A New Theory on Exercise’s Anti-Cancer Effect

Last fall, an international group of exercise oncologists published a major review of the literature on exercise and cancer. The news was good, if somewhat unsurprising. Regular exercise lowers your risk of developing a long list of cancers, in some cases by 10 to 25 percent; and if you do get cancer, exercise enhances the quality and possibly the expected length of your life.

But there was one notable omission from the review. The experts weren’t entirely sure how or why exercise has such a powerful effect on cancer cells. There are plenty of theories involving things like hormone levels, blood sugar, chronic inflammation, and oxidative stress, but no one has put all the pieces together.

It’s in that context that an opinion piece in the journal Trends in Cancer recently appeared, from a group led by Peter Biro of Deakin University in Australia. Biro and his colleagues propose a new theory in which the link between exercise and cancer is explained by what they call “energetic capacity.” In short, fit people are able to ramp up and sustain high levels of energy consumption, which gives them the ability to mount a more robust immune response when cancer cells attack and also helps them to withstand the energy-sapping effects of tumors that do get a foothold.

This is a hard theory to test experimentally, but the researchers explore four predictions that follow from their idea.

We All Have a Different Energetic Capacity

This may seem like a no-brainer, but it’s worth unpacking what they mean by energetic capacity. We get our energy from food, so in theory you might think that if it takes extra calories to fight off cancer, you can just down a few more sandwiches. But as a recent paper by Herman Pontzer and John Speakman argued, there are limits to how much energy our bodies can process. You simply can’t burn 10,000 calories a day, no matter how much you try to eat.

It’s also clear that some people can burn more energy than others, and that these differences are in part heritable. That means that if you’re in a situation where your body needs all the energy it can get, and it needs to sustain this output for days or weeks, some people will be able to handle this challenge better than others.

Your Energetic Capacity Is Linked to Your Metabolic Rate

Biro and his colleagues focus on two proxies for energetic capacity, since it’s impractical to actually measure total energy consumption over long periods of time. One is VO2 max, the gold-standard measure of aerobic endurance, which he refers to as “maximum metabolic rate.” The other is resting metabolic rate, which is basically the rate at which you burn calories when you’re asleep.

Interestingly, they argue that the two are closely linked, despite being at opposite ends of the spectrum. If you’re an endurance machine, then your engine—the organs involved in converting food into energy, such the heart, lungs, liver, and intestines—is bigger and requires more energy to maintain, even when it’s idling. The paper cites a series of earlier studies, on both animals and humans, showing that resting metabolic rate is correlated with maximum metabolic rate.

Exercise Causes (and Is Caused by) High Energetic Capacity

Nobody reading this will need much convincing that regular exercise raises your VO2 max and allows you to sustain higher energy outputs for longer periods of time. This is called training. But there’s also evidence pointing in the other direction, both in humans and (more compellingly) in rodents. If you’re born with a high metabolism, you’re more likely to spend your time spinning the exercise wheel in the corner of your cage or racking up KOMs on Strava.

Admittedly, the evidence is a little less clear-cut here. Some studies find that endurance training has no effect on resting metabolic rate, which conflicts with the idea that resting and maximal metabolic rates are linked. Still, the overall connection between exercise and energetic capacity—in both directions—seems clear.

High Energetic Capacity Helps You Fight Cancer

This is the crux of the argument. Cancer cells trigger an immune response that attempts to prevent such cells from transforming into an invasive cancer. This immune response costs energy, and tumors that do get a foothold also siphon off substantial amounts of energy. These energy costs, according to the new theory, are so high that they may push your energetic capacity to its limit.

The evidence for this claim comes mostly from rodents. For example, when mice follow an exercise program before having cancer induced, they’re able to produce more immune cells in response, and the cancer is less likely to develop. Conversely, exercise shortly after being infected produces a lower immune response, presumably because you don’t have enough energy for both challenges.

That’s how the pieces of the new theory fit together. While there are no direct tests of the overall argument, there are some intriguing hints scattered throughout the literature. For instance, when VO2 max was measured in 1.3 million Swedish men when they were teenagers, those who scored highest were 20 percent less likely to later die of cancer. Of course, this could also be because the fittest subjects were most likely to keep exercising throughout their life, and that had some other effect on inflammation or oxidative stress or blood sugar or whatever. There’s no smoking gun for the energetic-capacity hypothesis here.

Still, it’s an interesting idea, with a couple of possible implications. One is that the optimal amount of exercise for health purposes depends on your current level of fitness, since you don’t want to use up all of your energetic capacity in your workouts. More isn’t always better. To be fair, most coaches figured that out a long time ago, though athletes don’t always listen.

Another implication is that your actual fitness is more important than how much exercise you get. That dovetails with an idea endorsed by the American Heart Association a few years ago: that doctors should routinely check (or at least estimate) their patients’ VO2 max in the same way they check blood pressure. It also parallels data from the National Runners’ Health Study showing that a 10K race time is a better predictor of future heart disease than how much training you do. That makes Biro’s theory one of those ideas that I’m tempted to believe, even though the evidence isn’t really there yet, because it gives me the jolt I need when I’m heading out the door for a run. The goal isn’t to punch the clock and rack up a certain number of training hours—it’s to get faster tomorrow than I am today.

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