48 replies to this topic

[Turnbuckle]

 

I don't see how "increased libido and the accompanying nipple sensitivity" is a problem unless you're a monk.

 

I think you are joking perhaps, though it is impossible o tell from your post.

For a male to have nipple sensitivity requires a significant and very unhealthy alteration of hormonal balance. Even during anabolic steroid cycles, one does not expect this to happen, and a host of measures will be taken by the steroid user if this develops. Left unchecked it can result in gynecomastia  which is terrible and in many cases irreversible without surgery.

 

Not a problem, eh? OK...

 

We all learn from you and I personally respect your knowledge and contributions a lot. So why not just acknowledge that NR can do some things that are -maybe not entirely, but largely- independent of its effects on the mitochondria and that, if we are seeking optimal health and longevity, we should be cognizant of those effects too. This won't make anything that you said in the Mitochondrial Dynamics thread wrong; it will just require us all to take a broader perspective.

 

 

As I posted above in the "Mitochondrial and sex steroid hormone crosstalk during aging" link, mitochondria are involved in sex hormones. Hormones go down with mitochondrial dysfunction so you can expect them to go up if mitochondrial function is restored. I'm not saying it's impossible for NR to be involved in some other way and I will be interested to hear of whatever research you've uncovered that's on point. As for your worry about gynecomastia, that sounds like hypochondria. Put your mind at ease by either discontinuing NR or by getting your hormones tested.

[Ovidus]

Ok thanks Turnbuckle...

[Del369]

I took NR (HPN) for over a year and seeing your mention of mouth ulcers reminded me of my experience in the beginning, which was pretty similar, except I used Vit D3, and Pterostilbene (150mg) with with my NR (250mg p/d) with a glass of OJ each morning, added to that about half a teaspoon of Vit-C powder and L-Glutamine Powder, every time I feel cold/flu symptoms and when I felt the mouth ulcer symptoms I automatically thought of the immune system being weak and doubled/trebled up on the Vit-C dose (split over 2x day) and after a few days they always disappeared (mouth ulcers included)

Never thought much about it until I read this post but the increased Vit-C always seemed to help me over that one.

I stopped with NR when Alive by Nature introduced NMN and I take those now, they seem to hit me with noticeable immediate effects but funnily enough one thing I've not had with NMN is any sign of mouth ulcers.

[Ovidus]

I took NR (HPN) for over a year and seeing your mention of mouth ulcers reminded me of my experience in the beginning, which was pretty similar, except I used Vit D3, and Pterostilbene (150mg) with with my NR (250mg p/d) with a glass of OJ each morning, added to that about half a teaspoon of Vit-C powder and L-Glutamine Powder, every time I feel cold/flu symptoms and when I felt the mouth ulcer symptoms I automatically thought of the immune system being weak and doubled/trebled up on the Vit-C dose (split over 2x day) and after a few days they always disappeared (mouth ulcers included)

Never thought much about it until I read this post but the increased Vit-C always seemed to help me over that one.

I stopped with NR when Alive by Nature introduced NMN and I take those now, they seem to hit me with noticeable immediate effects but funnily enough one thing I've not had with NMN is any sign of mouth ulcers.

 

Of course the few anecdotal reports we have so far are not at all conclusive or constitute a scientific basis to draw conclusions from.
However, this is sounding like a bit too much of a coincidence. In my case, another thing I noted is that I have become more and more sensitive to NR over time. While it would take around 7-10 days for the mouth ulcers and other symptoms to develop, lately it happens in 2-3 days. No kidding; I begin NR on Monday and by Wednesday or Thursday I will have mouth ulcers.... really crazy.

 

Is a weakening of the immune system the only reason one may develop mouth ulcers? What other mechanism may be responsible?

[Del369]

Well I just go by gut instinct for everything so I'm not much of a measure for anything scientific sorry. I was just on vacation and took a left over bottle of NR with me instead of the NMN and I took them for 4 weeks daily (250mg p/d) and I didn't have any ulcers develop at all, mind you I was doing elevated Vit-C 1000mg (3x p/d) for about 3 weeks so maybe they were squashed at source.

[MikeDC]

no side effects showed up in all the clinical trials with very high NR doses. Try take some vitamin B12.

[sthira]

Is a weakening of the immune system the only reason one may develop mouth ulcers? What other mechanism may be responsible?

Cytomegalovirus is common, and CMV-related ulcers may appear under conditions of immunodeficiency. Maybe you've taken too much of the pyridin-nucleoside form of vitamin B3, and this superabundance has compromised your system and kicked up dormant CMV?

Tests are available. Give blood. Diagnosis is confirmed by resolution with ganciclovir therapy.

[MikeDC]

https://www.ncbi.nlm...pubmed/9825643/

[MikeDC]

Everything is toxic if taking too much. I don’t see a need for people to take more than 500mg a day. People are getting fantastic results with just 250mg or even 125mg.

[Ovidus]

 

Is a weakening of the immune system the only reason one may develop mouth ulcers? What other mechanism may be responsible?

Cytomegalovirus is common, and CMV-related ulcers may appear under conditions of immunodeficiency. Maybe you've taken too much of the pyridin-nucleoside form of vitamin B3, and this superabundance has compromised your system and kicked up dormant CMV?

Tests are available. Give blood. Diagnosis is confirmed by resolution with ganciclovir therapy.

 

 

Hmmm. How do I know if I am taking the "pyridin-nucleoside form of vitamin B3"?

 

I have taken this: https://www.vitamins...apsules/vs-1533

and I have also taken a product that merely says "Niacinamide" and came from a lab supply place with all sorts of purity tests... How can I tell if these were the pyridin-nucleoside form?

[hav]

Everything is toxic if taking too much. I don’t see a need for people to take more than 500mg a day. People are getting fantastic results with just 250mg or even 125mg.

 

The bulk teaspoon concentration I take is probably contains in the neighborhood of between 250mg and 500mg of NR and the effect is positive and noticeable.  I started with 125mg capsules for about a month and got no noticeable effect.

 

Howard

[Slobec]

Bright side?  http://www.freewebs....cin_therapy.pdf

[Slobec]

High dose Nicotinamide weaken immune system.

https://www.ncbi.nlm...les/PMC5419340/
High doses of nicotinamide lead to reduced regulatory T cells and immune intolerance. Loss of no longer needed symbiotic ‘old friends’ compounds immunological over-reactivity to cause allergic and auto-immune diseases. Inhibition of nicotinamide adenine dinucleotide consumers and loss of methyl groups or production of toxins may cause cancers, metabolic toxicity, or neurodegeneration. An optimal dosage of vitamin B3 could lead to better health, but such a preventive approach needs more equitable meat distribution.

 

Its probably bad methionine/glycine ratio and high phosphate/calcium (today is 6:1 in many developed countries) ratio that goes wrong with higher meat consumption, not few more  mg of B3? Our ancestors used to eat skin, joints etc (more glycine, proline...) and we are consuming pure meat.

[Turnbuckle]

 

High dose Nicotinamide weaken immune system.

https://www.ncbi.nlm...les/PMC5419340/
High doses of nicotinamide lead to reduced regulatory T cells and immune intolerance. Loss of no longer needed symbiotic ‘old friends’ compounds immunological over-reactivity to cause allergic and auto-immune diseases. Inhibition of nicotinamide adenine dinucleotide consumers and loss of methyl groups or production of toxins may cause cancers, metabolic toxicity, or neurodegeneration. An optimal dosage of vitamin B3 could lead to better health, but such a preventive approach needs more equitable meat distribution.

 

Its probably bad methionine/glycine ratio and high phosphate/calcium (today is 6:1 in many developed countries) ratio that goes wrong with higher meat consumption, not few more  mg of B3? Our ancestors used to eat skin, joints etc (more glycine, proline...) and we are consuming pure meat.

 

 

It is very likely that the continued high intake of NAM produces the same problem that a continued high intake of NR produces--the reduction of mitochondrial number (due to higher levels of mitophagy) and also the reduction of ATP production (due both from mito fission and lower numbers of mitochondria). Mice given high does of NR apparently experience this effect as exercise performance is reduced by 35%. The solution is then not an optimum dose of NAM as suggested by the above paper, but an oscillating dose, which is more in tune with a paleo diet of feast and famine and which clears out defective mtDNA.

[TMNMK]

Maybe I'm an oddball but I've taken what I would consider to be truly herculean doses of NR over extended periods of time to see where the acute toxicity barrier might be for me (I have quite a lot of it lying around from multiple different vendors and felt like I needed to make dent I guess). I haven't found the wall yet so the "dark side" of NR might vary person to person. It will be interesting to see what future studies have to say on that subject. One time I felt sort of dizzy and tingly for a few days but that quickly subsided. I'm not terribly scientific about it obviously, did increase dosage carefully as sometimes that wall can be a sharp edge.. but I know what overdose feels like and a little dizzy and tingly ain't even close.

 

(Oh and uh.. one might tag this as dangerous or irresponsible and I won't debate that whatsoever, but trust me I am capable of doing far worse to my body than pounding grams of NR)

 

As an aside, I wonder if anyone has considered making a pro-drug with different absorption characteristics, a peptide bond perhaps (yes label off-topic, I know ).

Edited by TMNMK, 23 February 2018 - 04:15 AM.

[Ovidus]

 

 

High dose Nicotinamide weaken immune system.

https://www.ncbi.nlm...les/PMC5419340/
High doses of nicotinamide lead to reduced regulatory T cells and immune intolerance. Loss of no longer needed symbiotic ‘old friends’ compounds immunological over-reactivity to cause allergic and auto-immune diseases. Inhibition of nicotinamide adenine dinucleotide consumers and loss of methyl groups or production of toxins may cause cancers, metabolic toxicity, or neurodegeneration. An optimal dosage of vitamin B3 could lead to better health, but such a preventive approach needs more equitable meat distribution.

 

Its probably bad methionine/glycine ratio and high phosphate/calcium (today is 6:1 in many developed countries) ratio that goes wrong with higher meat consumption, not few more  mg of B3? Our ancestors used to eat skin, joints etc (more glycine, proline...) and we are consuming pure meat.

 

 

It is very likely that the continued high intake of NAM produces the same problem that a continued high intake of NR produces--the reduction of mitochondrial number (due to higher levels of mitophagy) and also the reduction of ATP production (due both from mito fission and lower numbers of mitochondria). Mice given high does of NR apparently experience this effect as exercise performance is reduced by 35%. The solution is then not an optimum dose of NAM as suggested by the above paper, but an oscillating dose, which is more in tune with a paleo diet of feast and famine and which clears out defective mtDNA.

 

And how come I experienced no decline in any performance parameters? No decline in power output in the gym when working with weights, no general fatigue, no decline in aerobic performance on the treadmill.... none of these things at all. 
But I did experience inflammation for sure... how does this at all jive with your hypothesis? 
It does not, but you must explain everything that NR does by referring to its effects on mitochondria; you cannot even fathom it can have other significant effects.  No I do not have links to support my hypotheses, this is not what this thread is intended to do. However, if we are talking anecdotal experiences here -which is what we are discussing in this thread- your ideas do not fit the observations AT ALL... but keep trying to explain everything through mitochondrial effects. 

 

 

Maybe I'm an oddball but I've taken what I would consider to be truly herculean doses of NR over extended periods of time to see where the acute toxicity barrier might be for me (I have quite a lot of it lying around from multiple different vendors and felt like I needed to make dent I guess). I haven't found the wall yet so the "dark side" of NR might vary person to person. It will be interesting to see what future studies have to say on that subject. One time I felt sort of dizzy and tingly for a few days but that quickly subsided. I'm not terribly scientific about it obviously, did increase dosage carefully as sometimes that wall can be a sharp edge.. but I know what overdose feels like and a little dizzy and tingly ain't even close.

 

(Oh and uh.. one might tag this as dangerous or irresponsible and I won't debate that whatsoever, but trust me I am capable of doing far worse to my body than pounding grams of NR)

 

As an aside, I wonder if anyone has considered making a pro-drug with different absorption characteristics, a peptide bond perhaps (yes label off-topic, I know ).

I totally believe you, because I know how dramatically different people's reactions to a substance can be. 
I had been off NR as well as N+R for a few weeks until 5 days ago I decided to try a mere 250 mg of NR daily (I was using w pills a day of HPN's Niagen: https://hpnsupplemen.../product/niagen )

On day 3, yes in 72 hours, I began to get a sore throat. Of course a lot of guys will say that this was a mere coincidence, but nope, I do not think so. It was a very weird kind of lumpy, sore throat that I also got twice previously on NR and not at all something I get usually. 
On top of it, I was also getting inflamed gums, quite obviously they were getting sensitive as I was brushing them....
How the heck is all this possible? No idea.... Just saying what I experienced.

[ledgf]

I've only been on NR for nine months, and I often skip one day per week. But I've had zero negative effects. 

[Ambrosia]

I take NR in moderately large doses and notice no increase in length or frequency of colds or flu. More likely the opposite. But it's hard to say.  Sometimes I feel like I'm on the verge of coming down with a cold, a feeling that lingers a little while but never fully blossoms, and then fades away after a few days to a week.  My sense is that's my immune system doing a good job.

 

I'm just getting near finishing a rather large bulk purchase of HPN NR that I bought and refrigerated about 2 years ago.  I've been taking a teaspoon of it (about 2 grams) mixed into a shake every evening right before going to sleep.  No insomnia either, btw.  On the positive side I noticed a marked decrease in leg-muscle pain as soon as I started with it which declined even further after adding 6 grams gelatin to the shakes about 6 months ago.  I think what the gelatin did was minimize joint inflammation which was aggravating nearby muscles and connective tissue.  About 2 weeks ago I also added 500 mg of Baicalensis to the nightly shakes which pretty much completely wiped out the last of my joint, muscle, and connective tissue inflammation.  Having taken these 3 ingredients in a step-wise fashion, I don't know if either of the 2 later additions would have worked as well on its own.  I do know that I experienced an incremental improvement from each.  I'll probably take an NR vacation once I finish my supply in a month or few (I have a sense that HPN might not be as eager to deal as they once were)... I'll see how that goes.

 

Howard

 

From my experience, High dose Vitamin C is vastly superior to keep Flu / Cold out of the way, combine with Manuka Honey if it starts in your throat. Flu Season time you can feel the early signs kick in but the flu/cold will never materalize if you introduce high dose Vitamin C

[MikeDC]

It is very likely that the continued high intake of NAM produces the same problem that a continued high intake of NR produces--the reduction of mitochondrial number (due to higher levels of mitophagy) and also the reduction of ATP production (due both from mito fission and lower numbers of mitochondria). Mice given high does of NR apparently experience this effect as exercise performance is reduced by 35%. The solution is then not an optimum dose of NAM as suggested by the above paper, but an oscillating dose, which is more in tune with a paleo diet of feast and famine and which clears out defective mtDNA.

The same author followed up with a human study and found NR increases exercise performance in older adults and no effect on young adults.

I believe all the side effects from NR are due to B12 deficiency. It is a good idea to take high dose B12 when taking NR.