How High Intensity Exercise Might Create a "Metabolic Shield" Against Cancer

Ginny Robards
Ginny Robards
10 minute read
February 3, 2023
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We've known for some time that exercise is linked to lower risk of dying from cancer. And it seems that the more intense the activity, the greater the benefit.

I think some of the most persuasive evidence for this comes from research following professional and elite athletes.

When researchers in Paris analyzed data from 2814 French Olympians, from 1912-2012, they found that these athletes lived, on average, 6 and a half years longer than comparable individuals in the general population. When they investigated causes of death, they determined that the impressive longevity advantage enjoyed by Olympic athletes was mainly attributable to reduced likelihood of cancer.

This is further supported by a meta-analysis that included mortality data from a total of 42,807 professional/elite athletes. That analysis found that top athletes had a 27% lower risk of cardiovascular death and a whopping 40% lower risk of dying from cancer. In other words, people who spend the largest proportion of their lives participating in strenuous exercise seem to be remarkably protected from cancer mortality.

But interestingly, this may have less to do with reduced risk of developing cancer in the first place, and more to do with preventing it from spreading.

The Peril of Metastatic Cancer

You may already know that most cancers are categorized through a staging system, which characterizes both the size of the tumor and to what extent it has spread. 

Stages 0 and 1 indicate that the cancer is relatively small, and still situated where it initially sprouted. Stages 3 and 4 mean that the cancer has grown larger and has spread to surrounding tissues or to distant organs. Prognosis becomes much poorer as the cancer expands to distant parts of the body, and indeed the main cause of cancer-related death is metastasis. As an illustration of what a big difference this makes, the estimated 5-year survival rate for Stage I and II melanoma is more than 98%, but that falls all the way down to 30% for Stage IV melanoma.

Metastatic tumors are much more difficult to target due to their widespread distribution in the body, and they also tend to be more resistant to anti-cancer agents. That is why screening and early detection is so strongly emphasized, and why so much research has been directed at figuring out ways to prevent cancer from spreading.

Keeping Cancer at Bay

With that in mind, researchers affiliated with Tel Aviv University analyzed data from a random sample of 2,734 individuals extracted from the Israeli general population. These people were free of cancer at the start of the study, and were followed for 20 years.

Overall, physical activity was associated with a modestly lower likelihood of going on to develop cancer during the time that they were followed. However, when the researchers focused on cancer severity, the association became much stronger. Specifically, subjects who reported regular participation in high-intensity exercise had a 73% reduced risk of being diagnosed with metastatic cancer, compared to inactive counterparts. Wow! But the researchers were not satisfied with this finding. 

They wanted to know why exercise had this profound impact on metastases. And this is where the story gets really interesting.

A Question of Energy 

To gain some insight into underlying molecular mechanisms, the research team took a group of mice, and put some of them on a 12-week exercise program using a treadmill (rather than a running wheel). That way, they could control the speed, and force the rodents to engage in a consistent amount of high-intensity running.

During the study, they also implanted melanoma cells into some of the rodents to see whether, and to what extent, the cancer would spread, depending on their physical activity regimen. Sure enough, the animals that ran on the treadmill had significantly smaller tumors, and they also formed fewer metastases. Even when the researchers directly injected melanoma cells into the carotid artery — meaning that the melanoma cells could readily circulate through the blood to other parts of the body — exercise seemed to be protective against proliferation of these cells. Clearly something was making the body less hospitable for wandering cancer cells.

To figure out what was going on, the scientists carefully examined the internal organs of the exercising rodents. They zeroed in on the parts of the body where metastases typically are first found in both mice and humans, such as the lungs and lymph nodes. They noticed that the cells of all of the organs that they examined had more glucose receptors, and generally showed a boosted capacity for glucose uptake. They also found that these tissues had more mitochondria. Mitochondria, of course, are often referred to as “the powerhouse of the cell,” because they convert nutrients from the food we eat into usable energy in the form of ATP.

Overall, these cells had become more metabolically active.

Making Your Lymph Nodes Act Like Muscles?

It is already well established that intense exercise boosts the rate of sugar consumption by skeletal muscle. It also triggers an increase in the number of mitochondria in skeletal muscle in order to produce more energy to fuel intense activity. But until this study, these sorts of adaptations have never been seen before in organs like the lymph nodes or the lungs.

Taken together, it looks like high intensity activity transforms these organs into more efficient energy-consuming machines. In effect, it makes them behave more like skeletal muscle, at least from a metabolic standpoint. Why is this happening? Well, bear in mind that your lungs, lymph nodes, and other organs are powered by glucose. But when you are doing high intensity exercise, your hard-working muscles are getting first dibs. And when you train this way on a regular basis, your muscles get even better at soaking up glucose.

The researchers suggest that the metabolic stress of exercise reprograms the tissues of these organs to also take up more glucose, in order to compete with your sugar-hungry muscles. Now, here’s why that matters with respect to cancer progression.

The Metabolic Shield

Finally, the Israeli team analyzed tumor cells that had migrated over to these organs in sedentary animals, and compared them to those of the mice that had been training on the treadmill. Here, the trend was reversed — the melanoma cells from exercising mice were far less metabolically active.

This is a critical finding. You see, cancer cells need a lot of energy. In fact, one of the hallmarks of cancer progression is increased sugar uptake, which fuels uncontrollable growth and spread through the body. But if the cells that make up your lymph nodes are taking up more sugar, it basically cuts the supply lines to wandering cancer cells. This leaves them without enough fuel to grow in the regions of the body where they're most apt to proliferate.

In other words, the reason why melanoma cells in exercising individuals are less metabolically active is because they are being starved by surrounding healthy cells, which are consuming more carbohydrates. The researchers aptly characterize this as a “metabolic shield” against cancer.

Putting It Into Practice

This study suggests that exercise prevents cancer from spreading by reprogramming tissues throughout the body to ramp up sugar utilization, which in turn limits nutrient availability to malignant cells. But it’s important to remember that not just any physical activity will trigger these adaptations. 

Our body relies upon different energy systems depending on intensity. When you are performing low- to moderate-intensity activity, your body primarily burns fat for fuel. It’s only when you perform high-intensity exercise that your body switches over to carbohydrates. So brisk walking probably isn’t going to cut it here. 

If you’re not quite sure how to incorporate this into your own training, I have a suggestion. A nice program for high intensity interval training, and one that I use personally when training on a treadmill, is called Sprint 8. It is very time-efficient, but sneaky hard (don’t say I didn’t warn you). You start with a 3-5 minute warmup, followed by 8 rounds of 30 second sprints, punctuated by rest periods of around 90 seconds. Obviously, the sprint speed will vary from person to person, but it should be hard enough that you don’t feel like you could keep going longer than 30 seconds.

In just 20 minutes per workout, you can quickly boost your fitness and potentially help your body keep cancer at bay.

*Reminder and disclaimer: This generates a great hypothesis for how high intensity exercise can potentially combat metastatic progression in humans, but to date, there is no causal data to support this conclusively.

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