Dr. Rhonda Patrick: I think it is clear that we are dramatically underestimating the value of vigorous-intensity physical activity for reducing the risk of many negative health outcomes. The question is why. We have talked about adaptations to physical activity on the podcast with exercise physiologists such as Dr. Benjamin Levine and Dr. Martin Gibala.

I want to start with cardiovascular health and the adaptations that occur in the cardiovascular system because this is probably one of the most important concepts. It comes down to the idea that a stronger stimulus produces a greater adaptation. You can take anything to an extreme. Exercising nonstop would not be good, but that is not what we are talking about.

Remember that one minute of vigorous physical activity was equivalent to almost eight minutes of moderate-intensity physical activity for cardiovascular mortality. That is a big difference. One of the major adaptations comes down to increased blood flow. Getting your heart pumping and your blood moving causes shear stress on the interior lining of your arteries. Shear stress is the friction of blood flow against the vascular system.

The more vigorous the exercise, the faster your heart pumps and the more your blood flow increases. That produces stronger shear stress. This is not a bad type of stress. It causes the endothelial cells lining your arteries to adapt in ways that improve vascular and endothelial function. It also causes endothelial cells to secrete beneficial molecules, including nitric oxide and prostacyclin. Both compounds cause vasodilation and improve blood flow.

As you repeatedly produce this shear stress over time, you improve the flexibility of your arteries and make them more resilient. They can handle stress better, function better overall, and become more resistant to atherosclerosis. I think this is at the crux of why vigorous-intensity exercise is so beneficial for cardiovascular health.

Dr. Levine has discussed the stronger cardiovascular adaptations that can come from more vigorous-intensity exercise. In his study of middle-aged adults, he put people around age 50 on an exercise program that would be almost entirely vigorous according to the definition used in this study. How much was it, five hours a week?

Brady Holmer: About five hours a week.

Dr. Rhonda Patrick: Five to six hours a week, I think. According to the definition in this study, it was almost entirely vigorous because they were running, doing a Zone 2-type run, doing Norwegian 4x4 intervals, doing some high-intensity interval training, and including some resistance training. After two years, they reversed the structural aging of the heart by about 20 years. That is profound. The cardiovascular adaptations are real.

Brady Holmer: If you read randomized controlled trials comparing moderate-intensity training with high-intensity interval training, the effects on endothelial function and arterial stiffness are not even close. Even when researchers match the exercise volume, high-intensity interval training consistently produces greater improvements in vascular function.

It comes down to the shear stress you mentioned. Higher intensity creates more shear stress. Shear stress almost sounds like a bad name because it sounds harmful, but you do want more of it in this context. It is not simply a dose-response relationship or an area-under-the-curve effect. You cannot just do more low-intensity exercise because the intensity of the shear stress, rather than only its total amount over time, matters for those endothelial adaptations. High-intensity interval training is important in that respect.

Dr. Rhonda Patrick: That is a good point. It is like comparing a light breeze blowing across your face with a strong wind. A light breeze can last a long time, but it will not knock over trees. You need the stronger wind.

That is what you need with shear stress in your vascular system. It must be strong enough to signal to your body that this is stressful and it should respond. It is not so stressful that it is like a heart attack. It is just enough to produce adaptations so that your arteries and vascular system respond better when highly stressful situations occur.

I want to return to shear stress because it also plays a role in some of the mechanisms behind the reduction in cancer mortality. Dr. Kerry Courneya discussed this on the podcast. The reductions in cancer-related mortality were not as large as the type 2 diabetes risk reduction, but they were still significant. For each minute of vigorous activity, you would need about 3.5 minutes of moderate-intensity activity to get the same modeled reduction.

There are probably many mechanisms, but one is especially interesting. The shear stress that improves endothelial function and the function of your arteries and blood vessels may also help kill cancer cells. When a person has a primary tumor, the cancer cells do not necessarily remain at the tumor site. Cancer cells can escape through the lymphatic system and enter circulation. Once in circulation, they are called circulating tumor cells.

Circulating tumor cells are not like normal red or white blood cells. They have many mutations and are primed to die. They remain alive because they have increased proteins that stop cell death. There is a balance between proteins that promote cell death and proteins that prevent it. When the balance shifts toward cell death, the cell dies. If anti-apoptotic proteins remain elevated, a damaged cell can survive even when it otherwise should die.

This helps explain why chemotherapy and radiation can effectively kill cancer cells. These treatments create a major stress and a strong death signal for all cells. Cancer cells already carry substantial pro-death signaling, with anti-apoptotic signaling keeping them alive. Unfortunately, such treatments can also kill normal cells because the death signal is strong.

Circulating tumor cells are ready to die. I studied cancer in graduate school, so I know I went on a tangent. These cells have mechanosensors on their surfaces and are very sensitive to mechanical forces and movement. That can act as a death signal. The shearing forces of blood flow create friction against these cancer cells. The cells respond to that stress and die. This has been shown in vitro.

Physical activity among people with circulating tumor cells is associated with a lower likelihood of cancer recurrence or metastasis. Why are circulating tumor cells so dangerous? Imagine that a person had cancer and was successfully treated with chemotherapy, radiation, surgery, or some combination. The visible tumor may be gone and the person may be in remission. In the clinic, however, we do not perform single-cell analysis of every organ to ensure that not one cancer cell remains.

Individual cells can escape into circulation and travel to another organ, such as the liver. It might take two, three, or four decades before symptoms appear. Cancer recurrence can occur in another organ or even in the same organ. Circulating tumor cells can play a role in metastasis to other organs and recurrence in people whose cancer was treated successfully.

Shearing forces matter because they can kill circulating tumor cells. That is associated with improved outcomes for cancer recurrence and mortality, and it is reflected in this study's association between vigorous-intensity physical activity and lower cancer mortality.

That was a long explanation, but cancer is a passion of mine. Other mechanisms are probably involved, but I like the shear-force mechanism because people do not often think about it. Once you hear it and think about it, it makes sense.