2266 replies to this topic

[midas]

 

 

 

I'm 4 plus months on the recommended dosage and still reaping the benifits. My regiment: I take 125mg sublingual after waking on an empty stomach, have one cup of coffee. I then do 20 minutes on a VersaClimber followed by 5 minutes on an inversion bed. In the evening I take 125mg sublingual and go to bed. Rinse and repeat. I haven't been taking the 3-5 days off between bottles but this thread may have convinced me I could benefit more from a break.

 

As far as any useful data from these threads thats a tough call because as a group most of us are adding other substances to the mix that might be acting on similar pathways.

 

Just my thoughts.

 

Bryan

 

 

Bryan, something you may also want to consider is the fact that with sublingual dosing it can reduce the amount of the compound needed to achieve the normal dosage by two thirds. I have no idea if that applies to NR, but if it does, then you will be taking three times the dosage because you are taking it sub-lingually.

 

What we really need to see are the results of some human trials to put this to bed.....I have read somewhere that their are some under way but I don't know for sure if that is true.

Edited by midas, 03 July 2014 - 05:26 PM.

[Bryan_S]

 

Bryan, something you may also want to consider is the fact that with sublingual dosing it can reduce the amount of the compound needed to achieve the normal dosage by two thirds. I have no idea if that applies to NR, but if it does, then you will be taking three times the dosage because you are taking it sub-lingually.

 

What we really need to see are the results of some human trials to put this to bed.....I have read somewhere that their are some under way but I don't know for sure if that is true.

 

 

That was likely me

 

I've been pushing for follow up information from a ChromaDex press release. I received a comment that a PK study is coming from one of the Niagen (NR) associates, evidently it is ongoing, or will be soon and has not reached publication. I tried to narrow it down and "The Company expects to initiate in October 2013 its first human clinical study on NIAGEN nicotinamide riboside. The pharmacokinetics (PK) study on NIAGEN will measure its effectiveness as a precursor to NAD+, a coenzyme that has crucial roles in many biochemical and biologic processes." (Where is the data? When is it coming? Why is it delayed?) More could also be coming from Dr. Michael Jaehme, a researcher at GBB, who will investigate the uptake of NR into cells and how it is converted into the biologically active nucleotides NMN and NAD+.

 

So I could be mega dosing at the equivalent of 750mg taken as a capsule. Its time for all this speculation to end we need some up-to-date data. Thanks 

Edited by Bryan_S, 03 July 2014 - 05:57 PM.

[Razor444]

 

I'm 4 plus months on the recommended dosage and still reaping the benifits. My regiment: I take 125mg sublingual after waking on an empty stomach, have one cup of coffee. I then do 20 minutes on a VersaClimber followed by 5 minutes on an inversion bed. In the evening I take 125mg sublingual and go to bed. Rinse and repeat. I haven't been taking the 3-5 days off between bottles but this thread may have convinced me I could benefit more from a break.

 

 

How do you know the benefits aren't just from nicotinamide, rather than NR? Does it not bother you that you may be inhibiting SIRT1?

 

I've just inspected my Jarrow vitamin B complex, and it has a ton of B₃. I'll be promptly removing said complex from my regime, and adding a food which is high in the specific B vit I would like to target...

[M-K]

If the benefits were from NAM, I would have noticed them before adding NR and wouldn't have gotten old.  <grin>.  Remember, Nampt, needed to convert NAM to NAD, becomes impaired when we get up in age.  That's probably why we produce <~50% as much NAD sans NR.

Edited by M-K, 04 July 2014 - 01:19 AM.

[Bryan_S]

 

 

I'm 4 plus months on the recommended dosage and still reaping the benifits. My regiment: I take 125mg sublingual after waking on an empty stomach, have one cup of coffee. I then do 20 minutes on a VersaClimber followed by 5 minutes on an inversion bed. In the evening I take 125mg sublingual and go to bed. Rinse and repeat. I haven't been taking the 3-5 days off between bottles but this thread may have convinced me I could benefit more from a break.

 

 

How do you know the benefits aren't just from nicotinamide, rather than NR? Does it not bother you that you may be inhibiting SIRT1?

 

I've just inspected my Jarrow vitamin B complex, and it has a ton of B₃. I'll be promptly removing said complex from my regime, and adding a food which is high in the specific B vit I would like to target...

 

 

I've read several therapeutic papers that harold the longterm neuroprotective properties this was my original interest but the other findings only hit it home for me.

 

http://vivo.med.corn...horInAuthorship

 

http://www.ncbi.nlm....les/PMC2651433/

 

http://tonglab.biolo...ch/nad-eott.pdf

 

http://www.ncbi.nlm....nihms-96557.pdf

 

No I'm not bothered, the lack of PK data bothers me. We've been waiting on ChromaDex since last October. 

Quote

 

I've been pushing for follow up information from a ChromaDex press release. I received a comment that a PK study is coming from one of the Niagen (NR) associates, evidently it is ongoing, or will be soon and has not reached publication. I tried to narrow it down and "The Company expects to initiate in October 2013 its first human clinical study on NIAGEN nicotinamide riboside. The pharmacokinetics (PK) study on NIAGEN will measure its effectiveness as a precursor to NAD+, a coenzyme that has crucial roles in many biochemical and biologic processes." (Where is the data? When is it coming? Why is it delayed?) More could also be coming from Dr. Michael Jaehme, a researcher at GBB, who will investigate the uptake of NR into cells and how it is converted into the biologically active nucleotides NMN and NAD+.

 

[APBT]

Does anyone suspect that taking NR at the recommended dose might require taking anything else to compensate? I'm thinking riboflavin or a choline source. I had a nice initial boost in VO2max (I've been around 47 and increased to 49, measured using a Garmin 620 with a monitor that also measures heart rate variability using Firstbeat technology) followed by a slump to 46/47. I'm still trying to figure out what's going on.

 

My first thought would be what is the margin of error for Firstbeat?  Possibly +/- 2 points falls within that.  Which of their products are you using? 

 

Second, possibly you're slightly over-reaching in your training; mild dehydration, recovery/sleep deficit?

 

Third, improvements are not linear and if your base was 47 with a jump to 49, followed by a fall to 46/47, this may be normal.  Or, 49 may have been a transitory peak-performance.

 

I seem to recall from another post, you take a multi-vitamin and eat well, so I'd think it unlikely you're lacking adequate riboflavin or choline, considering you're only consuming 250 mg of NR (Niagen). 

Edited by APBT, 04 July 2014 - 04:08 AM.

[Primal]

rationale for choline? as a methyl donor? and B2 for FAD/FADH2?

 

[Primal]

did u guys ask HPN if they put any fillers in their niagen caps, or if its pure NR?

 

I asked them and they said The material is combined with silicon dioxide to ensure a smooth and even capsulation process.

 

I wonder if he got that right or confused it with another product. If there is indeed silicon dioxide, NR and nothing else, its fairly clean but still some really dont like silicon dioxide, especially for sublingual. Its not toxic like mercury but I'm not sure I want it accumulating in my brain either..

[niner]

 If there is indeed silicon dioxide, NR and nothing else, its fairly clean but still some really dont like silicon dioxide, especially for sublingual. Its not toxic like mercury but I'm not sure I want it accumulating in my brain either..

 

Silicon dioxide is just finely ground sand, isn't it?  Unless it's some sort of weird nanomaterial, I don't see how it would accumulate in the brain.

[stephen_b]

 

Does anyone suspect that taking NR at the recommended dose might require taking anything else to compensate? I'm thinking riboflavin or a choline source. I had a nice initial boost in VO2max (I've been around 47 and increased to 49, measured using a Garmin 620 with a monitor that also measures heart rate variability using Firstbeat technology) followed by a slump to 46/47. I'm still trying to figure out what's going on.

 

My first thought would be what is the margin of error for Firstbeat?  Possibly +/- 2 points falls within that.  Which of their products are you using? 

 

Second, possibly you're slightly over-reaching in your training; mild dehydration, recovery/sleep deficit?

 

Third, improvements are not linear and if your base was 47 with a jump to 49, followed by a fall to 46/47, this may be normal.  Or, 49 may have been a transitory peak-performance.

 

I seem to recall from another post, you take a multi-vitamin and eat well, so I'd think it unlikely you're lacking adequate riboflavin or choline, considering you're only consuming 250 mg of NR (Niagen). 

 

 

Hey APBT. Aside from the Firstbeat measurements, I've just been feeling like crap and haven't been able to sustain a fast pace at a reasonable heart rate. It's not subtle. I have been under a lot of stress lately due to events outside of my control, and that could be a factor.

 

Outside of the stress, I'm looking down the rabbit hole of methylation.

 

I am not clear just how applicable this study is, but the idea is that niacin depletes methyl groups when taken in large enough doses and it might affect some more than others (I'm heterogeneous for MTHFR). In PMID 6236852 for nicotinamide:

 

A large depletion of intracellular ATP, associated with a marked accumulation of NAD, occurred in slices in response to the addition of high amounts of nicotinamide. However, the loss of ATP was overcome, when nicotinamide was given together with 1-methylnicotinamide.

 

 

I have started taking some SAMe and dropping NR for a bit to see if it helps.

Edited by stephen_b, 04 July 2014 - 03:14 PM.

[MarcD]

I tried to dissolve 10g of NR in 100ml OliveOil with 0.8mg C60 / ml without success yesterday ... just for info... if someone else suffers from spontaneous craziness :-) 

[to age or not to age]

Okay, I'm back from Boston.  I had dinner with the speakers at Harvard Glenn Lab Symposium, including David SInclair and

Lenny Guarente.  Off the record, I was told that a minimum of 1/2gram to 1 gram of NR is necessary to achieve effects.

But, it is clear to me that the scientists believe this precursor works. Moreover, Chromadex will have serious competition, and soon.

This will come from two directions: Without naming names at this point, a company has been formed which will try to position

itself in the space between big pharma/FDA approved patented medicines and "supplement companies" where-in major researchers

have signed up as consultants (including nobel winners) - there  will be human tests, branding etc.

The 2nd direction (friendly competition among friends) will come from places like GSK, and will involve minimally changing

the precursor in order to patent it etc.

Further, after all the Sirtris/GSK speculation as to efficacy of these sirtuin activators, Human Trials are commencing now

with a novel molecule against inflammation markers and this will only take months.  The molecule will have implication for

many diseases of aging, but is being tested against inflammation because it is easy to quantify the efficacy quickly.

Scientists believe this will be a blockbuster drug.

On a side note, David is not thrilled that chomadex uses him and his work to sell their product, but he's too good a guy

to go after them.

I scheduled interviews for later in the summer with the GDF11 gang.

I am editing a couple of interviews; one is with Vince Giuliano, someone I have known since early 2010.  Vince has been

taking NR, c-60, curcumin and other anti inflammation compounds, plus resveratrol for 6 years.  He makes his own liposomal concoctions.  Anecdotally - Vince looks better now than he did 4 years ago, his arthritis is gone, as well as the slight tremor

I saw in my 2010 interview with him. VInce was born in 1929 so this is impressive.  His parents weren't particularly long lived. More to come. 

 

 

[APBT]

to age or not to age

 

Thank you for posting the update.  Hopefully increased competition will drive down the price of NR and, possibly improve the purity (less filler in caps).

 

Were you able to get any feedback on the questions below?

 

Is the circadian clock a crucial consideration in the timing of supplemental NAD+ precursor consumption?  If so, how?

Should NR be cycled?  If so, how?  Or, is it best to consume chronically?

Is nicotinic acid (NA, niacin) a reasonable replacement for NR?  Do they work similarly mg for mg?  Can they be used simultaneously for a synergistic effect?

How does resveratrol fit into the NR equation?  Dosage?

Is there any way for the consumer (outside of a research setting) to objectively and quantitatively measure the effects of NAD+ precursors  (e.g. blood tests)?

Is NR a PPAR-delta agonist?

 

Other user's questions:

 

Are NR and NMN methyl acceptors, like NA and NAM (1-methylnicotinamide (MNA), 1-methyl-2-pyridone-5-carboxamide (M2PY) and 1-methyl-4-pyridone-5-carboxamide (M4PY))? Ie does their metabolism and excretion use methyl groups? 

 

1) how much oral NR needs to be taken in one sitting to saturate the hydrolysis/phosphorylysis of NR in the intestine

2) what happens to additional oral NR, is it broken down to something other than niacinamide, or does it passively diffuse through the intestine, or whatnot.

3) If it diffuse through the intestine as is, does it survive the liver first past metabolism?

4) If it does, does the high level of NR in blood translate into levels of NAD in cells higher that can reasonably be obtained from niacin. For example this study doesnt look too good for NR (against niacin) - eg looking at graph D in figure 1

5) If significant NR reach the blood, does its metabolism require methyl groups (like that of niacin and niacinamide)

6) If oral NR does not beat niacin, is there other delivery methods that works better. It looks like many people here use sublingual niagen.

 

 

Edited punctuation, thanks Primal

Edited by APBT, 07 July 2014 - 03:45 PM.

[Primal]

 Off the record, I was told that a minimum of 1/2gram to 1 gram of NR is necessary to achieve effects.

But, it is clear to me that the scientists believe this precursor works. 

 

This is interesting, hopefully we get more details on this (as laid in APBT's post above)

 

The 2nd direction (friendly competition among friends) will come from places like GSK, and will involve minimally changing

the precursor in order to patent it etc.

 

like changing the crystalline types/amorphous?

 

 Further, after all the Sirtris/GSK speculation as to efficacy of these sirtuin activators, Human Trials are commencing now

with a novel molecule against inflammation markers and this will only take months.  The molecule will have implication for

many diseases of aging, but is being tested against inflammation because it is easy to quantify the efficacy quickly.

Scientists believe this will be a blockbuster drug.

 

which one is it? I didnt follow much of the sirtuin activators stuff but if human trials are commencing within months I'm sure some people here must have a good idea what is closest in the pipeline

 

I scheduled interviews for later in the summer with the GDF11 gang.

I am editing a couple of interviews; one is with Vince Giuliano, someone I have known since early 2010.  Vince has been

taking NR, c-60, curcumin and other anti inflammation compounds, plus resveratrol for 6 years.  He makes his own liposomal concoctions.  

 

So he doesnt take GDF11? you should ask him roughly the dosage of each compound, and his liposomal recipe

 

 

Other users' questions:

 

Are NR and NMN methyl acceptors, like NA and NAM (1-methylnicotinamide (MNA), 1-methyl-2-pyridone-5-carboxamide (M2PY) and 1-methyl-4-pyridone-5-carboxamide (M4PY))? Ie does their metabolism and excretion use methyl groups? 

 

1) how much oral NR needs to be taken in one sitting to saturate the hydrolysis/phosphorylysis of NR in the intestine

2) what happens to additional oral NR, is it broken down to something other than niacinamide, or does it passively diffuse through the intestine, or whatnot.

3) If it diffuse through the intestine as is, does it survive the liver first past metabolism?

4) If it does, does the high level of NR in blood translate into levels of NAD in cells higher that can reasonably be obtained from niacin. For example this study doesnt look too good for NR (against niacin) - eg looking at graph D in figure 1

5) If significant NR reach the blood, does its metabolism require methyl groups (like that of niacin and niacinamide)

6) If oral NR does not beat niacin, is there other delivery methods that works better. It looks like many people here use sublingual niagen.

 

 

I'm glad I count for more than one user 

[Kevnzworld]

Okay, I'm back from Boston.  I had dinner with the speakers at Harvard Glenn Lab Symposium, including David SInclair and
Lenny Guarente.  Off the record, I was told that a minimum of 1/2gram to 1 gram of NR is necessary to achieve effects.
But, it is clear to me that the scientists believe this precursor works. Moreover, Chromadex will have serious competition, and soon.
This will come from two directions: Without naming names at this point, a company has been formed which will try to position
itself in the space between big pharma/FDA approved patented medicines and "supplement companies" where-in major researchers
have signed up as consultants (including nobel winners) - there  will be human tests, branding etc.
The 2nd direction (friendly competition among friends) will come from places like GSK, and will involve minimally changing
the precursor in order to patent it etc.
Further, after all the Sirtris/GSK speculation as to efficacy of these sirtuin activators, Human Trials are commencing now
with a novel molecule against inflammation markers and this will only take months.  The molecule will have implication for
many diseases of aging, but is being tested against inflammation because it is easy to quantify the efficacy quickly.
Scientists believe this will be a blockbuster drug.
On a side note, David is not thrilled that chomadex uses him and his work to sell their product, but he's too good a guy
to go after them.
I scheduled interviews for later in the summer with the GDF11 gang.
I am editing a couple of interviews; one is with Vince Giuliano, someone I have known since early 2010.  Vince has been
taking NR, c-60, curcumin and other anti inflammation compounds, plus resveratrol for 6 years.  He makes his own liposomal concoctions.  Anecdotally - Vince looks better now than he did 4 years ago, his arthritis is gone, as well as the slight tremor
I saw in my 2010 interview with him. VInce was born in 1929 so this is impressive.  His parents weren't particularly long lived. More to come. 
 
 

This is great, but it should be posted in " David Sinclair strikes again " so more people with interest in this topic will see it .
I've anecdotally felt that my physiological response to NR wasn't apparent until the 500 mg level. I take 750mg daily

[Phoenicis]

4) If it does, does the high level of NR in blood translate into levels of NAD in cells higher that can reasonably be obtained from niacin. For example this study doesnt look too good for NR (against niacin) - eg looking at graph D in figure 1

 

Agreed Niacin did do quite well there, I've been on it for a month and think I've seen some decent results. When you factor in the price its a no brainer at this point in time.

 

In this paper the author even hypothesizes that the Naicin flush pathway can serve as a biomarker for NAD+ levels. He states that without adequate NAD the specific high affinity G-protein coupled receptors will not produce a flush response and observes that this is often the case with schizophrenics.

 

Glutamine is the rate limiting factor in converting NA to NAD+ by glutamine-dependent NAD+ synthetase (NADSYN1). The author of Schizophrenia paper therefore recommended taking glutamine with NA and said 10-15g/day achieve the best results. We might therefore hypothesize that if glutamine is taken with NA, it would then work even more efficiently than in the study you linked.

 

We know resveratrol upregulates NAMPT, which will help to convert NAM back into NAD. I think taking this effectively helps to close the NAD loop and would help to elevate overall NAD levels.

Edited by Phoenicis, 06 July 2014 - 10:10 PM.

[Razor444]

 

4) If it does, does the high level of NR in blood translate into levels of NAD in cells higher that can reasonably be obtained from niacin. For example this study doesnt look too good for NR (against niacin) - eg looking at graph D in figure 1

 

Agreed Niacin did do quite well there, I've been on it for a month and think I've seen some decent results. When you factor in the price its a no brainer at this point in time.

 

 

Niacin is converted to nicotinamide, in vivo. And NAM is a sirtuin inhibitor. As far as longevity goes, I don't know if the increase in NAD offsets that, though?

[Phoenicis]

 

 

4) If it does, does the high level of NR in blood translate into levels of NAD in cells higher that can reasonably be obtained from niacin. For example this study doesnt look too good for NR (against niacin) - eg looking at graph D in figure 1

 

Agreed Niacin did do quite well there, I've been on it for a month and think I've seen some decent results. When you factor in the price its a no brainer at this point in time.

 

 

Niacin is converted to nicotinamide, in vivo. And NAM is a sirtuin inhibitor. As far as longevity goes, I don't know if the increase in NAD offsets that, though?

 

 

NA is converted to Nam in vivo, but this is the work of NAD consuming enzymes; It becomes Nam after being converted to NAD. Even NMN would ultimately end up as Nam, after being converted to NAD.

 

• NA > NaMN > NaAD+ > NAD+ > Nam
• NMN > NAD+ > Nam

If you wanna decrease Nam you have to upregulate NAMPT with something like resveratrol.

 

See bellow:

 

 

Shinobi:

 

Nicotinamide (Nam) and nicotinamide riboside (NR) differ only through a ribosylation on NR.

 

Its difficult to raise NAD+ levels with Nam as the enzyme Nampt is saturated at low concentration. Moreover, Nam itself functions as a feedback inhibitor of sirtuins and PARPs, but this suppression of NAD+ consumption has benefits in ischemia-reperfusion injury, like stroke.

 

Nicotinic acid utilizes the Preiss-Handler pathway, which isn't subject to the Nampt bottleneck. High doses cause flushing which many dislike, but the same mechanism has antiinflammatory benefits.

 

NMN is the subject of Sinclair's study. While an intermediate for Nam and NR, it only can enter cells as NR. 

 

NR isn't rate-limited by NAMPT, and doesn't cause flushing, but only some tissues (in animals) express NR kinases to utilize it.

 

 

Intracellular NAD+ metabolism in humans. Tryptophan (Trp), nicotinic acid (Na), nicotinamide (Nam), nicotinamide riboside (NR),and nicotinic acid riboside (NaR) are utilized through distinct metabolic pathways to form NAD+. 

 

Tryptophan (Trp) is converted to NAD+ in the eight-step de novo pathway through quinolinate (Quin), which is converted to nicotinic acid mononucleotide (NaMN) by quinolinate phosphoribosyltransferase (QPRT). NaMN is then adenylylated by the products of the NMNAT1-3 genes to

form nicotinic acid adenine dinucleotide (NaAD+), which is converted to NAD+ by glutamine-dependent NAD+ synthetase (NADSYN1). 

 

Nicotinic acid (Na) is utilized in the three-step Preiss-Handler pathway. Nicotinic acid phosphoribosyltransferase (NAPRT1) forms NaMN by addition of the 5-phosphoribose group from 5-phosphoribosyl-1-pyrophosphate to Na. In two steps shared with the de novo pathway, NaMN is then converted to NaAD+ and NAD+ via activity of NMNAT1-3 and NADSYN1.

 

Nicotinamide (Nam) is utilized via nicotinamide phosphoribosyltransferase (Nampt), encoded by the PBEF1 (NAMPT) gene. Nampt catalyzes the addition of a phosphoribose moiety onto Nam to form nicotinamide mononucleotide (NMN). NMN is subsequently converted to NAD+ by the products of NMNAT1-3. Nam is produced by NAD+-consuming enzymes.

 

Nicotinamide riboside (NR) is phosphorylated by the products of nicotinamide riboside kinase genes (NRK1 and NRK2) to form NMN, which is converted to NAD+ by NMNAT1-3. NR may also be utilized by the product of the NP gene, purine nucleoside phosphorylase, for subsequent Nam salvage.

 

From Bogan, K. L., & Brenner, C. (2008). Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition. Annu. Rev. Nutr., 28, 115-130.

 

 

 

Edited by Phoenicis, 06 July 2014 - 10:07 PM.

[APBT]

I understand how posts can digress off of the thread topic. Often it is appropriate to address a comment that is somewhat off topic; but, as much as possible, I'd like to focus this thread on personal experiences with NR.

 

Post research or debate regarding NR verses NA, group buy options, etc... in separate (dedicated) threads.  Overall, I think it is more efficient to collate the data this way. 

 

If a post stimulates a question or comment that is off-topic, a suggestion would be to provide a link here and start a new topic or link to the appropriate existing thread and pose the question or comment there.

 

Edited to add third paragraph. 

Edited by APBT, 08 July 2014 - 04:14 AM.

[APBT]

I have copied and pasted posts #192 and #193 over in the David Sinclair Strikes Again thread.  Hopefully the discussion and questions will continue over there.

 

 

Edited by APBT, 09 July 2014 - 12:19 AM.

[kenj]

I think I'm going to skip dose every other day or something like that to get the most 'bang for the buck' experience as long as NR is still somewhat expensive.. Would that be reckless? :p

 

I would love to take 1+ gram every single day but I take many other supps too (resv, ptero, metf, c60, rla/q10, full vit/min, noots, etc.), and would like to continue taking those, too. I can't afford daily 'mega' gram NR dosage at this point. 

 

I, as others here have mentioned, do not really 'feel' NR at 250mg. However at 500-750mg before my cardio workouts it seems to help my endurance/joints for example. I'll take placebo, no problem.  

 

 

 

 

[Razor444]

I'm going to add niacin, as well.

 

Here's four quotes, with links to papers, which you may find convincing.

 

"More research is required to determine which clinical situations, what timing, and at what doses nicotinamide would augment or inhibit sirloins in way that best help to accomplish desired therapeutic outcomes. Since nicotinic acid can be used to generate NAD and does not have the inhibitory effects of nicotinamide, it might be a better choice when the goal is to augment sirtuin enzyme activity."  Source

 

"...induced by high-dose niacin (i.e., nicotinic acid given in the range of 2-6 grams) and resveratrol, since both increase sirtuin activity, causing post-translational protein modifications that alter expression of apolipoproteins, transporters, receptors and enzymes involved in lipid metabolism.27 However, nicotinamide riboside might be an even better partner for resveratrol since it increases the availability of NAD+ (and therefore sirtuin activity) without causing flushing." Source

 

"Why is nicotinic acid, but not niacinamide effective in improving dyslipidemia? Nicotinic acid activates Sirt1 in the liver. Sirt 1 deacetylates liver X receptor (LXR), a positive regulator of cholesterol and lipid homeostasis. Niacinamide, at the high doses required to impact dyslipidemia, inhibits sirtuin enzymes (via the mechanism shown above in The Sirtuin Deacetylation Reaction flowchart)." Source

 

"It is important to mention that, although only nicotinamide inhibits sirtuins, both nicotinic acid and nicotinamide lead to increased cellular NAD+ production." Source

 

 

Edited by Razor444, 09 July 2014 - 03:48 PM.

[Primal]

"Why is nicotinic acid, but not niacinamide effective in improving dyslipidemia? 

 

very good question

 

Nicotinic acid activates Sirt1 in the liver. Sirt 1 deacetylates liver X receptor (LXR), a positive regulator of cholesterol and lipid homeostasis. Niacinamide, at the high doses required to impact dyslipidemia, inhibits sirtuin enzymes (via the mechanism shown above in The Sirtuin Deacetylation Reaction flowchart)." Source

 

 

There are several hypotheses, for example coupling the receptor GPR109a/GPR109b. Unfortunately he doesnt mention if he has any experiments to back up his 

[jachbo]

I have read this thread and find it helpful.  I started Niagen on Monday , July 7, 2014.  My reason is that I am always tired and all the Dr says is that it comes with aging.

 

 

Dosage is 250 mg in the AM

I am female: 53

Good Health

Good Weight

Good BP and Cholesteral (Dr always ask if I am a runner and I laugh because I hate running, it is my least favorite form of execise.)

No energy at all.

 

I have not always been healthy, I had a Gastric Bypass for obesity almost 20 years ago and have lost 125 lbs.  I have been the same weight now for 16 years. 

I do have Pernisious Anemia which is treated with B12 injections every two weeks.

 

I have been trying to find out some of the negative side affects of Niagen,

 

The first and second day I saw no noticeable affect.

The third day I was tired, and had a tough time getting up in the AM.  I kept falling back to sleep.

The 4th day I felt lethargic all day and like I was getting the flu or something, headaches, bodyaches, upset stomach.

Today is the fifth day and I feel pretty lousy.  Instense headache, bodyaches, lethargic, tired, little appetite, moody.

 

I am trying to stick it out, thinking that it is something that my body has to adjust to.

 

Does anyone have any info. on this?

 

Has anyone exeprienced it?  How long did it last?

 

I have read the threads and seen some people mention feeling like they had been run over by a truck and that pretty much explains how I feel.

 

Candi

 

 

 

[M-K]

Candi, are you taking a high-potency B complex supplement?  There is a controversial view, dating back at least to Adele Davis, that taking large doses of individual B vitamins can deplete stores of the unsupplied vitamins and complimentary nutrients.  I subscribe to this view concerning most nutrients (and don't have time or inclination to debate it).  

 

My experience with Niagen has been the opposite of yours, but I take a hefty multi-shake daily.

[Candace Booker]

 I also drink  a shake that I make that contains, fruits, carrots, squash, eggplant, sweet potatoes and kale as well as a variety of other fruits and veggies. Because of the bypass, supplements are difficult.  They fill my stomach and I cannot eat.  I soak Gummie Vitamins in water and add them to the shake each day to get more vits.  I have noticed that by taking the Niagen with my morning coffee, it does not affect my daily intake all that much.  I would say I can only drink about 1/3 of my shake now. I have a hard time getting enough protein, so I add it to this also.

 

My body is no longer aching and I have cut down on my sleep by about 2 hours, so that is good.  I can sleep for 18 hours if I let my body wake up on it's own (I really meant tired when I said I was tired...LOL.)  I set my alarm for 12 hours and have found that now I am waking up at about 10.  I work from home because of this exhaustion, it was my only choice.

 

Maybe this is going to help after all, I just needed an adjustment period.  I need a miracle and have high hopes of getting my life back.

 

 

[niner]

I have read this thread and find it helpful.  I started Niagen on Monday , July 7, 2014.  My reason is that I am always tired and all the Dr says is that it comes with aging.

Maybe you need a new doctor. 53 isn't very old, and extreme tiredness is not a normal part of aging. It's great that your gastric bypass was so successful in terms of keeping the weight off, but it sounds like you might be deficient in some vitamins and/or minerals, and possibly some macronutrients as well. The gummy vites probably aren't enough for you; maybe you could figure out how to incorporate better vitamins into your diet, like adding the contents of capsules to your shake, or grinding up a tablet in a mortar and pestle. There are some vitamins formulated as liquids, but I don't know how good they are.

You might want to give c60-olive oil a try. It's liquid and you only need a very small amount.

[stephen_b]

I have been writing a bit here about NR and low energy. I noticed that I perked up quite a bit after my iodine/selenium combo (19 mg and 200 mcg respectively; I don't usually take 19 mg of I as KI, more typical is 1-2 mg when I do take it, but I felt that I needed a jump start). So mood, energy, and muscle recovery from an 8 mile marathon pace run with the thyroid precursors.

 

Curious, I googled niacin and thyroid. Two very small studies jumped out (PMID 7776715 and 1405773) that found that nicotinic acid can decrease thyroid hormone levels.

 

I'm perhaps a little hypothyroid by default and definitely under stress at the moment, which can also apparently impede conversion of T4 to T3. So it is plausible that NR might have had a hand in my recent malaise.

 

So, that's my anecdotal report. I'll supplement iodine more moderately over the next week with 1-2 mg iodine and 200 mcg selenium while taking the recommended dose of NR and report on how things turn out.

[stephen_b]

Ok, an update after 10 days. I tried supplementing with iodine/selenium along with the recommended 250 mg dose of NR. Result: flat mood/affect and lack of improvement in athletic performance (endurance running, specifically in the regime where carb metabolism is important). NR would be great for anxiety, but it makes me too flat emotionally and motivationally.

 

BUT, on the plus side I think I have the athletic part of the equation cracked. After upping my thiamine dose to 300 mg/twice daily, my running mojo is back, and VO2max is back up to 49, the highest it's been since I have been measuring it. Thiamine also gives me a very nice mood brightening effect.

 

So, were my initial results with improved athletic performance due to thiamine and not NR as I had thought? Did NR at 250mg or 375mg/day interfere with thiamine metabolism? Who knows, this is all anecdotal.

 

Next up: lower dose NR while maintaining at least 300 mg of thiamine.

[Kevnzworld]

Re: NR and thyroid function, homocysteine etc.
My personal belief after experimenting with various doses is that 750 mg split, twice a day is the optimal dosage for a mildly athletic , fit, 145lb male. ( me ).
I am getting my first complete blood test since beginning NR on Friday. It's helpful to have a blood test history for comparison. Both my thyroid function, and homocysteine levels are normal/optimal
I have had mild declining thyroid function beginning a few years ago, I normalized my numbers with a combination of iodine and Armour thyroid 1/2 grain. I also had elevated homocysteine which I lowered with 1000 mcg 5 methyl folate.