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Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ [...]

nanonug

Senior Member
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Virginia, USA
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876407/

Abstract
Nicotinamide adenine dinucleotide (NAD+) has emerged as a critical co-substrate for enzymes involved in the beneficial effects of regular calorie restriction on healthspan. As such, the use of NAD+precursors to augment NAD+ bioavailability has been proposed as a strategy for improving cardiovascular and other physiological functions with aging in humans. Here we provide the evidence in a 2 × 6-week randomized, double-blind, placebo-controlled, crossover clinical trial that chronic supplementation with the NAD+ precursor vitamin, nicotinamide riboside (NR), is well tolerated and effectively stimulates NAD+ metabolism in healthy middle-aged and older adults. Our results also provide initial insight into the effects of chronic NR supplementation on physiological function in humans, and suggest that, in particular, future clinical trials should further assess the potential benefits of NR for reducing blood pressure and arterial stiffness in this group.
 

Learner1

Senior Member
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Location
Pacific Northwest
There is a lot of marketing around nicotinamide riboside which is derived from in niacin and ribose and eventually converts to NAD+ and then to ATP.

This paper describes the 4 pathways the body uses to create NAD+. My doctors think at least 2 of mine are broken as I have trialed high doses of nicotinamide riboside for a month twice, 8 months apart.

I find taking NAD+ works best.
 

Attachments

  • dynamic regulation of NAD in mitochondria.pdf
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nanonug

Senior Member
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Location
Virginia, USA
I find taking NAD+ works best.

One of the limitations of the above study, from the perspective of people with SEID, is that it was done with "healthy" people (if you call aging healthy). I have no doubt that certain people with SEID will have trouble with NR considering it is two enzymatic conversions away from NAD+. At the same time, I don't think one should immediately conclude NR will never work for those with SEID.
 

tiredowl

Senior Member
Messages
170
Location
Norway
Currently trying this NIAGEN supplements as well, seem to be a bit energizing. But I became a bit worried when I read it could possibly feed virus/bacteria. Anyone know anything about this?
 

Learner1

Senior Member
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6,305
Location
Pacific Northwest
One of the limitations of the above study, from the perspective of people with SEID, is that it was done with "healthy" people (if you call aging healthy). I have no doubt that certain people with SEID will have trouble with NR considering it is two enzymatic conversions away from NAD+. At the same time, I don't think one should immediately conclude NR will never work for those with SEID.
I agree. The NR supplements are expensive, too, and require all the conversions to work.

Like I said, there's a lot of marketing around NR, and the companies selling it have been funding research.

From the research I've seen, NAD+ will do all the same things as NR, while working on most patients, where NR won't work on everyone.
Currently trying this NIAGEN supplements as well, seem to be a bit energizing. But I became a bit worried when I read it could possibly feed virus/bacteria. Anyone know anything about this?
Good point. It could. Treating the bugs first, then using NAD+ for more energy after dealing with the infections might be a better strategy. I haven't seen any studies on this, though.
 

nanonug

Senior Member
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1,709
Location
Virginia, USA
The NR supplements are expensive, too

True, they are not cheap. Right now I spend ~80 bucks a month on NR.

Like I said, there's a lot of marketing around NR, and the companies selling it have been funding research.

I checked the study and it explicitly says the authors have "no competing interests." This leads me to believe they are not associated with ChromaDex.

From the research I've seen, NAD+ will do all the same things as NR, while working on most patients, where NR won't work on everyone.

It's a fair conclusion. I would gladly try sublingual NAD+ if it's readily available and if there is some research on it.
 

tiredowl

Senior Member
Messages
170
Location
Norway
I agree. The NR supplements are expensive, too, and require all the conversions to work.

Like I said, there's a lot of marketing around NR, and the companies selling it have been funding research.

From the research I've seen, NAD+ will do all the same things as NR, while working on most patients, where NR won't work on everyone.

Good point. It could. Treating the bugs first, then using NAD+ for more energy after dealing with the infections might be a better strategy. I haven't seen any studies on this, though.
Has it been proven that it could possibly feed bacteria/virus though? I could only find one article that stated bacteria/virus uses NAD pathway to potentially grow. But not sure how that applies to human physiology.
Are CFS patients commonly NAD depleted?
 

Carl

Senior Member
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356
Location
United Kingdom

Learner1

Senior Member
Messages
6,305
Location
Pacific Northwest
True, they are not cheap. Right now I spend ~80 bucks a month on NR.
Having too high NADH in relation to NAD+ is related to cell senescence and many serious diseases.

I checked the study and it explicitly says the authors have "no competing interests." This leads me to believe they are not associated with ChromaDex.
Maybe not that specific study. Then there are the Elysium Basis folks...
It's a fair conclusion. I would gladly try sublingual NAD+ if it's readily available and if there is some research on it.
There are numerous studies on the benefit of NAD+. The LIAS NAD+ I'm using is sublingual.
 

Learner1

Senior Member
Messages
6,305
Location
Pacific Northwest
Are CFS patients commonly NAD depleted?
Yes and no. It's been noted by several researchers that we have problems with our energy metabolism.

https://www.healthrising.org/blog/2...duction-found-chronic-fatigue-syndrome-mecfs/

For some, its lack of substrate, genetics and/or infections have damaged mitochondrial membranes causing decreased ATP production. For others, as pointed out in the article, the mitochondria actually are producing normal amounts of ATP, and other energy production pathways are straining to make far more ATP than normal.

So, it all depends. I still think NAD+ is more of a crutch unless we're working on the other things keeping us sick. If the immune system and infections aren't placing so many demands on the body, we shouldn't need to make so much energy.
 

nanonug

Senior Member
Messages
1,709
Location
Virginia, USA
Having too high NADH in relation to NAD+ is related to cell senescence and many serious diseases.

Although I fail to see what this has to do with my monthly cost of NR, you are right. That's why it's important to make sure the electron transport chain is working properly, which will ensure recycling of NADH back to NAD+.

The LIAS NAD+ I'm using is sublingual.

What daily dosage do you take? Do you feel any immediate effect?
 

Murph

:)
Messages
1,794
Nobody seems to think Werner syndrome is relevant for ME/CFS but I thought I'd put this here just in case. NAD+ seems to fix their mitochondria.

Nat Commun. 2019 Nov 21;10(1):5284. doi: 10.1038/s41467-019-13172-8.

NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome.
Fang EF1,2, Hou Y3, Lautrup S4, Jensen MB5, Yang B3, SenGupta T4, Caponio D4, Khezri R6,7, Demarest TG3,8, Aman Y4, Figueroa D3, Morevati M3,9, Lee HJ10, Kato H11, Kassahun H3,4, Lee JH3, Filippelli D12, Okur MN3, Mangerich A12, Croteau DL3, Maezawa Y11, Lyssiotis CA13, Tao J14, Yokote K11, Rusten TE6,7, Mattson MP8,15, Jasper H5, Nilsen H4, Bohr VA16,17.
Author information

Abstract
Metabolic dysfunction is a primary feature of Werner syndrome (WS), a human premature aging disease caused by mutations in the gene encoding the Werner (WRN) DNA helicase. WS patients exhibit severe metabolic phenotypes, but the underlying mechanisms are not understood, and whether the metabolic deficit can be targeted for therapeutic intervention has not been determined. Here we report impaired mitophagy and depletion of NAD+, a fundamental ubiquitous molecule, in WS patient samples and WS invertebrate models. WRN regulates transcription of a key NAD+ biosynthetic enzyme nicotinamide nucleotide adenylyltransferase 1 (NMNAT1).

NAD+ repletion restores NAD+ metabolic profiles and improves mitochondrial quality through DCT-1 and ULK-1-dependent mitophagy. At the organismal level, NAD+ repletion remarkably extends lifespan and delays accelerated aging, including stem cell dysfunction, in Caenorhabditis elegans and Drosophila melanogaster models of WS. Our findings suggest that accelerated aging in WS is mediated by impaired mitochondrial function and mitophagy, and that bolstering cellular NAD+ levels counteracts WS phenotypes.
 

sb4

Senior Member
Messages
1,654
Location
United Kingdom
@Murph It appears in these studies they use nicotinamide mononucleutide and nicotinamide riboside but not the ones found in most supplements (Nicotinic acid, and niacinamide). It seems most anti aging studies insist on using these types.

As far as I am aware, there isn't much advantage to it but perhaps there is if studies keep using the same types. NAM reduces SIRT1 which can be good or not good depending. Nicotinic acid needs methylating to be excreted. I don't think the other forms have this problem so maybe higher concentration can be reached?

Do you think there is anything to these newer forms of NAD supplement @Hip
 

Learner1

Senior Member
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6,305
Location
Pacific Northwest
I have been using NAD+ and NMN which have greatly helped me , far more than niacin or niacinamide. Or NR, which did nothing for me. Currently, I take 125mg Alive by Nature BMN sublingually in the morning, and get 100mg NAD+ in IV form, which has a much greater effect, weakly.

More is not better, however. As a cancer survivor, I'm keenly aware that it can promote cancer under certain circumstances, so I am careful to not overdo it.

Any niacin family supplement can reverse methylation, so ensuring one hss enough methyl groups, through methylation cofactors, is important.

And, putting more gas into a broken system may not be a good idea. It's important to look at everything that mitochondria may need, and supply them, too, like phospholipids for membranes, CoQ10/MitoQ, PQQ, carnitine/ALCAR, B2, manganese, folate, B12, BCAAs...glutathione.

Additionally, the FDA is now trying to ban NAD and NADH this month- they need to hear from patients about why they are needed, along with ALCAR, DCA, curcumin, boswellia, etc. so if you think you may want to try them, you can provide input here:

https://naturopathic.org/page/LegislativeActionCenter#/
 

Hip

Senior Member
Messages
17,806
Do you think there is anything to these newer forms of NAD supplement @Hip

I have not tried them yet. Last time I looked, they were quite expensive, so I am waiting for the price to fall. Most things I try don't really help, and I don't like spending lots of money on a supplement only to find it does not work.

I've tried NADH (even used that before getting ME/CFS), and that has noticeable effects, but I have read reports from several people that after continued use it just stops working. So I only use it occasionally.



the FDA is now trying to ban NAD and NADH this month

From what I can work out from an MEAction article on this, the FDA are not considering banning these outright, but just banning them from being compounded in a formula containing other ingredients. So I think that means you will still be able to buy them as a pure single substance.
 

Learner1

Senior Member
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6,305
Location
Pacific Northwest
From what I can work out from an MEAction article on this, the FDA are not considering banning these outright, but just banning them from being compounded in a formula containing other ingredients. So I think that means you will still be able to buy them as a pure single substance.
No, you won't - you will only be able to buy comnercial product if you are not allergic to any of the ingredients, and as long as a commercial (OTC( product exists. If the FDA is successful, IV versions will not be available either. There are several clinics doing NAD+ for addiction trratment, which apparentky is successfil, and there are other patients like me getting IV, at a lower dose tban the addicts.
I have not tried them yet. Last time I looked, they were quite expensive, so I am waiting for the price to fall.
The price has come down. There are a few more products in the market. I pay about US $0.62 each for 125mg NMN tablets.
I've tried NADH (even used that before getting ME/CFS), and that has noticeable effects, but I have read reports from several people that after continued use it just stops working.
That's because one needs a higher NAD+/NADH ratio. If NADH is too high, health problems result. The game is to raise NAD+ and increase the NAD+/NADH ratio, which can be done with NAD+, NMN, and for some people, NR (NR does not work in everyone and it IS expensive).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683958/

https://www.frontiersin.org/articles/10.3389/fnut.2018.00062/full
 

Hip

Senior Member
Messages
17,806
That's because one needs a higher NAD+/NADH ratio.

So you are suggesting that the benefits of NADH (which are quite immediate, kicking in within hours) are eventually nullified after some weeks of supplementation because it decreases the NAD+/NADH ratio?
 

Learner1

Senior Member
Messages
6,305
Location
Pacific Northwest
@Learner1 What is the main difference between basic B3 and NMN/NMR? You benefit from these supps?
There are 4 pathways for making NAD+. One uses the IDO2 pathway to make it from tryptophan. One uses NMN. One uses NR.

Going from niacin to NAD+ takes a lot of steps and if you have problems it may not convert all the way. Going from NMN is direct, so less chance for problems. NR is one more step. I found my SNPs doing let me convert NR - I'd tested it at high doses for a month twice with no result.

To be clear, NADH did work for me, but it was expensive at a low dose. I dont think it would hsve worked long term, given what I've said above. NAD+ worked much better and is cheaper. NMN made me a little jittery at first, but as I experimented, I found that it smoothed out and I can use NAD+ and NMN interchangeably. I settled on NMN figuring making my body work to convert it was a good thing, but am not sure.

You can make niacin from B6. I never take niacin or niacinamide. They reverse methylation and I need methyl groups too much. My doctors think any of the niacin family supplements, like NAD+, will also affect methylation so good to be aware of thid snd be ready to support methylation.