The Science of Metabolic Flexibility, Zone 2, and Reversing Diabetes | A Masterclass

Iñigo San Millán (0:09)

I tested once in the laboratory an 81-year-old gentleman who was world champion, cycling world champion of the 80 to 85-year-old bracket, which believe me, it exists, right? Which is great to see, right? So anyways, I was fascinated because his metabolism, his metabolic efficiency during the test that I do was that of someone in their 30s or 40s, healthy and active, right? It was unbelievable.

I keep that test like a treasure, right? Because it's an absolute treasure to see those adaptations, right?

So anyways, right away, I thought, boy, you've been doing sports all your life, right? So man, you chose the right lifestyle, right? And he told me, actually, no, actually, until I was in the early 50s, I was obese, I was hypertensive, I used to smoke, I had a very poor lifestyle, I didn't exercise at all. And one day I started to ride and bike and think about life and things like that. And ever since then. So to your point, like you said, right, this was an individual, the early 50s, sedentary, very poor, healthy lifestyle. And then, whoop, you know, 30 years later, at 81 years old, his metabolic health was that of someone in their 30s, whose health was unbelievable, hard to believe in. And this is how that person, obviously, 81 year old, that's an example of what exercise can do for your longevity, right? That person was not on any medication.

Simon Hill (1:57)

What is your definition of metabolic health and why should the listener care about this?

Iñigo San Millán (2:03)

Yeah, that's a good question. And I think this is something that we're understanding more and more, right?

As you know, and many people know, right, the traditional definition of metabolic health is like a compendium of the multiple parameters like your lipid profile, your blood pressure levels, your glucose levels, right, and your body max index or at least your waist ratio. So circumsperence, sorry. So but as we know more at the adaptations or what happens at the cellular level, right, we are getting to an inflection point in the field of medicine where metabolism has gone from being the poor brother to being the crown prince, right? I mean, you look at the curriculum of medical schools, even still today, they barely have any courses or notions of metabolism at the cellular level. While at the research level, the advances have been immense, that we can already use to help people, as well as to understand diseases at a level that we have never been, right? So this is why metabolic health implies more mitochondrial function in place, also more fitness in place, longevity, right? So people nowadays are not happy just to have good cholesterol levels, right? Or good blood pressure, right? Or good A1C or glucose levels, right? People want to be fitter, want to live longer, not necessarily in the amounts of years, because we all want more, but to live better, right?

And want to be healthier. So all this, I would put it in the new basket, if you will, of metabolic health.

Simon Hill (4:08)

A lot of your work seems to focus on how efficiently we can take the, I guess, potential energy in food, be it carbohydrates or fat, and turn that from a chemical energy into a mechanical energy, contract the muscle and move the skeleton. Do you also consider sort of fuel partitioning?

I'm interested in some of Professor Roy Taylor's work. I'm not sure if you're familiar with him and his work looking at type 2 diabetes and this concept of personal fat threshold being sort of integral to metabolic health, in that once we kind of spill over or store fat beyond our subcutaneous fat capability, it starts to get in between and within organs, and that seems to also be a sort of key component of metabolic health.

Iñigo San Millán (5:09)

Yeah, absolutely. There's no doubt about it. That's a big component. Abdominal fat is highly associated with our cardiometabolic disease and also there's more and more research. One of the leading researchers is a my colleague here at the University of Colorado, Dr. Brian Bergman with his research in intramuscular fat, which is highly... And others, right? They have been doing research, extensive research on this, linking that intramuscular fat with insulin resistance and type 2 diabetes as well. So, yeah, definitely fat.

The connection between fat and metabolic disease is there for sure.

Simon Hill (6:01)

How much of the sort of cardiometabolic disease burden that we see today, do you feel is explained by sedentary lifestyles and a lack of specific cardiovascular training versus other things like nutrition, which you just mentioned?