48 replies to this topic

[Ovidus]

So much has been written about NR and so much of it has been positive, that I wanted to start a new thread and talk about the negatives of it. 

I had previously spoken about the very strong effects I had gotten from both NR as well as Nicotinamide Ribisode. Here: 

http://www.longecity...ndpost&p=827234

 

That post above is relatively long, so to sum up in bullet points, Nicotinamide + Ribose gave me: 
High Energy all day and Increased Performance in the Gym

Less Inflammation
Harder to fall asleep, but deeper sleep 

Significantly improved spontaneous recall of random memories and verbal fluency

Very much increased hunger -to the point it made eating properly near impossible
 

However, it also resulted in some side effects, some of which I noticed over time, and failed to fully sum up in the post above. The most worrisome of these was the following: 

http://www.longecity...ndpost&p=833030

As you can see in the post above, some others too had reported mouth sore/ ulcers while taking NR. Especially after a month or so on NR, I started to develop ulcers in my mouth out of nowhere, and these took far longer than normal to go away. This became quite an issue and on a few occasions it really interfered with my life -was quite terrible in other words.

 

Also, I did get sick like twice over a 4 month period. and both lasted relatively long. This is in stark contrast to me getting sick like once over the last 2 years. 

 

As of this point, I am off NR for 5 weeks or so, but still numerous side effects persist. I know this will sound not very credible and you may think this is me imagining things, but I am very convinced such is not the case. For example, I just had an ulcer in my mouth that took around twice as long to heal as it otherwise would (i.e. before I ever touched NR). Also, my hunger is continuing to be significantly elevated. I simply have to eat more frequently than I used to.

Another side effect I had not spoken of, which I later came to associate with NR, is anal bleeding during defecation. I am talking about a bit of blood on the toilet paper when wiping your butt. Again, fairly certain this is strongly associated with NR. I took NR during two stints and when I stopped NR and then restarted it, this came back pretty strongly. After fully stopping NR its frequency dropped but is significantly above baseline still.

 

Another incredible observation -again I know this sounds fantastic, but I am confident of it- is the lasting effect this had on my girlfriend. While taking NR, she started to orgasm far faster. The amount of time to reach an orgasm was cut by more than 50%. Amazingly, this effect has stayed with her, and it has been also 4 weeks or so since her last dose of NR.

 

Now in light of all these, it appears that NR is a very potent substance and should not be taken lightly. As I said a few times in past threads already, the longer time it takes for mouth sores to heal is worrisome and may point to either a weaker immune system (this is likely the case, because I was getting sick more and the sickness was lasting longer) or to slower regeneration of tissues that are regenerated frequently. 

 

Please add your own similar experiences and -just as importantly- propose potential reasons / MOAs that may be behind this.

 

Thanks

 

[Turnbuckle]

I had previously spoken about the very strong effects I had gotten from both NR as well as Nicotinamide Ribisode...That post above is relatively long, so to sum up in bullet points, Nicotinamide + Ribose gave me: 

 

 

 

This is a little confusing. Nicotinamide ribisode is NR, while Nicotinamide + ribose is N+R. Presumably you are comparing NR to N+R?

[Ovidus]

 

I had previously spoken about the very strong effects I had gotten from both NR as well as Nicotinamide Ribisode...That post above is relatively long, so to sum up in bullet points, Nicotinamide + Ribose gave me: 

 

 

 

This is a little confusing. Nicotinamide ribisode is NR, while Nicotinamide + ribose is N+R. Presumably you are comparing NR to N+R?

 

 

I am sorry I mistyped. 
I have used both Nicotinamide Riboside as well as Nicotinamide + Ribose. Both gave me strong and similar effects. After I realized that I could obtain essentially equal effect from N+R as I got from NR, I saw no reason to pay more and switched to N+R thereafter. One of things that happened as a result of this switch was that I was able to experiment with higher and higher dosages; actually, the dose crept up on me and I went as high as 2 grams of Nicotinamide + 4-5 grams of Ribose. However, except those brief periods of experimentation, my dose was around 1 gram of Nicortinamide + 2.5 grams of Ribose.

[stefan_001]

Welcome to the dark side :-) ! The NR force will be with you.

Edited by stefan_001, 10 February 2018 - 07:02 PM.

[MikeDC]

So you took NR and it was good. Then you switched to N+R with very high doses and got side effects and you attribute the side effects to NR?

[sthira]

...some others too had reported mouth sore/ ulcers while taking NR. Especially after a month or so on NR, I started to develop ulcers in my mouth out of nowhere, and these took far longer than normal to go away. This became quite an issue and on a few occasions it really interfered with my life -was quite terrible in other words.

Maybe it's coincidental that rapamycin users report mouth ulcers, too?

Another side effect I had not spoken of, which I later came to associate with NR, is anal bleeding during defecation. I am talking about a bit of blood on the toilet paper when wiping your butt. Again, fairly certain this is strongly associated with NR.

Were you at all constipated during your NR and N+R trials? Did you develop hemorrhoids? Did your diet change at all to include less fiber?

So you took NR and it was good. Then you switched to N+R with very high doses and got side effects and you attribute the side effects to NR?

This is a good point. I recall that Brenner et al advised doses of 250 mg to 500 mg per day, with periodic breaks between usage.

Edited by sthira, 10 February 2018 - 08:09 PM.

[Ovidus]

 

Another side effect I had not spoken of, which I later came to associate with NR, is anal bleeding during defecation. I am talking about a bit of blood on the toilet paper when wiping your butt. Again, fairly certain this is strongly associated with NR.

Were you at all constipated during your NR and N+R trials? Did you develop hemorrhoids? Did your diet change at all to include less fiber?

 

 

 

No, I was not constipated. I actually have a pretty good functioning digestive system and got constipated maybe like a dozen times in my 40+ years.
No change in diet during the period.

 

 

MikeDC, 

Stay the hell out of this thread; you are polluting the discussion. At least do not waste your time asking me questions in this or any other thread, because I will not respond to anything a lowlife stock-pumper like you may say. And do not contact me via PM either. 
 

[Oakman]

If you take a step back, it seems you are pointing out changes/issues with epithelial cells, i.e., your mouth, digestive tract, and anus, your GFs reproductive tract are all lined with epithelium. Perhaps there is some NR or N+R interactions with these tissues that sensitive individuals pickup on that the rest of the population does not...or perhaps it is mere coincidence. Alternatively, the issues may be a result of some substances in your diet, as your issues are from all connected on one long tract, the digestive tract.

[QuestforLife]

Nicotinamide can dry you out, I've noticed - with skin and hair. Might be a factor.

[QuestforLife]

One other negative - I ripped a tendon in one of my fingers when doing N + R. I was putting a fair amount of strain on my hands by doing weights and Judo during the week, and obviously repeated bouts of mitophagy reduced the number of mitochondria in my tendons - so not exactly a negative, just what N+R is supposed to do, but worth bearing in mind.

[MikeDC]

The symptoms match the reported symptoms for Nicotinamide overdose.

https://www.livestro...amide-overdose/

GASTROINTESTINAL PROBLEMS

Stomach upset -- such as abdominal pain, cramps, nausea, diarrhea and vomiting -- occurs when niacinamide is taken in appropriate doses. In the situation of an overdose, stomach upset worsens. Niacinamide can be taken with or without food; however, if stomach upset occurs, it should be taken with food to reduce the severity of the stomach upset. Niacinamide also causes loss of appetite and fluid retention in the stomach. Niacinamide can worsen existing ulcers, manifesting as black stools that may or may not be bloody. Ulcers are serious and should be reported immediately to a medical

Edited by MikeDC, 10 February 2018 - 11:21 PM.

[Ovidus]

If you take a step back, it seems you are pointing out changes/issues with epithelial cells, i.e., your mouth, digestive tract, and anus, your GFs reproductive tract are all lined with epithelium. Perhaps there is some NR or N+R interactions with these tissues that sensitive individuals pickup on that the rest of the population does not...or perhaps it is mere coincidence. Alternatively, the issues may be a result of some substances in your diet, as your issues are from all connected on one long tract, the digestive tract.

Very good point and a fresh way to look at the problem -agree with all except the girlfriend's easier orgasming. There the epithelial cells perhaps play either no or a very negligible role. 

 

Hmm.... in light of this anyone able to draw a connection between NR and epithelial cells?
 

[Ovidus]

One other negative - I ripped a tendon in one of my fingers when doing N + R. I was putting a fair amount of strain on my hands by doing weights and Judo during the week, and obviously repeated bouts of mitophagy reduced the number of mitochondria in my tendons - so not exactly a negative, just what N+R is supposed to do, but worth bearing in mind.

 

Woow, that does sound nasty indeed. I am thinking that it would be a major pain to deal with. Get well soon Sir.

 

In the "Manipulating Mitochondrial Dynamics" thread, I have just posted this comment in response to Trunbuckle's answer. Allow me to quote it here also, as I think the exact same applies here:

"These are very valid points which you have made earlier during this thread and your contributions are very valuable. But we are making the same mistake one more time: 
We are reducing NR (or N+R) only to its effects on mitochondria and almost assuming that it does nothing else -and that every effect of NR can be explained through its impact on mitochondria. That is the very approach that I respectfully disagree with."

 

Again, you too are assuming, it seems, that whatever good or bad NR did, it must have done through its action on mitochondria. That is very unlikely IMHO because this is a substance with wide ranging effects and it impacts very many systems in the organism. 

[MikeDC]

There is no dark side with either NR or Nicotinamide if you don’t overdose them. Overdosing anything can have side effects.

[Turnbuckle]

 

One other negative - I ripped a tendon in one of my fingers when doing N + R. I was putting a fair amount of strain on my hands by doing weights and Judo during the week, and obviously repeated bouts of mitophagy reduced the number of mitochondria in my tendons - so not exactly a negative, just what N+R is supposed to do, but worth bearing in mind.

 

Woow, that does sound nasty indeed. I am thinking that it would be a major pain to deal with. Get well soon Sir.

 

In the "Manipulating Mitochondrial Dynamics" thread, I have just posted this comment in response to Trunbuckle's answer. Allow me to quote it here also, as I think the exact same applies here:

"These are very valid points which you have made earlier during this thread and your contributions are very valuable. But we are making the same mistake one more time: 
We are reducing NR (or N+R) only to its effects on mitochondria and almost assuming that it does nothing else -and that every effect of NR can be explained through its impact on mitochondria. That is the very approach that I respectfully disagree with."

 

Again, you too are assuming, it seems, that whatever good or bad NR did, it must have done through its action on mitochondria. That is very unlikely IMHO because this is a substance with wide ranging effects and it impacts very many systems in the organism. 

 

 

Can you give us an example of a positive effect that is achieved without reference to mitochondria? And can you suggest how the ingestion of NAD precursors could be modified to increase this effect?

[recon]

How did you note for “Less inflammation”?

I’m sure that local inflammation response is quite visible but a general inflammation response would be quite difficult to pinpoint. Is it just general malaise?

[Rosanna]

Ovidus, maybe something to do with the immune response?  There is something called Behcets Disease, where the immune system attacks the blood vessels, also people on chemotherapy sometimes get similar symptoms (mucositis?) and I think chemo knocks out the immune response.

 

Also I think Rapamycin lowers the immune system (I was reading this from the dog ageing project where they are trialing it in dogs), so perhaps NR does too....There they state that this shouldn't happen in dogs at the low dose given, but could happen in higher doses (delayed wound healing, etc), so wondering if it's something to do with the dosage of NR as well?

 

Sorry for the speculation, it's the best I can do atm.

 

 

[Ovidus]

One other negative - I ripped a tendon in one of my fingers when doing N + R. I was putting a fair amount of strain on my hands by doing weights and Judo during the week, and obviously repeated bouts of mitophagy reduced the number of mitochondria in my tendons - so not exactly a negative, just what N+R is supposed to do, but worth bearing in mind.

Woow, that does sound nasty indeed. I am thinking that it would be a major pain to deal with. Get well soon Sir.

In the "Manipulating Mitochondrial Dynamics" thread, I have just posted this comment in response to Trunbuckle's answer. Allow me to quote it here also, as I think the exact same applies here:

"These are very valid points which you have made earlier during this thread and your contributions are very valuable. But we are making the same mistake one more time:
We are reducing NR (or N+R) only to its effects on mitochondria and almost assuming that it does nothing else -and that every effect of NR can be explained through its impact on mitochondria. That is the very approach that I respectfully disagree with."

Again, you too are assuming, it seems, that whatever good or bad NR did, it must have done through its action on mitochondria. That is very unlikely IMHO because this is a substance with wide ranging effects and it impacts very many systems in the organism.

Can you give us an example of a positive effect that is achieved without reference to mitochondria? And can you suggest how the ingestion of NAD precursors could be modified to increase this effect?

İ surely wouldn't be able to point to a specific effect and say that mitochondrial changes play no role at all in the emergence of that. Mitochondria play a role in everything.

However I am merely SPECULATİNG that the effects I observed involve other MOAs as well. For example the increased libido and the accompanying nipple sensitivity (in my case ie a male). Greater ATP output will increase libido yes. But these effects make me think that hormonal pathways where there is changes in the ratio of testosterone conversion to estrogen and DHT also played a role.

Am I sure? Of course not. And again that is just one example. But the point is that some major things in addition to mitochondrial effects may be going on.

[Ovidus]

How did you note for “Less inflammation”?

I’m sure that local inflammation response is quite visible but a general inflammation response would be quite difficult to pinpoint. Is it just general malaise?

General malaise yes is one indication. But there are several spots in my body that start to hurt when ı get more inflamed overall: my lower back where ı have a chronic issue, my foot where the connective tissue never healed properly and a few palces in my gums that flare up when ı get sick with anything...

[Ovidus]

Ovidus, maybe something to do with the immune response? There is something called Behcets Disease, where the immune system attacks the blood vessels, also people on chemotherapy sometimes get similar symptoms (mucositis?) and I think chemo knocks out the immune response.

Also I think Rapamycin lowers the immune system (I was reading this from the dog ageing project where they are trialing it in dogs), so perhaps NR does too....There they state that this shouldn't happen in dogs at the low dose given, but could happen in higher doses (delayed wound healing, etc), so wondering if it's something to do with the dosage of NR as well?

Sorry for the speculation, it's the best I can do atm.

Behcets Disease is a good guess and the part about mouth sores does fıt. However no other symptoms fit.
Both me and at least one other person had mouth sores while simultaneously complaining of longer lasting colds /flus.
The combination makes me think of weakened overall immune system. However we have no idea what about NR may be weakening the immune system, do we?

[MikeDC]

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.

Edited by MikeDC, 12 February 2018 - 04:34 PM.

[Turnbuckle]

 

 

Can you give us an example of a positive effect that is achieved without reference to mitochondria? And can you suggest how the ingestion of NAD precursors could be modified to increase this effect?

İ surely wouldn't be able to point to a specific effect and say that mitochondrial changes play no role at all in the emergence of that. Mitochondria play a role in everything.

However I am merely SPECULATİNG that the effects I observed involve other MOAs as well. For example the increased libido and the accompanying nipple sensitivity (in my case ie a male). Greater ATP output will increase libido yes. But these effects make me think that hormonal pathways where there is changes in the ratio of testosterone conversion to estrogen and DHT also played a role.

Am I sure? Of course not. And again that is just one example. But the point is that some major things in addition to mitochondrial effects may be going on.

 

 

 

Seems it goes both ways. You might find the following paper interesting--

 

 

Mitochondrial and sex steroid hormone crosstalk during aging

 

Decline in circulating sex steroid hormones accompanies several age-associated pathologies which may influence human healthspan. Mitochondria play important roles in biosynthesis of sex steroid hormones, and these hormones can also regulate mitochondrial function. Understanding the cross talk between mitochondria and sex steroid hormones may provide insights into the pathologies associated with aging. ...Decline in sex steroid hormones and accumulation of mitochondrial damage may create a positive feedback loop that contributes to the progressive degeneration in tissue function during aging. The review further speculates whether regulation between mitochondrial function and sex steroid hormone action can potentially influence healthspan.

https://www.ncbi.nlm...les/PMC3922316/

 

 

 

[MikeDC]

Red meat has 100mg/100g of Nicotinamide. you potentially can get 500mg Nicotinamide just from food each day. Any additional supplementation is just toxin.

[QuestforLife]

Mitochondria generally like to fuse before cell mitosis, so effects on stomach lining and immune system would be similar to chronic rapamycin dosing, namely arrest of cell division. Assuming that is you could take enough N+R to hold all your mitos in a fission state for at least several days.

[MikeDC]

I can’t believe people are still talking about using High dose Nicotinamide to influence mitochandria dynamics. It is quite clear that high dose Nicotinamide is having a large bad effect on heath.

Edited by MikeDC, 12 February 2018 - 05:56 PM.

[hav]

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

[Ovidus]

 

 

 

Can you give us an example of a positive effect that is achieved without reference to mitochondria? And can you suggest how the ingestion of NAD precursors could be modified to increase this effect?

İ surely wouldn't be able to point to a specific effect and say that mitochondrial changes play no role at all in the emergence of that. Mitochondria play a role in everything.

However I am merely SPECULATİNG that the effects I observed involve other MOAs as well. For example the increased libido and the accompanying nipple sensitivity (in my case ie a male). Greater ATP output will increase libido yes. But these effects make me think that hormonal pathways where there is changes in the ratio of testosterone conversion to estrogen and DHT also played a role.

Am I sure? Of course not. And again that is just one example. But the point is that some major things in addition to mitochondrial effects may be going on.

 

 

 

Seems it goes both ways. You might find the following paper interesting--

 

 

Mitochondrial and sex steroid hormone crosstalk during aging

 

Decline in circulating sex steroid hormones accompanies several age-associated pathologies which may influence human healthspan. Mitochondria play important roles in biosynthesis of sex steroid hormones, and these hormones can also regulate mitochondrial function. Understanding the cross talk between mitochondria and sex steroid hormones may provide insights into the pathologies associated with aging. ...Decline in sex steroid hormones and accumulation of mitochondrial damage may create a positive feedback loop that contributes to the progressive degeneration in tissue function during aging. The review further speculates whether regulation between mitochondrial function and sex steroid hormone action can potentially influence healthspan.

https://www.ncbi.nlm...les/PMC3922316/

 

 

 

 

 

Again, same basic direction and approach: your assumption is that whatever NR does, it does through its effect on the mitochondria. Your entire focus is on the effects that NR exerts through the mitochondria. I believe this approach is misguided. 
I mean no disrespect; also you are orders of magnitude more informed about biology than I am, so I cannot change your perspective, but still thank you for your valuable contributions.

 

 

With so many bottles of NR having been solved, am I the only one (along with 3-4 people who reported similar issues over time) who had the aforementioned problems?
If so, that is indeed extremely interesting.

 

Edited by Ovidus, 16 February 2018 - 09:53 PM.

[Turnbuckle]

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

Edited by Turnbuckle, 16 February 2018 - 10:31 PM.

[MikeDC]

One other negative - I ripped a tendon in one of my fingers when doing N + R. I was putting a fair amount of strain on my hands by doing weights and Judo during the week, and obviously repeated bouts of mitophagy reduced the number of mitochondria in my tendons - so not exactly a negative, just what N+R is supposed to do, but worth bearing in mind.

Woow, that does sound nasty indeed. I am thinking that it would be a major pain to deal with. Get well soon Sir.

In the "Manipulating Mitochondrial Dynamics" thread, I have just posted this comment in response to Trunbuckle's answer. Allow me to quote it here also, as I think the exact same applies here:

"These are very valid points which you have made earlier during this thread and your contributions are very valuable. But we are making the same mistake one more time:
We are reducing NR (or N+R) only to its effects on mitochondria and almost assuming that it does nothing else -and that every effect of NR can be explained through its impact on mitochondria. That is the very approach that I respectfully disagree with."

Again, you too are assuming, it seems, that whatever good or bad NR did, it must have done through its action on mitochondria. That is very unlikely IMHO because this is a substance with wide ranging effects and it impacts very many systems in the organism.

Can you give us an example of a positive effect that is achieved without reference to mitochondria? And can you suggest how the ingestion of NAD precursors could be modified to increase this effect?

İ surely wouldn't be able to point to a specific effect and say that mitochondrial changes play no role at all in the emergence of that. Mitochondria play a role in everything.

However I am merely SPECULATİNG that the effects I observed involve other MOAs as well. For example the increased libido and the accompanying nipple sensitivity (in my case ie a male). Greater ATP output will increase libido yes. But these effects make me think that hormonal pathways where there is changes in the ratio of testosterone conversion to estrogen and DHT also played a role.

Am I sure? Of course not. And again that is just one example. But the point is that some major things in addition to mitochondrial effects may be going on.

NAD+ function goes far beyond mitochandria. The most important longevity gene, Sirt1, is not located in mitochandria. DNA repair genes such as parp1 are not located in mitochandria.

[Ovidus]

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.