Doug says, "From your deep dive into nicotinamide riboside and NMN, do you think either is effective
and is one preferred over the other?
Do you still recommend taking TMG with NR?"
Let me back up a little bit here.
These are all different forms of niacin.
In the anti-aging community, many people are taking nicotinamide riboside, which is NR,
or nicotinamide mononucleotide, which is NMN.
The question is, is one of those better than the other?
Then he asks me, do I still recommend taking trimethylglycine or TMG with NR because extra
niacin depletes methyl groups and TMG is a methyl donor.
Yeah.
There are no human studies looking at NMN and how it's metabolized.
There are studies of NR.
No one has showed any positive benefits of supplementing NR in humans yet, but they haven't
really done any long-term studies or looked at many things, and they really haven't looked
at anything that I would really want to see for NR.
They've looked at things like glucose and lipids and other metrics of metabolic health
doesn't really do anything for that.
I know Charles Brenner is doing a study on fatty liver.
I don't want to bet money on it.
Well, no, I'm not really a betting man, but I'd be willing to bet like $200 or $300 on
three-to-one odds that he doesn't show the benefits on fatty liver that he's expecting
to, because the overwhelming thing about fatty liver is methyl donors.
He's published two papers showing that nicotinamide riboside causes an extreme increase in methylated
niacin metabolites, like extreme increase.
When they're feeding people 2000 milligrams of nicotinamide riboside, I don't know what
portion is being methylated and peed out in the urine, but I know it's very high.
This is what I would say.
My strong suspicion is that NMN is not absorbed intact.
It's broken down into NR and it's absorbed intact as NR, while NR is just absorbed intact
in NR.
I believe that both of those supplements are going to lead to NR getting into the liver.
I mean, I would use NR because there's more data on NR, and I wouldn't use NMN because
there isn't any data on it.
But it probably makes no difference at all because they're probably both absorbed as
NR.
Maybe if your digestion is weaker, you're going to do better within NR than NMN because
you probably almost certainly are not absorbing NMN intact.
If you're not digesting it, then you're absorbing less of it.
But probably for most people, it makes no difference.
I believe that both of these are going to generate NAD levels in the liver much more
effectively than nicotinic acid or niacinamide would, the two common niacin supplements that
are available on the market now and have been taken for ages.
I think it will be better at boosting NAD levels in the liver.
I think that will allow the liver to nourish many other tissues in the body to get a better
NAD response in those tissues.
My suspicion is that this is going to have a positive effect for anti-aging, for cellular
repair.
I think it's probably going to have a lot of promise for mental effects in the brain
where there's high NAD turnover for neurotransmitter release.
I think it's going to have probably really good effects in the gut where there's high
NAD turnover because the gut faces so much damage by just being forced to deal with everything
that you put into your body, unlike everything after the gut, after absorption, which has
really high quality control.
I think it's going to be great for skin issues.
Peter Attia told me in our recording that his patients who are taking it, the one thing
that people report positive benefits with is rosacea.
I think anything in the skin is going to be great for nicotinamide riboside and maybe
NMN had a lot of promise just to improve cellular repair in the skin.
I don't know for sure, but I'm going to guess that maybe if there's another tissue after
the brain, gut, and skin that have a lot of benefit, it's going to be the lungs.
But that's a wild guess on my part.
This is a bit speculative.
It looks good in animals so far.
I'm speculating that we're going to see these benefits if we do longer-term studies in humans,
but I think we will.
In terms of the dose, I think when we get down in humans, we're going to roll back the
dose.
I think 2000 milligrams is just taxing the methyl supply too much, and most people are
not consuming enough methyl donors in their diet to compensate for that.
I think at some point, in ten years when we have a lot more data, we're going to say,
yeah, let's pull the dose back to like 300 milligrams.
I think that in order to get the best NAD response and to tax the methylation system
the least, you want to take a smaller dose with every meal rather than taking a higher
dose once.
I would take like 150 milligrams max at a meal.
If you're going to take 450 milligrams, I'd take 150 at each of three meals.
If you want to take less than that, you either use the powder or empty half of it out in
a capsule.
Like take half the capsule, empty it out into your mouth with a meal, 150-milligram capsule
to do that.
It will give you 75 milligrams.
Take that three times a day.
Then there's no good test to really see whether it's doing anything for you.
You really have to judge it by your response.
Are you getting tangible benefits from it?
If so, then I think it's fine to keep it up.
But yeah, I would take 100 milligrams of TMG for every 200 milligrams of nicotinamide riboside
or nicotinamide mononucleotide.
Personally, I wouldn't use the NMN and use the NR because there's more data on it.
Thanks, Doug.