Anti-aging | NMN, NR, and Vitamin B3: Which is the Most Powerful Anti-Aging Supplement?


Who is the number one in anti-aging?

Huberman: I think you've captured the essence of rational fasting and irrational use of supplements. Along the lines of supplements, I want to ask about the effects of NMN, NR, Vitamin B3, and niacinamide?

I want to know what you do? And I also want to know what I should do?


I think most people want to know what they should do.

I know these are molecules that affect the Sirtuin pathway, which controls aging or the rate of epigenetic aging.

But how do NMN, NR, Vitamin B3, and niacinamide work? And how should these supplements be used? Should people choose to use supplements?

Sinclair: Well, my disclaimer is: I don't recommend anything, but I'll talk about what I do.

So, this information requires some scientific background:

When we were at MIT, we first discovered two genes in yeast cells, and then, when I moved to Harvard in 2000, I also found them in animals.

During my first postdoctoral period, Haim Cohen published a great paper a few months before, in which he discovered a gene that activates sirtuin 6. The gene in the middle, sirtuin 6, was very effective. Sirtuin 6 greatly extended the lifespan of male and female mice that he created, which is great.

So, what you want to do is naturally increase the activity of these sirtuins. They are genes, but they also produce proteins. Proteins are what genes usually produce or encode.

Then, as we discussed, these proteins take care of the body in many different ways.

So, how do you activate these genes to make the proteins they produce more active? You want to speed up that system, so exercise can do that, and fasting can do that.

How effective are supplements?

Well, the first sirtuin activator that we discovered, which can act on enzymes to help them clean and protect the body better, is resveratrol.

We studied thousands of different molecules. The best one is resveratrol found in vegetables.

Then we gave it to small organisms, worms, then flies and mice, and finally humans. We saw that it activated sirtuins (deacetylases).

So, resveratrol is one way to activate deacetylases.

You can think of resveratrol as the accelerator pedal of a car, it speeds things up. But sirtuins need something else to work—it's NAD (Nicotinamide adenine dinucleotide), which is a very small molecule that our bodies need but have very little of.

NAD is used by the body for chemical reactions, in a hundred different reactions. Without it, you would die in a matter of seconds, you need NAD.

The problem we see is that NAD levels increase with weight gain and decrease with age, and if you never starve, your body not only cannot fully utilize NAD, but also depletes it.

Eric Verdin, from the University of California, San Francisco (now at the Buck Institute in California) discovered an enzyme called CD38, which chews up and consumes NAD as we age.

So, it's a double hit—it's not only that you're not making as much NAD, but you're also consuming it, which is really bad.

Because what we and others have shown in my lab is that NAD levels are critically important for keeping these sirtuins and defenses at useful levels.

You can supplement with a lot of resveratrol, but if you don't have the fuel, you're basically speeding up a car without enough gasoline.

So, you need both NAD and resveratrol. That's what I do.

I take a NAD precursor called NMN (Nicotinamide mononucleotide), which the body uses to gradually make NAD molecules.

Through measurements of many individuals, we found that if you take NMN within the time period I take it (which I will discuss later), and you take it for about two weeks, the NAD levels in your blood will double.

Well, this is not public information. It's from clinical trials that haven't been published yet in the past two years.

There are other ways to increase NAD levels in people like me who are aging—I'm 52 by the way.

52 years old and still maintaining such youthful condition, Professor Sinclair truly deserves to be an expert in anti-aging.

Sinclair: You can also use NR (Nicotinamide riboside) for supplementation, to make NAD. Both NMN and NR can be purchased from companies in the United States.

NR is a phosphorous salt, which is a small molecule that the body needs. You might have heard of the atom phosphorus.

Let's take a step back. How is NR made? NR is typically made from Vitamin B3. You can also find it in milk and other foods.

But sometimes people ask me, why not take Vitamin B3? Doesn't it lead the body to produce NAD? The answer is no, it doesn't work very well. We know this from experiments.

But I think the reason is because of NAD itself. I mentioned that NAD is a small molecule, but it's relatively large compared to Vitamin B3.

It has those phosphorous salts on it, plus a sugar molecule, and it's attached to Vitamin B.

So, you put all these ingredients together and you form this very complex small molecule called NAD.

When you supplement with NMN, it contains all three components that the body needs to synthesize NAD.

If you only supplement with NR or just Vitamin B3—a smaller molecule—the body has to find the other components from elsewhere.

So, where do you get the phosphorous salt from? The body needs phosphorous salt to produce DNA, and it also needs it for bone production. I'm a bit concerned about something that requires such high doses of phosphorous salt.

We compared NMN and NR in mouse studies.

For example, a few years ago, we showed in a cell paper that mice ran farther on NMN, and older mice could run 50% farther because they had better blood flow and better energy.

But the same dose of NR had no such effect. In fact, it had no effect at all.


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