And here we're talking about things that are relatively low time investment, certainly don't have much financial cost in the sense that they could be done in gyms and with fancy equipment, but they don't require that.

Again, I want to point out that these are not like strict prescriptives, but if you had a magic wand, and because you are interested in the health of humans, let's talk about a few of these things that can improve glucose disposal and mitochondrial function, mitophagy, the removal of dead or dysfunctional mitochondria so they can be replaced.

Let's talk about the walking one first.

You said 7,000 steps a day.

I don't track my steps.

What are we really talking about there?

We're talking about taking the stairs and trying to walk as much as possible.

We were going to just give a really crude prescription.

You're a doctor, so you can prescribe things.

What would you tell people to do?

How many short walks per day?

Is it three?

Is it five?

What are we talking?

I would say at least three.

I would say aiming for more than that is good, though.

So to sort of just give a sense of the picture of walking, if walking were a pill, it would be the most impactful pill we've ever had in all of modern medicine.

There was a paper in JAMA, 6,300 participants followed for 10 to 11 years, and the people who simply walked 7,000 steps per day compared to less than that had an up to 70% lower risk of all-cause mortality in the follow-up period.

So not causality, but it's pretty incredible.

They've done follow-up research with slightly different numbers showing, again, though, like many thousands of people in the study followed for about 10 years, 8,000 to 12,000 steps per day was associated with 50% to 65% lower all-cause mortality.

And this has been played out in many studies showing about a 50% reduction in Alzheimer's, dementia, obesity, type 2 diabetes, depression, cancer, gastric reflux, just all across the board.

And I think the key thing is that it's not about the steps.

It's about the fact that muscle contraction is medicine.

When we contract our muscles, even in a very like low-grade way, like walking or doing a couple of air squats, we're activating AMPK, and we are essentially causing that cell to have a stimulus to push glucose channels to the cell membrane.

Most of the time, the glucose channels are like in vesicles, in little bags inside the cells.

They're not on the cell membrane.

So, of course, that's going to keep the glucose in your bloodstream not being processed by the mitochondria.

So when we think about steps, it's a proxy metric for just moving more throughout the day.

So let's take two people.

You have a person who's walking for 1 to 2 minutes every 30 minutes throughout the day.

Maybe they're exercising at the end of the day or the beginning of the day.

Maybe they're not.

That person is stimulating glucose channels to be at the membrane all day.

Now let's take another person who works out really hard for one hour in the beginning or the end of the day.

They feel great about it.

They're not going to reject that off their box, but they're sitting the entire rest of the day.

Yes, they have gotten the benefits from the exercise, but for a lot of that day, those glucose channels are inside the cell, not doing the work they could be doing.

So I think about these little teeny short walking breaks or push-up breaks or air squat breaks every 30 minutes or so throughout the day as me essentially inside the cell pushing the glucose channels in the cell membrane to make them constitutively active.

It's totally different physiology, and it's so easy.

So it's not about the steps.

It's about muscle contraction regularly throughout the day, and this has been shown out in actually more clinical research, which has taken – there's been several studies, two that I think are fascinating where they basically took two groups and they said, okay, we're going to have you walk 20 minutes before each meal three times a day, 20 minutes after each meal, so that's also three times a day, or for like 2 minutes every 30 minutes throughout the day.

So these are three separate groups.

Three separate groups.

So it's either 20 minutes before, either 20 minutes after, or?

Two to three minutes every 30 minutes, all added up to 60 minutes of walking or light jogging a day.

I'm kind of paraphrasing two different studies that showed the same thing.

One was jogging, one was walking, but it was basically chunks versus short walks every 30 minutes throughout the waking day.

The groups that do the short movement regularly throughout the day, even though the total time is the same across all the groups, have significantly lower 24-hour glucose level averages, 24-hour insulin level averages.

They are metabolically healthier, and I believe, and the research mechanistically has shown that it's because we're constitutively putting these channels of the membrane to take up the substrate, use the substrate.

So this is not to replace exercise, but I think it's a reframe.

I think the concept of exercise is something we're really very wedded to in our Western culture, and you look at more like the Blue Zones and the Centenarians, and it's like they're kind of moving as built into their everyday life.

So we've taken movement out of our everyday life as these knowledge workers, as we've been industrialized, and then we think that exercise replaces that all-day movement.

But biochemically, it does not.

So I think a big part of kind of digging ourselves out of this chronic disease mess and creating capacity for mitochondria is finding ways to take a lot of the activities we do now seated and just find a way to do more of them moving, standing, or walking.

Or if that's tough, you really need to sit at your desk all day, then every 30 minutes taking two minutes to do some just light movement, flex those muscles, get the glucose channels of the membrane, get the mitochondria active.

And I think another fascinating stat is our gym memberships in the U.S. have doubled since the year 2000, and obesity has gone up in the same period.

So there's some mismatch between our obsession with exercise and our actual outcomes that we're seeing, and I think it's that we have not actually rebuilt constitutive movement into our daily lives.

Very interesting, because I think a lot of people are now working out, so to speak, doing resistance training, which I think is terrific.

Terrific, yeah.

It used to be so restricted to niche subculture stuff like bodybuilding, pre-season football, military, et cetera, and now it's more ubiquitous for everybody, men, women, young, old.

It's terrific.

Same thing with things like yoga and cardiovascular training.

I mean, I like to study the history of exercise culture, and it wasn't but in the 60s when jogging was considered kind of like, whoa, that's like a really esoteric niche culture thing.

So lots changed.

I love the prescriptives you gave, because it's just very straightforward.

A couple of short walks, it just makes so much sense.

And I love the visual, and I hope people will really hold it in mind, so I'll reiterate it.

The translocation of these energy utilization stores, vesicles, as you call them, these little packets from the center of the cell out to the cell surface, where then they can be involved in metabolic processes and the utilization of energy in ways that otherwise they wouldn't, and glucose disposal being a big part of this.

So I have heard that a short walk after a meal will reduce blood glucose in a way that's really dramatic.

Huge amount, 30%, 35% just taking a walk around the block after a meal.

That's definitely a prescription I think everyone should do, because the research is so strong on it, is that building in simply a 10-minute walk around the block or a dance party in a kitchen, moving your muscles for 10 minutes after a meal, can drastically reduce your glucose response.

Because you're just bringing all those channels to the membrane, you're taking up the glucose, you're using it.

It's a whole different physiology than sitting on the couch after a meal.

That's very high impact, it's high leverage if it's after a meal.

So highly recommend that.

And the levels data and clinical data has shown that out time and time again.

Whenever I go to a city like New York, when I am forced to walk more, I always just feel so much better.

We also know that the optic flow that one experiences with walking has some interesting effects on the limbic pathways and quieting of some of the anxiety and stress-related pathways.

This links up with things like EMDR, although there are factors that are separate from EMDR.

Basically moving through space, not outer space, but walking through space with optic flow has a certain anxiety reduction function in the brain, which there are beautiful data there, in my opinion.

Okay, so that touches on walking.

You did mention higher intensity exercise.

So let's keep it within the cardiovascular realm for now.

So getting heart rate way, way up, breathing hard for some minutes each week, maybe a couple times per week, seems that's a good way to increase mitochondrial function and mitochondrial number.

Is that right?

Yeah.

So you take sort of each type of exercise.

We've got walking, we've got resistance training, we've got high intensity interval training, we've got endurance training, and then we've got sort of more like zone two.

So we've got these different flavors of how we get our heart rate up, how we get the blood flowing, what we signal to the cells.

And each one actually has like a slightly different impact on the mitochondria.

When we think about biogenesis, we're thinking mostly like endurance exercise and really more of that zone two.

And like that is really going to be a stimulus inside the cell to print more mitochondria.

When we think about improving mitochondrial fusion, high intensity interval training is really, really good for that.

When we think about resistance training, it's like that's like muscle hypertrophy.

We're going to be creating more muscle cells and we need more mitochondria for those.

So each one has kind of a different impact.

And I think this is where, honestly, I think the regular guidelines that we have even by our government actually make a lot of sense.

It's like work every major muscle group three times a week in a resistance type training and then work to get 75 to 150 minutes of moderate to strenuous activity.

So 75 minutes of strenuous activity or 150 minutes per week of moderate activity.

So that actually makes a lot of sense.

80% of Americans are not meeting those very basic guidelines and 20% of Americans don't get any physical activity really at all.

Activity for the average American is 3,000 to 4,000 steps per day, which is less than two miles.

So we are not even close to even meeting the basic recommendations that are out there.

But I think those are pretty reasonable.

Resistance training two to three times a week, most major muscle groups, and working to get the heart rate up moderate level for 150 minutes a week or strenuous for 75 minutes a week.

Those are going together to be potent stimuli for biogenesis, mitophagy, mitochondrial fusion, for increasing antioxidant enzymes that are going to protect the mitochondria from that oxidative stress.

The one that's just actually not in there, in sort of the basic recommendations for Americans, is the walking.

I would just absolutely add to that at least 7,000 steps per day based on what the data is showing, which honestly would probably take less than an hour total to do.

If you break it up throughout the day, it's just a few minutes a day.

So that right there are going to be like a big multifaceted set of signals for increasing mitochondrial capacity in different ways.

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