Fibroblast growth factor 21

So that's why these drugs are quite differently and, and we probably see both trials and also in the clinic that these can, when needed, be combined.

There's a whole new class of drugs which is also coming, the FGF21 analogs, which I think also brings a lot of hope because some of these we recently saw signals that even in advanced in stages with cirrhosis, there's reversal of cirrhosis.

I say, "Oh my God, this is really kind of a breakthrough that you see suddenly, okay, can we with drugs move people down from, let's say, a very dangerous place to a, a less dangerous place, and then it sort of spreads out." So now you have-- It's not comparable to the obesity.

You know, obesity, you have 40 whatever different assets, but here you still have a lot and a lot of phase three trials.

So I'm quite enthusiastic there that when there's so many players, it's very likely that we will be able, for the individual patient sooner or later, to find something that they can all tolerate, and they can all will benefit them.

What was the name of those analogs?

analogs?FGF21, [laughs] fibroblast growth factor one.

So there are different assets being de-developed by the big, different of the big companies now entering phase three, which has, yeah, shown again the strongest, I think, at least now it's a phase two signal, so we have to be a little bit careful because the s- the signal we've seen in phase three with, with semaglutide and resmetirom, but seems again and again the signal on, on cirrhosis, which is quite, I think, brings a lot of optimism to, to this and, and also to, to some of the other similar molecules.

I'm a sugar addict.

So when somebody gave me the green light and explained to me the FGF21 hormone... where sugar in the absence of protein and fat makes your body boost your metabolism, makes you lose weight.

And it's the same way with fat in the absence of protein and sugar.

And when I heard that, I was like, well, first of all, that's why fat fasting works.

And again, we see this very classical dose response where we have superiority against a placebo.

Now the FGF21 targeting agents, especially if we look at the impact of the harmony study on mesh, and I want you to focus on the far right where we have fibrosis improvement of at least one stage and mass mesh resolution.

Again, a very nice dose response, either in the 28 milligrams or the 50 milligram dose, where we also see superiority above placebo.

And remind you, this was in patients with MASH with at least F2 or F3 fibrosis.

There are also newer signals in the conversation.

Biomarkers like GDF-15 and FGF-21 get mentioned as possible indicators related to mitochondrial stress or metabolic strain.

But, and this is important, measuring mitochondrial health in humans is hard.

You can't just look at one number and declare someone's mitochondria good or bad.

And what's this hormone called?

Uh, it's called FGF21.

FGF...

Okay, I understand why you didn't, uh-

No, I, I couldn't agree more.

Um, you know, while, while we're just on the protein topic, um, One thing I also want to touch on is some of these very low-protein diets or protein-restrictive diets or leveraging FGF21.

You've seen guys like Mark Bell in the last couple of years popularize this sugar diet where you're basically consuming very low protein and high amounts of basically just carbohydrates via sugar.

I know you've maybe experimented with this a little bit or taken a slightly different approach to it, given a different – name can can you speak to this a little bit

And it might be more than that because they're measuring that after three days of doing it.

immediately after a meal it might actually be even higher than that so spiking this hormone it's massively it's causing all this um basically mitochondrial uncoupling which is just fancy way of saying your body is wasting all its energy it's consuming right so you can't actually use it for um everyday functions so you've got this massive metabolic debt that gets created And then, but it's really, really fascinating because it actually, and this was like, someone was commenting this on Instagram.

I quoted this paper and he was like, hold on, that paper says that FGF21 blocks lipolysis at the fat cells.

So it actually stops fat cells converting to fatty acids to be burnt.

The, the cellular biology and the proposed mechanisms are, are definitely worth noting, but with caution and context.

The longevity argument in this paper rests primarily on two cellular pathways: mTOR suppression and FGF21 activation.

So mTOR, mechanistic or formerly called mammalian target of rapamycin, is a cellular signaling pathway that regulates growth and metabolism.

Lower mTOR activity is associated in certain animal models with longer lifespan.

So the argument goes that eating less protein lowers mTOR activity and may extend lifespan.

That's the argument.

FGF21, or fibroblast growth factor twenty-one, is a metabolic hormone that responds to protein restriction and has been associated with various metabolic benefits in animal research.

So these are real mechanisms worth studying.