You talk about the NAD/NADH ratio. In your research you also talk about the
NADH/ NAD pH ratio. Could you refresh our memory and tell us whether these
ratios are meant to measure the same physiology called processes or not?
And if they are, could you just give us, just a quick feel for what they actually mean?
Got it. So the NADH to NAD ratio and the NAD pH to NADP plus ratio are things that are having real
consequences as ratios and biochemistry that are dictating what's going on in our body. The NAD pH
to NADH ratio is physiologically irrelevant, but is used as a biomarker of niacin status.
So if you look at a biochemistry textbook, that's telling you how things work in the body you're
going to see constant references to the NADH to NAD ratio or the NAD pH NADP plus ratio.
And you're never going to see any reference to the NAD pH to NADH ratio.
The NAD pH to NADH ratio is used to calculate the niacin number, which is used as a test for
niacin status. And the logic of the niacin number is that antioxidant defense is so
critical to cellular health that if you are nice and deficient, your NADH will go down,
but your NAD pH will stay constant as long as it can. And so generally you will have a very high
niacin number if you have an excellent amount of niacin and you'll have a very low niacin number,
meaning you'll have less your NADH, but the same NAD pH when you're low on niacin. So,
basically the expectation is NAD pH will remain relatively constant in deficiency
whereas niacin deficiency will selectively deplete the pool of NADH first. And so that's one thing
that's a marker of nutritional status. The other ratios are not markers of nutritional status,
but they're biochemically relevant. The marker of nutritional status
has no biochemical relevance. So the NADH to NAD ratio is,
you're going to have more NADH when you are well fed and less NADH when you are less well fed,
and you're going to have more NAD when you're burning energy, and you're going to have less
than a D when you're not burning energy. So you can sort of imagine the maximal NADH to NAD ratio
is going to be when you are overfed and sedentary, and the maximal or the minimal NADH to NAD ratio
is going to be when you're fasting and you're doing exercise. And there are other things that
can impact that such as whether you're running on one fuel or another, like ketones will change one
in the liver and change it in the opposite direction and the brain and stuff like that. But
thinking of it as fed versus... Energy in versus energy out, it's the best way to think about it.
The NAD pH to NADP plus ratio is going to be highest when you have a high activity of
the pentose phosphate pathway and is going to be lowest when you have low activity of that pathway.
It's generally going to be pretty constant because you want to operate that pathway quite
well whenever you can, but if it's low, that's going to compromise your antioxidant defense
and your ability to synthesize things like cholesterol, neuro-transmitters, fatty acids,
nucleotides and to recycle folate and vitamin K when it's high,
all those processes will run smoothly and recycling glutathione I didn't mention,
and also some detoxification as well. So generally the reason you want a high...
And so generally in health, you'll have a very high NAD pH to NADP plus ratio,
you'll have a very low NADH to NAD plus ratio. And so NAD pH is you generally want high in
health because it's helping you synthesize things, recycle things, and support antioxidant, defense,
and detoxification. NADH you generally want low meaning you want high NAD plus,
and that's because that's going to help you burn fuel in a very effective manner.
If your NADH goes up too much, then that's signifying the overfed sedentary state.
So those two ratios are biochemical. The other one, the ratio between those two different systems
is a marker of nutritional status. Does that help? Yes. It's very helpful. And so when you take
nicotinamide riboside, do you impact these three ratios throughout, or not? And what is
the benefits of NR supplements relative to these ratios relative to age better aging?
When you take NR, you will probably increase all those ratios but because you're increasing the
niacin number, that means you are having a better increase in the NADH pool than you are in the NAD
pH pool. And so if you're increasing that ratio, it by definition means that you're having a much
bigger impact on the NADH pool than the NAD pH pool. Now that's probably contextual, there might
be some people where that average situation doesn't play out or who are so deficient that
they need not more niacin than to support NAD pH, but that's a general rule. You will increase all
pools, but you will specifically favor NADH more than the other pool. And then,
NR is going to be better at supporting the production of any of those systems
then niacin or nicotinamide. Whereas an NMN is probably equivalent to NR.
Very nice. Thank you Chris. You're welcome Xavier.