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Nicotinamide Riboside [Curated]

nicotinamide riboside nicotinamide nad boosting charles brenner david sinclair leonard guarente niagen niacinamide nicotinamide mononucleotide

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#31 Bryan_S

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Posted 16 November 2015 - 07:17 PM

NIH researchers find potential target for reducing obesity-related inflammation

Monday, November 16, 2015

Lead researcher Michael N. Sack, M.D., Ph.D., a senior investigator at NIH’s National Heart, Lung, and Blood Institute, explained that he and his team identified the role of SIRT3 through an investigation involving 19 healthy volunteers who fasted for a 24-hour period.
 
“Previous research has shown that intermittent fasting or intermittent calorie restriction — by way of eating fewer calories for a few days a month — reduces inflammation,” said Dr. Sack. “We found through our study that this effect is mediated, in part, on a molecular level when SIRT3 blocks the activity of another molecule known as the NLRP3 inflammasome.” He explained that NLRP3 inflammasomes are components of an intracelluar immune response triggered when mitochondria undergo stress, such as from excess calorie intake.
 
By using cultured cells from a group of eight volunteers who did not fast, Dr. Sack and his team found evidence suggesting that SIRT3 can be activated not only through fasting, but also through the use of nicotinamide riboside, a vitamin B derivative. “Taken together, these early results point to a potential mechanism for addressing obesity-related inflammation, and thus diseases linked to this type of inflammation, such as asthma, Type 2 diabetes, rheumatoid arthritis, and atherosclerosis — conditions associated with a reduced quality of life and/or premature death,” Dr. Sack said.
 
Obesity remains a substantial health problem for the nation, affecting more than a third of adults and 17 percent of children, according to the Centers for Disease Control and Prevention. Efforts to manage weight, however, can be hindered by the effects of obesity-related diseases. “It is a vicious cycle,” said Dr. Sack. “Take asthma for example. An increase in obesity incidence has been associated with an increase in asthma incidence, but asthma makes it difficult for some to be physically active enough to lose weight.”
 
Dr. Sack and colleagues — who include researchers from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and Weill Cornell Medical College — are conducting a follow-up study at the NIH Clinical Center to determine whether the vitamin B derivative nicotinamide riboside can specifically reduce bronchial inflammation in individuals with asthma. If the results of the study are promising, Dr. Sack and colleagues will aim to conduct larger clinical trials to validate the findings and potentially inform treatment of obesity-related inflammation in asthma.
 
Update: http://medicalxpress...flammation.html Mentioned in the medical press 11-17-15
 
The earlier study on inflammation and Nicotinamide Riboside was also referenced: http://www.jci.org/articles/view/83260

Edited by Bryan_S, 17 November 2015 - 08:23 PM.

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#32 bluemoon

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Posted 16 November 2015 - 08:25 PM

ChromaDex Lead Ingredient NIAGEN® Nicotinamide Riboside Receives New Dietary Ingredient (NDI) Status From the FDA

http://investors.chr...icle&ID=2112546

 

 ...

Frank Jaksch Jr., founder and CEO of ChromaDex, commented, “Receiving NDI status from the FDA validates the safety dossier we have compiled for NIAGEN®.  Achieving NDI status is a significant milestone given that the FDA objected approximately 88% of NDI notifications in FY 2014. NDI status opens the door for the mainstream commercialization of NIAGEN® in dietary supplements.” 

 

But ChromaDex had been selling Niagen for over a year, right? 

 

I clicked to the report and was surprised to see this in it: "In August 2015, ChromaDex announced results from the first human clinical study which demonstrated that single doses of NIAGEN® nicotinamide riboside can elevate the co-enzyme NAD+ in the blood by as much as 2.7-fold and is safe."

 

I clicked to that clinical study link and got an error. 

 

I googled and found the August 12th press release: "The oral presentation and poster presented data which indicate that single doses of NIAGEN® NR can elevate the co-enzyme NAD+ in the blood by as much as 2.7-fold. In the first-in-humans clinical trial which involved dosing twelve healthy adult subjects, the group showed that blood cell NAD+ increased with single 100 mg, 300 mg and 1 gram doses of NIAGEN® NR. 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. 

 

I'm confused with respect to the 2.7 fold increase in NAD+ in blood and a 50% increase in blood at 300mg.


Edited by bluemoon, 16 November 2015 - 08:38 PM.


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#33 Bryan_S

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Posted 16 November 2015 - 08:40 PM

 

 

I clicked to that clinical study link and got an error. 

http://investors.chr...icle&ID=2078998

 

This is the proper link from Aug. 12, 2015

 

I've written them for clarification on these and other things like half-life. I'm assured we will see more details after the next long term human study concludes. Its currently running now.


Edited by Bryan_S, 16 November 2015 - 08:44 PM.


#34 bluemoon

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Posted 16 November 2015 - 10:29 PM

 

 

 

I clicked to that clinical study link and got an error. 

http://investors.chr...icle&ID=2078998

 

This is the proper link from Aug. 12, 2015

 

I've written them for clarification on these and other things like half-life. I'm assured we will see more details after the next long term human study concludes. Its currently running now.

 

 

Great, thanks. Guarente said in spring that the trial results will be out later this year. 

 

45 days left in the year -- not that I'm counting. 



#35 Bryan_S

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Posted 17 November 2015 - 01:19 AM

Its my impression they want to talk about the University of Iowa Department of Biochemistry (Brenner), University of Copenhagen and the University of Colorado Boulder study after the 8-week human study is completed. By the end of the year, I'm not holding my breath.


Edited by Bryan_S, 17 November 2015 - 01:20 AM.

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#36 Tom Andre F. (ex shinobi)

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Posted 17 November 2015 - 03:14 PM

Did you read this study: http://phisciences.c...c-Hydride-3.pdf

 

Im a meha hydrate consumer but it seems that it play a bad role on the NAD+/NADH ratio:

 

"In the body, 6 units of adenosine triphosphate (ATP) are produced per 2 units of NAD+ reduced. Theoretically, incorporating this reducing agent into a cellular environment could produce more cellular ATP as a function of increased NADH/NAD+ ratios"

 

So its good for short term energy (ATP) but actually bad for long term supplementation anti aging effect ?

 



#37 Bryan_S

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Posted 17 November 2015 - 07:04 PM

Did you read this study: http://phisciences.c...c-Hydride-3.pdf

 

Im a meha hydrate consumer but it seems that it play a bad role on the NAD+/NADH ratio:

 

"In the body, 6 units of adenosine triphosphate (ATP) are produced per 2 units of NAD+ reduced. Theoretically, incorporating this reducing agent into a cellular environment could produce more cellular ATP as a function of increased NADH/NAD+ ratios"

 

So its good for short term energy (ATP) but actually bad for long term supplementation anti aging effect ?

 

Its from 2002, its cast in the light of industrial and biochemical processes not human consumption. I did some further reading and its being marketed as a Antioxidant. On this note I did read a chemical assessment on this claim and they completely debunked the Antioxidant notion. Let's keep the discussion centered on bonafide scientific studies surrounding NAD precursors, Sirtuins, the B3's. All these studies are welcome but lets keep the topic conversation along the lines of NAD boosting to be true to our readers.

 

Tom if your passionate about this subject it needs its own thread.

 

Excerpts 

What Is the Scientific Evidence for Silica Hydride?
 
"There is no meaningful evidence to indicate that silica hydride products offer any health benefits."

 

"From the point of view of standard chemistry, however, the notion of enhancing health through hydride ions is highly problematic. A hydride is a hydrogen ion that carries two extra electrons, making it negatively charged. In its natural state, a hydrogen ion possesses no electrons and, therefore, carries a positive charge. When a hydrogen ion is forced to carry extra electrons, it becomes highly unstable and highly reactive. Hydrides are, in fact, so reactive that as soon as they contact a molecule of water they rip the water molecule to pieces. The result: the hydride disappears, leaving behind hydrogen gas (a substance that, within the body, is relatively inert) and hydroxide ions (the essence of alkalinity, and the active ingredient in Draino). Thus, if “silica hydride” supplements really did provide hydride ions, the ions would instantly disappear the moment they contacted anything moist, such as the mouth, the stomach, or the intestines. During its short existence, the hydride would have no time to act as an antioxidant or perform any other functions. It would simply leave behind a residue of alkalinity, a goal that could be accomplished more easily by, for example, consuming baking soda." http://therapy.epnet...chunkiid=214756


Edited by Bryan_S, 17 November 2015 - 08:21 PM.

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#38 Bryan_S

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Posted 18 November 2015 - 05:11 PM

NIH and ChromaDex Announce Material Cooperative Research and Development Agreement to Study the Effects of ChromaDex’s NIAGEN® Nicotinamide Riboside on Cockayne Syndrome and Ataxia Telangiectasia
 
The National Institute on Aging Has Preliminary Research That Supports Further Testing of NR for Possible Beneficial Effects on Xeroderma Pigmentosum
 

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#39 warner

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Posted 21 November 2015 - 01:57 PM

Bryan, if you didn't have such a negative reaction to niacin, would you be taking that instead of nicotinamide?

 

I think I've read now most of the related threads, and the impression I get is that, if you can tolerate it, niacin is better at raising NAD+ in the body than nicotinamide, and with less risk of SIRT1 inhibition.  So, for example, I'm thinking that 250 mg/d niacin (split into 2 doses) plus 250 mg/d NR (also split into 2 doses) is a pretty safe way to go.  What do you think?



#40 Bryan_S

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Posted 21 November 2015 - 05:06 PM

Bryan, if you didn't have such a negative reaction to niacin, would you be taking that instead of nicotinamide?

 

I think I've read now most of the related threads, and the impression I get is that, if you can tolerate it, niacin is better at raising NAD+ in the body than nicotinamide, and with less risk of SIRT1 inhibition.  So, for example, I'm thinking that 250 mg/d niacin (split into 2 doses) plus 250 mg/d NR (also split into 2 doses) is a pretty safe way to go.  What do you think?

 

I support some of these hybrid combinations but understand this is mainly theory but based on study results related to our circadian rhythms.

 

Niacin still has a longer road to get to NAD than the other 2 "available precursors" and Niacin can tax the liver at therapeutic doses as it dedicates resources to build upon this molecule.

 

The Gpr109a receptor is the root of the flush and over time this can be desensitized. I could given time begin to tolerate the flush. Still for the population as a whole getting people to embrace the flush without giving up the daily regiment is difficult. Obviously as seen on the Longecity forums there are very dedicated Niacin users. The effects with the Gpr109a receptor have been associated with good lipid (cholesterol) management and this has been the draw for many but now there seems to be a change in the general consensus as to where these benefits arise. Just raising NAD levels may be the key and the SIRT1 and SIRT3 activation that results may be where this lipid benefit arises. See Link

 

So if this is truly the case NR is the shortest route to NAD and SIRT1 and SIRT3 are both elevated as a primary effect and we also find the liver is not over taxed in the process. On the other hand cheap Nicotinamide (NAM) will also raise NAD levels and with this more SIRT3 is eventually produced but as we've read SIRT3 has a Nicotinamide binding pocket to inhibit activity so the end result is likely not as intense.

 

So I tend of look at all this thru the lens of nutrient sensors as it relates to reproduction and periods of famine. As we look at the Sirtuins they appear to modulate mitochondrial function to match nutrient supply. NR has the effect of a Calorie Restriction (CR) mimic and the cell responds by ramping up its vital maintenance process's protecting the cell until times of plenty. On the other hand Nicotinamide tells the cell I've got it good (nutritionally speaking) and in that world its not as imperative to extend the cells existence longer than normal for the reproduction of the organism.

 

In reality bumping up NAD with NA or NR will also eventually raise levels of NAM. We naturally swing between these states. As (NAM) levels increase eventually they begin to inhibit the very same (CR) benefits we seek. So its not just a black and white picture and these feedback loops are at work all thru the day and night. These nutrient swings are all tied to our circadian rhythm. So from this perspective I think we can help enhance each side of this cycle by supplementing with NR by day and using (NAM) Nicotinamide before bed.

 

Even as far back as 1976 the sedative effects of nicotinamide were being documented and this fits with the idea that its use helps reenforce our nighttime cycle. http://www.ncbi.nlm....v/pubmed/133816 Also from a nutritional standpoint the body doesn't need to gear up for the chase to feed itself if its being told nicotinamide levels are high. We can also find many other references to the use of nicotinamide in cases of schizophrenia to calm patients. I think the clinical observations are tied to a fundamental feedback loop telling the cell all is well, its time to relax.

 

So if this is the case and I think there is a lot of evidence to support this idea, we can enhance our natural cycle by timing what we take and what time we take it. JMHO


Edited by Bryan_S, 21 November 2015 - 05:10 PM.

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#41 warner

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Posted 21 November 2015 - 08:38 PM

Thanks Bryan for that detailed response.

 

I hadn't seen (or I missed) the notion of using circadian response to justify taking NAM before bed.  And given what we know about the response to, and half-life of, NR, it makes sense that the NAM won't be interfering with that.  However, it doesn't appear that we really know yet whether NAM or NA is the better choice, if augmenting NR.  Surmising what I've read on Longecity, if focused on increasing NAD+, then NA appears to be the better choice, but if sleep and flush issues are more important, then NAM may be better.

 

I asked Elysium Health whether using NR could be used to replace NA (or NAM) supplementation, and they responded that "It depends. If you're talking about its ability to increase NAD, then yes. If you take Niacin for other reasons then the answer would be no."  Now I suppose that's because of the various oddball effects of NA (or NAM), but, in reality, NR (if you could afford to take enough) may in fact completely replace all the really helpful effects of NA or NAM, but they just don't yet know the answer to that.

 

Given the recent benefits shown for B3 supplementation in the areas of Alzheimer's and skin cancer (where they used 2 doses per day of 500 mg NAM), and the various other benefits that have been known for much longer, it would make me nervous relying on only 250 mg/d NR without further evidence that this is sufficient and equivalent to larger doses of NA or NAM.  Thus your strategy of augmenting NR with NAM (or NA), but separating the dosage based on circadian rhythm, seems like a reasonable approach until more is known.

 

(btw, I'm 62 with several minor age-related problems that should be helped by NR, and will report on those at a later time in the appropriate thread)


Edited by warner, 21 November 2015 - 08:43 PM.


#42 Bryan_S

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Posted 22 November 2015 - 12:43 AM

I would take 100% NR if I could afford it but its too expensive to consider that in the 3 gram per day range I'd like. I've spoken with ChromaDex and they feel 1000mg is all that those of us in a supplementation regiment might take and the possibility of higher dosages might be used in the realm of treating disease. Currently the pricing structure discourages mega dosing. 

 

Back to the other conversation I have noticed if I take my NR to late in the evening it keeps me more alert and falling asleep can be a problem. Taking the NAM at the end of the day I've been sleeping great.

 

Did you see the post on NR and Hyperlipidemia? I haven't seen a lot of study in this area but it appears the attributes many seek from Niacin are available in NR and those benefits are SIRT3 related. At the moment I'm tapping my foot awaiting all the new PK results so we can approach our NR dosages with data to enhance our experience.



#43 warner

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Posted 22 November 2015 - 02:00 AM

I would take 100% NR if I could afford it but its too expensive to consider that in the 3 gram per day range I'd like. I've spoken with ChromaDex and they feel 1000mg is all that those of us in a supplementation regiment might take and the possibility of higher dosages might be used in the realm of treating disease. Currently the pricing structure discourages mega dosing. 

 

Back to the other conversation I have noticed if I take my NR to late in the evening it keeps me more alert and falling asleep can be a problem. Taking the NAM at the end of the day I've been sleeping great.

 

Did you see the post on NR and Hyperlipidemia? I haven't seen a lot of study in this area but it appears the attributes many seek from Niacin are available in NR and those benefits are SIRT3 related. At the moment I'm tapping my foot awaiting all the new PK results so we can approach our NR dosages with data to enhance our experience.

 

I am currently about half-way through the experiences thread, and hadn't seen the lipid reference (with your admonishment to return to this thread for further discussion  :) ).  Of course, this lipid stuff is one of the things that gives me pause about switching from NA to NAM, although I'm not sure when it's best to take the NA, unlike the NAM where taking it before bed makes sense.

 

An interesting issue for those of us with (early) glaucoma, is that NA increases IOP (intraocular pressure) as well as fluid accumulation in the retina (probably by increasing VEGF - vascular endothelial growth factor).  If too much fluid accumulates, you can get pockets of fluid in the retina that can disrupt and damage it.  And if IOP goes too high, it reduces blood flow to the retina, also damaging it.  In addition, one is most at risk from higher IOP at night, while sleeping, when blood pressure is low relative to IOP (not as much net pressure to push blood into eye), blood glucose is low (less fuel), and sleep apnea events may occur (less oxygen).  So the trick (for me) was to not take too much NA, and not take it before bed.  (One can hypothesize that these issues would also affect someone with AMD.)  Hopefully, the glaucoma case isn't like the cancer case, where, once something has gone wrong, treatments that might help reduce aging (estradiol supplementation, sirtuin activation, etc.) can actually make the existing cancer worse.  We'll see!

 

Anyway, for myself, I think I'll first just replace the NA with NR (250 mg/d) and see what happens to my eye and other conditions.  I'll eventually document all that stuff in the experiences thread.  For my wife, without such eye issues, she is trying the 250 mg NA (half night, half morning) plus 250 mg NR (half brunch, half dinner).  She has her own set of minor issues, so between the two of us we should cover quite a bit of ground wrt NR testing.  :)



#44 bluemoon

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Posted 22 November 2015 - 05:06 AM

  At the moment I'm tapping my foot awaiting all the new PK results so we can approach our NR dosages with data to enhance our experience

 

I think there are quite a few of us foot tapping about now. Elysium is already recommending 250mg with its product, not sure about the others. The 3-fold versus the 50% increase in NAD in blood at 250 mg hasn't been cleared up yet, but what are we likely to learn from studies? Resveratrol has been widely known for about ten years, and we still don't seem to have good information about dose except that Sinclair says he takes 1000 mg a day. What are you expecting the studies to show in coming weeks or months that is not known from the earlier ChromaDex studies?    


Edited by bluemoon, 22 November 2015 - 06:05 AM.


#45 Bryan_S

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Posted 22 November 2015 - 06:29 AM

 

I am currently about half-way through the experiences thread, and hadn't seen the lipid reference (with your admonishment to return to this thread for further discussion  :) ).  Of course, this lipid stuff is one of the things that gives me pause about switching from NA to NAM, although I'm not sure when it's best to take the NA, unlike the NAM where taking it before bed makes sense.

 

An interesting issue for those of us with (early) glaucoma, is that NA increases IOP (intraocular pressure) as well as fluid accumulation in the retina (probably by increasing VEGF - vascular endothelial growth factor).  If too much fluid accumulates, you can get pockets of fluid in the retina that can disrupt and damage it.  And if IOP goes too high, it reduces blood flow to the retina, also damaging it.  In addition, one is most at risk from higher IOP at night, while sleeping, when blood pressure is low relative to IOP (not as much net pressure to push blood into eye), blood glucose is low (less fuel), and sleep apnea events may occur (less oxygen).  So the trick (for me) was to not take too much NA, and not take it before bed.  (One can hypothesize that these issues would also affect someone with AMD.)  Hopefully, the glaucoma case isn't like the cancer case, where, once something has gone wrong, treatments that might help reduce aging (estradiol supplementation, sirtuin activation, etc.) can actually make the existing cancer worse.  We'll see!

 

Anyway, for myself, I think I'll first just replace the NA with NR (250 mg/d) and see what happens to my eye and other conditions.  I'll eventually document all that stuff in the experiences thread.  For my wife, without such eye issues, she is trying the 250 mg NA (half night, half morning) plus 250 mg NR (half brunch, half dinner).  She has her own set of minor issues, so between the two of us we should cover quite a bit of ground wrt NR testing.  :)

 

 

The Niacin (Na) issue would give me pause as well from an eye pressure standpoint. My wife shares this eye condition and I would be keenly interested if you begin to show benefits. I've read the appropriate nicotinamide supplementation might benefit glaucoma patients and NR is a more potent NAD precursor so you have intrigued me.

 

As far as the lipids are concerned we don't get that lowering benefit from NAM and the effect seems to stem from SIRT3 and this is attached to the Niacin (NA) and nicotinamide riboside (NR) precursors more specifically. I added the nicotinamide (NAM) to push my NAD higher than I could afford with the NR alone. With the NR I began to see benefits I hadn't expected in a skin condition called rosacea. I followed up on some reading and found those benefits were identified in some NAM studies. So rather than breaking the bank to push my NR dose higher I added the NAM and found the rosacea improved even further and the anti-inflammatory effects NR had originally helped with also got pushed one step further in the right direction. If I could afford to stay true to the NR alone I would do that and feel for my "conditions" the 1000mg's of NR I take is just enough to get me part way there and I get the final push from the NAM. So from a purist standpoint some might avoid the NAM all together, if they had deep enough pockets which I don't. 

 

In answer to the other question about the nicotinamide riboside pharmacokinetics (PK) studies. There is one study not listed in this link. They are detailing the human drug potential of NR over different doses and time scales. I'm waiting for the half-life data correlated with the NAD rise over various doses to outline some dosing regiments.



#46 warner

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Posted 22 November 2015 - 02:36 PM

The Niacin (Na) issue would give me pause as well from an eye pressure standpoint. My wife shares this eye condition and I would be keenly interested if you begin to show benefits. I've read the appropriate nicotinamide supplementation might benefit glaucoma patients and NR is a more potent NAD precursor so you have intrigued me.

 

Hmm... I seem to have gotten so caught up in blood flow and niacin effects, that I missed the obvious benefit I might have gotten from higher NAM (nicotinamide) doses.

 

Okay, well let me impart what I know about blood flow and niacin issues in a bit more detail, since it will put into perspective whatever results we later get with the NR, and also illustrates the complexity of B3 supplementation, and the larger issue of dealing with general aging vs. specific disease.  (btw, everyone gets glaucoma if they live long enough because there is a baseline rate of eye nerve degeneration that has been measured, but which doesn't result in glaucoma until a very advanced age in normal individuals.)

 

Glaucoma is usually treated by improving blood flow to the eye (retina and optic nerve) via reduction of IOP (intraocular pressure) by eye drops or surgical means.  The simple reason reduction of IOP is helpful is because blood flow into the eye is driven by the difference between your blood pressure and your IOP.  For otherwise healthy blood vessels, that difference needs to be at least 50 mm Hg.  In my case, for example, if my diastolic blood pressure is near 70, then IOPs greater than about 20 will further glaucoma progression, so I try to keep IOPs below 16 (I have a home tonometer to measure these).  Interestingly, my IOPs only go up about 1 unit for every 5 units of blood pressure, meaning that, when exercising with higher BP, my eyes are actually safer even though IOP goes up a few units (since the BP - IOP difference goes up faster than the IOP).  This also partly explains why more active individuals have reduced glaucoma risk, and slower glaucoma progression.

 

(There are also special risks associated with sleep that I alluded to in a previous post, and which I can describe in more detail if anyone is interested.)

 

What I found was that niacin (NA) supplementation of 125 mg/d or greater raised IOPs about 1-2 units (mm Hg), and also reduced visual field test (VFT) results (a VFT measures how well each eye perceives dim lights at various positions in one's visual field).  Since the general idea is that higher IOP reduces blood flow, which accelerates nerve degeneration, leading to reduced VFT results, it would seem that niacin supplementation would be a very bad idea for those with glaucoma!  And so I've kept it below 125 mg/d.

 

However, and this is the tricky part, it may be the case that, in spite of the higher IOPs and lower visual field results, I may have nonetheless been better off with higher niacin supplementation!  That's because its possible that my eye neurons were better off with the niacin, even though IOPs were a little higher, and the VFTs were a little lower.  The latter, in fact, was likely due to fluid accumulation in the retina (a known side effect of niacin).  So if the IOP doesn't go up too much, and the fluid accumulation is not too great, it's possible that your eye neurons are still better off with the higher levels of niacin.

 

So what I'm hoping is that the NR at 250 mg/d doesn't show the same negative effects on IOP and VFT seen with NA (and I guess NAM may have also worked).  I've only been on the NR for a few days, so not much to report yet.  However, on the first day I took both 250 mg of NR during the day, and 125 mg NA before bed.  On waking, my IOPs were 17.9 and 15.3 (left and right eyes; left eye is higher due history of sleeping on that side), which is higher than normal (more like 15 and 14).  This morning, after taking only the NR yesterday, and no NA before bed, my IOPs were 14.5 and 14, which is normal for me.

 

So that's good news:  the NR taken alone, even though at a higher dose than NA, does not appear to raise (next morning) IOP.  But we'll need a lot more data to pin that down, since IOPs are subject to a large number of influences.  For example, in addition to the BP connections mentioned above, any slight rise in adrenaline will raise IOPs quite a bit, and create a lot of noise in IOP measurements.  Even sitting down to write this response will raise my IOPs, so I took the measurements this morning before doing anything like that that would get me excited.  Anyway, it just means one needs a lot of IOP measurements to say anything meaningful about them (overcoming imprecision with more measurements).


Edited by warner, 22 November 2015 - 03:13 PM.

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#47 docmaas

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Posted 22 November 2015 - 05:29 PM

 

The Niacin (Na) issue would give me pause as well from an eye pressure standpoint. My wife shares this eye condition and I would be keenly interested if you begin to show benefits. I've read the appropriate nicotinamide supplementation might benefit glaucoma patients and NR is a more potent NAD precursor so you have intrigued me.

 

Hmm... I seem to have gotten so caught up in blood flow and niacin effects, that I missed the obvious benefit I might have gotten from higher NAM (nicotinamide) doses.

 

Okay, well let me impart what I know about blood flow and niacin issues in a bit more detail, since it will put into perspective whatever results we later get with the NR, and also illustrates the complexity of B3 supplementation, and the larger issue of dealing with general aging vs. specific disease.  (btw, everyone gets glaucoma if they live long enough because there is a baseline rate of eye nerve degeneration that has been measured, but which doesn't result in glaucoma until a very advanced age in normal individuals.)

 

Glaucoma is usually treated by improving blood flow to the eye (retina and optic nerve) via reduction of IOP (intraocular pressure) by eye drops or surgical means.  The simple reason reduction of IOP is helpful is because blood flow into the eye is driven by the difference between your blood pressure and your IOP.  For otherwise healthy blood vessels, that difference needs to be at least 50 mm Hg.  In my case, for example, if my diastolic blood pressure is near 70, then IOPs greater than about 20 will further glaucoma progression, so I try to keep IOPs below 16 (I have a home tonometer to measure these).  Interestingly, my IOPs only go up about 1 unit for every 5 units of blood pressure, meaning that, when exercising with higher BP, my eyes are actually safer even though IOP goes up a few units (since the BP - IOP difference goes up faster than the IOP).  This also partly explains why more active individuals have reduced glaucoma risk, and slower glaucoma progression.

 

(There are also special risks associated with sleep that I alluded to in a previous post, and which I can describe in more detail if anyone is interested.)

 

What I found was that niacin (NA) supplementation of 125 mg/d or greater raised IOPs about 1-2 units (mm Hg), and also reduced visual field test (VFT) results (a VFT measures how well each eye perceives dim lights at various positions in one's visual field).  Since the general idea is that higher IOP reduces blood flow, which accelerates nerve degeneration, leading to reduced VFT results, it would seem that niacin supplementation would be a very bad idea for those with glaucoma!  And so I've kept it below 125 mg/d.

 

However, and this is the tricky part, it may be the case that, in spite of the higher IOPs and lower visual field results, I may have nonetheless been better off with higher niacin supplementation!  That's because its possible that my eye neurons were better off with the niacin, even though IOPs were a little higher, and the VFTs were a little lower.  The latter, in fact, was likely due to fluid accumulation in the retina (a known side effect of niacin).  So if the IOP doesn't go up too much, and the fluid accumulation is not too great, it's possible that your eye neurons are still better off with the higher levels of niacin.

 

So what I'm hoping is that the NR at 250 mg/d doesn't show the same negative effects on IOP and VFT seen with NA (and I guess NAM may have also worked).  I've only been on the NR for a few days, so not much to report yet.  However, on the first day I took both 250 mg of NR during the day, and 125 mg NA before bed.  On waking, my IOPs were 17.9 and 15.3 (left and right eyes; left eye is higher due history of sleeping on that side), which is higher than normal (more like 15 and 14).  This morning, after taking only the NR yesterday, and no NA before bed, my IOPs were 14.5 and 14, which is normal for me.

 

So that's good news:  the NR taken alone, even though at a higher dose than NA, does not appear to raise (next morning) IOP.  But we'll need a lot more data to pin that down, since IOPs are subject to a large number of influences.  For example, in addition to the BP connections mentioned above, any slight rise in adrenaline will raise IOPs quite a bit, and create a lot of noise in IOP measurements.  Even sitting down to write this response will raise my IOPs, so I took the measurements this morning before doing anything like that that would get me excited.  Anyway, it just means one needs a lot of IOP measurements to say anything meaningful about them (overcoming imprecision with more measurements).

 

 

This is indeed interesting.  My IOPs have never been as low as they are now at 10/10.  I just checked my records and after starting supplementing with Niagen in February of this year -- generally 250mg/day and an additional 250mg on MWF when I swim -- in May they were tested at 10/10 and again just last month again at 10/10.   Here is my history:

 

05/15   10/10               latanoprost qhs OU
11/14   14/15               latanoprost qhs OU, last dose 2 days ago
02/14   12/13               latanoprost qAM OU 
10/13   11/12               latanoprost qhs OU 
03/13   10/12               latanoprost qhs OU
1/13    13/13               Travatan z qhs OU
12/11   14/17               Travatan z qhs OU, poor compliance over last 
                                        month
 
I typically have had difficulty remembering to take the drops and compliance has probably been 50-60% most of the time though I was a lot better when I had the 05/15 test so it was attributed to compliance.  compliance has been good most of the time since that 05/15 test but now I am thinking that the real benefit is coming from the NR.
 
I've been trying out larger doses the last month of up to 1gm trying to assess the benefit for my diabetes.  There does seem to be some benefit but not as acute as the NAC and glycine I take 2x/day.
 
Mike
 
 

 

 



#48 bluemoon

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Posted 22 November 2015 - 08:25 PM

 

In answer to the other question about the nicotinamide riboside pharmacokinetics (PK) studies. There is one study not listed in this link. They are detailing the human drug potential of NR over different doses and time scales. I'm waiting for the half-life data correlated with the NAD rise over various doses to outline some dosing regiments.

 

  

1) I still don't understand this ChromaDex statement from August:  "The oral presentation and poster presented data which indicate that single doses of NIAGEN® NR can elevate the co-enzyme NAD+ in the blood by as much as 2.7-fold. In the first-in-humans clinical trial which involved dosing twelve healthy adult subjects, the group showed that blood cell NAD+ increased with single 100 mg, 300 mg and 1 gram doses of NIAGEN® NR. 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.

 

Can someone explain the 2.7 fold increase versus the 50% fold increase stated in the above?

 

2) Of the three studies highlighted, a) one U. of Copenhagen study seems to do what ChromaDex has already stated above but adding 500mg. While of course important to see results after the ChromaDex study, we aren't likely to get much new information, right?

 

3) The other Copenhagen on the effects of 1000mg of NR on obese men study hasn't started and results are likely in late 2017. Why wouldn't they test at 250mg as well since that is often the suggested dose? The omission makes no sense to me.

 

4) Guarente said in April, "Studies with NAD+ precursors have begun, which indicate that NR is safe, and more data on the question of efficacy should be published later this year."  Bryan_S then posted that they seem to be waiting for the other studies to be published - so maybe Dec-Feb. But in August, Elysium announced it would start a 120 person double blind study this fall "that will focus on overall quality of life with specific measures related to metabolic health." Notice what is being measured wasn't specified. Nor is it clear if this is a first or second study.

 

At any rate, it seems like the next 'big' human NR trial results will be from Elysium, which adds pterostilbine to the mix, unfortunate for those who want just NR results.

Is any of the above incomplete or incorrect?  



#49 warner

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Posted 22 November 2015 - 08:25 PM

This is indeed interesting.  My IOPs have never been as low as they are now at 10/10.  I just checked my records and after starting supplementing with Niagen in February of this year -- generally 250mg/day and an additional 250mg on MWF when I swim -- in May they were tested at 10/10 and again just last month again at 10/10.   Here is my history:

 

05/15   10/10               latanoprost qhs OU
11/14   14/15               latanoprost qhs OU, last dose 2 days ago
02/14   12/13               latanoprost qAM OU 
10/13   11/12               latanoprost qhs OU 
03/13   10/12               latanoprost qhs OU
1/13    13/13               Travatan z qhs OU
12/11   14/17               Travatan z qhs OU, poor compliance over last 
                                        month
 
I typically have had difficulty remembering to take the drops and compliance has probably been 50-60% most of the time though I was a lot better when I had the 05/15 test so it was attributed to compliance.  compliance has been good most of the time since that 05/15 test but now I am thinking that the real benefit is coming from the NR.
 
I've been trying out larger doses the last month of up to 1gm trying to assess the benefit for my diabetes.  There does seem to be some benefit but not as acute as the NAC and glycine I take 2x/day.
 
Mike

 

I guess what we are hoping is that the "accelerated aging" of eye neurons seen in glaucoma patients can be brought back to the normal loss rate (or better) with NR.

 

Your sparse IOP data (not your fault, we should all have home tonometers) will be a bit tricky to interpret, for several reasons.  How accurate was the IOP measurement when it was taken?  What state were you in?  What state had you been in previous hours or days?  Etc.  For example, I can sometimes lower my IOPs by 1 or more units by simply sitting quietly after taking the first measurement (an adrenaline affect).  My morning IOPs are also a strong function of what happened the night before, where, for example, anything that causes disruption of sleep during the night will raise morning IOP (or even simply watching an exciting movie before bed).  Taking enough measurements every day over time will tell me whether one week differs from another, but even then those daily measurements need to be done in a consistent manner.

 

Moreover, any inconsistency in drop taking will cause a big change in IOPs.  The drops typically reduce IOPs pretty fast, and then they rise again during the course of the day (or until the next drop is taken).  I take my measurements in the morning, just before the next drop, so as to catch the worst case (since high overnight IOPs are most dangerous, and will affect one's morning IOP).  So, for example, if you're getting IOPs taken not long after applying your eye drops, then you're probably seeing unrealistically low results.  In other words, the drops don't reduce IOP to some consistent level that can be measured by your eye doctor, but rather drive your IOPs down and up during the day, making individual measurements suspect unless taken in a very consistent manner.

 

Further, all the glaucoma drops are affected by acclimation, with their effectiveness reduced over time (which is why, as some point, it is typical to have to resort to surgery to stop glaucoma progress... but hoping perhaps not with NR!).  So, for example, switching from Travatan Z to Latanoprost above (if I'm reading this correctly) you can see a significant IOP reduction with the change, although this may simply mean that you had become acclimated to Travatan Z, not that Latanoprost is actually any better long-term at reducing your IOPs.  In fact, we see the IOPs rise again as you continued to use Latanoprost.

 

"in May they were tested at 10/10 and again just last month again at 10/10"

 

Okay, so in isolation, the first 10/10 probably didn't mean much, given all the factors I just discussed.  But the fact that you got a second 10/10 just recently lends more credence to hypothesis that the NR had some effect.  Also, response to the Latanoprost should have, if anything, gotten worse over time, not better, lending further support to the hypothesis.  On the other hand,

 

"[compliance] was a lot better when I had the 05/15 test so it was attributed to compliance.  compliance has been good most of the time since that 05/15"

 

so those 2 data points are probably still confounded by better compliance.

 

Anyway, it's encouraging that the NR does not appear to be raising your IOPs, even when taking more than the 250 mg/d.  Given my experience with niacin, I wasn't expecting it to reduce IOP, but rather at best to simply slow glaucoma progression.  But it would be great if it also has some positive effect on IOP mechanics (i.e., improved more than one thing, which is what we're hoping for with NR).


Edited by warner, 22 November 2015 - 08:27 PM.


#50 warner

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Posted 22 November 2015 - 08:35 PM

 

1) I still don't understand this ChromaDex statement from August:  "The oral presentation and poster presented data which indicate that single doses of NIAGEN® NR can elevate the co-enzyme NAD+ in the blood by as much as 2.7-fold. In the first-in-humans clinical trial which involved dosing twelve healthy adult subjects, the group showed that blood cell NAD+ increased with single 100 mg, 300 mg and 1 gram doses of NIAGEN® NR. 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.

 

Can someone explain the 2.7 fold increase versus the 50% fold increase stated in the above?

I read that to mean that in some oddball study somewhere that saw a 2.7-fold increase (maybe Bryan recalls where that was), but "In the first-in-humans clinical trial" they saw 30-50%.



#51 docmaas

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Posted 22 November 2015 - 08:51 PM

 

This is indeed interesting.  My IOPs have never been as low as they are now at 10/10.  I just checked my records and after starting supplementing with Niagen in February of this year -- generally 250mg/day and an additional 250mg on MWF when I swim -- in May they were tested at 10/10 and again just last month again at 10/10.   Here is my history:

 

05/15   10/10               latanoprost qhs OU
11/14   14/15               latanoprost qhs OU, last dose 2 days ago
02/14   12/13               latanoprost qAM OU 
10/13   11/12               latanoprost qhs OU 
03/13   10/12               latanoprost qhs OU
1/13    13/13               Travatan z qhs OU
12/11   14/17               Travatan z qhs OU, poor compliance over last 
                                        month
 
I typically have had difficulty remembering to take the drops and compliance has probably been 50-60% most of the time though I was a lot better when I had the 05/15 test so it was attributed to compliance.  compliance has been good most of the time since that 05/15 test but now I am thinking that the real benefit is coming from the NR.
 
I've been trying out larger doses the last month of up to 1gm trying to assess the benefit for my diabetes.  There does seem to be some benefit but not as acute as the NAC and glycine I take 2x/day.
 
Mike

 

I guess what we are hoping is that the "accelerated aging" of eye neurons seen in glaucoma patients can be brought back to the normal loss rate (or better) with NR.

 

Your sparse IOP data (not your fault, we should all have home tonometers) will be a bit tricky to interpret, for several reasons.  How accurate was the IOP measurement when it was taken?  What state were you in?  What state had you been in previous hours or days?  Etc.  For example, I can sometimes lower my IOPs by 1 or more units by simply sitting quietly after taking the first measurement (an adrenaline affect).  My morning IOPs are also a strong function of what happened the night before, where, for example, anything that causes disruption of sleep during the night will raise morning IOP (or even simply watching an exciting movie before bed).  Taking enough measurements every day over time will tell me whether one week differs from another, but even then those daily measurements need to be done in a consistent manner.

 

Moreover, any inconsistency in drop taking will cause a big change in IOPs.  The drops typically reduce IOPs pretty fast, and then they rise again during the course of the day (or until the next drop is taken).  I take my measurements in the morning, just before the next drop, so as to catch the worst case (since high overnight IOPs are most dangerous, and will affect one's morning IOP).  So, for example, if you're getting IOPs taken not long after applying your eye drops, then you're probably seeing unrealistically low results.  In other words, the drops don't reduce IOP to some consistent level that can be measured by your eye doctor, but rather drive your IOPs down and up during the day, making individual measurements suspect unless taken in a very consistent manner.

 

Further, all the glaucoma drops are affected by acclimation, with their effectiveness reduced over time (which is why, as some point, it is typical to have to resort to surgery to stop glaucoma progress... but hoping perhaps not with NR!).  So, for example, switching from Travatan Z to Latanoprost above (if I'm reading this correctly) you can see a significant IOP reduction with the change, although this may simply mean that you had become acclimated to Travatan Z, not that Latanoprost is actually any better long-term at reducing your IOPs.  In fact, we see the IOPs rise again as you continued to use Latanoprost.

 

"in May they were tested at 10/10 and again just last month again at 10/10"

 

Okay, so in isolation, the first 10/10 probably didn't mean much, given all the factors I just discussed.  But the fact that you got a second 10/10 just recently lends more credence to hypothesis that the NR had some effect.  Also, response to the Latanoprost should have, if anything, gotten worse over time, not better, lending further support to the hypothesis.  On the other hand,

 

"[compliance] was a lot better when I had the 05/15 test so it was attributed to compliance.  compliance has been good most of the time since that 05/15"

 

so those 2 data points are probably still confounded by better compliance.

 

Anyway, it's encouraging that the NR does not appear to be raising your IOPs, even when taking more than the 250 mg/d.  Given my experience with niacin, I wasn't expecting it to reduce IOP, but rather at best to simply slow glaucoma progression.  But it would be great if it also has some positive effect on IOP mechanics (i.e., improved more than one thing, which is what we're hoping for with NR).

 

 

The switch from one drop to another was because the first was removed from the VA formulary.  None of the tests have been any closer than 5-6 hours from application of the drops and most more like 18 hours -- I suspect that it has always been at least 12 hours.  I usually apply the drops before bed.  The fact that both the 10/10 numbers occurred after the start of NR leads me to hope that NR is helpful but confounding cannot be ruled out.  

 

What kind of tonometer do you have?  They do seem quite expensive.  

 

My opthamologists and optometrists have never indicated any urgency about my glaucoma and only given positive feedback.  My visual field has remained good.  They were more enthusiastic when they saw 10/10 though.   I am also diabetic and there has been no sign of diabetic damage up to this point.

 

Mike



#52 warner

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Posted 22 November 2015 - 09:02 PM

The switch from one drop to another was because the first was removed from the VA formulary.  None of the tests have been any closer than 5-6 hours from application of the drops and most more like 18 hours -- I suspect that it has always been at least 12 hours.  I usually apply the drops before bed.  The fact that both the 10/10 numbers occurred after the start of NR leads me to hope that NR is helpful but confounding cannot be ruled out.  

 

What kind of tonometer do you have?  They do seem quite expensive.  

 

My opthamologists and optometrists have never indicated any urgency about my glaucoma and only given positive feedback.  My visual field has remained good.  They were more enthusiastic when they saw 10/10 though.   I am also diabetic and there has been no sign of diabetic damage up to this point.

 

Mike

 

Hi Mike.  I've got about 5 minutes to answer this, but will return later...

 

Yup, impractical for most to buy a home tonometer (mine cost more than $7000), but they keep working on this problem, and hopefully will soon have a solution.

 

Stable visual field plus 10/10 is as good as it gets (you need some pressure to keep the eyeball from collapsing  :) ).  If visual field declined from here, you'd be in for surgery, since you're at the limits of what drops can do.  OCTs can probably give you a more accurate view of what's happening with your glaucoma, but even they depend on consistent use, not always the case when poorly trained nurses are administering the test.  (I'll come back later and show some OCT images, since we are all interested in neuron aging, etc.)

 

Yup, you should be able to control diabetes, especially if not too advanced (i.e., controlled to the point that you don't really have "diabetes" day to day, and your blood sugar remains at a normal level).  One of the more preventable and treatable diseases, if caught early.


Edited by warner, 22 November 2015 - 09:05 PM.


#53 Hebbeh

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Posted 22 November 2015 - 09:39 PM

 

 

1) I still don't understand this ChromaDex statement from August:  "The oral presentation and poster presented data which indicate that single doses of NIAGEN® NR can elevate the co-enzyme NAD+ in the blood by as much as 2.7-fold. In the first-in-humans clinical trial which involved dosing twelve healthy adult subjects, the group showed that blood cell NAD+ increased with single 100 mg, 300 mg and 1 gram doses of NIAGEN® NR. 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.

 

Can someone explain the 2.7 fold increase versus the 50% fold increase stated in the above?

I read that to mean that in some oddball study somewhere that saw a 2.7-fold increase (maybe Bryan recalls where that was), but "In the first-in-humans clinical trial" they saw 30-50%.

 

 

The way I read it is they saw group average maximal increases of 50% but in at least one case saw individual (best responder) maximal blood increase of 2.7 fold.  Apples to oranges.  The 50% value was group average and the 2.7 fold increase in blood was not group average but apparently the best responder.  What this tells me is that some subjects saw as much as 2.7 fold increase and others saw very little if anything....to produce a group average of 30-50%.  This would explain why we have wildly varying reports of everything from non-responders to hugely apparent benefit.  If you have a NAD+ deficiency, you will probably see some degree of benefit....if you are apparently healthy, probably no discernible effect.  Which tells me you can't elevate NAD+ with NR above some degree of "normal" no matter the dose.  I am of the latter category...have been using various doses of NR on blind faith for almost a year with no discernible effect of any kind but continuing on the wishful thinking of the possible benefit of the science involved.  I believe these numbers explain a lot for all of us.

 

To add....I am 58 years old but in excellent health with no health conditions requiring treatment.

To add further....I have been supplementing with resveratrol for about 9 years now and C60/EVOO daily for 3 and half years (both since the beginning).


Edited by Hebbeh, 22 November 2015 - 10:02 PM.

  • Good Point x 2

#54 bluemoon

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Posted 22 November 2015 - 10:58 PM

Thanks for the replies. My guess is that if there was much variance around 50% at 300 mg in the ChromaDex study of 12 people then that will go in the paper for publication. I'm sure variance is included no matter what the variance is if a scientific paper.  



#55 warner

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Posted 22 November 2015 - 11:30 PM

Just a footnote about glaucoma drop compliance.  In general, the greatest reduction in IOP occurs soon after starting a new drop, and then lessens over time, as the eye becomes acclimated to the drug (at which point you switch drugs, or add another, until you run out of options and surgery is necessary).  The problem with acclimation to a particular drop isn't just that it doesn't work as well anymore, but that if you stop taking it, even for a day, your IOPs will usually go higher than what they were before you starting using that drop.  So, for example, if you started at 16 (mm Hg), and the drop takes you to 12, which then rises over a year or two to 14, missing a single dose may then take you to 18-20(!), and put your eye at risk.  Knowing that firsthand via my own IOP measurements has helped keep me very compliant.



#56 Bryan_S

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Posted 23 November 2015 - 02:09 AM

warner, On this topic of glaucoma and NR I think there is enough interest to dedicate a entire thread to this. Without question the neuroprotective effects seem to be what suffers of glaucoma would benefit from. I would also begin to research "nicotinamide riboside mitochondrial biogenesis" because increasing mitochondrial numbers within the cells of the eye would likely be of benefit. These effects have been associated with NR along with the SIRT1 and SIRT3 increases. I would also look over the previous post on the NLRP3 Inflammasome. All together Increasing cellular respiration, decreasing low-grade inflammation, increasing mitochondrial numbers and boosting NAD reserves seems to be a desired set of conditions in ameliorating many disease states not just glaucoma.

 

Hey bluemoon, I guess I'm the keeper of the data and can find most of what your asking. What I hope to learn is how long a single dose of NR carries us thru the day. I've contacted 2 researchers and ChromaDex directly chasing this answer. I've been asked to wait as the data is correlated and the longterm study is completed.

 

If last years 4-Hour-half-life data holds I already have a set of tables suggesting how often we might want to boost levels thru the day. Also they will be conducting long terms studies that will ask the question if the effectiveness of NR wanes with time. You see NR like all the other B3's is water soluble. As you consume a nutrient like this a certain amount of it is lost and excreted at a steady pace before it can do its intended job, so overdosing can waste money. The idea is to get as much as possible into the cells metabolic process without getting flushed down the drain. At some quantity a single mega dose starts to have diminishing returns because at those higher concentrations more is lost than can be utilized. So there is a theoretical dosing sweet spot where we would get the maximum NAD rise at the most economic rate.

 

I don't think any of us can afford to flush money down the drain. 

 

Depending on the PK data released a time released Niagen product might be warranted but there isn't enough data to say if this will work.

 

I cant reliably interpret the released data for you so don't take me to task. My take is a ceiling was reached at a 300mg oral dosage and a 50% rise was averaged among the participants. Giving them 1000mg only increased the time they spent at the 50% NAD rise and that didn't push levels higher just for longer.

 

As far as the 2.7 fold comment I think this represents 170% above normal levels. I think this figure was one of the maximum results or best of from the group.

 

The Aarhus University Hospital study for the University of Copenhagen is completed but unpublished. They would not comment on the outcome and have not published. They still have more studies to go as you inferred but 2-human studies have already been completed. This is the data I seek.

 

The University of Colorado Boulder is the next big one I know of 

http://www.colorado....volunteers.html

 

The one you mention "The company plans to initiate a placebo-controlled, double-blind, randomized study evaluating BASIS™ that will focus on overall quality of life with specific measures related to metabolic health. The trial will follow 120 people and Elysium Health plans to initiate it in the third quarter of 2015." So until its filed its flying under the radar. So far they haven't filed the paperwork.

BNN042.png

Some of us already add Pterostilbene to our NR regiments. In fact you can put together everything in BASIS™ yourself for much cheaper. Here is a list of ChromaDex suppliers. http://www.pteropure...ucts/index.html

 

 

I'm one of those malcontents who believes 250mg's is inadequate to produce "much" therapeutic change. Its a supplement dose just scratching the surface. I think its better than taking nothing but I don't think based on the Na or NAM research we could expect all that much change in someones heath at such a low dose. Now this is my opinion and certainly open to argument. I think that NR has so much going for it as a calorie restriction mimic. It gets to work faster and doesn't take as many bodily resources to get to NAD. Its also the preferred cellular exchange precursor along with NaR and called to action at sites of injury.

 

I believe when this product first became available it was trialled at around 17 dollars per bottle as a "supplement." Given what was available in the market I thought this was slightly expensive but tolerable for what it represented. Then some months later David Sinclair shook the B3 space with his nicotinamide mononucleotide (NMN) findings. Keep in mind this is not nicotinamide riboside (NR) and as we've learned (NMN) is likely reduced to (NR) at the cell membrane anyway. But just the same David Sinclair is a headlines grabber and although the (NR) research had already demonstrated many of his (NMN) results it was 'his' results that resonated with the Media and Press and the headlines of rejuvenating muscle from a 60-year old state to a 20-year old state creating a ton of "Irrational exuberance." 

 

I know all about Irrational exuberance. The master Louis Rukeyser explained the underpinnings of this state to me back in the 1980's. In the context of nicotinamide riboside (NR) it was close enough to nicotinamide mononucleotide (NMN) that people thought they could produce Sinclair's Lab results at home, on themselves. No one took into account the mega doses he used on the lab animals. So just like the Irrational exuberance that occasionally overwhelms the stock market and produces buying frenzies ChromaDex recognized they could get more for their new product with the hype Sinclair brought to the market. Being a publicly traded company this idea was good for shareholders and a new price point was determined with the buying frenzy Sinclair produced.

 

I still think they originally arrived at the proper price when Niagen was first introduced and it would now be more widely accepted at that price if they had not raised the price after the Sinclair hype. I think with the current price they've opened the door for the comparative/competitive research we're doing. If the pricing were more reasonable we wouldn't be looking at hybrid dosing with Na or Nam. So from a supplement standpoint I think its overpriced and the 250mg dose is insufficient, from a pharmaceutical standpoint it might be close to that value if it were marketed as a drug but as a supplement they are way off the mark.

 

So this is why I'm looking to get the most bang for the buck with the hybrid B3 approach.


Edited by Bryan_S, 23 November 2015 - 02:53 AM.


#57 warner

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Posted 23 November 2015 - 02:43 AM

I promised something about OCTs...  With respect to NR effects, glaucoma may be particularly interesting because it might be considered a case of advanced aging (faster than normal loss of eye neurons), and because such neuron loss can be very easily measured and monitored.  This can be done with an OCT (optical coherence tomography) machine, which very quickly gather info about the structure of the retina and optic disk in just a few seconds, using only harmless light.  The following chart shows part of a typical OCT report, the part that deals with glaucoma and loss of neurons around the optic disk/nerve:

 

Attached File  OCT RNFL.jpg   10.33KB   0 downloads

 

RNFL = retinal nerve fiber layer

OD = right eye, OS = left eye

TEMP = temporal (toward temple side of head)

SUP = superior (toward upper side of head)

NAS = nasal (toward nasal side of head)

INF = inferior (toward lower side of head)

...so TEMP->SUP->NAS->INF->TEMP on X-axis takes you on a loop around the optic disk

 

The black lines on the plot show the patient's current nerve fiber layer thickness around the optic disk, as compared to "normal" (green, no glaucoma) and less-than-normal (red).  So, in simple terms, if you lose enough nerve fiber (neurons) to drop into the red area, then you're very likely to have glaucoma symptoms, with some localized loss of vision corresponding to where the nerve fiber has degenerated/eroded. With glaucoma, this loss tends to first become acute in regions corresponding to one's peripheral vision.

 

In the case shown, this patient (myself in 2011), had some vision loss in his superior (upper) field of vision in both eyes, corresponding to the dip seen in both curves at the inferior (lower) part of the optic disk rim (what you perceive is the reverse of its projection onto the retina, so an inferior nerve loss produces a superior vision loss).  So, theoretically, this is a much better way of monitoring glaucoma progression, although it does depend on using the same make of machine each time, and well-trained operator.

 

So, anyway, I described all that just to illustrate that here is a case where one could precisely measure a kind of age-related nerve loss that may be affected by NR supplementation.  And since there is already evidence that B3 supplementation is helpful, there seems to be a reasonable chance that NR will do an even better job at slowing progression.

 

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

Another thing about my eye adventures you guys might find interesting is that my greatest glaucoma-related vision loss (documented with OCTs) was during a period of reduced calorie and carb consumption.  This was a good example of the pitfalls of exposing aging humans/mammals, with existing disease, to calorie restriction, and why NR (or whatever) is probably a much better way to go.  I can describe that experience in more detail if anyone is interested.



#58 sthira

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Posted 23 November 2015 - 04:27 AM

^^ I'm interested :-) maybe a new thread?

#59 warner

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Posted 23 November 2015 - 02:11 PM

^^ I'm interested :-) maybe a new thread?

Sounded like Bryan was willing to start a new thread about NR and Glaucoma.  Or maybe NR and eye disease, since stuff like diabetic retinopathy and AMD is much more common.  Perhaps he could start that by moving these off-topic glaucoma posts to the new thread.  What do you think Bryan?  (I'll refrain from posting more glaucoma stuff here until he indicates where the posts should go.  btw, IOPs were still normal this morning on 250 mg/d NR, which replaced 62.5 mg/d niacin, where latter was being kept low due to IOP and retinal fluid effects of niacin.)


Edited by warner, 23 November 2015 - 02:18 PM.


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#60 bluemoon

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Posted 23 November 2015 - 04:11 PM

 

I cant reliably interpret the released data for you so don't take me to task. 

 

 

I sure wasn't "taking you to task" on anything. I just put up a few points concerning where the NR trials might be at and wondered if you or anyone else could tie up a few loose ends included in my four points/questions.

 

So far, to my knowledge, Elysium' Basis has been cheapest if willing to add the 50mg of  pterostilbine, and if you are willing to commit to a year subscription, something I am not since I want to see what Procter & Gamble does fairly soon.

 

My hunch is that you may be correct with respect to 250mg being not enough for better effects. I think Sinclair said a year ago that you'd need at least 500mg a day of NR for "results" -- whatever those are. So i wondered if Elysium and other vendors thought sales would not take off if 500mg was recommended since it would be beyond what many would pay, especially in the likely long unproven time period. But the 100mg, 300mg and 1000mg study suggests 250mg is enough. 

 

I know all about irrational exuberance and did not succumb to it after Sinclair's NMN mice results for the reasons you stated. I thought Sinclair's results looked like they might be very promising in a few years and was surprised about the NR supplement approach when I first learned about it in spring of 2014 through Robert Pappa's interview. But I viewed NR as maybe a type of 'new generation' resveratrol after watching the Guarente clips. I didn't think he hyped it in that interview but simply said it looked quite promising and didn't want to wait for the pharmaceutical version.

 

I find it interesting that Sinclair thinks he should take 1000mg of resveratrol with his yogurt while Guarente seems to be adding 250mg of resveratrol a day to 250mg of NR and 50mg of pterostilibine. Technically, Guarente only said he was taking BASIS, not if he was taking a double dose, which I thought might be possible. Probably not double, but If so, I think he should say that. 


Edited by bluemoon, 23 November 2015 - 05:03 PM.






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