2255 replies to this topic

[stefan_001]

 

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.
 

 

When reading the personal experience topic it appears there is also effect on lower levels 125mg-250mg. The amount of people saying that is reasonable high so I would call that "evidence"....

[bluemoon]

 

 

When reading the personal experience topic it appears there is also effect on lower levels 125mg-250mg. The amount of people saying that is reasonable high so I would call that "evidence"....

 

 

True.

[Tom Andre F. (ex shinobi)]

 

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

 

 

I replied to you in a dedicated topic: http://www.longecity...silica-hydride/

 

[BigLabRat]

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.

 

Bryan, I'd be interested in the hybrid dosing options even if NR were cheap.

 

Nam, as you know, has many benefits that have not yet been demonstrated for NR. Like you, I take Nam at bedtime. I think your theories about Nam and circadian rhythm are spot on, but I began taking it at bedtime out of practical considerations: If I take it during the day, it makes me groggy.

 

As to Niacin--yes, it is a longer pathway to NAD+. But it is an independent pathway (as opposed to Nam and NR, which both move through NMN). And it seems to me that Niacin + NR might push NAD levels higher that NR alone, because the enzymes down the NA--->NAD pathway wouldn't be saturated.

 

Of course, I'm not sure how the pathways might be downregulated--or whether there is "cross-talk" between them. (Do you know references so I can get up to speed on this?)

[docmaas]

Bryan,

 

Would it be possible to have subgroups under the NR topic?  Specific diseases/maladies could spawn subgroups.  The advantage would be that for those with those maladies the relationship might be more visible and easily found if it were a subgroup of the NR thread.  Just an idea.

 

Mike

 

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.

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.

 

[Bryan_S]

Wow guys a lot of activity all of a sudden.

 

 

Sounded like Bryan was willing to start a new thread about NR and Glaucoma.

 

Sure I could start it but I have no problem if you guys start and manage it. I do see enough interest and lots of information to share.

 

 

 

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 do think 250mg is enough in a single dose but how long do you expect it to last? Based on the previously released half-life data of 4 hours your looking at a NAD bump that decays relatively fast. So the question of multiple dosing thru the day comes into question. If we can raise NAD by 50% how long would you like to keep it there? I'd like to keep it there for 8 to 12 hours per day.

 

 

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.

 

Keep in mind both are very similar molecules. Of these 2 pterostilibine is more readily absorbed. They are both SIRT1 activators and for what you get pterostilibine seems to be more bioactive. NR stimulates SIRT1 and SIRT3 so if we are trying to do more with SIRT1 why not SIRT3. This is what spurred my interest in Honokiol as a SIRT3 activator and why I added it. So which of these 2 guys has it right. I look at their relationship as the Master and Student and I feel Guarente takes a more measured approach to the data. I also like that he doesn't grandstand on his data and explains his ideas with better precision.

Edited by Bryan_S, 23 November 2015 - 11:57 PM.

[Tom Andre F. (ex shinobi)]

When you guys speak about niacin, you also speak about the flush free form (niacin as inositol hexaniacinate) ?

[warner]

When you guys speak about niacin, you also speak about the flush free form (niacin as inositol hexaniacinate) ?

I don't have any experience with that.  We used (wife still uses) Slo-Niacin, which Bernstein (of very low-carb for diabetes fame) used to recommend as a cheaper alternative to Niaspan.  However, we never escaped flushing with Slo-Niacin, and timing of the flush seems to have more to do with the nature of any meal you're taking it with.

 

wrt speculation in recent posts about ultimate value of NR, seems that even if it simply turned out to be a "better B3", having most of the positive effects of NA and NAM, w/o the drawbacks, then that would be a significant advance.  But hopefully NR does even more than that.

[Tom Andre F. (ex shinobi)]

 

When you guys speak about niacin, you also speak about the flush free form (niacin as inositol hexaniacinate) ?

I don't have any experience with that.  We used (wife still uses) Slo-Niacin, which Bernstein (of very low-carb for diabetes fame) used to recommend as a cheaper alternative to Niaspan.  However, we never escaped flushing with Slo-Niacin, and timing of the flush seems to have more to do with the nature of any meal you're taking it with.

 

wrt speculation in recent posts about ultimate value of NR, seems that even if it simply turned out to be a "better B3", having most of the positive effects of NA and NAM, w/o the drawbacks, then that would be a significant advance.  But hopefully NR does even more than that.

 

thanks. inositol hexaniacinate is not a slow release as far as i know, just a different form

 

actually maybe Im wrong but I make a link between the flushing effect and PGD2. Thats why I think anyone who want to take niacin should also take luteolin for exemple. Because otherwize, if we make the connexion with hair loss studies: it would bring directly to baldness.. (PGD2 connexion)

[stefan_001]

Perhaps this link was already posted in the other thread but as it is very extensive I thought repeating cannot hurt...:
http://www.sciencedi...550413112001921

[warner]

 

 

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 study I was trying to remember was talked about here:

http://weill.cornell...-precursor.html

"In 2007, the authors reported results of laboratory experiments finding that NR can increase NAD+ concentrations as high as 270 percent when compared with untreated control cells. No other known agent has been shown to achieve these types of increases in cells."

So that may be where the "2.7" came from, and may not have been a measurement from the much later human study.  We'll see.

[meth_use_lah]

Please stop with the logical fallacies. First when Chromadex manages to release the PK-data that was completed over a year ago I would consider their product.

 

A 2.7 fold maximum increase, 30% @ 100mg, 50% @ 300mg and 1000mg averages points to the possibility of a few B3-deficient individuals spiking a meaningless serum increase in the general pool to yield a 50% increase a cross the board.

 

Sinclair NMN-study in mice increases NAD slightly above 100%.

[Tom Andre F. (ex shinobi)]

I think the data wich shows also that the NAD level turn back to original state within a few hours is also meaningful.

[stefan_001]

Please stop with the logical fallacies. First when Chromadex manages to release the PK-data that was completed over a year ago I would consider their product.

 

A 2.7 fold maximum increase, 30% @ 100mg, 50% @ 300mg and 1000mg averages points to the possibility of a few B3-deficient individuals spiking a meaningless serum increase in the general pool to yield a 50% increase a cross the board.

 

Sinclair NMN-study in mice increases NAD slightly above 100%.

 

Always good to wait for data. Yet your reaction is somewhat inconsistent. You challenge a product over lack of data but on the otherhand you seem to make completely unfounded statements: "spiking a meaningless serum increase". You have "PK" data supporting the "meaningless" conclusion?

[Bryan_S]

Nicotinamide could halve Australia’s healthcare costs for skin cancers

 

http://www.nutraingr...or-skin-cancers

 

This is an interesting twist "A new health economics analysis paper has been presented to Australian lawmakers at Parliament House to show how nicotinamide could double the cost benefits of its use." Its being reported that the Australian healthcare system could save 2 dollars for every dollar spent on this preventive measure. Lawmakers at Parliament House are currently considering the details.

 

For more reading see || Nicotinamide Ontrac study nicotinamide ||

[Bryan_S]

Effects of High Fat Diet Induced Obesity on Mitochondrial Biogenesis and Function – Impact of Exercise or Nicotinamide Mononucleotide (NMN)

 

http://www.fasebj.or...upplement/777.8

 

Don't know how we missed this one but a full Longecity search say's we did.

 

Abstract

"Exercise has known beneficial impacts on the metabolic outcomes of obesity. Exercise improves metabolism by up-regulating mitochondrial activity, through increased levels of nicotinamide adenine dinucleotide (NAD⁺). Recent studies suggest that the NAD⁺ precursor nicotinamide mononucleotide (NMN) acts as an exercise mimetic by increasing NAD⁺ levels. Here we compared the effects of exercise and NMN on the metabolic consequences of high-fat diet (HFD) induced obesity. Sixty female C57BL6/J 5 week old mice were allocated across 5 interventions: Chow sedentary: CS; Chow exercise: CEX; HFD sedentary: HS; HFD NMN: HNMN; HFD exercise: HEX (12/group). After 6 weeks of diet exercise groups underwent treadmill exercise (15m/min for 45 minutes), 6 days per week for 6 weeks. NMN (500mg/kg body weight) was injected (IP) every day for the last 17 days. No significant alteration in body weight was observed in response to exercise or NMN. HEX and HNMN mice both showed significantly improved glucose tolerance compared to the HS group. Mitochondrial copy number was increased by NMN treatment (HNMN vs HS) but not by exercise. However, exercise, but not NMN, significantly ameliorated the HFD-induced reduction in muscle citrate synthase activity. All HFD groups showed reduced PGC1 protein. Overall these data suggest that exercise and NMN improve glucose tolerance through different mechanisms involving mitochondria in a HFD induced obese mouse model."

[Logic]

 

 

When you guys speak about niacin, you also speak about the flush free form (niacin as inositol hexaniacinate) ?

I don't have any experience with that.  We used (wife still uses) Slo-Niacin, which Bernstein (of very low-carb for diabetes fame) used to recommend as a cheaper alternative to Niaspan.  However, we never escaped flushing with Slo-Niacin, and timing of the flush seems to have more to do with the nature of any meal you're taking it with.

 

wrt speculation in recent posts about ultimate value of NR, seems that even if it simply turned out to be a "better B3", having most of the positive effects of NA and NAM, w/o the drawbacks, then that would be a significant advance.  But hopefully NR does even more than that.

 

thanks. inositol hexaniacinate is not a slow release as far as i know, just a different form

 

actually maybe Im wrong but I make a link between the flushing effect and PGD2. Thats why I think anyone who want to take niacin should also take luteolin for exemple. Because otherwize, if we make the connexion with hair loss studies: it would bring directly to baldness.. (PGD2 connexion)

 

 

Is it intra or extracellular GPD2 that causes balding?

Ie: Is flushing it from cells/the body not perhaps a good idea?

People get less of a flush as they get used to Niacin due to there being less PGD2 to be flushed. From within the cell?

 

Thx for the Luteolin heads up.

Aspirin??

[stefan_001]

http://www.nih.gov/n...ed-inflammation


NIH researchers find potential target for reducing obesity-related inflammation

“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.

[meth_use_lah]

 

Please stop with the logical fallacies. First when Chromadex manages to release the PK-data that was completed over a year ago I would consider their product.

 

A 2.7 fold maximum increase, 30% @ 100mg, 50% @ 300mg and 1000mg averages points to the possibility of a few B3-deficient individuals spiking a meaningless serum increase in the general pool to yield a 50% increase a cross the board.

 

Sinclair NMN-study in mice increases NAD slightly above 100%.

 

Always good to wait for data. Yet your reaction is somewhat inconsistent. You challenge a product over lack of data but on the otherhand you seem to make completely unfounded statements: "spiking a meaningless serum increase". You have "PK" data supporting the "meaningless" conclusion?

 

 

I'm trying to explain to you that what can be inferred from the released PK-data is currently meaningless, Chromadex could however very easily obliterate my argument by releasing the PK-data but have decided to not do so. 

[bluemoon]

 

 

 

 

 

I'm trying to explain to you that what can be inferred from the released PK-data is currently meaningless, Chromadex could however very easily obliterate my argument by releasing the PK-data but have decided to not do so. 

 

 

It was my understanding that Elysium claimed they would put up human trial data regardless of the results, while I never expected that from ChromaDex. Unfortuntaely that means that if they hold to that we would get "Basis" results, not just from NR. But is there a reason to think Elysium has changed its mind with respect to their claim when they opened shop last winter?

[Bryan_S]

Based in the August 12th release of the 3-dose clinical study I worked up a simplistic dosage schedule. I've been waiting for ChromaDex to confirm this table since the end of September and they have asked me to wait for confirmation pending the results of the multi-week study but as we can see that study is still a ways off. So I'm going to post this "as is" without ChromaDex's confirmation with a disclaimer. So everyone should accept this table may be inaccurate until confirmation. It has also been shared with a few others on this forum but as a group we lack access to the latest study data to make a final accuracy determination. So call this a best guess.

 

Based on half-life data obtained from ChromaDex in 2014 the fall-off decay of NR has been "crudely" calculated in this table. I don't claim to have a background in Pharmacology or have any education in the Half-life of Drugs. What I started with is a basic chart showing the decay of an initial dose of 250mg's over 12-hours shown vertically. This table was built upon with the goal of sustaining and maintaining sufficient blood serum levels to maintain a theoretical maximum of NAD levels with an additional 125mg's added every 2 hours to prop up the previous dose as it decays. As we get more reliable data we can update this table for accuracy, so for now lets stop the quarreling and just agree that until something better comes along we can at least look at the basic half-life decay and make some educated assumptions against the data they have released.

 

This table and seeing the basic Half-Life decay is the primary reason I believe a single 250mg dose has a short window of benefit and why I believe the initial dose needs to be reenforced to extend its useful duration.

 

It should also be noted we do not know the possible health implications of sustaining NR levels thru repeated 12-hour intervals. This table depicts just one hypothetical approach put forth soley for discussion, I'm sure after some conversation we will identify others but any and all conversation on this topic should not be viewed as a dosage recommendation because there are no currently recommended dosage schedules for any health aliments or even as a nutritional supplement.

 

"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."

 

If everyone feels this table is to forward looking without the next PK studies in hand I can take this chart down until we have the final data.

Attached Files

•  4-Hour-Half_life.png   188.06KB   2 downloads

Edited by Bryan_S, 29 November 2015 - 07:50 PM.

[bluemoon]

 

 

If everyone feels this table is to forward looking without the next PK studies in hand I can take this chart down until we have the final data.

 

 I think it should stay up since based on reasonable information. It will be interesting to compare with the studies coming out. 

[Tom Andre F. (ex shinobi)]

 

 

 

When you guys speak about niacin, you also speak about the flush free form (niacin as inositol hexaniacinate) ?

I don't have any experience with that.  We used (wife still uses) Slo-Niacin, which Bernstein (of very low-carb for diabetes fame) used to recommend as a cheaper alternative to Niaspan.  However, we never escaped flushing with Slo-Niacin, and timing of the flush seems to have more to do with the nature of any meal you're taking it with.

 

wrt speculation in recent posts about ultimate value of NR, seems that even if it simply turned out to be a "better B3", having most of the positive effects of NA and NAM, w/o the drawbacks, then that would be a significant advance.  But hopefully NR does even more than that.

 

thanks. inositol hexaniacinate is not a slow release as far as i know, just a different form

 

actually maybe Im wrong but I make a link between the flushing effect and PGD2. Thats why I think anyone who want to take niacin should also take luteolin for exemple. Because otherwize, if we make the connexion with hair loss studies: it would bring directly to baldness.. (PGD2 connexion)

 

 

Is it intra or extracellular GPD2 that causes balding?

Ie: Is flushing it from cells/the body not perhaps a good idea?

People get less of a flush as they get used to Niacin due to there being less PGD2 to be flushed. From within the cell?

 

Thx for the Luteolin heads up.

Aspirin??

 

 

PGD2 was found in balding scalp tissue. The half life for PGD2 is very short, but not enough to not attack the hair. Problem remain that curent COX inhibitor also downregulate PGE2 for instance wich is necessary for hair.

 

[warner]

"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."

(As noted before, I would ignore the reference to "2.7-fold" increase, since it may not even refer to the same study, but rather be historical data presented in the "poster".)

 

Seems like big thing you don't know is whether doses greater than what's needed to reach +50% have the benefit of keeping NAD+ levels higher for a longer time (or some other undocumented benefit).  If not, then any dose much greater than about 250 mg at any one time is going to end up pissing away (or wherever it goes) a lot of costly NR.  Also, a dose of 1000 mg/d (over 12 hours), no matter how you take it, based on Bryan's "accumulated totals", would be pissing away a lot of NR.

 

For more cost-sensitive folks, to achieve 12 hours of elevated NAD+, I would simply take either 125 mg twice per day (250 mg total) with 6 hours between dosing, or take 125 mg three times per day (375 mg total) with 4 hours between dosing.  The latter should keep you near or above about +25% for most of the 12 hours, with peaks of about +50% at 4 and 8 hours.

 

But the game would be different if the excessive doses have some benefit not yet documented.

[Bryan_S]

Since the 300mg dose generated the +50% I see this as a max target to work towards but your suggestions are worth charting. No matter the dose we are going to eliminate some down the drain. Would like to write some more but I've got to head into work, will log back in later.

 

Edit:

Still at work but I have a few minutes. To be honest I have more questions than answers. The more and more I read about our NAD dependent enzymes and their roll in NAD depletion and disease it makes me wonder, "how much do we need to bolster our NAD production as we age?" Seriously, currently NAD deficiency is only "associated" with disease, which physician is going to make that leap and proclaim we need to supplement NAD levels and by how much.

 

Today I posted on another connection to another NAD dependent enzyme called BRCA1 on the Alzheimer's forum. The more we uncover about our NAD dependency the more these enzymes (or lack thereof) appear to be associated with a host of health ailments and disease. So treating this one condition could have a profound downstream effect on many ailments of aging. Their production not only their utilization also seem to be tied directly to the cells NAD pool. So again the question arises, if they are associated with disease can restoring our NAD levels help intervene and save off future health issues and again what is our target?

 

So where do we start? Let's flip this question around and ask how much do our NAD levels drop with age?

 

 

 

Source Correlation between NAD+ levels and Age in (A) Males (B) Females.. From: Age-Associated Changes In Oxidative Stress and NAD+ Metabolism In Human Tissue http://www.ncbi.nlm....rt=imagesdocsum

 

This is scary, I think the the tail is in the numbers and I feel sickened by these charts.

 

I look at the graph above and could easily see a response of 2.7 fold in an aging individual, especially if they were already somewhat physically fit and had the production capacity. Exercise increases our capacity for Oxygen consumption and increases our mitochondrial response. I've been all over the internet looking for a correlation between falling NAD levels and where a critical point is reached where our NAD dependent enzymes enter an energy crisis.

 

Oxidative stress is an indicator and we show signs of that as we grow older.

 

We have also read studies showing NAD⁺-dependent enzymes at the endoplasmic reticulum so if you are running low on NAD proper protein production is also compromised.

 

From the lack of what I can find this NAD connection has not been fully established and charted tied to all its dependencies but its been shown that the production of these enzymes also wanes with our falling NAD levels. So the 2 seem to be intertwined and connected. In experiments where these enzymes were inhibited NAD levels jump back up. So we can conclude they use an awful lot of NAD and these enzymes do such an important job we can't just turn them off because this would be worse than the NAD depleted state we produce with age. So again how much is enough?

 

I think as these NAD charts suggest our bodies would use all we could generate because we would be hard pressed to produce the amounts we once did in our youth. As we grow older and levels fall lower I think this question of how much do we need grows larger. Where as a young 20 year old is much closer to the desired levels we seek.

 

So I have more questions than answers. If we can find studies that support research depicting our NAD usage we can make some assumptions about meaningful supplementation but I expect this will represent a sliding scale depending on age and how much to fill the gap.

Edited by Bryan_S, 01 December 2015 - 02:23 AM.

[warner]

Since the 300mg dose generated the +50% I see this as max target to work around but your suggestions are worth charting. No matter the dose we are going to eliminate some down the drain. Would like to write some more but I've got to head into work, will log back in later.

Probably fair to assume that any dose above that which first achieves the max of +50% is going to be relatively more wasteful (unless, of course, there is something not yet documented about excessive dosing that is advantageous).  And since both 300 mg and 1000 mg get us to +50%, it is likely that some dose a bit less than 300 mg will also get us near +50%.  Based on that, I considered 250 mg to probably be near the upper dose that is not excessive (and wouldn't be surprised if someone already knew that when choosing tablet sizes!).

 

At this point, with so little info, seems like a strategy that keeps one between about +30 and +50% for 12 hours may be a good compromise between cost and effectiveness, and 3 doses of 125 mg, spaced 4 hours apart, may get you pretty close to that, depending how exactly one sums the overlapping dose effects.  Even using your method, which applies the half life to the dose mass, after the first 4 hours we would have 62.5 mg left from the first dose to be added to the second dose of 125 mg = 187.5 mg, which probably gets us to at least +40% (and not much different from simply adding +15% remaining from 1st dose and +30% from 2nd dose = +45%).

 

-----------

wrt the NAD loss charts, it looks to me like, starting at age 60, a 50% rise in NAD would take you back 20 to 30 years (to 30-40 years of age), assuming things were that simple.  So I don't find that discouraging, at least not with respect to NR dosing.  It may even be that the limit of about +50% is directly related to aging, with the upper bound being about what your 30 year old body was happy with.

Edited by warner, 01 December 2015 - 02:48 AM.

[stefan_001]

 

Since the 300mg dose generated the +50% I see this as a max target to work towards but your suggestions are worth charting. No matter the dose we are going to eliminate some down the drain. Would like to write some more but I've got to head into work, will log back in later.

 

Edit:

Still at work but I have a few minutes. To be honest I have more questions than answers. The more and more I read about our NAD dependent enzymes and their roll in NAD depletion and disease it makes me wonder, "how much do we need to bolster our NAD production as we age?" Seriously, currently NAD deficiency is only "associated" with disease, which physician is going to make that leap and proclaim we need to supplement NAD levels and by how much.

 

Today I posted on another connection to another NAD dependent enzyme called BRCA1 on the Alzheimer's forum. The more we uncover about our NAD dependency the more these enzymes (or lack thereof) appear to be associated with a host of health ailments and disease. So treating this one condition could have a profound downstream effect on many ailments of aging. Their production not only their utilization also seem to be tied directly to the cells NAD pool. So again the question arises, if they are associated with disease can restoring our NAD levels help intervene and save off future health issues and again what is our target?

 

So where do we start? Let's flip this question around and ask how much do our NAD levels drop with age?

 

 

 

 

Source Correlation between NAD+ levels and Age in (A) Males (B) Females.. From: Age-Associated Changes In Oxidative Stress and NAD+ Metabolism In Human Tissue http://www.ncbi.nlm....rt=imagesdocsum

 

This is scary, I think the the tail is in the numbers and I feel sickened by these charts.

 

I look at the graph above and could easily see a response of 2.7 fold in an aging individual, especially if they were already somewhat physically fit and had the production capacity. Exercise increases our capacity for Oxygen consumption and increases our mitochondrial response. I've been all over the internet looking for a correlation between falling NAD levels and where a critical point is reached where our NAD dependent enzymes enter an energy crisis.

 

Oxidative stress is an indicator and we show signs of that as we grow older.

 

We have also read studies showing NAD⁺-dependent enzymes at the endoplasmic reticulum so if you are running low on NAD proper protein production is also compromised.

 

From the lack of what I can find this NAD connection has not been fully established and charted tied to all its dependencies but its been shown that the production of these enzymes also wanes with our falling NAD levels. So the 2 seem to be intertwined and connected. In experiments where these enzymes were inhibited NAD levels jump back up. So we can conclude they use an awful lot of NAD and these enzymes do such an important job we can't just turn them off because this would be worse than the NAD depleted state we produce with age. So again how much is enough?

 

I think as these NAD charts suggest our bodies would use all we could generate because we would be hard pressed to produce the amounts we once did in our youth. As we grow older and levels fall lower I think this question of how much do we need grows larger. Where as a young 20 year old is much closer to the desired levels we seek.

 

So I have more questions than answers. If we can find studies that support research depicting our NAD usage we can make some assumptions about meaningful supplementation but I expect this will represent a sliding scale depending on age and how much to fill the gap.

 

 

Hi Brian,

 

This is an interesting topic. So basicly you are speculating that with increasing age the amount of NAD+ consumed goes down as the body adjusts to lower level. If that is true then I am wondering whether the half-life of NR should be different depending on your age. Supplementing 250mg at age of 75 years should have a longer half life then at lets say 40 years old. That could be easy to test.

 

In general I would expect there to be a correlation between NAD+ consumption and half life. If we would need that big amounts I would expect a shorter half life.

 

Stefan

 

Edited by stefan_001, 01 December 2015 - 02:58 PM.

[Tom Andre F. (ex shinobi)]

 

 

Since the 300mg dose generated the +50% I see this as a max target to work towards but your suggestions are worth charting. No matter the dose we are going to eliminate some down the drain. Would like to write some more but I've got to head into work, will log back in later.

 

Edit:

Still at work but I have a few minutes. To be honest I have more questions than answers. The more and more I read about our NAD dependent enzymes and their roll in NAD depletion and disease it makes me wonder, "how much do we need to bolster our NAD production as we age?" Seriously, currently NAD deficiency is only "associated" with disease, which physician is going to make that leap and proclaim we need to supplement NAD levels and by how much.

 

Today I posted on another connection to another NAD dependent enzyme called BRCA1 on the Alzheimer's forum. The more we uncover about our NAD dependency the more these enzymes (or lack thereof) appear to be associated with a host of health ailments and disease. So treating this one condition could have a profound downstream effect on many ailments of aging. Their production not only their utilization also seem to be tied directly to the cells NAD pool. So again the question arises, if they are associated with disease can restoring our NAD levels help intervene and save off future health issues and again what is our target?

 

So where do we start? Let's flip this question around and ask how much do our NAD levels drop with age?

 

 

 

 

Source Correlation between NAD+ levels and Age in (A) Males (B) Females.. From: Age-Associated Changes In Oxidative Stress and NAD+ Metabolism In Human Tissue http://www.ncbi.nlm....rt=imagesdocsum

 

This is scary, I think the the tail is in the numbers and I feel sickened by these charts.

 

I look at the graph above and could easily see a response of 2.7 fold in an aging individual, especially if they were already somewhat physically fit and had the production capacity. Exercise increases our capacity for Oxygen consumption and increases our mitochondrial response. I've been all over the internet looking for a correlation between falling NAD levels and where a critical point is reached where our NAD dependent enzymes enter an energy crisis.

 

Oxidative stress is an indicator and we show signs of that as we grow older.

 

We have also read studies showing NAD⁺-dependent enzymes at the endoplasmic reticulum so if you are running low on NAD proper protein production is also compromised.

 

From the lack of what I can find this NAD connection has not been fully established and charted tied to all its dependencies but its been shown that the production of these enzymes also wanes with our falling NAD levels. So the 2 seem to be intertwined and connected. In experiments where these enzymes were inhibited NAD levels jump back up. So we can conclude they use an awful lot of NAD and these enzymes do such an important job we can't just turn them off because this would be worse than the NAD depleted state we produce with age. So again how much is enough?

 

I think as these NAD charts suggest our bodies would use all we could generate because we would be hard pressed to produce the amounts we once did in our youth. As we grow older and levels fall lower I think this question of how much do we need grows larger. Where as a young 20 year old is much closer to the desired levels we seek.

 

So I have more questions than answers. If we can find studies that support research depicting our NAD usage we can make some assumptions about meaningful supplementation but I expect this will represent a sliding scale depending on age and how much to fill the gap.

 

 

Hi Brian,

 

This is an interesting topic. So basicly you are speculating that with increasing age the amount of NAD+ consumed goes down as the body adjusts to lower level. If that is true then I am wondering whether the half-life of NR should be different depending on your age. Supplementing 250mg at age of 75 years should have a longer half life then at lets say 40 years old. That could be easy to test.

 

In general I would expect there to be a correlation between NAD+ consumption and half life. If we would need that big amounts I would expect a shorter half life.

 

Stefan

 

 

 

Stefan,

 

Maybe Im wrong, but you would also have less  NAD+ also following the consumption. Actually, it would just be less and less efficient to supplement with Niacin or NR.. This would explain why B3 vitamin dont stop aging. All we do here, is maybe just review why B3 still important, nothin more..

 

Thats why I would advice Bryan for instance, to look depper into the NQO1 topic. Especially since beta-lapachone is not a parp inhibitor in healthy cells.

 

This topic cant just focus on NR..

 

[stefan_001]

 

 

 

Since the 300mg dose generated the +50% I see this as a max target to work towards but your suggestions are worth charting. No matter the dose we are going to eliminate some down the drain. Would like to write some more but I've got to head into work, will log back in later.

 

Edit:

Still at work but I have a few minutes. To be honest I have more questions than answers. The more and more I read about our NAD dependent enzymes and their roll in NAD depletion and disease it makes me wonder, "how much do we need to bolster our NAD production as we age?" Seriously, currently NAD deficiency is only "associated" with disease, which physician is going to make that leap and proclaim we need to supplement NAD levels and by how much.

 

Today I posted on another connection to another NAD dependent enzyme called BRCA1 on the Alzheimer's forum. The more we uncover about our NAD dependency the more these enzymes (or lack thereof) appear to be associated with a host of health ailments and disease. So treating this one condition could have a profound downstream effect on many ailments of aging. Their production not only their utilization also seem to be tied directly to the cells NAD pool. So again the question arises, if they are associated with disease can restoring our NAD levels help intervene and save off future health issues and again what is our target?

 

So where do we start? Let's flip this question around and ask how much do our NAD levels drop with age?

 

 

 

 

Source Correlation between NAD+ levels and Age in (A) Males (B) Females.. From: Age-Associated Changes In Oxidative Stress and NAD+ Metabolism In Human Tissue http://www.ncbi.nlm....rt=imagesdocsum

 

This is scary, I think the the tail is in the numbers and I feel sickened by these charts.

 

I look at the graph above and could easily see a response of 2.7 fold in an aging individual, especially if they were already somewhat physically fit and had the production capacity. Exercise increases our capacity for Oxygen consumption and increases our mitochondrial response. I've been all over the internet looking for a correlation between falling NAD levels and where a critical point is reached where our NAD dependent enzymes enter an energy crisis.

 

Oxidative stress is an indicator and we show signs of that as we grow older.

 

We have also read studies showing NAD⁺-dependent enzymes at the endoplasmic reticulum so if you are running low on NAD proper protein production is also compromised.

 

From the lack of what I can find this NAD connection has not been fully established and charted tied to all its dependencies but its been shown that the production of these enzymes also wanes with our falling NAD levels. So the 2 seem to be intertwined and connected. In experiments where these enzymes were inhibited NAD levels jump back up. So we can conclude they use an awful lot of NAD and these enzymes do such an important job we can't just turn them off because this would be worse than the NAD depleted state we produce with age. So again how much is enough?

 

I think as these NAD charts suggest our bodies would use all we could generate because we would be hard pressed to produce the amounts we once did in our youth. As we grow older and levels fall lower I think this question of how much do we need grows larger. Where as a young 20 year old is much closer to the desired levels we seek.

 

So I have more questions than answers. If we can find studies that support research depicting our NAD usage we can make some assumptions about meaningful supplementation but I expect this will represent a sliding scale depending on age and how much to fill the gap.

 

 

Hi Brian,

 

This is an interesting topic. So basicly you are speculating that with increasing age the amount of NAD+ consumed goes down as the body adjusts to lower level. If that is true then I am wondering whether the half-life of NR should be different depending on your age. Supplementing 250mg at age of 75 years should have a longer half life then at lets say 40 years old. That could be easy to test.

 

In general I would expect there to be a correlation between NAD+ consumption and half life. If we would need that big amounts I would expect a shorter half life.

 

Stefan

 

 

 

Stefan,

 

Maybe Im wrong, but you would also have less  NAD+ also following the consumption. Actually, it would just be less and less efficient to supplement with Niacin or NR.. This would explain why B3 vitamin dont stop aging. All we do here, is maybe just review why B3 still important, nothin more..

 

Thats why I would advice Bryan for instance, to look depper into the NQO1 topic. Especially since beta-lapachone is not a parp inhibitor in healthy cells.

 

This topic cant just focus on NR..

 

 

 

Hello Tom Andre, I tend to agree that supplementing NR may not stop aging but delay it only for some time. It also poses some questions how soon you should start with NR, younger may be better --> Can the body at later age still benefit from the NAD+ boost? Then again from my parents (75 years old) I know they do at least somewhat. Interestingly they also state that they perceive that increasing doses leads to increased effect (they used to take 125mg in morning and 125mg in evening. Now they are at 125mg morning and 250mg evening). I dont know too much about NQO1 so I will start with some reading. But if there are things upstream that will maintain self supply of sufficient  NAD+ levels that is certainly worth while to look at.

 

Edited by stefan_001, 01 December 2015 - 04:39 PM.

[Tom Andre F. (ex shinobi)]

I first heard about NQO1 gène here: http://www.anti-agin...-interventions/

 

He explained very well because at this time, we dint have the niagen data release. And he already speculated that the NAD+ would fastly return back to original due to the NQO1 gène..

 

Then I also wrote a topic more specialised with beta-lapachone here: http://www.beta-lapa...f-healthy-life/

 

You can found many studies wich show beta lapachone increase all biomarker in mamals of NAD+ and also increase lifespan more than CR. I contacted the author and they are sure you can even get better result by playing with the dosage, but would have cost them lot of time

 

You have also direct result on the mitochondria structure and its really impressive the way it protect it and even return them to normal

Edited by Tom Andre F. (ex shinobi), 01 December 2015 - 05:09 PM.