I've never felt any effect from taking NR at any dose.
Probably because you have sufficient levels of NAD....
How many different doses have you tried?....
How old are you?...
What is your state of health?...
Middle age
?
Posted 29 December 2016 - 01:13 AM
I've never felt any effect from taking NR at any dose.
Probably because you have sufficient levels of NAD....
How many different doses have you tried?....
How old are you?...
What is your state of health?...
Middle age
?
Posted 29 December 2016 - 05:07 AM
Posted 01 January 2017 - 04:12 PM
Update. Previously in October, after increasing NR dosing from 250 > 375 > 500mg I had right upper chest soreness. Because of this, I paused all supplementation to get 'clear', then restarted at 250mg w/150mg pterostilbene/ 200mg EnduraQ in the AM before food, then soon added 125mg more evenings w/150mg pterostilbene before bed. I kept this level (375mg/day). This went well for a couple weeks, but soon I began feeling the right chest soreness (exact same spot as before) yet again. Sigh.
Thinking I knew the cause this time, I wanted to determine if reducing NR intake could make the soreness go away, so I stopped the PM 125mg dose. But rather than reduce my overall NAD+ production, I attempted to maintain higher NAD+ levels through NAD+ de novo pathway generation.
I kept the AM 250mg NR/150mg pterostilbene before food, but I purchased Dynveo's Grape Seed Extract (http://www.longecity...es-nad-in-mice/). I began supplementing with 200mg GSE, 500mg Tryptophan (to ensure de novo pathway requirements) along with 200mg EnduraQ (iso-quercetin) before bed (9-10PM). Over the course of a ~week, the soreness completely disappeared!
A few possibilities exist for this result.
1) NR is the cause, not excessive NAD+ production. Reducing NR eliminated the problem
2) Reducing NR (and so NAD+) eliminated the problem. Overall NAD+ production is down as a result, in spite of GSE supplementation
3) Reducing NR eliminated the problem. Overall NAD+ production is = or better due to de novo NAD+ generation
4) Less pterostilbene helped
I don't know which has occurred, but right now I'm satisfied with the results and sticking to this regimen to see if any further anomalies appear over time. As as been postulated, perhaps 250mg NR is the best dose to avoid side effects. And perhaps a synergy using the de novo pathway to generate additional NAD+ avoids problems while maintaining NAD+ levels is a workable possibility.
I realize there a lot of assumptions with this, but perhaps others who have experienced side effects could try a similar regimen and report results.
Edited by Oakman, 01 January 2017 - 04:20 PM.
Posted 01 January 2017 - 07:19 PM
Posted 01 January 2017 - 10:56 PM
No, I don't have the same symptoms you describe, but my lifestyle may be similar. I drink a lot (beer; I don't drink anything hard anymore), eat pretty badly (pizza and doritos are supposedly bad right?), and have taken... way more drugs than anyone I know who is still alive (let your imagination fly, I should have miles and status at this point). But no, NR has not given me any poor effects, none of the tendon or muscle pains that some people report, even at >2g/d. Only thing is I notice my energy seems to be higher and I seem to be in a better mood at 250mg/d than the higher doses. Not sure why that is, but for me less is more.
No, I don't have the same symptoms you describe, but my lifestyle may be similar. I drink a lot (beer; I don't drink anything hard anymore), eat pretty badly (pizza and doritos are supposedly bad right?), and have taken... way more drugs than anyone I know who is still alive (let your imagination fly, I should have miles and status at this point). But no, NR has not given me any poor effects, none of the tendon or muscle pains that some people report, even at >2g/d. Only thing is I notice my energy seems to be higher and I seem to be in a better mood at 250mg/d than the higher doses. Not sure why that is, but for me less is more.
Posted 01 January 2017 - 11:41 PM
Posted 02 January 2017 - 12:23 AM
Update. Previously in October, after increasing NR dosing from 250 > 375 > 500mg I had right upper chest soreness. Because of this, I paused all supplementation to get 'clear', then restarted at 250mg w/150mg pterostilbene/ 200mg EnduraQ in the AM before food, then soon added 125mg more evenings w/150mg pterostilbene before bed. I kept this level (375mg/day). This went well for a couple weeks, but soon I began feeling the right chest soreness (exact same spot as before) yet again. Sigh.
Thinking I knew the cause this time, I wanted to determine if reducing NR intake could make the soreness go away, so I stopped the PM 125mg dose. But rather than reduce my overall NAD+ production, I attempted to maintain higher NAD+ levels through NAD+ de novo pathway generation.
I kept the AM 250mg NR/150mg pterostilbene before food, but I purchased Dynveo's Grape Seed Extract (http://www.longecity...es-nad-in-mice/). I began supplementing with 200mg GSE, 500mg Tryptophan (to ensure de novo pathway requirements) along with 200mg EnduraQ (iso-quercetin) before bed (9-10PM). Over the course of a ~week, the soreness completely disappeared!
A few possibilities exist for this result.
1) NR is the cause, not excessive NAD+ production. Reducing NR eliminated the problem
2) Reducing NR (and so NAD+) eliminated the problem. Overall NAD+ production is down as a result, in spite of GSE supplementation
3) Reducing NR eliminated the problem. Overall NAD+ production is = or better due to de novo NAD+ generation
4) Less pterostilbene helped
I don't know which has occurred, but right now I'm satisfied with the results and sticking to this regimen to see if any further anomalies appear over time. As as been postulated, perhaps 250mg NR is the best dose to avoid side effects. And perhaps a synergy using the de novo pathway to generate additional NAD+ avoids problems while maintaining NAD+ levels is a workable possibility.
I realize there a lot of assumptions with this, but perhaps others who have experienced side effects could try a similar regimen and report results.
Or 5/ our GSE helped to relieve this ?
Glad you fixed your issue, you should test now to get back the initial stack maybe in order to see if my option 5 is possible or not ?
Btw, enduraQ is EMIQ (enzymatically modified iso quercitrin not quercetin
Cheers
Posted 17 January 2017 - 05:42 PM
Have to share my own peculiar experience. Note that I've started taking it for longevity but also as a potential help with my excessive sleepiness problems (basically, i get incredibly sleepy, not tired (!), during the day, and feel very groggy when I wake up no matter how long I've slept).
Started on 275mg a day in the morning (and 150mg Pterostilbene). The effect was almost immediately noticeable. Feel very alert throughout the day. Even had trouble falling asleep at night (never been a problem for me, if anything I get sleepy too early). This lasted for 3 wonderful days. Felt "unsleepy" and alert as I haven't in years.
Sadly, on day 4 - crash! Incredible sleepiness throughout the day. Continued taking it for another 7 days. Felt even more sleepy than I normally do. Decided to completely stop. On day 3 of stopping I regained "normality" - I was back. On the same day (maybe unwisely) started a new regimen of ~100mg a day, spread throughout, sublingually. Basically what I did is open the capsule and placed about 1/9 of the content under the tongue, every 4 hours or so. Felt great again. Weirdly - for on exactly 3 days. Then on day 4 - crash!
I've been doing that for about a week now. At times I feel ok, other times I feel incredibly sleepy (more than usual!). I'm not sure, but I also think that I get sleepy a short while after a dose.
What gives?!
It definitely worked positively on me, and definitely affects me negatively now. Tried the "undermethylation" hypothesis (added methylcobalamin and methylfolate) with no effect. Also, every night I've been having very vivid dreams since started taking it. Next I'm going to try to trick the system (though I'm very skeptical) - 2 days on (275mg each day) / 2 days off. Any other suggestions, theories?
Posted 17 January 2017 - 05:47 PM
Methylation is a strong possibility. There are always other factors to weed out that you might not be taking into account because the new thing introduced is getting the focus.
Try 400mcg of active methyl folate every day.
I don't get the big crash that others get and that may be because I don't have the defective gene for that.
You should also consider Doctor's Best B-Complex once a day which has the 400mcg of methyl folate but also other B vitamins to balance things out.
I don't get why I'm one of the few people on this thread experiencing nothing negative from NR but methylation may be highly relevant.
I also get really good sleep on evenings when I take NR (I usually just take 375 in the morning). Others get insomnia. Being insomnia prone one would think I would too, but quite the opposite.
Edited by Nate-2004, 17 January 2017 - 05:49 PM.
Posted 17 January 2017 - 05:48 PM
Very interesting review because you definitely not the only one to notice this...
I dont have more theory and im not a fan of the salvage pathway but you should try niacin, see if you feel same. Try it for a week or so at 100mg a day
We dont know what give this crash yet but its exactly what was reported here on this forum
Posted 17 January 2017 - 07:22 PM
Methylation is a strong possibility. There are always other factors to weed out that you might not be taking into account because the new thing introduced is getting the focus.
Try 400mcg of active methyl folate every day.
I also get really good sleep on evenings when I take NR (I usually just take 375 in the morning). Others get insomnia. Being insomnia prone one would think I would too, but quite the opposite.
Been taking active methyl folate (1000mcg daily) and that didn't seem to work. I also take Biotin (B7) and methylcobalamin (B12). I doubt that there's really a B deficiency but I'll try to supplement with the rest.
When taking NR multiple times a day I also take it in the evening, didn't seem to make a difference (but that was in the period when it only made me more sleepy).
I'm determined to get to the bottom of this because it's amazing how alert it makes me feel in the 2-3 days after starting. However, it's very debilitating when it reverses effect, so it's a "dangerous game" for me. It was a life-saver when it worked, but really ruined my days when it didn't. There's definitely something to it, if I can just get it right.
High hopes for a 2-on/2-off method (some seem to have had success with every other day), though I'm not sure about the logic behind it.
Posted 17 January 2017 - 08:28 PM
Methylation is a strong possibility. There are always other factors to weed out that you might not be taking into account because the new thing introduced is getting the focus.
Try 400mcg of active methyl folate every day.
I also get really good sleep on evenings when I take NR (I usually just take 375 in the morning). Others get insomnia. Being insomnia prone one would think I would too, but quite the opposite.
Been taking active methyl folate (1000mcg daily) and that didn't seem to work. I also take Biotin (B7) and methylcobalamin (B12). I doubt that there's really a B deficiency but I'll try to supplement with the rest.
When taking NR multiple times a day I also take it in the evening, didn't seem to make a difference (but that was in the period when it only made me more sleepy).
I'm determined to get to the bottom of this because it's amazing how alert it makes me feel in the 2-3 days after starting. However, it's very debilitating when it reverses effect, so it's a "dangerous game" for me. It was a life-saver when it worked, but really ruined my days when it didn't. There's definitely something to it, if I can just get it right.
High hopes for a 2-on/2-off method (some seem to have had success with every other day), though I'm not sure about the logic behind it.
Do not take more than 400mcg daily of methyl folate. I don't know why some companies sell versions with more but it's not good for you to get too much. 400 is the max you should ever supplement. That may be part of the problem.
There are two peaks coinciding with what seems to be a circadian rhythm, it's better to take it first thing on an empty stomach. HPN brand has a document they send with recommendations.
Try the B complex instead, Doctor's Best. They're a tested brand on Labdoor with a solid record.
Posted 17 January 2017 - 09:00 PM
I have had some of these experienes as well from super vivid dreams to being sleepy. And more short term lasting things. But they all wore off as time passed. My own thoughts have been that either I have always had those but because of the NR I observed myself closer or then the body was going through "reboots". I take now and then a multivitamin or a B tablet but never noticed a real impact. Soon using NR for 2 years daily.
Edited by stefan_001, 17 January 2017 - 09:01 PM.
Posted 17 January 2017 - 10:52 PM
There is a lot of variation among us as to who responds how to what. Some of this can be revealed by genetic testing. Methylation issues in particular are pretty detailed in the genome and a good test from 23andME, ancestry.com or genos can reveal a lot. Even so while the snps are revealed the actual solutions are vague and controversial to say the least. Promethease.com has a testing page that discloses the efficacy of the various testing entities. Recently Ancestry.com has upgraded the chip they use and now reports more useful snps than does 23andMe unless 23andMe has changed in the last 2 months or so. Check them out. I have just received my genos kit. It is quite a bit more expensive but also generates a lot more data, the whole exome in fact.
However, the main point is that advice about anyone's reaction to any issues are probably more likely to be off target than on so I suggest we keep that in mind when discussing these topics.
Mike
Posted 21 January 2017 - 10:06 PM
Posted 22 January 2017 - 03:44 AM
Methylation is a strong possibility. There are always other factors to weed out that you might not be taking into account because the new thing introduced is getting the focus.
Try 400mcg of active methyl folate every day.
I also get really good sleep on evenings when I take NR (I usually just take 375 in the morning). Others get insomnia. Being insomnia prone one would think I would too, but quite the opposite.
Been taking active methyl folate (1000mcg daily) and that didn't seem to work. I also take Biotin (B7) and methylcobalamin (B12). I doubt that there's really a B deficiency but I'll try to supplement with the rest.
When taking NR multiple times a day I also take it in the evening, didn't seem to make a difference (but that was in the period when it only made me more sleepy).
I'm determined to get to the bottom of this because it's amazing how alert it makes me feel in the 2-3 days after starting. However, it's very debilitating when it reverses effect, so it's a "dangerous game" for me. It was a life-saver when it worked, but really ruined my days when it didn't. There's definitely something to it, if I can just get it right.
High hopes for a 2-on/2-off method (some seem to have had success with every other day), though I'm not sure about the logic behind it.
Do not take more than 400mcg daily of methyl folate. I don't know why some companies sell versions with more but it's not good for you to get too much. 400 is the max you should ever supplement
This is incorrect - it all depends on the status of your MTHFR SNPs - if you are heterozygous there is 30% loss of function and if you are homozygous it is ~70%.
In these cases, going over 400mcg is highly recommended. Only for the wild( non-mutated) variant, the 400mcg recommendation holds true.
Posted 29 January 2017 - 06:27 PM
I've been taking 250mg NR since July 2016. I'm 39.
I do not believe I've noticed results that could not be explained by placebo effect or other factors (pterostilbene). When I first took it, I experienced a huge energy boost, which eventually tapered back off to normal energy levels. In October 2016, I added 60mg trans-pterostilbene. To be honest, I noticed this more than NR. I have always had shaky hands, and could never take clear photographs until image stabilization technology became more available. I noticed that the shakes in my hands started to decrease, and they are now rock steady at all times. I presume that to be most likely beyond what placebo effect is likely capable of. I believe my memory, while not perfect, improved noticeably and continues to improve. My alertness and production at work is markedly improved. My mood is more calm, and I feel that I handle more external stress factors with greater ease than I handled less stress in the past.
To be honest, while I was on NR alone, while I did notice improvements I could not describe them as outside of the realm of placebo effect. When I added pterostilbene, I noticed enough improvement that I personally feel placebo could not easily explain it (especially since I wasn't expecting much from pterostilbene, and wasn't even aware of all the potential benefits (I googled them after the fact when I started noticing them, I originally just thought it would be good to take an antioxidant for the long term).
I will continue with my regime of both. It's obviously working, and I'm not interested in breaking something that works.
If I could do it all over again, I might have started with the pterostilbene. I feel like it may actually provide the most noticeable immediate benefit.
At the end of the day though, how do we measure whether NR is slowing our aging? Not an easy thing to do. So I will keep taking it. But at some point, prices will either have to come down, or extremely compelling evidence in humans will have to surface, showing that it does in fact offer some kind of life extension.
When I read this thread, the overall sense I get is a neutral one. Equal numbers of people noticing some positive effects as negative ones. Honestly not compelling. But again, if this does act as a life extender and we only have a few short years of personal experience data, I don't think that's enough to draw a conclusion either way.
The years ahead will be interesting!
p.s....and I would gladly trade all of these benefits in if it could just help with my receading hair line
Edited by jjgallow, 29 January 2017 - 06:32 PM.
Posted 30 January 2017 - 05:21 PM
Posted 30 January 2017 - 06:35 PM
Chest Pains---
Has anyone else had an mild pains on NR?
I had a few issues and stopped before, got the all clear after test so started NR again, after a few weeks its back again ( tightness in left side, shoulder and arm pains, but more worried about a constent on off tight/presure of tingle in the lett sode chest. It does not hurt and comes with maybe mild indigestion.
Im going back for more test wednesday and a ECG for the heart.
Im 29 and niagen does really really well for me but i may have to stop again until its checked over.
Ived ordered the new grapeseed extract from denvo to see how i get on with this.
Are you ONLY taking NR and having these pains? Is there any other supplement you are taking?
Posted 30 January 2017 - 06:39 PM
Posted 10 February 2017 - 11:21 AM
I've been taking NAD+ since August 2016. Initially 250mg/day then down to 125mg/day. The only thing I've been able to notice is muscle pain is non-existent after a weight training session. No increased in energy noted while I run my regular 4km run or in any situation.
Posted 11 February 2017 - 07:10 AM
In spite of persistent soles-of-feet pains (see above), I resumed taking NR in October. I believe mega-dosing NR helped mitigate adverse effects of c60 and olive leaf. I posted my update here:
http://www.longecity...e-5#entry805323
Edited by Empiricus, 11 February 2017 - 07:19 AM.
Posted 15 February 2017 - 01:08 PM
I am 50 years old and have Spinocerebellar Ataxia Type 1. My father and my aunt also have SCA1. They were in wheelchairs. SCA1 is like Huntington's Disease. Last month I started all of us on a regimen of 80g of trehalose and 500 mg daily of nicotinamide riboside. My father has gone from exclusive use of a wheel chair to now using a walker. I have gone from not being able to stand on one leg to now balancing no problem. Also I have been running 3 to 4 times a week for 30 minutes since I was age 14. In the last month my pace fell from 10 minutes per mile to 9 minutes per mile. I also have a home gym and have been working out 3 times a week for more than 2 decades. I had fallen to 4 chin ups at 5 sets and have returned to 5 sets of 7 so far. I'm not sure what a healthy person would expect to see from taking NR, but I can tell you for someone who has extensive cellular damage that is in need of repair the results are nothing less than astonishing. This is a n=3 study, but it is almost impossible for this to be placebo effect given the unrelenting nature of SCA1.
I intend to take the time to read all 34 pages, but what I'm curious about is are there any other people on this thread who have a diagnosed neurological disorder that have tried NR?
Joe in NY
EDIT: I should add that based on additional research I intend to add 100mg of Pterostilbene to our n=3 study.
Edited by 2Sunny, 15 February 2017 - 01:23 PM.
Posted 15 February 2017 - 04:53 PM
I am 50 years old and have Spinocerebellar Ataxia Type 1. My father and my aunt also have SCA1. They were in wheelchairs. SCA1 is like Huntington's Disease. Last month I started all of us on a regimen of 80g of trehalose and 500 mg daily of nicotinamide riboside. My father has gone from exclusive use of a wheel chair to now using a walker. I have gone from not being able to stand on one leg to now balancing no problem. Also I have been running 3 to 4 times a week for 30 minutes since I was age 14. In the last month my pace fell from 10 minutes per mile to 9 minutes per mile. I also have a home gym and have been working out 3 times a week for more than 2 decades. I had fallen to 4 chin ups at 5 sets and have returned to 5 sets of 7 so far. I'm not sure what a healthy person would expect to see from taking NR, but I can tell you for someone who has extensive cellular damage that is in need of repair the results are nothing less than astonishing. This is a n=3 study, but it is almost impossible for this to be placebo effect given the unrelenting nature of SCA1.
I intend to take the time to read all 34 pages, but what I'm curious about is are there any other people on this thread who have a diagnosed neurological disorder that have tried NR?
Joe in NY
EDIT: I should add that based on additional research I intend to add 100mg of Pterostilbene to our n=3 study.
Hi Joe,
I am really very glad that taking NR works out so well for you and your relatives! I can't remember ( from the almost two years that I posted on this thread) anyone with a neurological disorder, but perhaps they will react.
There seems to be a pattern however that those who have a severe medical condition profit most from taking NR while those who are sort of oldish (like me, I am almost 65) only feel some extra energy. Younger healthy persons do not 'feel' anything at all.
I hope you keep posting new developments! Since this is an experiences thread any hunch is welcome.
Edited by Harkijn, 15 February 2017 - 04:54 PM.
Posted 15 February 2017 - 06:01 PM
I am 50 years old and have Spinocerebellar Ataxia Type 1. My father and my aunt also have SCA1. They were in wheelchairs. SCA1 is like Huntington's Disease. Last month I started all of us on a regimen of 80g of trehalose and 500 mg daily of nicotinamide riboside. My father has gone from exclusive use of a wheel chair to now using a walker. I have gone from not being able to stand on one leg to now balancing no problem. Also I have been running 3 to 4 times a week for 30 minutes since I was age 14. In the last month my pace fell from 10 minutes per mile to 9 minutes per mile. I also have a home gym and have been working out 3 times a week for more than 2 decades. I had fallen to 4 chin ups at 5 sets and have returned to 5 sets of 7 so far. I'm not sure what a healthy person would expect to see from taking NR, but I can tell you for someone who has extensive cellular damage that is in need of repair the results are nothing less than astonishing. This is a n=3 study, but it is almost impossible for this to be placebo effect given the unrelenting nature of SCA1.
I intend to take the time to read all 34 pages, but what I'm curious about is are there any other people on this thread who have a diagnosed neurological disorder that have tried NR?
Joe in NY
EDIT: I should add that based on additional research I intend to add 100mg of Pterostilbene to our n=3 study.
That's is fantastic news Harkijn.
Off topic: I have a little knowledge of H.D and from recollection the defective proteins disrupt the autophagy process. Delayed onset is associated with increased autophagy (Mattson's study on fasting in HD mice). One of the problems though in persuading those with HD I believe, to fast, (and supported to some extent by fairly recently large by study on dementia*) is that delayed onset of HD symptoms had for some time correlated with excess weight. I wonder if this research explains it: inhibiting IGF1 reduces autophagosome production - we associate, I thought, overexpression of IGF with high calorie-intake (?)**. If both fasting and feasting stimulate autophagy to a similar effect, fasting would surely be a better alternative, or still perhaps feast and fast :-)
On topic: My understanding is quite limited, but I'd understood increasing NAD+ increased mitophagy, I wasn't aware it increased autophagy too as this paper suggests - might this explain the contribution of NR to you and your family's improvement?
*although Alzheimers onset may correlate oppositely with excess weight.
** this 20 year old study indicates increased levels of free IGF-1 in obese people, though I've not researched what that signifies.
Edited by ambivalent, 15 February 2017 - 06:23 PM.
Posted 15 February 2017 - 06:49 PM
I am 50 years old and have Spinocerebellar Ataxia Type 1. My father and my aunt also have SCA1. They were in wheelchairs. SCA1 is like Huntington's Disease. Last month I started all of us on a regimen of 80g of trehalose and 500 mg daily of nicotinamide riboside. My father has gone from exclusive use of a wheel chair to now using a walker. I have gone from not being able to stand on one leg to now balancing no problem. Also I have been running 3 to 4 times a week for 30 minutes since I was age 14. In the last month my pace fell from 10 minutes per mile to 9 minutes per mile. I also have a home gym and have been working out 3 times a week for more than 2 decades. I had fallen to 4 chin ups at 5 sets and have returned to 5 sets of 7 so far. I'm not sure what a healthy person would expect to see from taking NR, but I can tell you for someone who has extensive cellular damage that is in need of repair the results are nothing less than astonishing. This is a n=3 study, but it is almost impossible for this to be placebo effect given the unrelenting nature of SCA1.
I intend to take the time to read all 34 pages, but what I'm curious about is are there any other people on this thread who have a diagnosed neurological disorder that have tried NR?
Joe in NY
EDIT: I should add that based on additional research I intend to add 100mg of Pterostilbene to our n=3 study.
That's is fantastic news Harkijn.
Off topic: I have a little knowledge of H.D and from recollection the defective proteins disrupt the autophagy process. Delayed onset is associated with increased autophagy (Mattson's study on fasting in HD mice). One of the problems though in persuading those with HD I believe, to fast, (and supported to some extent by fairly recently large by study on dementia*) is that delayed onset of HD symptoms had for some time correlated with excess weight. I wonder if this research explains it: inhibiting IGF1 reduces autophagosome production - we associate, I thought, overexpression of IGF with high calorie-intake (?)**. If both fasting and feasting stimulate autophagy to a similar effect, fasting would surely be a better alternative, or still perhaps feast and fast :-)
On topic: My understanding is quite limited, but I'd understood increasing NAD+ increased mitophagy, I wasn't aware it increased autophagy too as this paper suggests - might this explain the contribution of NR to you and your family's improvement?
*although Alzheimers onset may correlate oppositely with excess weight.
** this 20 year old study indicates increased levels of free IGF-1 in obese people, though I've not researched what that signifies.
Thank you both!
I believe since this is my first day I am restricted from posting links, but I have read several dozen papers all related in one way or another to the general category of what are called PolyQ disorders. The two papers that got me interested in NR initially are:
NAD+ Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair
Neuroprotective role of SIRT1 in mammalian models of Huntington’s disease through activation of multiple SIRT1 targets
I completely agree with the general sentiment that as a supplement for a healthy young individual NR is probably of limited value. It's potential as a cellular repair enhancer though is huge. I'm off to run some errands right now, but I'd love to share the long list of papers I have collected on all the different ailments that may be helped by NR. If NR lives up to half the mouse studies, it will be a revolution in human health. It's unfortunate that more folks with neurological disorders aren't trying this because I honestly believe it can help many, many people. Sadly, I have tried to contact scientists and patient advocate groups, but have had the proverbial door slammed in my face every time because Niagen is perceived as snake oil. Tragic that they won't even look when the science is increasingly compelling.
For me I look at NR as a SIRT1 activator rather than an autophagy enhancer. You are correct though as SCA1 symptoms stem from mutant protein build up in brain cells and inducing autophagy plays a role in the studies that have shown benefit, however the molecule most studied in regard to autophagy of the ataxin 1 protein is trehalose. Hence the reason I take trehalose AND NR. Trehalose has not been shown to have any cellular repair capability so that is why I take it with NR. One promotes autophagy of the mutant protein and the other helps repair the damage. Of course, it's all pie in the sky until some research finally decides to try treating a polyQ patient with NR. Trehalose on the other hand is moving to Phase 3 trials but the company running the research is injecting trehalose into patients via IV. Trehalose is a sugar substitute you can buy on Amazon for $9 lb, but the pharma company doing the trehalose IV research is planning on charging $300,000 a year to inject sugar water into patient arms. You can imagine my desire to try oral ingestion instead.
Edited by 2Sunny, 15 February 2017 - 06:58 PM.
Posted 15 February 2017 - 10:15 PM
very informative 2Sunny,
Perhaps you coud start an SCA1 and HD thread in the medicines and diseases forum - it would be great to know what you've researched, where there is overlap with HD and what supplements might be recommended (I might put a supplement thread for HD here).
Posted 16 February 2017 - 05:08 PM
very informative 2Sunny,
Perhaps you coud start an SCA1 and HD thread in the medicines and diseases forum - it would be great to know what you've researched, where there is overlap with HD and what supplements might be recommended (I might put a supplement thread for HD here).
Super idea. I'm obviously new to the site and haven't really had a chance to explore at all so I appreciate the advice! It's great to finally find a site where hysterical administrators aren't going to go crazy when you mention a supplement.
Posted 16 February 2017 - 07:25 PM
I'll look forward to it, although I'd stall my optimism, you might find the occasional hysterical moderator :-)
Posted 16 February 2017 - 08:52 PM
I am 50 years old and have Spinocerebellar Ataxia Type 1. My father and my aunt also have SCA1. They were in wheelchairs. SCA1 is like Huntington's Disease. Last month I started all of us on a regimen of 80g of trehalose and 500 mg daily of nicotinamide riboside. My father has gone from exclusive use of a wheel chair to now using a walker. I have gone from not being able to stand on one leg to now balancing no problem. Also I have been running 3 to 4 times a week for 30 minutes since I was age 14. In the last month my pace fell from 10 minutes per mile to 9 minutes per mile. I also have a home gym and have been working out 3 times a week for more than 2 decades. I had fallen to 4 chin ups at 5 sets and have returned to 5 sets of 7 so far. I'm not sure what a healthy person would expect to see from taking NR, but I can tell you for someone who has extensive cellular damage that is in need of repair the results are nothing less than astonishing. This is a n=3 study, but it is almost impossible for this to be placebo effect given the unrelenting nature of SCA1.
I intend to take the time to read all 34 pages, but what I'm curious about is are there any other people on this thread who have a diagnosed neurological disorder that have tried NR?
Joe in NY
EDIT: I should add that based on additional research I intend to add 100mg of Pterostilbene to our n=3 study.
That's is fantastic news Harkijn.
Off topic: I have a little knowledge of H.D and from recollection the defective proteins disrupt the autophagy process. Delayed onset is associated with increased autophagy (Mattson's study on fasting in HD mice). One of the problems though in persuading those with HD I believe, to fast, (and supported to some extent by fairly recently large by study on dementia*) is that delayed onset of HD symptoms had for some time correlated with excess weight. I wonder if this research explains it: inhibiting IGF1 reduces autophagosome production - we associate, I thought, overexpression of IGF with high calorie-intake (?)**. If both fasting and feasting stimulate autophagy to a similar effect, fasting would surely be a better alternative, or still perhaps feast and fast :-)
On topic: My understanding is quite limited, but I'd understood increasing NAD+ increased mitophagy, I wasn't aware it increased autophagy too as this paper suggests - might this explain the contribution of NR to you and your family's improvement?
*although Alzheimers onset may correlate oppositely with excess weight.
** this 20 year old study indicates increased levels of free IGF-1 in obese people, though I've not researched what that signifies.
Thank you both!
I believe since this is my first day I am restricted from posting links, but I have read several dozen papers all related in one way or another to the general category of what are called PolyQ disorders. The two papers that got me interested in NR initially are:
NAD+ Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair
Neuroprotective role of SIRT1 in mammalian models of Huntington’s disease through activation of multiple SIRT1 targets
I completely agree with the general sentiment that as a supplement for a healthy young individual NR is probably of limited value. It's potential as a cellular repair enhancer though is huge. I'm off to run some errands right now, but I'd love to share the long list of papers I have collected on all the different ailments that may be helped by NR. If NR lives up to half the mouse studies, it will be a revolution in human health. It's unfortunate that more folks with neurological disorders aren't trying this because I honestly believe it can help many, many people. Sadly, I have tried to contact scientists and patient advocate groups, but have had the proverbial door slammed in my face every time because Niagen is perceived as snake oil. Tragic that they won't even look when the science is increasingly compelling.
For me I look at NR as a SIRT1 activator rather than an autophagy enhancer. You are correct though as SCA1 symptoms stem from mutant protein build up in brain cells and inducing autophagy plays a role in the studies that have shown benefit, however the molecule most studied in regard to autophagy of the ataxin 1 protein is trehalose. Hence the reason I take trehalose AND NR. Trehalose has not been shown to have any cellular repair capability so that is why I take it with NR. One promotes autophagy of the mutant protein and the other helps repair the damage. Of course, it's all pie in the sky until some research finally decides to try treating a polyQ patient with NR. Trehalose on the other hand is moving to Phase 3 trials but the company running the research is injecting trehalose into patients via IV. Trehalose is a sugar substitute you can buy on Amazon for $9 lb, but the pharma company doing the trehalose IV research is planning on charging $300,000 a year to inject sugar water into patient arms. You can imagine my desire to try oral ingestion instead.
Did some question asking, its likely your experiment with NR is correct and not placebo. You probably improved your own and your families life, apart from feeling physically better you should feel great about yourself.
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