NAD, Hype Or Miracle Molecule?

[Will Brink]

Confused over all the hype over NAD? I get down to the facts vs hype over this molecule and even had an NAD infusion done myself!

Nicotinamide adenine dinucleotide (NAD) is an essential cofactor found in all living cells, essential for energy production. To get a tad more technical, it’s found in two forms, oxidized and reduced, abbreviated as NAD+ and NADH. Without getting overly technical, NAD is an essential molecule for cellular energy production and function, healthy youthful cells have high levels, older cells, not so much. What else is new? That is, with aging, comes a reduction in all manner of essential pathways and molecules, and enzyme, etc. cells require to function optimally, and NAD appears to be one of the most important

Unless you have been living under the proverbial rock, you know NAD is a hot topic these days. The ratio of reduced to oxidized NAD appears to be a crucial factor to the function of NAD, and from here on, we’re concerned with NAD+ and how to elevate it in cells. As every cell in your body requires energy, low levels of NAD+ are associated with a wide range of pathology, from cognitive deterioration, and related brain diseases, to cardiovascular function, to DNA repair, and a long list of age related declining cellular function best avoided.

Cont:

NAD Hype Or Miracle? | BrinkZone.com

 

[MikeXL]

I am betting hype

 

[Will Brink]

I am betting hype

I'd say read article and decide for yourself. Jury is still out for me, but I did get an NAD infusion and it clearly holds promise. How much, for who, etc is unclear until some human trials get published.

 

[JimBob]

Cut to 1:09:30
#46 – Chris Masterjohn, Ph.D.: Navigating the many pathways to health and disease – NAD and sirtuins, methylation, MTHFR and COMT, choline deficiency and NAFLD, TMAO, creatine and more

 

[JPB]

As I previously discussed, there is a better way to go about this:
Increasing NAD+

Benefits of pricey NR and NMN are no better than just niacinamide. They now realize NR and NMN get converted in the liver to niacinamide. To keep the dollars flowing they now offer sublingual versions. Don't fall for the hype.

Optimal mitochondrial function has circadian patterns, pay attention to this in your niacinamide supplementation.

As far as infusion is concerned, I do not consider that a practical approach although there may be short term benefits. However I believe the same benefits can be attained gradually over time with simple oral niacinamide.

If you want the research backing this up it is all out there, have a go at it. I think you'll reach similar conclusions.

 

[Will Brink]

As I previously discussed, there is a better way to go about this:
Increasing NAD+

Benefits of pricey NR and NMN are no better than just niacinamide. They now realize NR and NMN get converted in the liver to niacinamide. To keep the dollars flowing they now offer sublingual versions. Don't fall for the hype.

Optimal mitochondrial function has circadian patterns, pay attention to this in your niacinamide supplementation.

As far as infusion is concerned, I do not consider that a practical approach although there may be short term benefits. However I believe the same benefits can be attained gradually over time with simple oral niacinamide.

If you want the research backing this up it is all out there, have a go at it. I think you'll reach similar conclusions.

Source? Niacinamide converts to NAD+/NADH, not the other way around, but may also increase Niacinamide in some tissue via tissue flux so the process is not one way apparantly. NAD+/NADH. NAD+ levels drop as we age substantially suggesting conversion of Niacinamide to NAD+ is reduced with age.

Typical of aging, conversion to active compounds from their precursors drops drastically so using what bypasses the limiting enyzyme(s) often takes care of that problem, or at least helps considerably.

Younger people unlikely to benefit from NR, as their conversion from precursors is GTG, there's also data to suggest there may be benefits to NR as the conversion, even in healthy people, it limited and NAD+ levels of "normal" may of value. There's many examples where aging reduced conversion to active compounds, and or, there may be benefits from bypassing the limiting enzymes to conversion, not unlike creatine vs precursors, EPA/DHA vs LNA, or Glu-cys moieties found in whey for increased GSH. The data suggests simply taking niacinamide is not equivalent to taking NR, especially in aging populations.

Annu Rev Nutr. 2008;28:115-30. doi: 10.1146/annurev.nutr.28.061807.155443.
Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition.


Abstract

Although baseline requirements for nicotinamide adenine dinucleotide (NAD+) synthesis can be met either with dietary tryptophan or with less than 20 mg of daily niacin, which consists of nicotinic acid and/or nicotinamide, there is growing evidence that substantially greater rates of NAD+ synthesis may be beneficial to protect against neurological degeneration, Candida glabrata infection, and possibly to enhance reverse cholesterol transport. The distinct and tissue-specific biosynthetic and/or ligand activities of tryptophan, nicotinic acid, nicotinamide, and the newly identified NAD+ precursor, nicotinamide riboside, reviewed herein, are responsible for vitamin-specific effects and side effects. Because current data suggest that nicotinamide riboside may be the only vitamin precursor that supports neuronal NAD+ synthesis, we present prospects for human nicotinamide riboside supplementation and propose areas for future research.

 

[sokaiya]

glad you brought this up. so sick of seeing stupid ads for this supplement. And it's one of those supplements to convince the population you need to take it every single day for the rest of your life in order to reduce/prevent aging, lol whatever.

 

[Will Brink]

glad you brought this up. so sick of seeing stupid ads for this supplement. And it's one of those supplements to convince the population you need to take it every single day for the rest of your life in order to reduce/prevent aging, lol whatever.

Did you read the article? While more data needed, this one may be legit. I would not be so quick to dismiss NR as a supplement for raising NAD+ levels. Now, whether raising NAD+ levels = the magic elixer to aging is another matter, but what exists for data is compelling.

 

[sokaiya]

Did you read the article? While more data needed, this one may be legit. I would not be so quick to dismiss NR as a supplement for raising NAD+ levels. Now, whether raising NAD+ levels = the magic elixer to aging is another matter, but what exists for data is compelling.

Chris Masterjohn covers it.

Niacin in any form, in excess consume methyl groups etc.

 

[Will Brink]

Chris Masterjohn covers it.

Niacin in any form, in excess consume methyl groups etc.

It's not a form of Niacin per se, but a downstream metabolite and if it consumed methyl groups to any great extent, the animal data, etc would not be so promising nor would low NAD+ levels be so strongly associated with so much negative age related stuff. No, that one is overly simplified. In some cases, for example creatine, you saves methyl groups as the production of creatine use more methyl groups than any reaction in the body. So, some times taking a metabolite, or the end product is a benefit, some times it's not...I have not looked at the full metabolic pathway for the production of NAD to see where methylation heavy reactions takes place, but I suspect it's not where as simple as your statement. If you can supply a source on that one via journals, I'll read it for sure.

 

[JPB]

https://www.cell.com/cell-metabolism/fulltext/S1550-4131(18)30196-7

"Intravenous administration of nicotinamide riboside or mononucleotide delivered intact molecules to multiple tissues, but the same agents given orally were metabolized to nicotinamide in the liver. "

 

[Will Brink]

https://www.cell.com/cell-metabolism/fulltext/S1550-4131(18)30196-7

"Intravenous administration of nicotinamide riboside or mononucleotide delivered intact molecules to multiple tissues, but the same agents given orally were metabolized to nicotinamide in the liver. "

I addressed that above and have read that study. I linked to a human study that found NR raised NAD+ levels in humans, and in addition to animal studies, we know not all orally ingested NR is converted the nicotinamide in the liver. That may also be why, per my article, infusions for those willing to that, + oral NR may be the optimal approach to keep NAD+ elevated, but we need more data on that one. I agree that it may be more beneficial to use methods that bypass first pass liver metabolism, but oral NR is still effective it appears.

Note also, that study is not oral NR vs NAD+ intravenous, but oral NR vs intravenous NR, so possible apples and oranges.

 

[JPB]

The debate will continue until there are more studies. My real-world results with niacinamide tell me all I need to know for now. Pay attention to what I say about circadian pattern matching AM to early afternoon dosing so converting enzymes and pathways are replenished nightly. The cost factor with NAM is about 80-90% less than going with NR or NMN. Keep in mind leading researchers in the field, ie Brenner and Sinclair, have vested interests.

 

[JPB]

I am not saying NR or NMN do not work, only that oral NR and NMN get converted to NAM. NAM is many times more cost effective.

 

[Will Brink]

The debate will continue until there are more studies. My real-world results with niacinamide tell me all I need to know for now.

What does that actually mean? What tests have you done? I can say I feel my energy levels and mood have been elevated since I got that NAD+ infusion, but I'm also fully aware that may be placebo and expectation bias on my end, and until there's solid data, my n=1 subjective experience does not amout to jack chit.

Pay attention to what I say about circadian pattern matching AM to early afternoon dosing so converting enzymes and pathways are replenished nightly.

Per above, that conversion appears to drop off sharply with age, as does the conversion to many things we need for optimal health. As mentioned, younger people, say below 40, unlikelt to get much, if any benefits from NR or NAD+ infusions, but, there may be therapeutic reasons for some to use it regardless of age.

The cost factor with NAM is about 80-90% less than going with NR or NMN. Keep in mind leading researchers in the field, ie Brenner and Sinclair, have vested interests.

The cost of flax oil is less than fish oil, but the poor conversion rates, which only get worse with age, and other factors, makes the $ you may save a moot issue.

As always, confirmation by labs that don't have a vested interest is essential to make solid conclusions here.

 

[Will Brink]

I am not saying NR or NMN do not work, only that oral NR and NMN get converted to NAM. NAM is many times more cost effective.

As I keep repeating, that appears to change with age, so it probably applies well to a 25 year old, but not to a 63 year old person, and so forth. We have something like 5% of the NAD+ levels we had by 80 years old. There's more going on there than your overly simple conclusion that NR/NAM are interchangable in their impact on NAD+ status. It also appears to be tissue specific, adding yet another variable to consider.

 

[JPB]

You appear confused. If conversion rates decline with age that applies to NR and NMN as well, since they are simply converted to NAM in the liver. Believe what you want to believe. As I already said the debate will continue and neither you are I have enough data to state the final word. I never said my results were the final word. But they are good enough for me, and I wanted to pass this along to others. I am glad you have chimed in on this topic and appreciate your efforts, although I am surprised that at this point and after educating yourself on this topic, you are not reaching the same conclusions I have. If you were to advise somebody on this topic, to do something actionable, what would you advise at this time?

 

[JPB]

NAD IV Therapy Pricing | Denver NAD Center | Centennial, CO
NAD+ IV Therapy, Treatments & Infusions in Los Angeles, CA
https://www.nadtreatmentcenter.com/nad-prices

 

[Will Brink]

You appear confused. If conversion rates decline with age that applies to NR and NMN as well, since they are simply converted to NAM in the liver. Believe what you want to believe. As I already said the debate will continue and neither you are I have enough data to state the final word. I never said my results were the final word. But they are good enough for me, and I wanted to pass this along to others. I am glad you have chimed in on this topic and appreciate your efforts, although I am surprised that at this point and after educating yourself on this topic, you are not reaching the same conclusions I have. If you were to advise somebody on this topic, to do something actionable, what would you advise at this time?

I have addressed that repeatedly, so either you're not as well informed as you think you are and or lack the sci/med background for the discussion, or you're intentionally being obtuse. Either way, you're now wasting my time at this point.

So yes, we will wait until there's further data to answer the Qs that need answering, and there's not much else to say. I'm more optimistic about the use of NR and other modalities to raise NAD+ due to aging, and you're convinced other approaches are as effective regardless of age and or in those diseases where higher levels of NAD+ may be of benefit.

Here some possibilities as to why NAD+ decline with age:

"...an NADase called CD38 whose levels rise during aging. Their results also add to the body of evidence indicating that loss of SIRT3 activity in mitochondria is a cause of age-related metabolic decline:

Why NAD+ Declines during Aging: It’s Destroyed

And what is the rate limiting step to NAD+ production?

"nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in this pathway"

Best paper I have read so far on the age related decline and why:

NAD + biosynthesis, aging, and disease

Hence again, as explained, bypassing the rate limiting step in a pathway, be it due to age and or possible benefits of doing so, is common approach to boosting various beneficial compounds.

 

[JPB]

You started with an informative article, but infer fundamentally misleading conclusions. That things like NMN, NR, or NAD infusions are worthy of consideration. Yes you keep bringing up the issue of conversion like somehow this make NR or NMN superior. My point is the issue of conversion applies to all of these molecules in essentially the same manner. So it is a mute point. All these molecules must be converted. Age related changes in conversion applies to all of them, given no or very little oral NMN or NR makes it past the liver before being converted to NAM. What NR or NMN gets past the liver must still be converted. The issue of conversion, and related affected pathways, is partially why I advocate cyclical circadian dosing patterns. And the infusion method is clearly not practical as a long-term strategy, although there may be interventional upside for those with specific disease states.