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Combination with niacin (nicotonic acid) and timing?

niacin nicotinamide riboside nicotinic acid

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#31 Turnbuckle

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Posted 05 September 2017 - 07:01 PM

 

I tried the OP idea this morning, using 500 mg of niacin, 1.5 g of niacinamide and 5 g of ribose, along with AMPK activators (all in one dose) and went out to the gym an hour and a half later. I think the results were at least as good as 2g/5g of N+R with the same activators. Perhaps better, but hard to tell until I try it a few more times. One difference (other than a flush) was a slightly unpleasant head feeling that developed several hours later--which was similar to what I get from taking large amounts of niacinamide without ribose. So I took another 5 g of ribose and the feeling went away after a few minutes. Ribose has a short half-life--

Following consumption, ribose is rapidly absorbed and reaches its highest concentration in the blood after around 45 minutes. The half-life in the bloodstream is around half an hour. Moreover, ribose does not accumulate in the tissues and is not stored in cells in free form.
http://www.naturafou...fie/Ribose.html


Still, this seems odd as niacin has such a short half-life compared to niacinamide.

This brings up an interesting point. Since ribose has a much shorter half life than nicotinamide, it might help to sip a drink with more ribose over the course of a workout in case the original dose was metabolized into other uses before being used in the intended pathway.

 

 

If you are looking to get a faster burn via the idea in "exercise like a girl," I would not recommend it. Take extra ribose after exercise if needed, but ribose during or immediately before exercise is going to supply extra energy and eliminate that advantage. I know because I tried it (half an hour before).


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#32 Leon93

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Posted 09 January 2018 - 02:16 PM

I wonder what a better dosage is for long-term supplementation: 500mg or 1g? Some sources claim 500mg is too low. Thing is that I´m on a budget, so I would prefer 500mg, but only if it does something off course. I´m 24 years old so perhaps I need less as well than others. 

 

Then there´s also a concern one needs to supplement acute release, rather than extended or sustained release, due to hightened diabetes risk. But perhaps biting/chewing an extended/sustained release pill causes it to be exact like an acute release?


Edited by Leon93, 09 January 2018 - 02:20 PM.


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#33 stefan_001

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Posted 09 January 2018 - 08:40 PM

I wonder what a better dosage is for long-term supplementation: 500mg or 1g? Some sources claim 500mg is too low. Thing is that I´m on a budget, so I would prefer 500mg, but only if it does something off course. I´m 24 years old so perhaps I need less as well than others. 

 

Then there´s also a concern one needs to supplement acute release, rather than extended or sustained release, due to hightened diabetes risk. But perhaps biting/chewing an extended/sustained release pill causes it to be exact like an acute release?

 

Hey Leon, at your age of 24 I would not take any. Unless you have a specific reason I see it very unlikely any extra NAD+ would help you. I could imagine that when you get closer to 30 you may start at a low dose to see whether you can slow the aging process. You are in a great situation, research is progressing in anti-aging so by the time you reach 30 there may be much more clarity.


Edited by stefan_001, 09 January 2018 - 08:40 PM.

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#34 Leon93

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Posted 09 January 2018 - 09:00 PM

Ah thanks for answering Stefan, however I just made a new post and then saw your reply. 

Are you very sure? I saw some graphs earlier that even people of my age already have somewhat declined NAD+ levels.

At the moment I´m taking a healthy diet, glucosamine, glycine and andrographis for anti-aging. I´m considering valerian at the moment.


Edited by Leon93, 09 January 2018 - 09:10 PM.


#35 stefan_001

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Posted 10 January 2018 - 08:59 PM

Ah thanks for answering Stefan, however I just made a new post and then saw your reply. 

Are you very sure? I saw some graphs earlier that even people of my age already have somewhat declined NAD+ levels.

At the moment I´m taking a healthy diet, glucosamine, glycine and andrographis for anti-aging. I´m considering valerian at the moment.

 

True NAD+ levels start to fall probably already at your age. But the question is when does it start to have an impact? Boosting NAD+ is a work around and at least it helps me but I am double your age so you have some time to watch the science develop a bit more before starting to experiment. At least that's my 2 cents.
 


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#36 Leon93

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Posted 14 January 2018 - 12:27 PM

Thank you for replying again. As far as I know, a raise in NAD+ at my age would give some anti-aging benefits. It would even give some phenotype quality benefits. 

But what if I took a lesser dosage? About 500mg instead of 1gram? Given I´m pretty young and I noticed some older members take 1 gram, I don´t think 500mg would be an unreasonable dosage. Only thing is some sites (like the niacin page of examine.com) claim one has to take at least 1 gram daily to notice benefits. But I´m not sure if they considered young people like myself when making that conclusion.



#37 stefan_001

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Posted 14 January 2018 - 01:00 PM

Thank you for replying again. As far as I know, a raise in NAD+ at my age would give some anti-aging benefits. It would even give some phenotype quality benefits. 

But what if I took a lesser dosage? About 500mg instead of 1gram? Given I´m pretty young and I noticed some older members take 1 gram, I don´t think 500mg would be an unreasonable dosage. Only thing is some sites (like the niacin page of examine.com) claim one has to take at least 1 gram daily to notice benefits. But I´m not sure if they considered young people like myself when making that conclusion.

 

the 1 gram people are really the exception, from what I hear most people in their 40s and above take between 250-500mg. Nobody knows the answer to your dosing question at such young age. You have time to wait for more research to come out.



#38 Leon93

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Posted 14 January 2018 - 08:18 PM

Thank you once again. That´s an interesting reply. I read some take 250-500mg, but thought most take about at least 1g from what I´ve read. And I consider most members at this site are at least in their 30s.

It´s especially interesting since user:believer advises to take at least 1g a day: http://www.longecity...d/#entry838443 

Would you know anything whether biting an extended or sustained niacin release pill would give the same effects as an acute one?



#39 stefan_001

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Posted 14 January 2018 - 10:25 PM

i would not know the answer to the niacin pill. If you bite and chew then it will probaly have some sublingual absortion. If I were your age I would pay attention to keeping skin young and healthy, sun damage, wrinkles will not go away with NR or NMN later.



#40 Leon93

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Posted 01 February 2018 - 03:27 PM

Just to be completely sure, nicotinamide (niacinamide) does not cause NAD+ to rise right? As it doesn´t cause any flush, which I read is essential for NAD+.


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#41 Turnbuckle

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Posted 01 February 2018 - 03:56 PM

Flushing has nothing to do with NAD.


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#42 Tom Andre F. (ex shinobi)

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Posted 09 September 2018 - 12:44 PM

I wouldn't so much comment on the wisdom of combining NA with NR, as council against the use of NA. After all these years, it's still not clear whether NA reduces risk of cardiovascular events in people at high risk (ie, in the people in whom you'd most expect it to benefit) — and, in the meantime, it's now pretty clear that it raises the risk of diabetes:
 
 
A possible mechanism linked to lipid metabolism is niacin's effects on free fatty acids, which it initially suppresses but leads to a later rebound. Such a rebound would axially induce transient insulin resistance via the Randle cycle. That would seem to be more consistent with a transient, reversible effect.

A somewhat obscure second possible mechanism is through metabolic conversion of niacin to N-methylnicotinamide, the major metabolite of nicotinamide, whose function is still unclear.

Trammell and Brenner (2016a) found that 100 and 300 mg of oral NR had little effect on levels of N-methylnicotinamide in human PBMC, but 1000 mg/d caused a substantial increase; in mouse liver, nicotinamide riboside elevated N-methylnicotinamide close to twice as much as niacin does.
 
[...]

Perhaps most mechanistically worrisome are the recent studies linking niacin's activation of the "niacin receptor" GPR109A/PUMA-G:
 

High levels of PUMA-G transcripts and protein were detected in all β cells, and about 40% of α cells. PUMA-G transcripts increased more than 3-fold in islets incubated with [the inflammatory cytokine] interferon γ. Cyclic adenosine monophosphate accumulation, induced by IBMX/forskolin, was inhibited by [nicotinic acid/niacin] .... Static incubation of islets with NA led to an approximately 30% reduction of GSIS. The results indicated that PUMA-G stimulation by NA in islet β cells inhibited GSIS likely via activation of the Gi signaling pathway.
PMID: 21441844

GPR109A was significantly reduced in islets from diabetic individuals and animal model of db/db mice as compared to their respective controls. Further, GPR109A levels in insulinoma were also reduced dramatically as compared to islets found in corresponding non-tumor normal tissues. Quantitative RT-PCR analysis demonstrated that GPR109A transcripts were severely down-regulated in rodent insulinoma cell lines as compared to that of freshly isolated islets from mice. Finally, human and murine GPR109A expression cassettes were transfected into INS-1 cells, which resulted in reduced accumulation of cAMP and insulin secretion after incubation with niacin.
PMID 27570060


If this is correct, then it's important to know that nicotinamide riboside does not engage the niacin receptor.

The effect of niacin on beta-cells could also be an acute and reversible effect, but seems more intuitively likely to be durable than something as clearly related to metabolic flux as an FFA-mediated effect, particularly granted that "GPR109A was significantly reduced in islets from diabetic individuals and animal model of db/db mice". It would be interesting to see islets from diet-induced diabetic mice transplanted into healthy syngeic mice to see if function recovered. On the other hand, this is evidence of impaired function, not actually of the death of beta-cells.

 

 

Michael,

 

niacin cant be converted into nicotinamide, so then into N-methylnicotinamide. Only the opposite can happen. So this is a concern only related with niacinamide and NR.

 

On the other hand, if the GPR109A is the part involved for Niacin  increasing fasting glucose, then it explains why the long term study done on it showed a return to normal at the end of the study unlike the short term ones.

 

I believe this is a dose dependant response and THE answer for its method of action :

 

https://www.ncbi.nlm...les/PMC4586547/

 

"enterocyte GPR109a is expressed and functional in the local control of intestinal glucose absorption, and that type 2 diabetic and high glucose conditions upregulate the GPR109a expression, thus enhancing niacin-induced intestinal glucose uptake in the mice. Our laboratory has recently reported the novel role of niacin, via its activation of GPR109A, in pancreatic islets [10]. In that study, niacin was found to increase fasting glucose concentrations, reduce glucose-stimulated insulin secretion (GSIS) and insulin secretion, and impair glucose tolerance, thereby inducing pancreatic islet dysfunctions in high-fat diet (HFD) induced obese mice [10]. In this regard, the present study establishes a previously undiscovered role of niacin in local regulation of glucose homeostasis at the level of the small intestine in normal and diabetic states."

 

"In conclusion, the present study is the first to report that niacin is able to bind to the niacin receptor GPR109a to stimulate SGLT1- and GLUT2-mediated jejunal glucose uptake in hyperglycemia observed in diabetes."

 

So we clearly want to avoid high dose (above 500mg maybe even..) and avoid time released.

 

Back to this receptor : it is also a positive thing since its anti inflamatory and has cntrol on sleep quality / circardian rythm :

 

https://www.ncbi.nlm...les/PMC4201464/

 

things gets more complicated when we read that butyrate is also an agonist for this receptor, but we know butyrate control glucose (it decreases fasting glucose) :

 

"Butyrates (GPR109A agonists) are also known to inhibit inflammation through inhibiting NFκB in Crohn’s disease [57]. Butyrates decrease pro-inflammatory cytokine (TNFα, IL-6 and IL-1β) expression via inhibition of NFκB activation and IκB degradation [58]. Butyrates also inhibit NFκB activation via GPR109A and increases IκB levels in-vitro in intestinal epithelial cell lines [59]."

 

and :

 

https://www.ncbi.nlm...pubmed/24412617

 

"GPR109A (encoded by Niacr1) is a receptor for butyrate in the colon. GPR109A is also a receptor for niacin, which is also produced by gut microbiota and suppresses intestinal inflammation. Here we showed that Gpr109a signaling promoted anti-inflammatory properties in colonic macrophages and dendritic cells and enabled them to induce differentiation of Treg cells and IL-10-producing T cells. Moreover, Gpr109a was essential for butyrate-mediated induction of IL-18 in colonic epithelium. Consequently, Niacr1(-/-) mice were susceptible to development of colonic inflammation and colon cancer. Niacin, a pharmacological Gpr109a agonist, suppressed colitis and colon cancer in a Gpr109a-dependent manner. Thus, Gpr109a has an essential role in mediating the beneficial effects of gut microbiota and dietary fiber in colon.

 

So your comment here are welcome, but to me it start to over complicated the picture. My today conclusion for this is that all has to come in balance, why take such high amount vitamin B3 ? I know our end goal is to increase NAD+ but isnt low dose long run a better strategy to keep the balance under control ?

 

 

Also, some of the last studies you quoted mentions they dont have full data access and they dont even speak about the dosages used, and it look like the dosage used for cholesterol treatment means in g...

 

Most people here wouldnt use even a dose close to 1g and avoid the time released form. Personally I use 100mg (wich is like to take 200mg NR) daily along a mult B because if you look at well, all the others data done on biotin, P5P etc show a glucose balance with them. So maybe there is also a methylation cycle to respect, and this is true also for NR users probably

 

 

 

 


Edited by Michael, 11 September 2018 - 06:49 PM.
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#43 Michael

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Posted 11 September 2018 - 11:05 PM

Michael,
 
niacin cant be converted into nicotinamide, so then into N-methylnicotinamide. Only the opposite can happen. So this is a concern only related with niacinamide and NR.


(First, it's best to specify "nicotinic acid" (NA), not "niacin:" despite popular usage in the supplement community, "niacin" actually refers to any form of B3 — NA, NAM, NR, or NMN).
 
It's true that NA can't be directly converted to MeNAM the way NAM can, but any NAD+ precursor can and will elevate MeNAM when the NAD+ derived from it is consumed by SIRTs, PARPs, CD38, etc — see eg. the NAD metabolome chart in Trammell and Brenner PMID 27721479. See also Trammell and Brenner PMID 27721479 Figure 5 (e) for the rise in MeNAM in mouse liver after administration of NR, NAM, and NA, and these three studies plus PMID 1837687 for the effect of NA on MeNAM in humans.
 
There's also methylnicotinic acid (AKA trigonelline), which is directly formed from NA, but about whose metabolic effects much less is known.
 

On the other hand, if the GPR109A is the part involved for Niacin  increasing fasting glucose, then it explains why the long term study done on it showed a return to normal at the end of the study unlike the short term ones.
 
I believe this is a dose dependant response and THE answer for its method of action :
 
https://www.ncbi.nlm...les/PMC4586547/
 

"enterocyte GPR109a is expressed and functional in the local control of intestinal glucose absorption, and that type 2 diabetic and high glucose conditions upregulate the GPR109a expression, thus enhancing niacin-induced intestinal glucose uptake in the mice ... in normal and diabetic states  ... [N]iacin is able to bind to the niacin receptor GPR109a to stimulate SGLT1- and GLUT2-mediated jejunal glucose uptake in hyperglycemia observed in diabetes.  [in addition to its effects in inhibiting glucose-sensitive insulin secretion"

 
So we clearly want to avoid high dose (above 500mg maybe even..) and avoid time released.

 


Very important finding on the SGLT1 mechanism — thanks.
 
You'll get no argument from me that higher doses are riskier; however, we really just don't know what a safe dose is, or how it might vary from one B3 form to another.
 

Back to this receptor : it is also a positive thing since its anti inflamatory and has cntrol on sleep quality / circardian rythm :
 
https://www.ncbi.nlm...les/PMC4201464/
 
things gets more complicated when we read that butyrate is also an agonist for this receptor, but we know butyrate control glucose (it decreases fasting glucose) :
 
"Butyrates (GPR109A agonists) are also known to inhibit inflammation through inhibiting NFκB in Crohn’s disease %5B57%5D. Butyrates decrease pro-inflammatory cytokine (TNFα, IL-6 and IL-1β) expression via inhibition of NFκB activation and IκB degradation %5B58%5D. Butyrates also inhibit NFκB activation via GPR109A and increases IκB levels in-vitro in intestinal epithelial cell lines %5B59%5D."
 
and :
 
https://www.ncbi.nlm...pubmed/24412617
 
"GPR109A (encoded by Niacr1) is a receptor for butyrate in the colon. GPR109A is also a receptor for niacin, which is also produced by gut microbiota and suppresses intestinal inflammation. [...] Niacin, a pharmacological Gpr109a agonist, suppressed colitis and colon cancer in a Gpr109a-dependent manner. Thus, Gpr109a has an essential role in mediating the beneficial effects of gut microbiota and dietary fiber in colon.
 
So your comment here are welcome, but to me it start to over complicated the picture. My today conclusion for this is that all has to come in balance, why take such high amount vitamin B3 ? I know our end goal is to increase NAD+ but isnt low dose long run a better strategy to keep the balance under control ?

 
It's certainly complicated; messing with metabolism always is ;) . Re: these specific sources, note that butyrate here as in most studies is acting in the GI tract itself, which doesn't address the evidence for MeNAM and/or NA proper inhibiting or being toxic to beta-cells.
 
In general, I'd agree that a lower dose is a safer bet; indeed, there are several studies suggesting that more RDAish doses of NM/NMN are safer or more effective. The ideal strategy, short of repairing the cellular and molecular damage that underlies the dysregulation of the NAD+ metabolome with age, would entail more modest control over all the levers of the NAD+ metabolome instead of flooding the system with high doses of NAD+ precursors: a foundation of exercise and CR (and at minimum obesity-avoidance), plus low doses of NAD+ precursors, adequate but non-megadose intake of methylating nutrients, plus possibly CD38 inhibitors, plus possibly NAMPT and/or NMNAT1-3 activators, plus inhibitors of NAM methylation — and possibly cycling some or all of these.
 

Also, some of the last studies you quoted mentions they dont have full data access and they dont even speak about the dosages used, and it look like the dosage used for cholesterol treatment means in g...
 
Most people here wouldnt use even a dose close to 1g and avoid the time released form. Personally I use 100mg (wich is like to take 200mg NR) daily along a mult B because if you look at well, all the others data done on biotin, P5P etc show a glucose balance with them. So maybe there is also a methylation cycle to respect, and this is true also for NR users probably

 
The OP, however, said explicitly "I take niacin because I have bad lipid numbers despite being very thin and exercising caloric restriction".


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#44 aribadabar

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Posted 12 September 2018 - 06:25 PM

 adequate but non-megadose intake of methylating nutrients, plus possibly CD38 inhibitors, plus possibly NAMPT and/or NMNAT1-3 activators, plus inhibitors of NAM methylation — and possibly cycling some or all of these.

 

 

Do you have any preferred substances in each of these categories?


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