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The Neuro Experience
Neurophysiologist: Why 30 Minutes of Exercise Changes 13 Types of Cancer
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But cancer. I'm petrified of cancer. It's just so scary to know that we don't know where it's hiding. Most people are never given a clear explanation of a, what cancer actually is, B, how it progresses. Why Metastasis is the reason that most people die from solid tumors. The lethal part is when cancer cells escape, they travel and then they establish new tumor in organs like the liver, the lungs, the brain. Cancer cells don't teleport to metast. They have to physically enter circulation, survive a hostile journey, evade immune surveillance, and then successfully colonize a new environment. That means that metastasis is not just a growth problem, it's a survival and trafficking problem. One of the most interesting lines of evidence involves circulating tumor cells and shear stress. As shear stress increased, survival of circulating tumor cells decreased and. Oh, my God. This is probably most favorite part of the entire episode. I'm Louise Nicola and this is the Neuro Experience. All right, team, we need to talk about cancer and exercise. And I want to be really clear about why we're having this conversation because there's a version of this topic that gets communicated in a way that's either overly motivational or overly simplistic. And both of those approaches miss. The most important factor, which is exercise, is not a vague, healthy habit in the context of cancer. It's a physiological signal that changes the environment that cancer cells are trying to survive in. Now, the reason why I'm doing this episode is because cancer is one of the most common and feared diagnosis in the world, and yet most people are never given a clear explanation of A, what cancer actually is and B, how it progresses, why metastasis is what kills people. And then once you understand that biology, where exercise fits into this picture, into this puzzle in a way that's evidence based rather than just hopeful. And, you know, you know, I study Alzheimer's disease. Alzheimer's disease is the number one killer amongst women in both Australia and the uk. Quite personally, quite transparently, I'm not scared of getting Alzheimer's disease because I know I'm in control. I know it's a preventable disease and I know what to do. And obviously it's my entire life's work. I know what to do in that aspect. But cancer, I'm petrified of cancer. It's how I lost my grandmother, it's how I lost my mother's sister. And it's just something that scares me. I know it's not in my control. And as an intraoperative neurophysiologist, I see Cancer every day, cancer of the brain, glioblastoma. And I see it, so I'm around it. And it's just so scary to know that we don't know where it's hiding. We don't have imaging yet that can show up, you know, of certain types of cancer. I'm not talking about breast or prostate cancer, but, you know, pancreatic cancer, ovarian cancer. These cancers are often diagnosed in stage four. So it scares me a lot. And I'm always looking for ways to if we can prevent it. And I've come across a large body of evidence to suggest that there is a real strong link and correlation between exercise and cancer cancer. And it turns out that we only really need 30 minutes a day to down regulate 13 types of cancers. So here's exactly what we're going to cover today, and I'm going to do it in a step by step way, because if you don't build the foundation first, the exercise part sounds like a claim rather than a conclusion. So first, I'm going to explain what cancer is in plain language, what it means when someone says a tumor is local versus metastatic, why treatments work when they work, and why treatments fail when they fail. And I'm going to spend extra time on metastases because that's the part of the story most people don't fully understand, and it changes how you think about prevention and treatment. Second, once we've built that foundation, I'm going to walk you through the evidence linking exercise to cancer outcomes, and I'm going to separate this into three buckets. So. So it's easy to follow because the data is very different depending on the phase we're talking about. But we're going to start with prevention, meaning what we know from large population studies about whether physically active people get less cancer over time and which cancers show the strongest associations. Then we're going to move into exercise during treatment, meaning randomized controlled trials in people receiving chemotherapy or radiation, where researchers look at fatigue, treatment tolerance, dose reductions, function, and in some cases, tumor response. And then we'll talk about survivorship and reoccurrence, meaning what happens after primary treatment is done, why reoccurrence is psychologically brutal, part of the cancer experience, and what the evidence says about exercise and risk of the cancer coming back. Thirdly, if you stay with me and if you've got a pen and paper, once we've covered the human outcomes, I'm going to finish with mechanisms, because, well, the question to me isn't just how does Exercise help. It's always, how could exercise plausibly influence cancer biology? And that's where we'll walk through everything we know about blood flow, tumor, oxygenation, immune surveillance, muscle mass, metabolic signaling like insulin and IGF1, and one specific mechanism that I think is underappreciated, which is the mechanical stress that exercise creates inside the bloodstream and what that may mean for circulating tumor cells. I hope you stay with me through all of this, because it's not credible to pretend exercise is always beneficial in every context. We need to be honest about limitations, about where evidence is observational rather than randomized, and about situations where exercise needs careful modifications. So I'll go into all of that. So let's talk about cancer itself, because if you don't understand the disease, you can't understand why exercise matters. Cancer, in the simplest language, is a breakdown of normal cellular rules. Every cell in your body is supposed to follow instructions. When to grow, when to divide, when to repair, and when to die. A healthy cell has breaks, it has self destruct mechanisms, and it listens to the environment it's in. Cancer is what happens when a cell accumulates changes like genetic mutations and epigenetic changes that allow it to ignore those breaks, avoid self destruction, and keep dividing when it shouldn't. Now that's the initiation part. But initiation alone doesn't explain why cancer is so dangerous. Because a small cluster of abnormal cells is not automatically lethal, right? We know that cancer becomes dangerous when it gains the ability to invade nearby tissues, and then more importantly, when it gains the ability to spread to distant organs. What is that called? That spread is metastasis. And you can think of this as stage one cancer. It forms in a certain area of the body, and then when parts of that tumor break off, and we call those little parts circulating tumor cells, and they travel through the bloodstre and they collect and form and they go to another part of an organ system of the body that is what we call metastases. Metastasis is the reason that most people die from solid tumors. If someone has early stage breast cancer, for example, and it says, and it stays in the breast, the breast itself is not a vital organ for survival. And the same idea holds for prostate cancer and several other cancers. So the lethal part is not the primary tumor sitting in the original tissue. The lethal part is, is when cancer cells escape, as I mentioned, they travel and then they establish new tumor in organs like the liver, the lungs, the brain, or the bone. Because those organs are what you cannot lose. That's what gets Me, that's why it's so scary, right? So when you hear stage, one of the ways to think about it is local versus systemic. Early stage cancer is often local, and treatment is aimed at removing or destroying the primary tumor. Then you've probably heard doctors say advanced stage cancer, which implies systemic behavior, detectable metastases, or very high likelihood of microscopic spread. And here is probably the most critical part that will matter later when we, when we get to exercise. Cancer cells don't teleport to metastasize. They have to physically enter circulation, the blood, or the. The lymph system. They have to survive a hostile journey, evade immune surveillance, and then successfully colonize a new environment, which is unbelievably difficult for a cell to do. And yet cancer is dangerous precisely because a small number of cells can occasionally succeed. That means that metastasis is not just a growth problem, It's a survival and trafficking problem. And the body's immune system, blood flow dynamics, and metabolic environment all influence whether those cells thrive or fail. Now, if we connect this to treatment, the reason why treatments work when they work is because they either remove the tumor completely or they reduce tumor burden to the point where the immune system can control what remains, or they eliminate enough malignant cells that metastases never establishes. And the reason why, unfortunately, treatments fail is often because microscopic disease, it was already present, or because a subset of cells were resistant to therapy, or because metastases had already begun. But what was still below the level of detection? And that's what I spoke about earlier, especially with pancreatic tumors and pancreatic cancer, it's a, it's often too small to detect in, like, stage one, stage two. It's just horrific. That's the foundation, because once you understand that cancer is about cells breaking rules and that death is usually about metastases, the question becomes, what factors influence the internal environment that these cells are trying to survive in, and what factors influence where the treatment is tolerated, completed, and effective? Before I move on, I want to make it very clear that I am not an oncologist. I'm a researcher, and I've done a lot of work on the correlation by a lot of work, a lot of research, and putting papers forward on the mechanisms between exercise and cancer. So if you learn anything from this, make sure that you obviously discuss it with your doctor. And if you do have a diagnosis of cancer, getting to your oncologist and speaking to them about all of the interventions that we're about to discuss. And now let's move into exercise now that I've given that disclaimer, I want to do it properly. I want to do it by looking at evidence category by category, starting with prevention. So let's talk about it. Prevention. Cancer prevention from exercise. So when we talk about exercise and cancer prevention, we're not talking about one study or one cancer or one mechanism. We're talking about a pattern that shows up across multiple large prospective cohorts. And the reason those cohorts matter is because they follow people for years, they measure lifestyle, and they watch who develops disease. And one of the most cited examples of this is the NIH AARP Diet and Health Study, which followed more than 150,000 adults and found that highly physical activity levels were associated with lower incidence of several cancers, including colorectal cancer, breast cancer. And importantly, those associations remained even after adjusting for body mass index. One of the best ways to improve brain energy metabolism is to make sure that you have adequate ketones circulating in your body. This is why I ingest ketone iq. I'm obsessed with ketones. They're one of the brain's most efficient energy sources, especially as we age and glucose handling changes. I use it for deep work or for long days when I want to focus without caffeine or crashes. But I also use it just in my day to day to make sure that I am neurologically adequately fueled. If you haven't tried ketones, you must. These ones taste great and you can get 30% off your subscription@ketone20.com neuroplus get a free gift with your second shipment. I mean, you see similar signals in this study, in the nurses health study and the health professionals follow up study where physical activity was associated with reduced colon cancer and in women, reduced breast cancer, again with adjustments for weight, smoking, alcohol and dietary patterns. So let's pause here. I'm going to tell you why adjustment matters, because this is the place where people collapse the logic into exercise prevents cancer because it makes you lose weight. That's not the data that it shows. In fact, what the researchers show were that when they adjusted, statistically, adjusted for BMI and the association persists, it tells us that exercise is doing something beyond weight loss. And that pushes us towards mechanisms like insulin regulation, chronic inflammation, immune surveillance and muscle metabolism. And this is also where I want to be precise, because not every cancer shows the same relationship with exercise. And that's not a weakness of the field, that's just a reflection of biology. Because cancer isn't one disease and different tissues respond differently to metabolic and immune signals. The cancers with the most consistent evidence base Tend to be colorectal cancer, Postmenopausal breast cancer, Endometrial cancer. And there's emerging evidence for additional cancers. But the strength of the evidence varies. Now, from here, I really want to take the next step, which is what happens when someone is not trying to prevent cancer in the abstract but is actually diagnosed and entering treatment. Because that's where exercise stops being a long term risk modifier and becomes something much more immediate, Affecting fatigue, muscle loss, dose completion, and in some cases, even tumor response. If prevention evidence is largely from large prospective cohorts, Treatment evidence is where you start to see randomized controlled trials. And this matters because in cancer research, Randomized trials are the standard that changes guidelines, Changes clinical practice, and changes what oncologists are willing to recommend. So there was a landmark trial, and it was called the care trial, which stands for combined aerobic and resistance exercise. And it looked at breast cancer patients undergoing chemotherapy. And what made this trial important Is that it wasn't trying to prove that exercise is nice and that it helps with weight loss and makes you happy. It was trying to test whether exercise could actually preserve function and reduce treatment toxicity In a high stress biological context, Meaning people receiving drugs that cause fatigue, Muscle loss, nausea, and systemic inflammation. So in the care trial, patients were randomized into different exercise prescriptions, including resistance training, anaerobic training. And what you consistently see across that body of work Is that exercise during chemotherapy Improves physical function and reduces fatigue. And in some analyses, resistance training in particular helped preserve lean mass. Which matters because lean mass is not just about strength. It's about metabolic reserve, it's about drug metabolism, and it's about whether the body can tolerate stress without spiraling into progressive deconditioning. My favorite go to snack lately is iq bar snacks. IQ bars, iq mix, hydration sticks, and iq joe mushroom coffee Are clean, low sugar, brain and body fuel. I keep iq bars in my bag for long days, Especially because you guys know how much I travel. I use the iq mix post workout and iq joe when I want clarity without overdoing coffee. And right now, IQ Bar is offering 20 off plus free shipping. And it's super easy. All you have to do is text neuro to six four triple zero. Again, that is neuro to six four triple zero. With what I just mentioned. We also see a similar pattern in other trials, Such as the erase trial. That's where exercise interventions were tested in cancer populations with outcomes that included not only fatigue and fitness, but also psychological endpoints like fear of cancer progression which is a big one, by the way, and we don't talk about that a lot, but there is actually a cognitive neuroscientist, I think she's out of Harvard, talks about the way that you think about longevity, the way that you think about aging, the way that you think about diseases really matters to the disease itself, really matters to how long you're going to live. Because the reality is that cancer treatment isn't just a physiological stressor, it's a psychological one. And if you can reduce symptoms while also improving a patient's sense of control and stability, you're improving the lived experience of treatment, which isn't a minor outcome. When treatment can last months or years, it's a huge outcome. So now the question people always ask at this point is, you're telling me exercise improves fatigue and function, but does it do anything that would matter to an oncologist in the way a drug matters? Meaning does it influence treatment completion, dose reductions, and the ability to stay on schedule? Because that's where long term outcomes are shaped. And this is where the evidence becomes particularly compelling, because when patients cannot tolerate treatment, oncologists are forced into dose reductions or delays. And dose intensity matters in so many cancers. So if an intervention improves the probability that patients complete what they're prescribed, that's not wellness, that's treatment support. In multiple trials, including work connected to the research line, exercise has been associated with improved treatment tolerance. And in some contexts, patients in resistance training arms were more likely to complete planned chemotherapy dose on schedule. And I'm being careful with language here, because not every trial shows the same magnitude of effect, but the directionality is consistent enough that it has influenced guideline bodies, including the American Society of Clinical Oncology, which issued formal guidance recommending that patients receiving curative intent treatment be advised to engage in both aerobic and resistance exercise, because the evidence base has moved beyond safe into clinically meaningful. Now, at this point, we need to make a distinction that most people never hear. It's one of the most important distinctions in the entire episode. So hear me strong on this, because there's exercise that helps people tolerate treatment. And then there's a separate question, which is whether exercise changes the tumor's response to treatment and itself. That's when we start talking about tumor profusion, oxygenation, and the delivery of chemotherapy and radiation to the tumor. Micro environment tumors are fascinating by nature. They develop abnormal blood vessels. And the reason that matters is because chemotherapy drugs need to reach tumor tissues through blood flow, and radiation works for far better in oxygenated Tissue and than in hypoxic tissue, low oxygen. So if you have a tumor that's poorly perfused and doesn't have a lot of oxygen, you can have a situation where treatment is given, but the micro environment is limiting its effectiveness. And we've seen this actually in preclinical studies published in journals like cancer research, which show that exercise can normalize tumor vasculature, meaning it can improve the structure and function of blood vessels within tumor tissue. And that normalization improves oxygenation and drug delivery. And that's the mechanism foundation that made researchers ask whether this could translate to humans. And it did translate to humans in a way that is really difficult to ignore. In a clinical study in rectal cancer patients published in medicine and science in sports and exercise, patients who exercised during neoadjuvant chemo radiation were more likely to achieve a pathologic complete response, Meaning when surgeons removed tissue after the chemo radiation phase, there was no detectable tumor left. And that outcome is not a surrogate marker. It's not a quality of life score. It's a real endpoint that cancer clinicians care about. So when you hear that natural question becomes, how could exercise be doing that? Because it sounds almost unbelievable until you connect it back to the tumor environment. Because if exercise increases perfusion, improves oxygenation, and improves delivery of therapeutic agents, then you've created a plausible pathway by which the same treatment becomes more effective. I want to go a bit further because I want to add nuance, because not every patient can or should do high intensity exercise during treatment. And not every cancer context has been studied equally. And some side effects can be exasperated by the wrong prescription. Which is why exercise oncology is not about telling everybody to just join a bootcamp. It's about appropriate dosing, supervision when necessary, and realistic plan that matches the patient's symptoms and the toxicity profile of their treatment. Okay, so let's move on to another hard bucket, which is the third bucket. And it's all about survivorship and reoccurrence, because survivorship sounds like the end of the story. But for many patients, it's the beginning of a different kind of stress. Because once treatment is over, the body is deconditioned, the person is psychologically changed, and the fear that the cancer will return can be persistent and consuming. So what do we know? Well, in survivorship research, we have two streams of evidence to pay attention to. One stream is about symptoms and function, Meaning exercise can help people recover from the physiological damage of treatment, Rebuild muscle, rebuild cardiovascular capacity, improve sleep, and reduce Anxiety and depression. Answer here across multiple randomized trials and meta analyses in exercise oncology is yes, exercise improves these outcomes. And this is one of the most robust parts of the evidence base. Even mild dehydration affects memory, mood and focus. And most people don't realize it. We literally use electrolytes in our brain. And I use cure hydration. It's a plant based electrolyte mix with no added sugar. And it's built on oral rehydration science. So water actually gets into your cells. I use it when I'm traveling, I use it on crazy days, but I use it just every single day. And I want you all to know that you don't need to be sweating to take hydration like this. If you want to try this, you can get 20% off at cure hydration.com neuro or use code neuro and you will get a bonus. This is an FSA HSA eligible, so go through, put that code in if you want to hydrate better. And then the second stream is, is the question everybody really wants answered, which is does exercise reduce reoccurrence and cancer specific mortality? And this is where the evidence base is stronger in some cancers than others and is still evolving. And it's also where study design matters because much of what we know comes from observational cohort studies of cancer survivors where researchers look at physical activity levels after diagnosis and follow people for reoccurrence and mortality outcomes. For example, there was a phenomenal study in colon cancer. This work was published in the New England Journal of Medicine which examined physical activity in stage 3 colon cancer survivors and found that higher levels of physical activity after treatment were associated with improved disease free survival and overall survival. And that's a landmark finding because it literally links post diagnosis behavior to outcomes that actually matter. There's also great work in breast cancer survivorship. Large observational studies and pooled analysis have consistently shown that higher levels of physical activity after diagnosis are associated with reduced breast cancer specific mortality. Although the magnitude varies and confounding is always a concern. Which is why the field has been publishing towards, you know, bigger, larger randomized control trials designed specifically to test these endpoints. But come on, the evidence is there. And one of the most important reasons we have to be careful here is because observational findings can be influenced by who is able to exercise. Because people who are healthier, who have less aggressive disease or who have better baseline function may exercise more. So you can automatically interpret association as causation even when the association is strong. So here's a question I have. Let's just take a pause here, because one of the questions I've always had is, if reoccurrence is often driven by microscopic metastatic cells that either escaped early or remained dormant, what does exercise plausibly do in that phase? So what does exercise do when the tumor is gone? What happens? And that's where we have to talk about metastasis, immune surveillance, circulation, and muscle. Again, because these aren't separate topics. They're the same story. So metastases is a trafficking problem and a survival. Cancer cells have to enter circulation, survive immune surveillance, survive mechanical stress, and then successfully colonize an organ that is not their original environment and that's metastatic. And there's mechanistic work that suggests exercise could influence several of these bottlenecks. One of the most interesting lines of evidence involves circulating tumor cells and shear stress. And oh, my God, this is probably my most favorite part of the entire episode. In microfluidic studies published in PNAS and Nature Communications, researchers exposed human cancer cells to flow conditions designed to mimic what happens during increased blood flow. And as she stress increased survival of circulating tumor cells decreased. When I say sheer stress, okay, I'm talking about the shunting of blood when you are in zone five. Remember, zone five is that 90% of maximum heart rate or above. Think about it. On the stairmaster at the Gym on level 15 and above, you're fighting for your life. So you've got the sheer force of blood just shunting through your system, all of this, okay? And it's believed that that sheer force can eliminate circulating tumor cells, which gives a mechanistic plausibility to the idea that repeated bouts of increased blood flow could make the circulatory environment less forgiving to tumor cells attempting to metastasize. I want you to really take that in. We are not at a point where we can say, go for a run or go on the stairmasters and you've solved metastases, because that would be so absurd. But what we can say is that exercise creates biological and mechanical conditions to make several steps in the metastatic process more difficult. We want to make it difficult for them. And that's a meaningful concept where metastasis. Metastasis is what kills people. Let's talk about regenerative skin repair, because when I think of skin aging, I think of it the same way of my brain aging, right? I don't want to look old and wrinkly. 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Well, exercise mobilizes natural killer cells and cytotoxic T cells. And in preclinical models, exercise increases immune cell infiltration into tumor tissue. And while human evidence is more complex, the concept is clear. Exercise is repeatedly activating and redistributing immune function. And immune function is central to suppressing malignant and cells. Those two mechanisms are phenomenal. And then there's metabolic signaling. This is what we always talk about. You've probably heard several physicians, several researchers talking about one thing. Exercise improves insulin sensitivity. It lowers insulin and IGF1 signaling. And exercise also reduces chronic inflammation, which changes the growth signals available to residual malignant cells. What else does exercise do? Well, there's the concept of muscle. Because survivorship often involves rebuilding from a state of physiological depletion. And the patients with low muscle mass are at a higher risk, not only for physical decline, but also for worse long term outcomes. And this is actually based on imaging prognostic studies. So let's slow it down and say something that actually matters. Physiologically, I would say this is where people either become overly hopeful or overly fatalistic. Exercise is, is not a guarantee and it's not an insurance policy in the sense people emotionally want it to be, because biology doesn't make promises. But exercise is one of the few interventions that repeatedly shows benefits across the entire cancer continuum, from reducing risk of certain types of cancers to improving treatment tolerance, to improving quality of life, to plausibly influencing mechanisms related to reoccurrence and metastatic potential. And this is why in modern oncology, exercise has moved from being nice to being increasingly described as a pillar of care. Before I close this episode, because this was just part One, I really wanted to introduce the evidence for exercise as a whole on cancer metastases, prognosis, prevalence. We need to do two things though. We need to talk about what this actually means because credibility depends on limitations and we need to give people a practical way to think about implementation without turning the this into, you know, generic fitness advice. So first, limitations. Not all cancers show the same relationship with exercise prevention in these studies. And that's expected because cancer is not one disease. Not all patients can tolerate the same intensity during treatment. And there are situations where symptoms can be exasperated by exercise, particularly severe gastrointestinal toxicity, radiation related skin injury and neuropathy. And there's other safety concerns with bone metastases where fracture risk must be accepted or respected. If you're starting to get gray hair, then this is for you. 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You know, we've got a lot of the observational evidence is quite compelling. In cancers like colon and breast cancer, it's not the same as randomized evidence. So we have to be honest about that. But from a practical frame, I want to leave you with this. Not a workout plan, but a decision framework. So if you're listening to this as prevention, the strongest evidence supports meeting public health guidelines for moderate to vigorous physical activity with added resistance training, because the data shows that both aerobic capacity and muscle mass are biologically protective. If you're listening to this during treatment, treatment, the goal is not performance, it's preservation, meaning preserve muscle, preserve function, preserve sleep, preserve mood, and support treatment completion. And that usually means a combination of aerobic and resistance exercise scaled to what you can tolerate, ideally within medical guidelines. If you're listening to this and you're a survivor, the goal becomes about rebuilding physiological reserve that treatment eroded and continuing a pattern of repeated immune and metabolic signaling like, you need to go out there and regain your muscle mass, regain your strength, regain your aerobic activity and capacity. And if there's one sentence that captures the entire scientific arc, it's that exercise does not work as a motivational concept. It works as a repeated physiological stress that remodels metabolism, immunity, circulation, and muscle. And those are the systems cancer interacts with at every stage. I'll see you for part two.