Why NMN and NR is not curing our CFS?

vortex

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Lets talk NAD.

It should be a miracle cure for us.

Everything you read about NAD+ being able to fix mitochondria should cure us

But I dont hear much success with it

at least from people taking oral precursors.

It just doesnt make sense.

I have experimented with it and researched it alot and see an obvious conflict with CFS and NAD.

Most people who have CFS have mthfr which causes low glutathione.

Alot of people have had success treating their CFS by treating their mthfr and restoring glutathione.

Anyone who has done this knows the dose is tricky and if you push your dose too far you can
overmethylate and the cure is to take niacin which soaks up methyl units and limits methylation.

But if you look at NAD, it is a nicotinamide/niacin based molecule.

So if people start taking a bunch of NAD stuff, they will shut down their methylation and that would make their cfs worse.

So does anyone have any solutions or workaround to be able to take nad stuff while keeping their
methylation up?

The first impulse seems to be to take extra methylfolate to compensate for the NAD methylation inhibition.

Is it just that simple?

I am going to start experimenting with this but would like to get some input.

I am just wondering if this is even possible?

Can you get normal methylation levels while taking large doses of nicotinamide
supplements just by taking more methylation supps?
 

Mary

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@vortex - here's a thread which talks about the same issue which might shed some light for you. FWIW, I tried NAD several years ago and didn't notice any benefit, though it does help some people. I originally tried NADH in 2004 - 20 mg. a day, it was pricey, but it gave me 10 very good days with no crashing, no PEM, and I would have kept taking it only it stopped working, just like that. I've periodically retried taking it over the years with no apparent benefit so just don't bother because it is so expensive.
 

vortex

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@Mary Did you try NAD as in oral precursors or IV NAD? I am still trying to get more data on the difference in effects of both. I am wondering if you can use ones reaction to oral to determine if IV NAD is going to work.

Also, do you have MTHFR?
 

Mary

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@Mary Did you try NAD as in oral precursors or IV NAD? I am still trying to get more data on the difference in effects of both. I am wondering if you can use ones reaction to oral to determine if IV NAD is going to work.

Also, do you have MTHFR?
It was an oral supplement just called NAD, by Now Vitamins, and was quite a bit cheaper than NADH. I don't think they make it any more. Maybe it was no good! I haven't seen it for several years.

I do have one MTHFR defect. I take lots of methylcobalamin (5,000 - 10000 mcg. a day), and 1600 mcg. methylfolate.

I also take niacin, but only at night, because it helps me with sleep. If I take it during the day it makes me tired, maybe from slowing down methylation. It also sensitizes or stimulates GABA receptors, another reason it might make me tired during the day.
 

alex3619

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Everything you read about NAD+ being able to fix mitochondria should cure us
Actually this is incorrect. We probably have an NAD deficiency, but fixing it wont fix the cause of the deficiency, and if there are feedback issues, then fixing a deficiency in a set point might even make us worse. This will only be useful if there is a metabolic trap due to low NAD (I don't care much about NAD+) and we kick out of the trap.

This is an entirely separate argument from the possibility that NAD will help us, or harm us.

Its unclear if treating methylation will help. It might. Its an empirical question given we don't have a controlled trial.

I think I ttried NADH at some point. It might have had a slight effect, but nothing major.
 

vortex

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Alex, At first I thought maybe your first point may have some validity and worthy of discussion but when you drifted and said "Its unclear if treating methylation will help"?

You obviously havent spent much time on the methylation forum, besides I didnt ask if treating methylation will help. So I am not sure why you are even making commentary on that if you arent experienced with it and it is off topic and is a separate conversation.
 
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alex3619

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You obviously havent spent much time on the methylation forum, besides I didnt ask if treating methylation will help.
I was a debate partner for Rich van Konyenburg for five years, back in the early days when he was first into this. Heck, I was one of the people who put him on this path. He and I and Marty Pall spent five years debating all this, and its connection to nitrosative stress and glutathione. I do not follow it any more, its not a widely useful path in my view. It does not mean it does not help some or some of the time. It is one of those things that needs to be tested in an individual, and you cannot generalise to others with any reliability.
 

vortex

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Sorry for the confusion, I should have made it clear I already take methylfolate and my comment meant
to take extra methylfolate OVER AND ABOVE what I am already taking to compensate for the inhibition
caused by the NAD.

I should have made that clear and did not mean to imply that I was asking if methylation was valid or helpful
in the first place. So apologies for the confusion and the rude comment.
 

vortex

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Btw, I sure miss Rich. I never got a chance to thank him for changing my life.

I have been doing the methylation protocol for 6 years and it has gotten me from being bedridden to about 80% recovered.

I was a difficult case, I have had cfs for 25 years. I was horribly toxic from having low glutathione for all those years.

I was looking at the methylation panel data and study Neil nathan did and his patients were having their glutathione bounce back and feeling better in 6 months but I took several years.

I kept plugging away at it, herxing away on microdoses but I stuck with it.

Most people would have given up and just assumed it didnt work or it wasnt right for them, heck some people just say it made them feel weird so they abandoned it and never tried it again. The only thing that kept me going was looking at the data on my hdri methylation panel and knowing where my numbers where and where they needed to be.
I want to try to recover or improve as much as possible so I am still trying stuff which is why I am interested in the NAD but I have to try to figure out how to do both. I think it would be useful to work on this problem as I think some people try nad and perhaps impair their methylation and it causes them to feel worse and so they just label nad as being not helpful, but if my theory is correct and the problem can be overcome alot of people could potentially be helped by nad that arent responding well to it now.
 

JES

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"It is unclear if treating methylation helps" is a perfectly valid statement based on the current scientific evidence of methylation treatments in CFS/ME. You might remember a user "Freddd" from this forum who cured his condition with super high MB12 etc., but it was clear that he had some genetic issues with processing B12. I remember there was a big following on PR of these methylation treatments around five years ago, but apart from a few anecdotal reports, there was no success. It has become clear to me that methylation treatments only work for a small subset of people here, which may be due to some rare genetic alternations like Freddd had. MTHFR itself is far too common to be causing problems alone, as almost half of the population has a form of it.

Ron Davis, who is world's top ME/CFS researcher, has found metabolic blocks in ME/CFS, but nothing I know of points to methylation in his discovery. There is now a lot of evidence of pyruvate dehydrogenase being blocked in ME/CFS, which might cause multiple downstream metabolic problems. So there is a high chance that many of the mitochondrial problems we experience are a downstream effect of a block elsewhere.
 

triffid113

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Re:the cure is to take niacin which soaks up methyl units and limits methylation.

Can anyone explain this? It's news to me. I have many methylation genetic defects (18) and am wanting to try NR. I got my methylation under control fairly well and don't want to derail it.

Also a question to Alex...are you sure that Freddd's protocol wouldn't work for y'all? Because folks I know from back then who stuck with it, admittedly having to separate capsules to make super tiny doses to start, were cured. It seemed to me most people were looking for a 1 pill solves all solution, perhaps due to expense. Lots of sick people can barely afford to survive I know. But of course you keep up on all this and I have no idea what happened in the past 5 years. Just wanting to ask you to be careful because I recall several people with cfs who were cured by that protocol...um if one can say cured if one is dependent of these supplements 4 life.
 

JES

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Also a question to Alex...are you sure that Freddd's protocol wouldn't work for y'all? Because folks I know from back then who stuck with it, admittedly having to separate capsules to make super tiny doses to start, were cured. It seemed to me most people were looking for a 1 pill solves all solution, perhaps due to expense. Lots of sick people can barely afford to survive I know. But of course you keep up on all this and I have no idea what happened in the past 5 years. Just wanting to ask you to be careful because I recall several people with cfs who were cured by that protocol...um if one can say cured if one is dependent of these supplements 4 life.
Most people here aren't looking for a one pill solution, in fact there were several of us who went to extraordinary length in order to understand methylation and what it takes to fix it. There was a thread with over 100 pages here on PR which was quite active when Freddd used to be more around. Apart from Freddd (who AFAIK had some rare genetic defects with utilizing B12), I don't reckon anyone here wrote they were cured. But I could be wrong of course so feel free to provide a link to those posts.
 

prioris

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Most ME/CFS is primarily brain inflammation with FMS secondary. It's way beyond mitochondria for most people. NAD primarily helps under methylated people. I'm an over methylated person.
 
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I'd like to try NMN. Are there specific brands which are recommended more highly than others, like the B12 that Freddd recommends? I am considering the pure sublingual powder from Alive by Nature.
 

prioris

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I'd like to try NMN. Are there specific brands which are recommended more highly than others, like the B12 that Freddd recommends? I am considering the pure sublingual powder from Alive by Nature.
TRU NIAGEN Nicotinamide Mononucleitide NMN is most well known so I'd start with that. Lot of favorable reviews too.

There is also MAAC10 Nicotinamide Riboside NR