine, two clinically effective drugs for treating diabetes, have recently been shown to exert their actions through modulating the gut microbiota. In this study, we demonstrated that metformin and berberine similarly shifted the overall structure of the gut microbiota in rats. Both drugs showed reverting effects on the high-fat diet-induced structural changes of gut microbiota. The diversity of gut microbiota was significantly reduced by both berberine- and metformin-treatments. Nearest shrunken centroids analysis identified 134 operational taxonomic units (OTUs) responding to the treatments, which showed close associations with the changes of obese phenotypes. Sixty out of the 134 OTUs were decreased by both drugs, while those belonging to putative short-chain fatty acids (SCFA)-producing bacteria, including Allobaculum, Bacteriodes, Blautia, Butyricoccus, and Phascolarctobacterium, were markedly increased by both berberine and, to a lesser extent, metformin. Taken together, our findings suggest that berberine and metformin showed similarity in modulating the gut microbiota, including the enrichment of SCFA-producing bacteria and reduction of microbial diversity, which may contribute to their beneficial effects to the host.
http://www.ncbi.nlm....pubmed/26396057

 

All thx to Lumia's thread here:
http://www.longecity...and-probiotics/

NB:  The other herbs discussed and the need for probiotics.

 

As mentioned before:

• The gut, the barrier between us and near instant death by septicemia, has a turnover of just 5 days.
• This means that it ages faster than the rest of us, becoming ever more leaky, allowing toxins, pathogens and possibly even improperly digested foodstuffs through.
• It also becomes more dysbiotic with age, speeding up this aging faster than the rest of us effect.
• Telomere length probably becomes an issue far sooner at a cell turnover of just 5 days.
• The stem and progenitor cells replacing the senescent gut cells are located closeby enough to benefit from oral telomerase activators: http://www.ncbi.nlm....les/PMC2965634/

More info/proof here:

http://www.longecity...g-in-zebrafish/

 

For those daring enough to venture off this NR reservation:  

• AGEs are the other main reason for inflammation.
• AGE formation is catalysed (greatly speeded up to beyond the natural rate of clearance..?) by the accumulating of Iron, copper, etc and heavy metals...
• All AGE blockers and breakers are chelators..!?

 

 

I agree with all your points and I'll add to the first point that I still think people are way too optimistic about gene editing. I realize that CRISPR is very promising and certainly more robust as a solution but as I said earlier, there's going to be political barriers that will delay this option. It is pretty revolutionary from what I understand. Fountain of Youth type stuff.

 

As for microbiota, this is another excellent avenue that I'm pursuing right now. What I took and am trying from this thread and subsequent links therein, the key bacterial species that may reduce "inflammaging" considerably are Akkermansia, Bifidobacterium and Christensenellaceae. I know that synolitics is one avenue we're pursuing for targeting the rise in CD38 but I think this may be another factor, if inflammation is the cause. I'm less of an expert than you guys. What you quoted there above is very interesting as well. I don't know whether this also affects CD38 but it would be interesting to try and make that connection.

 

Side note (off topic): According to conclusions in that thread and the biologist specializing in the microbiome on Reddit, ways to possibly increase these particular species in your microbiome are to increase mucin levels by adding Glutamine, FOS, N-A-G, Fish Oil and perhaps even mucin on its own to your regimen. I've added all of those except mucin over the past 25 days now. I doubt I will notice anything for another 30 days or possibly much more because it takes a lot of time to change your microbiome in any way. It took me a year to increase the level of bifidobacterium with just regular probiotics and yogurt in addition to prebiotics like bananas, apples and whole grains like steel cut plain oatmeal from Quaker. My overall mood this year compared to last is considerably less anxious and far less depressed. There is a lot of association with that species and mood so I attribute some of that to this change, though I make other efforts in terms of exercise and mindset changes.

Edited by Nate-2004, 08 July 2016 - 08:02 PM.

[Harkijn]

Looking at the bright side again: the fact that more and more people from other 'reservations ' (quoting Logic) come to this one to do their thing, points to the growing interest in the NR story, as indications of it's use accumulate.

[Bryan_S]

Bryan, I just moderate what you say about niacin being a "poor patient compliance". In your link they do not cover the topic at all unlike what did lifeextension with Dr. William Davis cardiologist (but he is one of the many people that believe the flush is actually what show people its working :

 

http://www.lifeexten...7/3/atd/Page-01 :

 

 

"the flush is actually what show people its working" Maybe so but why do we need it? "More than 40 percent of the patients treated with standard niacin discontinued it because of adverse effects, compared with 6 percent of patients taking extended-release tablets." http://www.aafp.org/...0601/p3371.html

I'm not saying this is insurmountable because there are conditioning regiments and time released formulations but just consider the number of people that will take statins rather than Niacin. Its been proven people (and their Doctors) want the path of least resistance/pain. (see TABLE 6 Niacin (Nicotinic Acid)) for methods to take Niacin.

 

Also consider from the same article "Physicians are not the only parties at fault in the fight against CHD. Patient compliance is typically poor. Treatment of lipid abnormalities is a lifelong battle. Approximately one half of the patients taking lipid-lowering drugs discontinue their medication after one year, and 75 percent stop after two years."

 

Tom if you are truly on the Niacin bandwagon I'll tip my hat to you because this thread supports the NAD precurcers. However taking the RDA of Niacin, which you've suggested in your regiment, will hardly tip the scales in my opinion. Take into consideration we also live in a society that fortifies our grains with Niacin so most of us are already at or near the RDA and have been for decades. Now that's not to say you can't ovoid Niacin if you try.

 

I also can't find literature saying we need the flush. I can however find plenty on its pathway.

http://www.ncbi.nlm....les/PMC2779993/

 

The flush is a choice and if you want to try a regiment in the 1 to 2 gram region where Niacin has been used therapeutically you'll find as I that it diminishes but does not go away. So we can go around in circles claiming which precursor is best at raising NAD but there is no data to compare them in terms of efficiency and they both take different paths.

 

So since you're only dosing near the RDA range you're not speaking from experience. My wife is another example of someone who will not Niacin because of the Flush. Take a walk on the other side and you will see why there are compliance problems with the general population taking Niacin at therapeutic dosages. So I don't diminish its value medically if you can take the flush but I'm not convinced its better than Nicotinamide Riboside and the flush doesn't appear to be necessary. 

 

Targeting Sirtuin 1 to Improve Metabolism: All You Need Is NAD+?

"the hypothesis that the therapeutic efficacy of niacin is mediated by GPR109A activation needs to be revisited. First, even if GPR109A has a relatively high affinity for NA (EC50, ∼100 nM), such levels of NA are rarely found in plasma unless pharmacologically primed (Kirkland, 2009), indicating that the activation of GRP109A by NA is probably fortuitous but not biologically relevant in the basal state. Second, many of the beneficial effects of niacin, such as the lipid-lowering effects (Kamanna and Kashyap, 2008), take place at concentrations higher than those required for GPR109A activation but lead to intracellular NAD+ accumulation (Jackson et al., 1995). It is therefore tempting to speculate that some of the effects promoted by niacin might be achieved through an NAD+-induced activation of SIRT1 and the consequent deacetylation of the multiple SIRT1 targets that act as critical regulators of fatty acid, lipid and sterol homeostasis in eukaryotes, such as PGC-1α, FOXOs, LXR, or SREBP-1c (described in section II.C). An additional appealing possibility to explain the effects of niacin involves the fact that it leads to adiponectin release from the white adipose tissue (Vaccari et al., 2007; Westphal et al., 2007). Adiponectin then activates AMPK in muscle and liver tissues, which would enhance NAD+ content and SIRT1 activity (Cantó et al., 2009; Iwabu et al., 2010). Therefore, future work is urgently needed to elucidate the contribution of SIRT1 as a potential mediator of niacin's beneficial health effects."

Edited by Bryan_S, 10 July 2016 - 06:41 AM.

[Nate-2004]

Is there anything wrong with taking both Niacin AND Nicotinamide Riboside together? I am trying that right now but not sure if I should be. I can handle the flush as it doesn't really affect me much (could be the NR somehow). I figure it would save on the amount of NR I'd have to take.

 

While I have noticed a considerable improvement in many areas in terms of energy and work outs I've yet to notice an effect on my neurodegenerative movement disorder. Bryan are there any studies on how NR might affect neurodegernation and movement disorders? Essential Tremor in my case and Parkinson's? Perhaps it would take more therapeutic levels of the stuff?

Edited by Nate-2004, 10 July 2016 - 06:44 PM.

[stefan_001]

 

Bryan, I just moderate what you say about niacin being a "poor patient compliance". In your link they do not cover the topic at all unlike what did lifeextension with Dr. William Davis cardiologist (but he is one of the many people that believe the flush is actually what show people its working :

 

http://www.lifeexten...7/3/atd/Page-01 :

 

 

"the flush is actually what show people its working" Maybe so but why do we need it? "More than 40 percent of the patients treated with standard niacin discontinued it because of adverse effects, compared with 6 percent of patients taking extended-release tablets." http://www.aafp.org/...0601/p3371.html

I'm not saying this is insurmountable because there are conditioning regiments and time released formulations but just consider the number of people that will take statins rather than Niacin. Its been proven people (and their Doctors) want the path of least resistance/pain. (see TABLE 6 Niacin (Nicotinic Acid)) for methods to take Niacin.

 

Also consider from the same article "Physicians are not the only parties at fault in the fight against CHD. Patient compliance is typically poor. Treatment of lipid abnormalities is a lifelong battle. Approximately one half of the patients taking lipid-lowering drugs discontinue their medication after one year, and 75 percent stop after two years."

 

Tom if you are truly on the Niacin bandwagon I'll tip my hat to you because this thread supports the NAD precurcers. However taking the RDA of Niacin, which you've suggested in your regiment, will hardly tip the scales in my opinion. Take into consideration we also live in a society that fortifies our grains with Niacin so most of us are already at or near the RDA and have been for decades. Now that's not to say you can't ovoid Niacin if you try.

 

I also can't find literature saying we need the flush. I can however find plenty on its pathway.

http://www.ncbi.nlm....les/PMC2779993/

 

The flush is a choice and if you want to try a regiment in the 1 to 2 gram region where Niacin has been used therapeutically you'll find as I that it diminishes but does not go away. So we can go around in circles claiming which precursor is best at raising NAD but there is no data to compare them in terms of efficiency and they both take different paths.

 

So since you're only dosing near the RDA range you're not speaking from experience. My wife is another example of someone who will not Niacin because of the Flush. Take a walk on the other side and you will see why there are compliance problems with the general population taking Niacin at therapeutic dosages. So I don't diminish its value medically if you can take the flush but I'm not convinced its better than Nicotinamide Riboside and the flush doesn't appear to be necessary. 

 

 

 

Here some testing data of NA use in rats at various doses. Low dosing seems irrelevant. The control diet rats are roughly on RDA level of NA. NR has been reported to increase NAD+ in the blood in humans upto 2.7 times. Here they report 50% increase in the rats at 1000mg/kg which is roughly similar to 1000mg dosing for a human. Yes rats are not humans but its both in-vivo as opposed to cell lines. Its from this study:

http://www.ncbi.nlm..../pubmed/7782898

Attached Files

•  NA increase.JPG   72.55KB   3 downloads

Edited by stefan_001, 10 July 2016 - 08:31 PM.

[Harkijn]

June 6 Vincent Giuliano held a public speech about anti-aging strategies, as per his announcement on the aging firewalls website. Does anyone have access to a transcript of that speech? It would be interesting to get an update on his views on NA and NAM which were so negative in 2010. I posted a request on the website but it must be lost in virtual space... Come to think of it  no  guest comment whatsoever has ever been posted on that website......

[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.

Edited by Logic, 11 July 2016 - 03:17 PM.

[Tom Andre F. (ex shinobi)]

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.

 

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.

 

Edited by Tom Andre F. (ex shinobi), 11 July 2016 - 04:21 PM.

[Nate-2004]

Interesting Logic,

 

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

 

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.

 

 

 

As I understand it, Niacin causes homocysteine to be excreted by white adipose tissue but you say this can be helped with B6 and B9 right? Why stay at the RDA then? By the way, this study shows that larger doses of L-Carnosine may suppress WAT and innervate BAT.  Not sure if that helps. It's a single study on rats.

 

I think the homocysteine issue is certainly cause for concern and more study on that with regards to NAD replacement precursors should be pursued in addition to finding ways of getting CD38 under control.

[Tom Andre F. (ex shinobi)]

 

 

As I understand it, Niacin causes homocysteine to be excreted by white adipose tissue but you say this can be helped with B6 and B9 right? Why stay at the RDA then? By the way, this study shows that larger doses of L-Carnosine may suppress WAT and innervate BAT.  Not sure if that helps. It's a single study on rats.

 

I think the homocysteine issue is certainly cause for concern and more study on that with regards to NAD replacement precursors should be pursued in addition to finding ways of getting CD38 under control.

 

 

This has to do with lot of things. Mostly: there is people said to be overmethylated and other undermethylated and very prone to dangerous homocysteine level.

 

All have to come in balance. So B3s are very methyl consumer while in the opposite B6,B9 (anti aging firewell suggest to use the max RDA not less not more: 400mcg per day) and B12 are shown to directly reduce homocysteine level since they are pro methyl.

 

People with mood disorder etc and definied as overmethylated get cured using B3 and then they can come again to the pro methyl in the mean time. What is sure is we need sulfur since food are less and less rich in it, so I also add some MSM and garlic (SAMe precursor) also shown to be good for cardio system.

 

Homocysteine as someone stated here was shown to shrink telomeres by 3 fold. Another study that i can give the link if i found it back showed that once your homocysteine raised even only one time in your life, even if then you managed it using B12 etc.. you still keep your death state to die from cardio problem... The authors didnt know why but strongly advised to always make sure to control it. Thats also why I really dont want to play more with precursor such as NA or NR until we have more data. For now I use quite low dose and make sure i get enough others Bs along

 

EDIT: the study :

 

http://www.ncbi.nlm....pubmed/19821378

 

Abstract

BACKGROUND:

Cardiovascular disease such as coronary artery disease, stroke and congestive heart failure, is a leading cause of death worldwide. A postulated risk factor is elevated circulating total homocysteine (tHcy) levels which is influenced mainly by blood levels of cyanocobalamin (vitamin B12), folic acid (vitamin B9) and pyridoxine (vitamin B6). There is uncertainty regarding the strength of association between tHcy and the risk of cardiovascular disease.

OBJECTIVES:

To assess the clinical effectiveness of homocysteine-lowering interventions (HLI) in people with or without pre-existing cardiovascular disease.

SEARCH STRATEGY:

We searched The Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (issue 3 2008), MEDLINE (1950 to August 2008), EMBASE (1988 to August 2008), and LILACS (1982 to September 2, 2008). We also searched in Allied and Complementary Medicine (AMED; 1985 to August 2008), ISI Web of Science (1993 to August 2008), and the Cochrane Stroke Group Specialised Register (April 2007). We hand searched pertinent journals and the reference lists of included papers. We also contacted researchers in the field. There was no language restriction in the search.

SELECTION CRITERIA:

We included randomised clinical trials (RCTs) assessing the effects of HLI for preventing cardiovascular events with a follow-up period of 1 year or longer. We considered myocardial infarction and stroke as the primary outcomes. We excluded studies in patients with end-stage renal disease.

DATA COLLECTION AND ANALYSIS:

We independently performed study selection, risk of bias assessment and data extraction. We estimated relative risks (RR) for dichotomous outcomes. We measured statistical heterogeneity using I(2). We used a random-effects model to synthesise the findings.

MAIN RESULTS:

We included eight RCTs involving 24,210 participants with a low risk of bias in general terms. HLI did not reduce the risk of non-fatal or fatal myocardial infarction, stroke, or death by any cause (pooled RR 1.03, 95% CI 0.94 to 1.13, I(2) = 0%; pooled RR 0.89, 95% CI 0.73 to 1.08, I(2) = 15%); and pooled RR 1.00 (95% CI 0.92 to 1.09, I(2): 0%), respectively.

AUTHORS' CONCLUSIONS:

Results from available published trials suggest that there is no evidence to support the use of HLI to prevent cardiovascular events.

 

Edited by Tom Andre F. (ex shinobi), 11 July 2016 - 05:05 PM.

[Nate-2004]

Homocysteine as someone stated here was shown to shrink telomeres by 3 fold. Another study that i can give the link if i found it back showed that once your homocysteine raised even only one time in your life, even if then you managed it using B12 etc.. you still keep your death state to die from cardio problem... The authors didnt know why but strongly advised to always make sure to control it. Thats also why I really dont want to play more with precursor such as NA or NR until we have more data. For now I use quite low dose and make sure i get enough others Bs along

 

That sounds incredibly scary to me. Is this because of telomere length? I should definitely get my levels checked. Now I have no idea if they ever rose at any time in my life though.

[Tom Andre F. (ex shinobi)]

 

Homocysteine as someone stated here was shown to shrink telomeres by 3 fold. Another study that i can give the link if i found it back showed that once your homocysteine raised even only one time in your life, even if then you managed it using B12 etc.. you still keep your death state to die from cardio problem... The authors didnt know why but strongly advised to always make sure to control it. Thats also why I really dont want to play more with precursor such as NA or NR until we have more data. For now I use quite low dose and make sure i get enough others Bs along

 

That sounds incredibly scary to me. Is this because of telomere length? I should definitely get my levels checked. Now I have no idea if they ever rose at any time in my life though.

 

 

A more recent study confirm what was found:

 

http://www.ncbi.nlm....pubmed/23440809

 

BACKGROUND:

Cardiovascular disease (including coronary artery disease, stroke and congestive heart failure), is a leading cause of death worldwide. Homocysteine is an amino acid with biological functions in methionine metabolism. A postulated risk factor is elevated circulating total homocysteine levels, which are associated with cardiovascular events. This is an update of a review previously published in 2009.

 

To assess the clinical effectiveness of homocysteine-lowering interventions in people with or without pre-existing cardiovascular disease.

SEARCH METHODS:

We searched The Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (2012, Issue 2), MEDLINE (1950 to Feb week 2 2012), EMBASE (1980 to 2012 week 07), and LILACS (1986 to February 2012). We also searched ISI Web of Science (1970 to February 2012). We handsearched the reference lists of included papers. We also contacted researchers in the field. There was no language restriction in the search.

SELECTION CRITERIA:

We included randomised controlled trials assessing the effects of homocysteine-lowering interventions for preventing cardiovascular events with a follow-up period of one year or longer. We considered myocardial infarction and stroke as the primary outcomes. We excluded studies in patients with end-stage renal disease.

DATA COLLECTION AND ANALYSIS:

We performed study selection, 'Risk of bias' assessment and data extraction in duplicate. We estimated risk ratios (RR) for dichotomous outcomes. We measured statistical heterogeneity using I(2). We used a random-effects model.

MAIN RESULTS:

In this updated systematic review, we identified four new randomised trials, resulting in a total of 12 randomised controlled trials involving 47,429 participants. In general terms, the trials had a low risk of bias. Homocysteine-lowering interventions compared with placebo did not significantly affect non-fatal or fatal myocardial infarction (pooled RR 1.02, 95% CI 0.95 to 1.10, I(2) = 0%), stroke (pooled RR 0.91, 95% CI 0.82 to 1.0, I(2) = 11%) or death by any cause (pooled RR 1.01 (95% CI 0.96 to 1.07, I(2): 6%)). Homocysteine-lowering interventions compared with placebo did not significantly affect serious adverse events (cancer) (1 RR 1.06, 95% CI 0.98 to 1.13; I(2) = 0%).

AUTHORS' CONCLUSIONS:

This updated Cochrane review found no evidence to suggest that homocysteine-lowering interventions in the form of supplements of vitamins B6, B9 or B12 given alone or in combination should be used for preventing cardiovascular events. Furthermore, there is no evidence suggesting that homocysteine-lowering interventions are associated with an increased risk of cancer.

 

 

 

 

you can see above that the patients stayed at high risk for stroke and cardio disease unfortunately. Anyway, back to topic:

 

http://www.yeastgeno...070635/overview

 

nicotinamide riboside hydrolase activity = Catalysis of the reaction: nicotinamide riboside + H2O = nicotinamide + D-ribose

[Harkijn]

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.

 

[Nate-2004]

 

 

Homocysteine as someone stated here was shown to shrink telomeres by 3 fold. Another study that i can give the link if i found it back showed that once your homocysteine raised even only one time in your life, even if then you managed it using B12 etc.. you still keep your death state to die from cardio problem... The authors didnt know why but strongly advised to always make sure to control it. Thats also why I really dont want to play more with precursor such as NA or NR until we have more data. For now I use quite low dose and make sure i get enough others Bs along

 

That sounds incredibly scary to me. Is this because of telomere length? I should definitely get my levels checked. Now I have no idea if they ever rose at any time in my life though.

 

 

A more recent study confirm what was found:

 

http://www.ncbi.nlm....pubmed/23440809

 

BACKGROUND:

Cardiovascular disease (including coronary artery disease, stroke and congestive heart failure), is a leading cause of death worldwide. Homocysteine is an amino acid with biological functions in methionine metabolism. A postulated risk factor is elevated circulating total homocysteine levels, which are associated with cardiovascular events. This is an update of a review previously published in 2009.

 

To assess the clinical effectiveness of homocysteine-lowering interventions in people with or without pre-existing cardiovascular disease.

SEARCH METHODS:

We searched The Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (2012, Issue 2), MEDLINE (1950 to Feb week 2 2012), EMBASE (1980 to 2012 week 07), and LILACS (1986 to February 2012). We also searched ISI Web of Science (1970 to February 2012). We handsearched the reference lists of included papers. We also contacted researchers in the field. There was no language restriction in the search.

SELECTION CRITERIA:

We included randomised controlled trials assessing the effects of homocysteine-lowering interventions for preventing cardiovascular events with a follow-up period of one year or longer. We considered myocardial infarction and stroke as the primary outcomes. We excluded studies in patients with end-stage renal disease.

DATA COLLECTION AND ANALYSIS:

We performed study selection, 'Risk of bias' assessment and data extraction in duplicate. We estimated risk ratios (RR) for dichotomous outcomes. We measured statistical heterogeneity using I(2). We used a random-effects model.

MAIN RESULTS:

In this updated systematic review, we identified four new randomised trials, resulting in a total of 12 randomised controlled trials involving 47,429 participants. In general terms, the trials had a low risk of bias. Homocysteine-lowering interventions compared with placebo did not significantly affect non-fatal or fatal myocardial infarction (pooled RR 1.02, 95% CI 0.95 to 1.10, I(2) = 0%), stroke (pooled RR 0.91, 95% CI 0.82 to 1.0, I(2) = 11%) or death by any cause (pooled RR 1.01 (95% CI 0.96 to 1.07, I(2): 6%)). Homocysteine-lowering interventions compared with placebo did not significantly affect serious adverse events (cancer) (1 RR 1.06, 95% CI 0.98 to 1.13; I(2) = 0%).

AUTHORS' CONCLUSIONS:

This updated Cochrane review found no evidence to suggest that homocysteine-lowering interventions in the form of supplements of vitamins B6, B9 or B12 given alone or in combination should be used for preventing cardiovascular events. Furthermore, there is no evidence suggesting that homocysteine-lowering interventions are associated with an increased risk of cancer.

 

 

I'm guessing that this implies that the study was done on those with previously or existing high homocysteine levels and that the damage was already done. I wonder if there is some way to undo the damage.

 

I didn't start taking this B complex from Doctor's Best till a month after I started NR. This one has the min/max suggestion of 400mcg of B9 and it has B12 and B6 as well. Anecdotally speaking when I started taking this my mood and energy improved significantly. 

 

I don't know whether or not I was under or over methylated at any point in life or during that month, but who knows.  I wonder if by taking Na (B3) in higher and higher doses one has to then take B6 and B12 in higher and higher doses. Would that not be true?

Edited by Nate-2004, 11 July 2016 - 06:22 PM.

[Bryan_S]

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.

 

Safety assessment of nicotinamide riboside, a form of vitamin B3 There is a safety profile don't suggest there isn't.

 

There have been no studies associating higher homocysteine levels to Nicotinamide Riboside. This is absurd, you provide no evidence of this at all. Niacin on the other hand does show evidence of increasing homocysteine levels.

 

Is this now become a witch hunt were if we throw enough unsubstantiated doubt at Nicotinamide Riboside something will stick. Gentlemen I don't have enough hours in a day to run down all of your "opinions." If you make a statement like "All this study confirm that all precursor looks bad way to increase NAD+ since you will expose yourself then to homocysteine etc" then link and point to the exact study findings your citing.

 

Tom you want so bad for all the precursors to be the same to make your point that this is not the way to go. If you think NAD Repletion/NAD boosting through Nicotinamide Riboside increases the risk of Cardiovascular disease, present your data. You want to be the scientist but linking unrelated studies to (NR) wont get you there and does this thread a disservice.

 

What you have done is say Niacin has this problem and it can be corrected by taking other supplements like "B6, B9 or B12 given alone or in combination and should be used for preventing cardiovascular events" No association to Nicotinamide Riboside has been demonstrated.

[Tom Andre F. (ex shinobi)]

 

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.

 

Safety assessment of nicotinamide riboside, a form of vitamin B3 There is a safety profile don't suggest there isn't.

 

There have been no studies associating higher homocysteine levels to Nicotinamide Riboside. This is absurd, you provide no evidence of this at all. Niacin on the other hand does show evidence of increasing homocysteine levels.

 

Is this now become a witch hunt were if we throw enough unsubstantiated doubt at Nicotinamide Riboside something will stick. Gentlemen I don't have enough hours in a day to run down all of your "opinions." If you make a statement like "All this study confirm that all precursor looks bad way to increase NAD+ since you will expose yourself then to homocysteine etc" then link and point to the exact study findings your citing.

 

Tom you want so bad for all the precursors to be the same to make your point that this is not the way to go. If you think NAD Repletion/NAD boosting through Nicotinamide Riboside increases the risk of Cardiovascular disease, present your data. You want to be the scientist but linking unrelated studies to (NR) wont get you there and does this thread a disservice.

 

What you have done is say Niacin has this problem and it can be corrected by taking other supplements like "B6, B9 or B12 given alone or in combination and should be used for preventing cardiovascular events" No association to Nicotinamide Riboside has been demonstrated.

 

 

Bryan sorry but I do not make any personal attack. And so far you always said to not have any financial interest into niagen isnt ?

 

What I see is the opposite, while you advice people to take large and frequent dose of niagen (the first few pages of this thread), you should rely on data that show there is no effect on the methyl process (very unlikely) unlike niacinamide. You propose this safety paper. Great. However very short period and no homocysteine monitored. This study monitored on a short period if whever or NR was mutagenic using different dosage versus control and niacinamide group.

 

More than that: your paper authors state the following:

 

each group was gavaged daily with either vehicle (water), 300, 1000, 3000 mg/kg of Niagen or 1260 mg/kg/day of nicotinamide, which is equivalent to 3000 mg/kg/day of Niagen on a molar basis.

 

And indeed niagen is half nicotinamide (niacinamide) and half ribose. So thats was my speculation but will come back to that point just after

 

Its important to note that all their biomarker showed that Niagen showed exact same result as niacinamide then as you can all in this study, for instance in the conclusion they give me a good point:

 

In addition, NR is thought to exhibit the same toxicity profile as nicotinamide, because evidence from a single dose pharmacokinetic study in humans suggests that it is metabolized in a manner similar to nicotinamide (unpublished results). Because there are no publicly available 90-day studies on either nicotinamide or NR, a toxicology study was completed where 300, 1000, or 3000 mg/kg body weight/day of NR, or 1260 mg/kg body weight/day of nicotinamide, which is equivalent to 3000 mg/kg/ day dose of NR on a molar basis, was administered to rats over the course of 90 days. Adverse effects at 3000 mg/kg body weight/day of NR included treatment-related adverse effects in liver, kidneys, testes, epididymides and ovaries. These effects included increases in clinical chemistry parameters related to hepatocyte damage (ALT, ALP, and GGT) and a corresponding increase in liver weight, centrilobular hepatocellular hypertrophy, and single cell necrosis. In addition, thyroid follicular cell hypertrophy and increased kidney weight with exacerbation of chronic progressive nephropathy were observed.

 

That being said, since nicotinamide is much more old studied molecule, we have that :

 

http://www.ncbi.nlm....pubmed/23768418

 

Nicotinamide had gene-specific effects on the methylation of CpG sites within the promoters and the expression of hepatic genes tested that are responsible for methyl transfer reactions (nicotinamide N-methyltransferase and DNA methyltransferase 1), for homocysteine metabolism (betaine-homocysteine S-methyltransferase, methionine synthase and cystathionine β-synthase) and for oxidative defence (catalase and tumour protein p53). It is concluded that nicotinamide-induced oxidative tissue injury, insulin resistance and disturbed methyl metabolism can lead to epigenetic changes. The present study suggests that long-term high nicotinamide intake may be a risk factor for methylation- and insulin resistance-related metabolic abnormalities.

 

http://www.ncbi.nlm....pubmed/18996527

 

In tissue culture nicotinamide treatment led to an increase in adipose tissue homocysteine secretion.

 

http://www.ncbi.nlm....pubmed/21918528

 

It also revealed that hypertensives had an abnormal methylation pattern, characterized by elevated fasting plasma levels of unmethylated substrates, nicotinamide, Hcy and norepinephrine. Therefore, it seems likely that high nicotinamide intake may be involved in the pathogenesis of Hcy-related cardiovascular disease.

 

etc...

 

Finally it seems more than likely that we should rely on current data that suggest half NR weight should be considered as nicotinamide isnt ? so when one point high dosage for NAD+ boosting, they have to also take these facts above into account.

 

Especially since nicotinamide is released already from NAD+ ase enzyme and since this vitamin form is already present in average foods.

 

Some persons here experienced bad sides from B3s so cautious even with NR.

 

EDIT: Bryan you said consume 1g of niagen per day, so means you get around 500mg nicotinamide + the ones from your NAD+ release + the ones from your normal food intake. If you think its safe then its fine. But is such amount high enough to really get significant boost over NAD+ ? its also the second concern closely linked to the first

 

 

 

Edited by Tom Andre F. (ex shinobi), 11 July 2016 - 08:03 PM.

[stefan_001]

 

 

 

 

 

Bryan sorry but I do not make any personal attack. And so far you always said to not have any financial interest into niagen isnt ?

 

 

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......

 

Edited by stefan_001, 11 July 2016 - 09:04 PM.

[Nate-2004]

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......

 

 

1. This is clearly not the case. He is not trying to sell beta-lapachone, he doesn't have any. He found a source for it and wanted to know if people wanted to pool funds into buying it from that source.

2. I gave both Bryan and Tom positive feedback because it's a very interesting discussion and I'd like to see what comes of it. I'm very interested in knowing whether Tom is right about this, not saying he is but I'm really concerned about the safety of both Na and NR and Logic posted something earlier about it breaking down into Nicotinamide and D-Riboside in the gut which is also incredibly interesting. NR is super expensive, if I'm wasting money on something that isn't the best means of increasing NAD+ I'd love to know the truth. This discussion is quite valuable and I'm hoping it leads to better understanding.

Edited by Nate-2004, 11 July 2016 - 09:18 PM.

[docmaas]

C'mon guys drop the ulterior motive/conspiracy crap and keep to the topic. Please.

 

FTR I don't see either of you as promoting one or the other for profit motives but rather because there is something about your chosen alternative that you find compelling or at least more so.   Since this is the NR thread NR and it's cousins should be the topic.  

 

Tom has, as requested, started his own thread o BL and largely stuck to it.  I'm subscribed to both and am interested in both.  

 

Mike

[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......

 

 

1. This is clearly not the case. He is not trying to sell beta-lapachone, he doesn't have any. He found a source for it and wanted to know if people wanted to pool funds into buying it from that source.

2. I gave both Bryan and Tom positive feedback because it's a very interesting discussion and I'd like to see what comes of it. I'm very interested in knowing whether Tom is right about this, not saying he is but I'm really concerned about the safety of both Na and NR and Logic posted something earlier about it breaking down into Nicotinamide and D-Riboside in the gut which is also incredibly interesting. NR is super expensive, if I'm wasting money on something that isn't the best means of increasing NAD+ I'd love to know.

 

 

1. yep ofcourse...and you know that because its written on an anonymous internet forum?

2. Is NR super expensive? If you stick to the recommended dosage its about 40USD / month. I dont find that expensive at all.

Edited by stefan_001, 11 July 2016 - 09:22 PM.

[Nate-2004]

1. yep ofcourse...and you know that because?

2. Is NR super expensive? If you stick to the recommended dosage its about 40USD / month. I dont find that expensive at all.

 

 

1. Because I follow that thread and talked to him in PM about it and whether it was worthwhile. Like Mike said, let's drop the silly conspiracy stuff and get back to what Tom and Bryan are debating.

2. We all know that the recommended dose on the bottle is not the most effective NAD+ boosting amount. I'm taking 500-1000mg/day. That's expensive. Even 40 a month is expensive for a supplement. It depends on your income.

[stefan_001]

 

1. yep ofcourse...and you know that because?

2. Is NR super expensive? If you stick to the recommended dosage its about 40USD / month. I dont find that expensive at all.

 

 

1. Because I follow that thread and talked to him in PM about it and whether it was worthwhile. Like Mike said, let's drop the silly conspiracy stuff and get back to what Tom and Bryan are debating.

2. We all know that the recommended dose on the bottle is not the most effective NAD+ boosting amount. I'm taking 500-1000mg/day. That's expensive. Even 40 a month is expensive for a supplement. It depends on your income.

 

 

1. each his opinion

2. I have a different experience, and personally I don't see myself going over 500mg. Being able to put 40SD to the side is a matter of priority, but thats my view.

[Tom Andre F. (ex shinobi)]

 

 

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 ?