Dr. Rhonda Patrick: I think the biggest headline from this study was that vigorous-intensity physical activity was not just twice as effective as moderate-intensity activity. We're talking about anywhere from four times to almost 10 times better, which is pretty big.

First, when it comes to all-cause mortality, one minute of vigorous-intensity physical activity was equivalent to about four minutes of moderate-intensity activity. All-cause mortality means death from all non-accidental causes. You can get a bigger bang for your buck. Vigorous activity was four times as potent as moderate activity in reducing the risk of all-cause mortality. That's pretty big.

It gets even bigger when we look at cardiovascular-related mortality. This is a really important point because cardiovascular disease is the number one cause of death in the United States and many other developed nations, including many European countries. What I'm about to say will blow people's minds. I know it blew mine. For every one minute of vigorous-intensity physical activity, you had to perform 7.8 minutes, or almost eight minutes, of moderate-intensity activity to get the same reduction in cardiovascular-related mortality.

If you're thinking, "I'm spending 75 minutes doing intense, vigorous types of exercise, such as running or cycling. How much time would I have to spend doing moderate-intensity activity to get the same benefit for reducing my cardiovascular-disease mortality risk?" You'd have to multiply it by essentially eight. That's huge.

Another big one is type 2 diabetes. This one is not as surprising to me, and probably not to you either. For every one minute of vigorous-intensity physical activity, you had to spend about 9.4 minutes doing moderate-intensity activity. Vigorous activity was almost 10 times as powerful for reducing the risk of developing type 2 diabetes.

That is not so surprising because we know exercise intensity drives many of the metabolic adaptations and benefits that occur from exercise, including improvements in insulin sensitivity and blood-glucose regulation. But nearly 10 times is still nuts. Why is that?

I've talked a lot about why vigorous intensity seems to be key for improving metabolic health, including in a podcast or solocast on vigorous-intensity exercise. When you work harder, work your muscles harder, and force your muscles to produce energy more quickly, you are not using your mitochondria all the time. You will use your mitochondria, but sometimes you will also make energy without them. You then make something called lactate as a "byproduct," although it is not necessarily a byproduct. It is an active metabolite.

Why is that important? Lactate is not only a metabolite. In some ways, it acts as a hormone. It is a signaling molecule that signals other proteins and organs to work harder and respond to the hard work that is happening.

Vigorous-intensity exercise causes your muscles to contract. Muscle contractions can increase 50 to 100 times over rest. That's a lot. Those contractions force glucose into your muscle, which is a big sink for glucose. Your muscle must also transport that glucose across its membrane. That's where lactate comes in. When you're working hard, your muscles produce lactate. That lactate signals the muscle to increase GLUT4 transporters. These transporters bring glucose out of the circulation and into the muscle. Lactate signals an increase in the number of GLUT4 transporters or their translocation to the muscle-cell surface.

As activity becomes more intense, you bring in more glucose because more of those transporters are present. The transporters also remain active for a while. They are not present only while you're working out and then immediately go back. They stay active and continue bringing in more glucose.

It's unbelievable to think about how beneficial vigorous-intensity activity is when you're looking at almost 10 times the efficiency. I've seen a couple of studies showing that 15 minutes of vigorous-intensity activity can be equivalent to 45 minutes of moderate-intensity activity for glucose regulation. Other studies have shown ratios around one to five. But this study looked at outcomes, not just biomarker data. It looked at new diagnoses of diabetes and suggested an almost one-to-10 ratio. It was 9.4, so almost one to 10.

I think this confirms what we've seen in biomarker data from randomized controlled trials. We've had Marty Gibala on the podcast talking about many trials showing that volume-matched high-intensity interval training can improve insulin sensitivity, blood-glucose regulation, and other metabolic markers more than moderate-intensity continuous exercise. The ratio was not necessarily one to 10. It may have been one to three or one to five, but volume-matched high-intensity training produced greater improvements. Here, we're talking about an even larger difference when we look at an actual type 2 diabetes diagnosis.

Brady Holmer: I feel like it aligns with a lot of Martin Gibala's studies. His group has done sprint-interval training studies where people do less than 10 minutes of exercise per workout and compare that with a 45- to 60-minute workout. It almost aligns with what we're seeing in this study, including the one-to-10 ratio between sprint-interval training and moderate training in some randomized controlled trials.

The diabetes-risk signal was probably the most drastic, with that one-to-10 ratio of moderate to vigorous activity. Exercise is important, but movement throughout the day is especially important for glucose control. If you do a workout in the morning and do nothing for the rest of the day, you're probably going to be fairly insulin-sensitive throughout the day. But 10- to 15-minute bouts of movement throughout the day can be even better if you're trying to improve glucose control.

I think that's one reason vigorous exercise looked so beneficial in this study, which objectively measured every type of physical activity people performed. If you move more throughout the day, you have better glucose control. You're likely to have better long-term outcomes for diabetes risk, including lower HbA1c, better insulin sensitivity, and lower fasting glucose. I think that's why this shows up in the actual outcomes, which are probably more important to most people than biomarker data.

Dr. Rhonda Patrick: Right. Exercising throughout the day makes a lot of sense. This study, published in Nature Communications, picked that up because of the accelerometer data. But I also want to emphasize lactate signaling. With vigorous-intensity exercise, it is not just a muscle-contraction, glucose-in effect. The GLUT4 transporters remain active and ready for a longer period during the day, perhaps somewhat into the next day, and definitely for 24 hours. I think that's another powerful effect of exercise intensity.

We also know that when you engage in more vigorous-intensity exercise, lactate signals to another protein called PGC-1α, which is responsible for the growth of new mitochondria. This is mitochondrial biogenesis, and it occurs in your muscle cells. It improves the metabolism of glucose and other substrates, such as fatty acids.

I think there is a long-term effect. If we're looking at type 2 diabetes, we're not just looking at biomarkers. You might not necessarily pick it up if you're only looking at blood-glucose regulation or insulin sensitivity. But over several years, if you have more healthy mitochondria on top of improved glucose regulation through the glucose transporters, you're probably also going to see a healthier metabolic profile.

Brady Holmer: For sure. Unless you were measuring with a continuous glucose monitor, you might not see that. I don't know how much stock to put in a fasting biomarker, such as fasting blood glucose, measured only once a year. What does that really mean? Now that we have access to CGMs and related technology, I think you could see it in that data.

Dr. Rhonda Patrick: Right. We do not have good biomarkers for mitochondrial health. That has not been translated to the clinic yet, although researchers can measure it and do.

Some of the studies Marty Gibala previously cited on the podcast found that, for volume-matched exercise, high-intensity interval training was better at increasing mitochondrial biogenesis than moderate-intensity exercise. Again, it has to do with a stronger stimulus causing the adaptation. When you force your muscles to work so hard that they cannot produce all the energy they need using mitochondria alone, they must also use glucose without mitochondria. Your muscle is like, "Dude, I need more mitochondria. This isn't working." That's an adaptation that happens, and it makes sense.

I've received many questions from people who thought Zone 2 training was best for mitochondria. It depends on what we're talking about. Zone 2 does increase mitochondrial biogenesis. But if you become more vigorous, you can get a stronger stimulus. Vigorous activity excludes Zone 2 in what we're discussing here. Generally speaking, the more intense the stimulus, the greater the adaptation, to a degree. Obviously, you don't want to go to the complete extreme where all you do is work out.

Brady Holmer: I'm not going to say that's all you do, but you definitely work out a lot. Sometimes it seems like that. My wife will tell you that sometimes it seems like that.