2255 replies to this topic

[rlb373]

I'm not sure I follow your math. You seem to be confusing mg NR/kg of diet with mg/kg of body weight unless the "divide by 12" is some magic number that converts mg NR/kg of lab chow in mice to mg NR/kg of human body weight. I've seen numbers like 1/12 mentioned for mice to human conversion for direct consumption of a particular substance (due to their higher metabolic rate) so, unless these mice are eating 1kg of lab chow a day (seems unlikely, "C57BL/6JRcc mice received a semi-purified mildly obesogenic (40 en% fat)" - 360 kCal/day from fat alone) your calculation is incorrect  

 

In the referenced "Molecular Nutrition  paper" linked by midas Posted 21 February 2017 #1819 on page 61 (http://onlinelibrary....201600878/full scroll down if you don't see anything) from " Table 1. Composition of diets" it is clear that the chow consisted of xx mg of NR per Kg of chow. It's not clear how much chow/day the mice ate but 1.8g was mentioned in a testing phase. At that rate, they were getting 1.8/1000*30mg = 0.054 mg of NR/day.

 

They don't mention how much their mice weighed but a quick google search shows "

Adult weight Males 20-30 g, Females 18-35g

 

So lets pick 25 g or 0.025 kg. and thus 0.054/0.025 = 2.16 mg NR/kg mouse body weight. Dividing by 12 gives 0.18 mg/kg human equivalent and thus, for a 75 kg human, 13.5 mg/day! According to wikipedia, the human RDA for niacin is " For niacin labeling purposes, 100% of the Daily Value was 20 mg, but as of May 2016 it has been revised to 16 mg". Hmm, just about the human RDA

 

So what are we to make of this? My take is that this experiment wasn't designed to test anything we are interested in and that what they showed was that, perhaps, the RDA for mice is about 30 mg/Kg chow of NR which also seem to be roughly what it is for rats for Niacin as shown here: http://ratfanclub.org/nutreq.html (20mg/KG chow)

 

 From the Molecular Nutrition  paper: "...we conclude that 30 mg NR/kg diet constitutes the optimal concentration to support metabolic health."

 

I assume that is for mice. So divide by 12 to get 2.5 mg NR/kg, right? 

 

55 kg =   120 lb    140 mg NR

65 kg =   145 lb    155 mg 

75 kg =   165 lb    190 mg 

90 kg =   200 lb    200 mg  

100 kg = 220 lb    250 mg 

 

 

That still wouldn't necessarily mean that this is the ideal amount especially if someone has a condition assuming NR would help. It will be interesting to compare with the June/July Chromadex trial results at 300 mg and 1000 mg.

 

[Florian E.]

"There are so many different types of cancers with so many different causes. To think ONE substance can kill em all is just utterly ridiculous."

 

I certainly have doubts on the claim that NR can cure all cancers but the above statement I will disagree.

 

Let's think on a different perspective and rephrase a bit. "To think ONE substance can kill all VIRUSES is just utterly ridiculous." But the DRACO drug seems to be able to kill all viruses (though the research never funded to human trials). I do believe the root cause of the cancer might be similar for all types, just that we have not yet really found the reason. IF the reason is found, then ONE substance should kill them all!

 

Cancer might be due to DNA copying error? DNA damage? Mutation? Hope scientist one day can find the root cause of ALL cancer.

 

Although viruses is a very different topic... i couldn't find any evidence that DRACO is able to kill all viruses. What i found was that it can kill "many viruses".

Regarding cancer, yes DNA mutation is a major factor. But scientists are still not sure if it's the only factor. And dna mutation can have many causes. (current article: http://www.news-medi...es-Cancer.aspx)

Yes, you can minimize risks for dna damage. But some portion is more or less just luck or bad luck. 

But since this is all off-topic, let's not further spam this thread with the discussion.

 

 

 

 From the Molecular Nutrition  paper: "...we conclude that 30 mg NR/kg diet constitutes the optimal concentration to support metabolic health."

 

I assume that is for mice. So divide by 12 to get 2.5 mg NR/kg, right? 

 

55 kg =   120 lb    140 mg NR

65 kg =   145 lb    155 mg 

75 kg =   165 lb    190 mg 

90 kg =   200 lb    200 mg  

100 kg = 220 lb    250 mg 

 

 

That still wouldn't necessarily mean that this is the ideal amount especially if someone has a condition assuming NR would help. It will be interesting to compare with the June/July Chromadex trial results at 300 mg and 1000 mg.

 

 

I recently read about optimum dosage between 300-500 mg here -> http://alivebynature...optimum-dosage/

 

 

 

• There is an upper limit on the increase of NAD+ levels achievable through NR supplementation
• Maximum NAD+ elevation is maintained at a dosage between 300mg and 500mg –likely close to 500mg per day

more or less

 

[bluemoon]

 

 

So lets pick 25 g or 0.025 kg. and thus 0.054/0.025 = 2.16 mg NR/kg mouse body weight. Dividing by 12 gives 0.18 mg/kg human equivalent and thus, for a 75 kg human, 13.5 mg/day! According to wikipedia, the human RDA for niacin is " For niacin labeling purposes, 100% of the Daily Value was 20 mg, but as of May 2016 it has been revised to 16 mg". Hmm, just about the human RDA

 

So what are we to make of this? My take is that this experiment wasn't designed to test anything we are interested in and that what they showed was that, perhaps, the RDA for mice is about 30 mg/Kg chow of NR which also seem to be roughly what it is for rats for Niacin as shown here: http://ratfanclub.org/nutreq.html (20mg/KG chow)

 

 

 

 

The paper states: "Nine-week-old male C57BL/6JRcc mice received a semi-purified mildly obesogenic (40 en% fat) diet containing 0.14% L-tryptophan and either 5, 15, 30, 180, or 900 mg NR per kg diet for 15 weeks."

 

I added the uncertainty in how I converted to humans with "..., right?"

 

My interpretation gives a conversion to humans that mostly matches what Elysium, HPN, Thorne, etc recommend a day at 250 mg while your conversion to humans is about 15 mg a day. I hope you are right since supplementing with NR would be almost free.

 

I'm not sure why you think these researchers would design a study to find the optimal dose in mice but "not designed to test anything" humans would be interested in.

 

I've never heard of a mouse study that was run for the betterment of only mice. (But again, I might have been wrong above.)    

[Michael]

So what are we to make of this? My take is that this experiment wasn't designed to test anything we are interested in and that what they showed was that, perhaps, the RDA for mice is about 30 mg/Kg chow of NR which also seem to be roughly what it is for rats for Niacin as shown here: http://ratfanclub.org/nutreq.html (20mg/KG chow)

It was absolutely designed to test things we are interested in — including addressing questions that none of us stopped to think about, not only on dose but also on genetics of human translatability.

[bluemoon]

 

So what are we to make of this? My take is that this experiment wasn't designed to test anything we are interested in and that what they showed was that, perhaps, the RDA for mice is about 30 mg/Kg chow of NR which also seem to be roughly what it is for rats for Niacin as shown here: http://ratfanclub.org/nutreq.html (20mg/KG chow)

It was absolutely designed to test things we are interested in — including addressing questions that none of us stopped to think about, not only on dose but also on genetics of human translatability.

 

 

 So you are confident that what you had written linked to above is correct: "The Dietary Reference Intake for B3 in humans is 16 mg/day, so that would suggest 32 mg daily, and a more dubious advantage for NR over other forms of the vitamin."

 

Elysium, HPN and Thorne including what Charles Brenner takes - all 250 mg - is eight times more than necessary if 75 kg?

[Michael]

 

 

So what are we to make of this? My take is that this experiment wasn't designed to test anything we are interested in and that what they showed was that, perhaps, the RDA for mice is about 30 mg/Kg chow of NR which also seem to be roughly what it is for rats for Niacin as shown here: http://ratfanclub.org/nutreq.html (20mg/KG chow)

It was absolutely designed to test things we are interested in — including addressing questions that none of us stopped to think about, not only on dose but also on genetics of human translatability.

 

 
 So you are confident that what you had written linked to above is correct: "The Dietary Reference Intake for B3 in humans is 16 mg/day, so that would suggest 32 mg daily, and a more dubious advantage for NR over other forms of the vitamin."

 

That depends what you mean by "am I confident." Am I confident that that's what the animal study suggests? Yes. Am I confident that that means that's the optimal dose for humans? No — that's why I said "that would suggest" rather than "combined with this paper, that proves that ...". I'm of course not confident of the human implications of any of the rodent data — especially not with this new wrinkle:
 

Elysium, HPN and Thorne including what Charles Brenner takes - all 250 mg - is eight times more than necessary if 75 kg?

Right, but Chromadex and everyone following from them are (a) extrapolating from animal studies that use a single high dose (or in one case, use two extremely high doses), and then pulling back from the implied super-high dose because of their 90-day rodent toxicology work: this is the only dose-ranging study with non-toxicological health effects; and (b) they're assuming human translatability of that rodent health work, which the apparent genetic difference now puts into doubt.

 

There's a ton of human evidence on B3 already, as documented in the National Academy of Medicine report on which the DRI is based; if the NR data we've been watching is all predicated on a genetic quirk, then an optimal dose within the ballpark of the DRI certainly seems more parsimonious, even granted NR's apparent superiority for generating NAD+ in some tissues.

 

However, we won't really have clarity on that issue until we see a bunch of dose-ranging studies with health effects in rodents other than C57Bl/6 mice.

 

And even then, of course: we ain't mice .

[bluemoon]

That depends what you mean by "am I confident." Am I confident that that's what the animal study suggests? Yes. Am I confident that that means that's the optimal dose for humans? No — that's why I said "that would suggest" rather than "combined with this paper, that proves that ...". I'm of course not confident of the human implications of any of the rodent data — especially not with this new wrinkle:

 

 

 

 

I originally meant about your calculation but assumed you were confident in that since I see you had written it recently so then was curious about that dose relative to the recommended 250 mg dose. I did know that you were skeptical of any dose of NR so something didn't make sense to me but now you cleared that up - and probably did earlier, but I didn't catch it.

 

Depending on how much of the trial results Chromadex release in a few weeks, a lot more should be known on at least the effects of 100 mg, 300 mg and 1000 mg of NR on humans with respect to glucose levels, lipid levels, blood pressure, heart rate and six minute walking test.  I went back to read the transcript of the March webcast and noticed the CEO said they would release at least the top-line results, which at the time I assumed to be a pretty detailed summary but maybe not. 

[stefan_001]

 

 

So what are we to make of this? My take is that this experiment wasn't designed to test anything we are interested in and that what they showed was that, perhaps, the RDA for mice is about 30 mg/Kg chow of NR which also seem to be roughly what it is for rats for Niacin as shown here: http://ratfanclub.org/nutreq.html (20mg/KG chow)

It was absolutely designed to test things we are interested in — including addressing questions that none of us stopped to think about, not only on dose but also on genetics of human translatability.

 

 

 So you are confident that what you had written linked to above is correct: "The Dietary Reference Intake for B3 in humans is 16 mg/day, so that would suggest 32 mg daily, and a more dubious advantage for NR over other forms of the vitamin."

 

Elysium, HPN and Thorne including what Charles Brenner takes - all 250 mg - is eight times more than necessary if 75 kg?

 

 

The adipocytes are clearly smaller in the 900NR case. Normally larger adipocytes are a sign of obesity. The nnt note may not be the full story as the mice used here show slightly more weight gain than the ones with the nnt defect, that should then not be the case. In any case I would think that the nnt gene only impacts beta cells.
 

[Michael]

 

 

So what are we to make of this? My take is that this experiment wasn't designed to test anything we are interested in and that what they showed was that, perhaps, the RDA for mice is about 30 mg/Kg chow of NR which also seem to be roughly what it is for rats for Niacin as shown here: [/font]http://ratfanclub.org/nutreq.html (20mg/KG chow)

It was absolutely designed to test things we are interested in — including addressing questions that none of us stopped to think about, not only on dose but also on genetics of human translatability.

The adipocytes are clearly smaller in the 900NR case. Normally larger adipocytes are a sign of obesity.

 
The 900NR group has fewer large-sized adipocytes, but also fewer small-sized ones — and more medium-sized ones; add it up, and "No differences were found in body weight, cumulative feed intake, lean mass or fat mass, when comparing mice with 5, 15, 30, 180 or 900 mg NR/kg diet".
 
In any case, the key question here is the functional effects on metabolism, not the distribution of adipocyte sizes — and here they found that the higher doses did not improve metabolic function, but instead made it worse. Fasting metabolic flexibility, maxΔRERCHO1→FAO, was better at 30 NR than at higher or lower doses, although only statistically significantly better as compared to 5NR; "Refeeding metabolic flexibility, maxΔRERFAO→CHO2, was significantly greater in 30NR than in 5NR, 15NR, or 900NR ... No differences were seen in blood glucose, serum TG or NEFA among NR doses (Fig. 3A-C). Serum insulin, leptin, adiponectin, leptin/adiponectin ratio and HOMA-IR index exhibited a tendency towards a dose-response curve, without reaching statistical significance (Fig. 3D-H). In all cases, except adiponectin which shows opposite behaviour, the measured value decreased and then increased, with 30NR being the turning point" — that is, the dose-response curve on markers of insulin resistance were U-shaped, with the nominal insulin resistance lowest at 30 NR and then rising again at higher doses. The suggestion in the trend is that high-dose NR caused the animals to pump out more insulin just to maintain the same glucose level.

Stefan wrote: The nnt note may not be the full story as the mice used here show slightly more weight gain than the ones with the nnt defect.
 
But that just reinforces the point. The whole reason everyone is watching mouse studies on the effects of NR is on the hypothesis that they'll translate to humans. Normal humans have an intact NNT gene, or SNPs that are by comparison functionally minor; the mutation of NNT in C57BL/6 mice is so severe that no mature NNT protein can be detected in their cells.
 
Stefan wrote: In any case I would think that the nnt gene only impacts beta cells.

No: NNT is needed to transfer reducing equivalents from NADH to NADP⁺, to generate the NADPH needed to detoxify ROS  in the mitochondria, both directly and by regenerating thioredoxin and glutathione: it's necessary to maintain redox homeostasis and efficient ATP synthesis in every single cell in the body. "NNT expression differs between cell types, being highest in the heart and kidney. Approximately half of the mitochondrial NADPH in the brain is believed to depend on the action of the NNT, and its inhibition causes significant oxidative stress."(1)
 
The effects in beta-cells are important to the mutation's effects on metabolism and susceptibility to weight gain, but it does a lot of other less-than-obvious things as well:
 

The key role of the NNT and the network of interactions taking place in cytosolic glucose metabolism highlight that the pathways involved in maintenance of the NAD and NADP pools in their separate redox states are highly interconnected. Indeed, in addition to the malate-asparate and citrate-α-ketoglutarate shuttles providing separate transmission of NAD and NADP redox state between cytosol and mitochondria, a pyruvate-malate shuttle in which the redox state of the cytosolic NADP pool is coupled to that of the mitochondrial NAD pool has also been observed {109}.
 
Additional complexity in these redox networks also arises from the reversibility of a number of the reactions. For example, during ischaemia, the citric acid cycle may reverse and consume NADH {39}, the NNT may oxidise NADPH to produce NADH when the membrane potential is collapsed {104} or lactate dehydrogenase may reverse, using lactate as a metabolic substrate, producing NADH in the cytosol alongside pyruvate for aerobic ATP production {110}. Indeed, it has been suggested that lactate secreted by astrocytes may serve as the primary energy source for neurons in the brain {111}. Thus, the highly contrasting intracellular roles of the NAD and NADP pools and their separate redox states are supported by a complex and interconnected network of pathways.

 
Because of all of this, when you knock out the mitochondrial form of SOD, most mouse strains use NNT to partially make up for it; because they lack functional NNT, giving C57Bl/6 the same MnSOD mutation leads to much more severe effects. The more you then back-cross them with strains of mouse with functional NNT, the more they're able to cope with the MnSOD mutation:
 

congenic Sod2−/− mice on a C57BL/6J background (B6 Sod2−/−) develop a fetal form of dilated cardiomyopathy, and most of them die about day 15 (ED15) of gestation. On the other hand, Sod2−/− mice generated on a DBA/2J (D2 Sod2−/−) background develop normally through gestation and do not have dilated cardiomyopathy. However, these mice develop severe metabolic acidosis and have an average lifespan of 8 days. F1 mice (B6D2F1 Sod2−/−) generated from the two parental strains have a cardiac phenotype similar to that of D2 Sod2−/− mice, but with a milder form of metabolic acidosis. Consequently, these mice are able to survive for up to three weeks without any pharmacological intervention (13). Consistent with our observation, a different Sod2 mutant strain (SOD2^m1BCM) generated on a B6/129 mixed genetic background was shown to survive for up to 3 weeks after birth and had a phenotype similar to that of B6D2F1 Sod2−/−^tm1Cje (14).(2)

Reference
1: Blacker TS, Duchen MR. Investigating mitochondrial redox state using NADH and NADPH autofluorescence. Free Radic Biol Med. 2016 Nov;100:53-65. doi: 10.1016/j.freeradbiomed.2016.08.010. Epub 2016 Aug 9. Review. PubMed PMID: 27519271; PubMed Central PMCID: PMC5145803.
 
2: Huang TT, Naeemuddin M, Elchuri S, Yamaguchi M, Kozy HM, Carlson EJ, Epstein CJ. Genetic modifiers of the phenotype of mice deficient in mitochondrial superoxide dismutase. Hum Mol Genet. 2006 Apr 1;15(7):1187-94. Epub 2006 Feb 23. PubMed PMID: 16497723.

Edited by Michael, 19 April 2017 - 05:10 PM.

[bluemoon]

 

But that just reinforces the point. The whole reason everyone is watching mouse studies on the effects of NR is on the hypothesis that they'll translate to humans. Normal humans have an intact NNT gene, or SNPs that are by comparison functionally minor; the mutation of NNT in C57BL/6 mice is so severe that no mature NNT protein can be detected in their cells. 

 

 

But it has been shown since 2015 that NR increases NAD+ in mice as well as humans based on Chromadex's small study, Elysiums larger 8 week study last summer at 250 mg and 500 mg and Charles Brenner's study of himself for a week at 1000 mg. Brenner emphasized in his talk in December that the mouse model is not a good way to show NR would change lipid levels in humans.

 

So we just have to wait a few weeks for Chromadex to announce in June or July the results of its 140 person trial on the effects of NR at 100 mg, 300 mg and 1000 mg levels to know if the genetic mutation in the mouse studies has been that relevant.  

[ambivalent]

Apologies if this has been referenced previously:

 

Suggestions of some U shaped dose-dependent characteristics here with NMN:

 

http://alivebynature...st-nad-booster/

 

'NMN administration can stimulate energy metabolism and general locomotor activity in aged mice, however the lower dose appears to have been more effective.'

 

 

'There were conflicting indications on the most effective dosage in this research.

300 mg/kg/day was more effective for body weight gain, insulin sensitivity, tear production, and bone mineral density.

100 mg/kg/ day improved oxygen consumption, energy expenditure, and physical activity more.'

 

 

referencing paper:

 

http://www.cell.com/...4131(16)30495-8

 

 

[stefan_001]

I read the text but in "numbers" the average surface area of the adipocytes at 900NR is 20% less than at 30NR, that is a clear difference.

The NNT comment was about the mice specifically. The NNT defect carrying mice on high fat diet (without NR) in other studies show slightly less weight gain than the strain of mice used here which don't have the defect. That doesn't make sense in my mind. The reduced Nnt activity should have impaired glucose tolerance and lead to more obesity than 6JRcc strain on HFD.

Indeed the serum levels insulin seem higher. When looking in figure 4 it is difficult to find correlation between values. It would seem that the mice are in different serum level states. Interestingly NAM serum levels peak in the 900NR except are exceptionally low in the liver.

Edited by stefan_001, 19 April 2017 - 07:14 PM.

[Michael]

But it has been shown since 2015 that NR increases NAD+ in mice as well as humans

The minor caveat is that an increase in NAD+ in humans has only been shown in PBMC: we don't know what it's doing in any solid tissue.

The major caveat, as I've emphasized before, is that elevated NAD+ is not, itself, a health benefit. Of course one needs some level of NAD+ to function properly, but it doesn't follow that more and more NAD+ leads to more and more functional benefits. Moreover, while Trammel & Brenner PMID 27721479 shows a faster rise in PBMC NAD+ at higher doses in humans, and an ensuing higher 20-h AUC, the 300 and 1000 mg doses both reach the same peak, and they all seem to reach the same plateau level: the higher AUC is due to the faster initial rapid rise, plus the transient higher peak at 300 or 1000 mg. It's not clear that higher dosages would lead to higher steady-state NAD+ with extended dosing. Indeed, in the study we're discussing, all doses lead to more or less the same level of NAD+ in the liver (or, if anything, the optimal 30NR dose may be a little lower than the others). We want to know the functional effects, not trace out metabolic curiosities. There's a story that makes sense why some extra NAD+ would benefit an animal with an NNT loss-of-function mutation in a way that would be irrelevant to an animal whose NNT is intact.
 

So we just have to wait a few weeks for Chromadex to announce in June or July the results of its 140 person trial on the effects of NR at 100 mg, 300 mg and 1000 mg levels to know if the genetic mutation in the mouse studies has been that relevant.

Surely someone out there has had hir basic bloodwork done since taking this stuff ...? (Yes, I know: that'd be anecdotal "evidence" ). In any case, I'd treat the results of such a study with some caution: we already know that nicotinamide nicotinic acid raises HDL and lowers TG (and modestly reduces LDL). It's been hypothesized that this may involve the GPR109A receptor, which NR doesn't stimulate, but this is far from nailed down. And it's not clear, after decades of trying, whether niacin does or does not protect against cardiovascular and total death, while it does increase the risk of diabetes.
 

I read the text but in "numbers" the average surface area of the adipocytes at 900NR is 20% less than at 30NR, that is a clear difference.

I'm not sure it's a clear difference, but it is there, at least numerically; again, tho' what we should care about is metabolic function (and, secondarily, overall adiposity for aesthetic reasons). Surface area distribution is either a curiosity, or is somehow linked to the poorer metabolic flexibility resulting from high-dose NR.
 

The NNT comment was about the mice specifically. The NNT defect carrying mice on high fat diet (without NR) in other studies show slightly less weight gain than the strain of mice used here which don't have the defect. That doesn't make sense in my mind. The reduced Nnt activity should have impaired glucose tolerance and lead to more obesity than 6JRcc strain on HFD.

First, to be clear, C57Bl/6J mice do have impaired glucose tolerance relative to other strains. I think you know this, but the way you wrote the sentence above says the opposite. And C57Bl/6J are more prone to obesity in response to a high-fat diet than many other strains, which makes sense but may not be the whole story.

 

Edit: corrected nicotinamide--> nicotinic acid; slip of the brain, poiinted out by mikeinnaples

Edited by Michael, 20 April 2017 - 05:47 PM.

[ambivalent]

My rather cavalier experiment of very high doses of NR over 5 weeks was certainly anecdotal evidence of a U-shaped effect of NR - although there were confounding factors. I made something of a write it up in the NR experiences thread at the time, but clarity was in short supply.

 

Briefly, my doses ranged between 1500mg, 7500mg /day with the occasional day off (always with Trans-ptrero). Heightened clarity occurred quite dramatically on day 4 after a second dose of 2500. Energy levels changed significantly in the first couple of weeks: feeling great to being washed out for a couple of days. Skin was improving in softness pretty consistently with some possible increase in facial mass. Mental clarity fluctuated but high levels of clarity were still attainable a few weeks after starting. There were often clear responses to additional doses beyond the two or three grams already taken early in a day (skin, clarity).

 

Perhaps around 10 days after changing location to coastal national park I started to run into quite heavy allergy problems (not long before I had phenomenal stamina and lung capacity on a challenging walk). Historically, I experienced some allergy problems around this time of the year before but in recent years I was spared symptoms, most likely sue to fasting and dietary change; however, those countermeasures weren't deployed with vigour in the months leading up.  NR, though, was naturally the chief suspect, especially as symptoms were more severe to previous experiences.

 

Upon stopping NR and taking some natural and unnatural ante histamines the bloated-face deflated and I improved but still had low energy and reduced lung capacity. On the couple of occasions I subsequently took NR and Niacinamide (500mg both/separate occasions) there was a very clear hay-fever like response, followed by brain fog and feeling fairly lousy the rest of the day. So it was very clear to me that NR was involved and most likely aided and abetted by seasonal effects. Nicotinic acid had no such effects, only positive.

 

Anyway, trying to stumble to an explanation without much domain knowledge I dug around.  It seems there is evidence of another person confidently reporting a histamine reaction to NR with research pointing to Nicotinamide increasing histamine.  It also seems that NAD is involved in catalysing the removal of histamine. So it appears NR might increase both histamine and NAD.

 

So I would hypothesize from my experience that at low doses of NR the increased NAD can counter the histamine, but at much higher doses of NR with bounded NAD levels, albeit elevated, histamine production soars unchecked by NAD. So there would certainly appear to be a sweet spot; however it would have been better to have tried this without the confounding factor of the environment.

 

Two-three weeks on I've been bumping along the bottom, despite change in environment, feeling pretty low on energy, intermittent  dry cough but certainly not ill-looking as back then. I hope the prevailing factor now is the pollen. I took 250mg for the first time since I quit, an hour or so ago, feeling sharper with a slight increase in the dry cough. Any further updates will be in the NR-experience thread.  

 

*I took large doses, around 300mg, of c60oo in the month leading up to the NR period.

 

   

Edited by ambivalent, 20 April 2017 - 01:11 PM.

[mikeinnaples]

Surely someone out there has had hir basic bloodwork done since taking this stuff ...? (Yes, I know: that'd be anecdotal "evidence" ). In any case, I'd treat the results of such a study with some caution: we already know that nicotinamide raises HDL and lowers TG (and modestly reduces LDL). It's been hypothesized that this may involve the GPR109A receptor, which NR doesn't stimulate, but this is far from nailed down. And it's not clear, after decades of trying, whether niacin does or does not protect against cardiovascular and total death, while it does increase the risk of diabetes.

 

 

To be clear, Niacin and Nicotinamide should not be used interchangeably. I have seen several examples in this topic so far so just want to clear that up.

 

Niacin is Nicotinic Acid. Nicotinic Acid is not Nicotinamide.

 

 

Nicotinamide = C6H6N2O

Nictonic Acid = C6H5NO2

 

 

They have different pharmacological properties and should not be confused with one another. Nicotinic Acid (Niacin) is much better than Nicotinamide in regards to cholesterol for example.

Edited by mikeinnaples, 20 April 2017 - 01:20 PM.

[MikeDC]

The second blood test was before Niagen. The first one is 9 month after Niagen at 250mg daily dose.

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[PeaceAndProsperity]

9 months is extremely long for such a negligible effect from NR.

[soulprogrammer]

cholesterol from 209 to 191       reduction of 8.6%

triglycerides from    171 to 124  reduction of  27.5%

 

That is quite significant (esp for triglycerides)! 9 months is not too long, and this is not drugs!

 

Hello, P&P, 27.5% is negligible????

 

Of course, you can take some drugs probably it will reduce in 1 month, but it certainly has a lot of side effects. Unlike NR, which is a form of vitamin.

Edited by soulprogrammer, 20 April 2017 - 03:50 PM.

[MikeDC]

cholesterol from 209 to 191 reduction of 8.6%
triglycerides from 171 to 124 reduction of 27.5%

That is quite significant (esp for triglycerides)! 9 months is not too long, and this is not drugs!

Hello, P&P, 27.5% is negligible????

Of course, you can take some drugs probably it will reduce in 1 month, but it certainly has a lot of side effects. Unlike NR, which is a form of vitamin.

I have also reduced 12 lbs after increasing dose from 250mg to 375 mg and 500 mg since the beginning of the year. Losing weight is easier than before.

[MikeDC]

cholesterol from 209 to 191 reduction of 8.6%
triglycerides from 171 to 124 reduction of 27.5%

That is quite significant (esp for triglycerides)! 9 months is not too long, and this is not drugs!

Hello, P&P, 27.5% is negligible????

Of course, you can take some drugs probably it will reduce in 1 month, but it certainly has a lot of side effects. Unlike NR, which is a form of vitamin.

The blood test was done in 9 month. It doesn't mean the effect took 9 months. 191 is perfectly good level to stablize. It could stay the same in the next blood test.

My eyebag is also getting smaller. I think only 25% left.
The most important improvement is my skin and face. My skin is extremely soft and smooth and face is 10 years younger.

[Harkijn]

I have also reduced 12 lbs after increasing dose from 250mg to 375 mg and 500 mg since the beginning of the year. Losing weight is easier than before.

 

 

 

Mike, your posts are factual and precise, so we sorely need them at the Experiences thread. Why let your contributions go to waste here, where they are being disregarded  because people focus on trying to interprete scientific research?

[stefan_001]

 

cholesterol from 209 to 191 reduction of 8.6%
triglycerides from 171 to 124 reduction of 27.5%

That is quite significant (esp for triglycerides)! 9 months is not too long, and this is not drugs!

Hello, P&P, 27.5% is negligible????

Of course, you can take some drugs probably it will reduce in 1 month, but it certainly has a lot of side effects. Unlike NR, which is a form of vitamin.

The blood test was done in 9 month. It doesn't mean the effect took 9 months. 191 is perfectly good level to stablize. It could stay the same in the next blood test.

My eyebag is also getting smaller. I think only 25% left.
The most important improvement is my skin and face. My skin is extremely soft and smooth and face is 10 years younger.

 

 

Its a really good result. P&P apparently thinks Niagen should turn you into an immortal like in the Marvel movies but stabilizing your health and slightly improving it to extend your health span as we age is a small miracle in itself.
 

[Alphatrial]

This is all fascinating to read. I have several thoughts and would like to know is anyone can fill me in with this.

- Does anyone have experience with hyper pigmentation of the skin? Topical use of just pill form.
- Anyone using NR with Crohn's disease?
- Same question for neuropathy...
- Same question for macular degeneration....

Lots of questions I know.

Sebastiaan


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[PeaceAndProsperity]

Just based upon what food I eat and what liquid I drink I gain and lose over a kg everyday. And you think 12 lbs over such a long duration is anything? Come on!

 

A 27% reduction in triglycerides over 9 months is extremely poor when you can take a vitamin and in about one day much further reduce triglyceride levels. In 9 months you should be at a young person's levels if you were taking the right stuff.

 

[MikeDC]

This is all fascinating to read. I have several thoughts and would like to know is anyone can fill me in with this.

- Does anyone have experience with hyper pigmentation of the skin? Topical use of just pill form.
- Anyone using NR with Crohn's disease?
- Same question for neuropathy...
- Same question for macular degeneration....

Lots of questions I know.

Sebastiaan


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I have not seen any improvement of age spot or grey hair.

[PeaceAndProsperity]

I have not seen any improvement of age spot or grey hair.

Didn't you swear on NR reversing gray hair?

 

[stefan_001]

 

I read the text but in "numbers" the average surface area of the adipocytes at 900NR is 20% less than at 30NR, that is a clear difference.

I'm not sure it's a clear difference, but it is there, at least numerically; again, tho' what we should care about is metabolic function (and, secondarily, overall adiposity for aesthetic reasons). Surface area distribution is either a curiosity, or is somehow linked to the poorer metabolic flexibility resulting from high-dose NR.

 

Well larger surface area goes hand in hand with obesity which in turn correlates to poorer metabolic function. It would have been interesting to have more detailed numbers on the particular mice they cut up to see whether 900NR had more hyperplasia. Or more morphology images to confirm what we see in the 900NR is fluke. Looking at the overall fat weight the surface area data suggests there would be more hyperplasia, that would have been an interesting side effect. Anyways all speculation and mice are mice. This study I agree indicates less may be better, then again for the other NAD+ health benefits the boost may still need to be bigger, compromises may be needed or cycling. Time to move to rats and humans,

Edited by stefan_001, 20 April 2017 - 07:15 PM.

[stefan_001]

http://circres.ahajo...16.310022.short

SMCs refuleled with NR:
Furthermore, there was evidence for oxidized DNA lesions, double-strand DNA strand breaks and pronounced susceptibility to single-strand breakage. This was linked to suppressed poly(ADP-ribose) polymerase-1 activity and was reversible upon re-supplying NAD+ with nicotinamide riboside

[soulprogrammer]

"A 27% reduction in triglycerides over 9 months is extremely poor when you can take a vitamin and in about one day much further reduce triglyceride levels. "

 

Which vitamin can achieve a reduction of 27% or more in triglycerides in one day? I mean seriously, P&P,  could you point me/link me to any research paper which say so, it will definitely benefit many people I believe.

 

 

http://circres.ahajo...16.310022.short

SMCs refuleled with NR:
Furthermore, there was evidence for oxidized DNA lesions, double-strand DNA strand breaks and pronounced susceptibility to single-strand breakage. This was linked to suppressed poly(ADP-ribose) polymerase-1 activity and was reversible upon re-supplying NAD+ with nicotinamide riboside

 

Can you do a layman summary of the paper? I read the paper it is really difficult to understand without proper medical science background.

[Michael]

 

http://circres.ahajo...16.310022.short

SMCs refuleled with NR:
Furthermore, there was evidence for oxidized DNA lesions, double-strand DNA strand breaks and pronounced susceptibility to single-strand breakage. This was linked to suppressed poly(ADP-ribose) polymerase-1 activity and was reversible upon re-supplying NAD+ with nicotinamide riboside

 
Can you do a layman summary of the paper? I read the paper it is really difficult to understand without proper medical science background.

 

It has already been explained to you.

 

If you have access to the paper, you might consider posting it for others to consider ...